WorldWideScience

Sample records for experimental focal brain

  1. Experimental Focal Cerebral Ischemia

    DEFF Research Database (Denmark)

    Christensen, Thomas

    2007-01-01

    brain damage. Finally, the effect on infarct volume one week after MCAO of treatment with Pinokalant, a new broad-spectrum cation channel blocker, was examined in the seventh study. The results of these studies are presented and discussed in relation to the current knowledge of the pathogenetic...... recruitment of penumbra to infarct resulting in mitigation of the final ischemic brain damage. The pathogenetic mechanisms involved in ischemic cell death in the penumbra encompass excitotoxic mechanisms mediated by activation of ionotropic glutamate receptors, loss of cellular calcium homeostasis...... are irreversibly damaged after only 15-30 minutes of ischemia. In contrast, cells in the penumbra may – although threatened and functionally impaired – remain viable for several hours following arterial occlusion but will eventually also succumb if ischemia persists. In this way the initially viable tissue...

  2. COX-2 regulation and TUNEL-positive cell death differ between genders in the secondary inflammatory response following experimental penetrating focal brain injury in rats.

    Science.gov (United States)

    Günther, Mattias; Plantman, Stefan; Davidsson, Johan; Angéria, Maria; Mathiesen, Tiit; Risling, Mårten

    2015-04-01

    Traumatic brain injury is followed by secondary neuronal degeneration, largely dependent on an inflammatory response. This response is probably gender specific, since females are better protected than males in experimental models. The reasons are not fully known. We examined aspects of the inflammatory response following experimental TBI in male and female rats to explore possible gender differences at 24 h and 72 h after trauma, times of peak histological inflammation and neuronal degeneration. A penetrating brain injury model was used to produce penetrating focal TBI in 20 Sprague-Dawley rats, 5 males and 5 females for each time point. After 24 and 72 h the brains were removed and subjected to in situ hybridization and immunohistochemical analyses for COX-2, iNOS, osteopontin, glial fibrillary acidic protein, 3-nitrotyrosine, TUNEL and Fluoro-Jade. COX-2 mRNA and protein levels were increased in the perilesional area compared to the uninjured contralateral side and significantly higher in males at 24 h and 72 h (p genders. COX-2 regulation differed between genders after TBI. The increased COX-2 expression in male rats correlated with increased apoptotic cell death detected by increased TUNEL staining at 24 h, but not with neuronal necrosis measured by Flouro-Jade. Astrogliosis and microgliosis did not differ, confirming a comparable level of trauma. The gender-specific trait of the secondary inflammatory response may be connected to prostaglandin regulation, which may partially explain gender variances in outcome after TBI.

  3. Effects of the Combination Therapy with ‍Candesartan and Alpha Tocopherol on Brain injury and Edema Following Brain Ischemia in Experimental Model of Transient Focal Cerebral Ischemia in Rats

    Directory of Open Access Journals (Sweden)

    Hamdollah Panahpour

    2016-07-01

    Full Text Available Background & objectives: Stroke is third leading cause of death and disability in the most of human communities. Several experimental studies have shown that combination therapy with drugs that act via different mechanisms can produce amplified protective effects. We examined the effects of combination therapy with candesartan and alpha tocopherol against cerebral ischemia. Methods: Male Sprague-Dawley rats were divided into five groups (n=24: sham, control ischemic, candesartan treated (0.3 mg/kg, alpha tocopherol treated (30 mg/kg and combined treated ischemic groups. Transient focal cerebral ischemia was induced by 90-min-long occlusion of the left middle cerebral artery followed by 24-h-long reperfusion. Neurological deficit score was evaluated at the end of the reperfusion period. Thereafter, the animals were randomly used for measurement of the infarct volumes and investigation of ischemic brain edema formation using a wet/dry method. Results: Induction of cerebral ischemia produced considerable brain infarction in conjunction with severely impaired motor functions and edema formation. Combined treatment with candesartan and alpha tocopherol significantly reduced the infarct volume and lowered the water content in the ischemic lesioned hemisphere. These effects on brain edema and oxidative stress biomarkers were significantly more than the monotherapy with candesartan. Conclusion: The combination therapy with candesartan and alpha tocopherol can noticeably decrease ischemic brain injury and attenuate edema formation likely via increasing the antioxidant activity.

  4. Visual agnosia and focal brain injury.

    Science.gov (United States)

    Martinaud, O

    Visual agnosia encompasses all disorders of visual recognition within a selective visual modality not due to an impairment of elementary visual processing or other cognitive deficit. Based on a sequential dichotomy between the perceptual and memory systems, two different categories of visual object agnosia are usually considered: 'apperceptive agnosia' and 'associative agnosia'. Impaired visual recognition within a single category of stimuli is also reported in: (i) visual object agnosia of the ventral pathway, such as prosopagnosia (for faces), pure alexia (for words), or topographagnosia (for landmarks); (ii) visual spatial agnosia of the dorsal pathway, such as cerebral akinetopsia (for movement), or orientation agnosia (for the placement of objects in space). Focal brain injuries provide a unique opportunity to better understand regional brain function, particularly with the use of effective statistical approaches such as voxel-based lesion-symptom mapping (VLSM). The aim of the present work was twofold: (i) to review the various agnosia categories according to the traditional visual dual-pathway model; and (ii) to better assess the anatomical network underlying visual recognition through lesion-mapping studies correlating neuroanatomical and clinical outcomes. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

  5. Aromatase and neuroinflammation in rat focal brain ischemia.

    Science.gov (United States)

    Zhong, Yu H; Dhawan, Jasbeer; Kovoor, Joel A; Sullivan, John; Zhang, Wei X; Choi, Dennis; Biegon, Anat

    2017-11-01

    Accumulating evidence suggests that expression of aromatase, the enzyme responsible for the conversion of androgens to estrogens, is transiently upregulated in rat stroke models. It was further suggested that increased aromatase expression is linked to neuroinflammation and that it is neuroprotective in females. Our goal was to investigate aromatase upregulation in male rats subjected to experimental stroke in relationship to neuroinflammation, infarct and response to treatment with different putative neuroprotective agents. Intact male rats were subjected to transient (90min) middle cerebral artery occlusion (MCAO) and administered selfotel (N-methyl-d-aspartic acid (NMDA) receptor competitive antagonist), TPEN (a zinc chelator), a combination of the two drugs or vehicle, injected immediately after reperfusion. Animals were killed 14days after MCAO and consecutive brain sections used to measure aromatase expression, cerebral infarct volume and neuroinflammation. Quantitative immunohistochemistry (IHC) demonstrated increased brain aromatase expression in the peri-infarct area relative to contralesional area, which was partially abrogated by neuroprotective agents. There was no correlation between aromatase expression in the peri-infarct zone and infarct volume, which was reduced by neuroprotective agents. Microglial activation, measured by quantitative autoradiography, was positively correlated with infarct and inversely correlated with aromatase expression in the peri-infarct zone. Our findings indicate that focal ischemia upregulates brain aromatase in the male rat brain at 14days post surgery, which is within the time frame documented in females. However, the lack of negative correlation between aromatase expression and infarct volume and lack of positive correlation between microgliosis and aromatase do not support a major role for aromatase as a mediator of neuroprotection or a causal relationship between microglial activation and increased aromatase

  6. Cube propagation for focal brain atrophy estimation

    DEFF Research Database (Denmark)

    Pai, Akshay Sadananda Uppinakudru; Sørensen, Lauge; Darkner, Sune

    2013-01-01

    Precise and robust whole brain, ventricle, and hippocampal atrophy measurements are important as they serve as biomarkers for Alzheimer’s disease. They are used as secondary outcomes in drug trials, and they correlate with the cognitive scores. When two successive scans are non-linearly aligned...

  7. Management of HIV-associated focal brain lesions in developing ...

    African Journals Online (AJOL)

    Background. HIV-associated focal brain lesions (FBLs) are caused by opportunistic infections, neoplasms, or cerebrovascular diseases. In developed countries toxoplasma encephalitis (TE) is the most frequent cause followed by primary CNS lymphoma (PCNSL). Guidelines based on these causes have been proposed ...

  8. Selenium toxicity and porcine focal symmetrical poliomyelomalacia: description of a field outbreak and experimental reproduction.

    Science.gov (United States)

    Wilson, T M; Scholz, R W; Drake, T R

    1983-10-01

    An acute afebrile paretic condition was diagnosed in 18 of 225 feeder pigs between eight to ten weeks of age. Nine pigs died acutely, seven pigs were euthanatized and two appeared to recover. Macroscopic lesions in the ventral horns of the cervical and lumbar/sacral spinal cord enlargements consisted of focal, bilateral, depressed areas. Histopathologically, the lesion consisted of endothelial proliferation, glial cell reaction and microcavitation. Similar lesions were observed in some brain stem motor nuclei. High selenium levels were detected in the pig feed and in pig tissues and blood. Two of five experimental pigs fed a commercial grower ration and supplemented with 52 ppm selenium as sodium selenite developed paresis and paralysis after a 29 day feeding trial. Histopathological lesions of focal symmetrical poliomyelomalacia confined to the cervical and lumbar/sacral spinal cord enlargements, and identical to those in the field cases, were produced. Select brain stem motor nuclei were also affected.

  9. Porcine focal symmetrical poliomyelomalacia: experimental reproduction with oral doses of encapsulated sodium selenite.

    Science.gov (United States)

    Wilson, T M; Hammerstedt, R H; Palmer, I S; deLahunta, A

    1988-01-01

    Sodium selenite (encapsulated as doses of 1.4 mg, 2.6 mg and 4.2 mg per kilogram of body weight) was given orally on a daily basis to male weaner pigs, and features of these animals were compared to a control group. Porcine focal symmetrical poliomyelomalacia was produced in all experimental groups between 3 and 20 days after initiation of the treatment. Analysis of blood and several tissues revealed an elevated selenium content for all pigs. Histological lesions in the brain and the cervical lumbar/sacral spinal cord enlargements included endothelial proliferation, neuronal degeneration, microcavitation and glial cell reaction.

  10. Porcine focal symmetrical poliomyelomalacia: experimental reproduction with oral doses of encapsulated sodium selenite.

    OpenAIRE

    Wilson, T.M.; Hammerstedt, R H; Palmer, I S; deLahunta, A

    1988-01-01

    Sodium selenite (encapsulated as doses of 1.4 mg, 2.6 mg and 4.2 mg per kilogram of body weight) was given orally on a daily basis to male weaner pigs, and features of these animals were compared to a control group. Porcine focal symmetrical poliomyelomalacia was produced in all experimental groups between 3 and 20 days after initiation of the treatment. Analysis of blood and several tissues revealed an elevated selenium content for all pigs. Histological lesions in the brain and the cervical...

  11. Spontaneous gesture and spatial language: Evidence from focal brain injury

    Science.gov (United States)

    Göksun, Tilbe; Lehet, Matthew; Malykhina, Katsiaryna; Chatterjee, Anjan

    2015-01-01

    People often use spontaneous gestures when communicating spatial information. We investigated focal brain-injured individuals to test the hypotheses that (1) naming motion event components of manner-path (represented by verbs-prepositions in English) are impaired selectively, (2) gestures compensate for impaired naming. Patients with left or right hemisphere damage (LHD or RHD) and elderly control participants were asked to describe motion events (e.g., running across) depicted in brief videos. Damage to the left posterior middle frontal gyrus, left inferior frontal gyrus, and left anterior superior temporal gyrus (aSTG) produced impairments in naming paths of motion; lesions to the left caudate and adjacent white matter produced impairments in naming manners of motion. While the frequency of spontaneous gestures were low, lesions to the left aSTG significantly correlated with greater production of path gestures. These suggest that producing prepositions-verbs can be separately impaired and gesture production compensates for naming impairments when damage involves left aSTG. PMID:26283001

  12. Automatic 3D graph cuts for brain cortex segmentation in patients with focal cortical dysplasia.

    Science.gov (United States)

    Despotović, Ivana; Segers, Ief; Platisa, Ljiljana; Vansteenkiste, Ewout; Pizurica, Aleksandra; Deblaere, Karel; Philips, Wilfried

    2011-01-01

    In patients with intractable epilepsy, focal cortical dysplasia (FCD) is the most frequent malformation of cortical development. Identification of subtle FCD lesions using brain MRI scans is very often based on the cortical thickness measurement, where brain cortex segmentation is required as a preprocessing step. However, the accuracy of the selected segmentation method can highly affect the final FCD lesion detection. In this work, we propose an improved graph cuts algorithm integrating Markov random field-based energy function for more accurate brain cortex MRI segmentation. Our method uses three-label graph cuts and preforms automatic 3D MRI brain cortex segmentation integrating intensity and boundary information. The performance of the method is tested on both simulated MR brain images with different noise levels and real patients with FCD lesions. Experimental quantitative segmentation results showed that the proposed method is effective, robust to noise and achieves higher accuracy than other popular brain MRI segmentation methods. The qualitative validation, visually verified by a medical expert, showed that the FCD lesions were segmented well as a part of the cortex, indicating increased thickness and cortical deformation. The proposed technique can be successfully used in this, as well as in many other clinical applications.

  13. Diffuse and Focal Brain Injury in a Large Animal Model of PTE: Mechanisms Underlying Epileptogenesis

    Science.gov (United States)

    2017-10-01

    electrode technology , and wireless enclosure have significant interest and applications outside of PTE. There are many free roaming large animal...Electrophysiology Diffuse brain injury Focal brain injury Axonal pathology Epilepsy monitoring unit Chronic Implantation Wireless telemetry...Conclusions: A) Contusion injury validation and neuropathology B) Grid electrode development and testing C) Wireless Large Animal Custom Enclosure

  14. Phagocytosis executes delayed neuronal death after focal brain ischemia

    OpenAIRE

    Neher, Jonas J.; Emmrich, Julius V.; Fricker, Michael; Mander, Palwinder K.; Théry, Clotilde; Brown, Guy C.

    2013-01-01

    Brain ischemia is a major cause of death and disability worldwide, but the cellular mechanisms of delayed neuronal loss and brain atrophy after cerebral ischemia are poorly understood and thus currently untreatable. Surprisingly, we find that after cerebral ischemia, brain macrophages phagocytose viable and functional neurons, causing brain atrophy and motor dysfunction. Our data show that delayed neuronal death and functional impairment after cerebral ischemia can be prevented by blocking sp...

  15. Boosting Focally-Induced Brain Plasticity by Dopamine

    National Research Council Canada - National Science Library

    Kuo, Min-Fang; Paulus, Walter; Nitsche, Michael A

    2008-01-01

    .... Transcranial direct current stimulation (tDCS) induces cortical excitability enhancement by anodal and depression by cathodal brain polarization, which is not restricted to specific subgroups of synapses...

  16. Brain Source Imaging in Preclinical Rat Models of Focal Epilepsy using High-Resolution EEG Recordings.

    Science.gov (United States)

    Bae, Jihye; Deshmukh, Abhay; Song, Yinchen; Riera, Jorge

    2015-06-06

    Electroencephalogram (EEG) has been traditionally used to determine which brain regions are the most likely candidates for resection in patients with focal epilepsy. This methodology relies on the assumption that seizures originate from the same regions of the brain from which interictal epileptiform discharges (IEDs) emerge. Preclinical models are very useful to find correlates between IED locations and the actual regions underlying seizure initiation in focal epilepsy. Rats have been commonly used in preclinical studies of epilepsy; hence, there exist a large variety of models for focal epilepsy in this particular species. However, it is challenging to record multichannel EEG and to perform brain source imaging in such a small animal. To overcome this issue, we combine a patented-technology to obtain 32-channel EEG recordings from rodents and an MRI probabilistic atlas for brain anatomical structures in Wistar rats to perform brain source imaging. In this video, we introduce the procedures to acquire multichannel EEG from Wistar rats with focal cortical dysplasia, and describe the steps both to define the volume conductor model from the MRI atlas and to uniquely determine the IEDs. Finally, we validate the whole methodology by obtaining brain source images of IEDs and compare them with those obtained at different time frames during the seizure onset.

  17. Experimental Realization of a Metamaterial Detector Focal Plane Array

    Science.gov (United States)

    Shrekenhamer, David; Xu, Wangren; Venkatesh, Suresh; Schurig, David; Sonkusale, Sameer; Padilla, Willie J.

    2012-10-01

    We present a metamaterial absorber detector array that enables room-temperature, narrow-band detection of gigahertz (GHz) radiation in the S band (2-4 GHz). The system is implemented in a commercial printed circuit board process and we characterize the detector sensitivity and angular dependence. A modified metamaterial absorber geometry allows for each unit cell to act as an isolated detector pixel and to collectively form a focal plane array . Each pixel can have a dedicated microwave receiver chain and functions together as a hybrid device tuned to maximize the efficiency of detected power. The demonstrated subwavelength pixel shows detected sensitivity of -77dBm, corresponding to a radiation power density of 27nW/m2, with pixel to pixel coupling interference below -14dB at 2.5 GHz.

  18. Experimental realization of a metamaterial detector focal plane array.

    Science.gov (United States)

    Shrekenhamer, David; Xu, Wangren; Venkatesh, Suresh; Schurig, David; Sonkusale, Sameer; Padilla, Willie J

    2012-10-26

    We present a metamaterial absorber detector array that enables room-temperature, narrow-band detection of gigahertz (GHz) radiation in the S band (2-4 GHz). The system is implemented in a commercial printed circuit board process and we characterize the detector sensitivity and angular dependence. A modified metamaterial absorber geometry allows for each unit cell to act as an isolated detector pixel and to collectively form a focal plane array . Each pixel can have a dedicated microwave receiver chain and functions together as a hybrid device tuned to maximize the efficiency of detected power. The demonstrated subwavelength pixel shows detected sensitivity of -77 dBm, corresponding to a radiation power density of 27 nW/m(2), with pixel to pixel coupling interference below -14 dB at 2.5 GHz.

  19. Increased segregation of brain networks in focal epilepsy: An fMRI graph theory finding.

    Science.gov (United States)

    Pedersen, Mangor; Omidvarnia, Amir H; Walz, Jennifer M; Jackson, Graeme D

    2015-01-01

    Focal epilepsy is conceived of as activating local areas of the brain as well as engaging regional brain networks. Graph theory represents a powerful quantitative framework for investigation of brain networks. Here we investigate whether functional network changes are present in extratemporal focal epilepsy. Task-free functional magnetic resonance imaging data from 15 subjects with extratemporal epilepsy and 26 age and gender matched healthy controls were used for analysis. Local network properties were calculated using local efficiency, clustering coefficient and modularity metrics. Global network properties were assessed with global efficiency and betweenness centrality metrics. Cost-efficiency of the networks at both local and global levels was evaluated by estimating the physical distance between functionally connected nodes, in addition to the overall numbers of connections in the network. Clustering coefficient, local efficiency and modularity were significantly higher in individuals with focal epilepsy than healthy control subjects, while global efficiency and betweenness centrality were not significantly different between the two groups. Local network properties were also highly efficient, at low cost, in focal epilepsy subjects compared to healthy controls. Our results show that functional networks in focal epilepsy are altered in a way that the nodes of the network are more isolated. We postulate that network regularity, or segregation of the nodes of the networks, may be an adaptation that inhibits the conversion of the interictal state to seizures. It remains possible that this may be part of the epileptogenic process or an effect of medications.

  20. Alzheimer and vascular brain diseases: Focal and diffuse subforms

    Directory of Open Access Journals (Sweden)

    Eliasz Engelhardt

    Full Text Available Alois Alzheimer is best known for his description of the pre-senile neurodegenerative disease named after him. However, his previous interest in vascular brain diseases, underlying cognitive and behavioral changes, was very strong. Besides describing the Arteriosclerotic atrophy of the brain and the arteriosclerotic subtype of Senile dementia which he viewed as main forms of vascular brain diseases, he also identified and described a series of conditions he considered subforms. These may be divided, as suggested by the authors of the present paper, into 3 groups: gliosis and sclerosis, subcortical atrophies, and apoplectic. The subforms of the three groups present characteristic neuropathological features and clinical, cognitive and behavioral manifestations. These provide the basis, together with part of the main forms, for the contemporary condition known as Vascular Cognitive Impairment.

  1. Network localization of neurological symptoms from focal brain lesions.

    Science.gov (United States)

    Boes, Aaron D; Prasad, Sashank; Liu, Hesheng; Liu, Qi; Pascual-Leone, Alvaro; Caviness, Verne S; Fox, Michael D

    2015-10-01

    A traditional and widely used approach for linking neurological symptoms to specific brain regions involves identifying overlap in lesion location across patients with similar symptoms, termed lesion mapping. This approach is powerful and broadly applicable, but has limitations when symptoms do not localize to a single region or stem from dysfunction in regions connected to the lesion site rather than the site itself. A newer approach sensitive to such network effects involves functional neuroimaging of patients, but this requires specialized brain scans beyond routine clinical data, making it less versatile and difficult to apply when symptoms are rare or transient. In this article we show that the traditional approach to lesion mapping can be expanded to incorporate network effects into symptom localization without the need for specialized neuroimaging of patients. Our approach involves three steps: (i) transferring the three-dimensional volume of a brain lesion onto a reference brain; (ii) assessing the intrinsic functional connectivity of the lesion volume with the rest of the brain using normative connectome data; and (iii) overlapping lesion-associated networks to identify regions common to a clinical syndrome. We first tested our approach in peduncular hallucinosis, a syndrome of visual hallucinations following subcortical lesions long hypothesized to be due to network effects on extrastriate visual cortex. While the lesions themselves were heterogeneously distributed with little overlap in lesion location, 22 of 23 lesions were negatively correlated with extrastriate visual cortex. This network overlap was specific compared to other subcortical lesions (P network overlap in cortical areas previously implicated in symptom expression (P brain regions involved in symptom expression; and (ii) publically available human connectome data can be used to incorporate these network effects into traditional lesion mapping approaches. Because the current technique

  2. Experimental focal cerebral ischemia : Optimization of models and therapeutic interventions

    NARCIS (Netherlands)

    Shanbhag, Nagesh Chandrakant

    2016-01-01

    Stroke is the second most common cause of death and leading cause of adult disability, accounting for 11% of total deaths worldwide. Ischemic stroke (80% of all cases) results from a blood clot formation in an artery to or in the brain resulting in ischemic damage and neurological impairment. Many

  3. Management of HIV-associated focal brain lesions in developing coun

    African Journals Online (AJOL)

    guidelines and approaches to the management of HIV-associated FBL have been effective in developed countries. In developing countries infections are the main cause of FBL associated. ORIGINAL ARTICLE. 5. SA JOURNAL OF RADIOLOGY • July 2005. Management of. HIV-associated focal brain lesions in developing ...

  4. In vivo inhibition of incorporation of (U-/sup 14/C)glucose into proteins in experimental focal epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Coutinho-Netto, J.; Boyar, M.M.; Abdul-Ghani, A.S.; Bradford, H.F.

    1982-08-01

    The in vivo incorporation of (/sup 14/C) from (U-/sup 14/C)-glucose into rat brain proteins from different cortical areas was examined in three different experimental focal epilepsies: cobalt, freeze-lesions, and tityustoxin. When (U-/sup 14/C)-glucose was injected intraperitoneally into awake and unrestrained animals with marked signs of epileptic hyperactivity, the inhibition of incorporation of (/sup 14/C)-amino acids into trichloracetic acid (TCA)-insoluble proteins was highest in the focal (sensorimotor) area when compared with distant regions (approx. 60%), but less when compared with the contralateral (sensorimotor) region (approx. 23%). Greatly decreased incorporation caused by both cobalt and freeze-lesion-induced epilepsies was also observed in the contralateral area when a comparison was made with distant regions (approx. 50%), but there were no significant differences in protein-specific radioactivity between the different distant areas.

  5. Abnormal functional brain network in epilepsy patients with focal cortical dysplasia.

    Science.gov (United States)

    Jeong, Woorim; Jin, Seung-Hyun; Kim, Museong; Kim, June Sic; Chung, Chun Kee

    2014-11-01

    Focal cortical dysplasia (FCD) is the second most common pathological entity in surgically treated neocortical focal epilepsy. Despite the recent increase of interest in network approaches derived from graph theory on epilepsy, resting state network analysis of the FCD brain has not been adequately investigated. In this study, we investigated the difference in the resting state functional network between epilepsy patients with FCD and healthy controls using whole-brain magnetoencephalography (MEG) recordings. Global mutual information (MIglob) and global efficiency (Eglob) were calculated for theta (4-7 Hz), alpha (8-12 Hz), beta (13-30 Hz), and gamma (31-45 Hz) bands in 35 epilepsy patients with FCD and 23 healthy controls. Resting state FCD brains had stronger functional connectivity (MIglob) in the beta and gamma bands and higher functional efficiency (Eglob) in the beta and gamma bands than those of the controls (ptype I and II brains in the beta band were higher than those of healthy control brains (ptype II brains were higher than those of control and FCD type I brains (ptype of FCD. The resting state network analysis could be useful in a clinical setting because we observed network differences even when there was no prominent interictal spike activity. Copyright © 2014 Elsevier B.V. All rights reserved.

  6. Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

    Directory of Open Access Journals (Sweden)

    Jintanaporn Wattanathorn

    2011-01-01

    Full Text Available Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO. Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA, superoxide dismutase (SOD, catalase (CAT, and glutathione peroxidase (GSH-Px in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia.

  7. Zingiber officinale Mitigates Brain Damage and Improves Memory Impairment in Focal Cerebral Ischemic Rat

    Science.gov (United States)

    Wattanathorn, Jintanaporn; Jittiwat, Jinatta; Tongun, Terdthai; Muchimapura, Supaporn; Ingkaninan, Kornkanok

    2011-01-01

    Cerebral ischemia is known to produce brain damage and related behavioral deficits including memory. Recently, accumulating lines of evidence showed that dietary enrichment with nutritional antioxidants could reduce brain damage and improve cognitive function. In this study, possible protective effect of Zingiber officinale, a medicinal plant reputed for neuroprotective effect against oxidative stress-related brain damage, on brain damage and memory deficit induced by focal cerebral ischemia was elucidated. Male adult Wistar rats were administrated an alcoholic extract of ginger rhizome orally 14 days before and 21 days after the permanent occlusion of right middle cerebral artery (MCAO). Cognitive function assessment was performed at 7, 14, and 21 days after MCAO using the Morris water maze test. The brain infarct volume and density of neurons in hippocampus were also determined. Furthermore, the level of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px) in cerebral cortex, striatum, and hippocampus was also quantified at the end of experiment. The results showed that cognitive function and neurons density in hippocampus of rats receiving ginger rhizome extract were improved while the brain infarct volume was decreased. The cognitive enhancing effect and neuroprotective effect occurred partly via the antioxidant activity of the extract. In conclusion, our study demonstrated the beneficial effect of ginger rhizome to protect against focal cerebral ischemia. PMID:21197427

  8. Selenium toxicity and porcine focal symmetrical poliomyelomalacia: description of a field outbreak and experimental reproduction.

    OpenAIRE

    Wilson, T.M.; SCHOLZ, R. W.; Drake, T R

    1983-01-01

    An acute afebrile paretic condition was diagnosed in 18 of 225 feeder pigs between eight to ten weeks of age. Nine pigs died acutely, seven pigs were euthanatized and two appeared to recover. Macroscopic lesions in the ventral horns of the cervical and lumbar/sacral spinal cord enlargements consisted of focal, bilateral, depressed areas. Histopathologically, the lesion consisted of endothelial proliferation, glial cell reaction and microcavitation. Similar lesions were observed in some brain ...

  9. Dominant expression of angiogenin in NeuN positive cells in the focal ischemic rat brain.

    Science.gov (United States)

    Huang, Li; Huang, Yining; Guo, Huailian

    2009-10-15

    Angiogenin (ANG) is a potent angiogenic factor. The purposes of this study were to observe the change of the expression level of ANG and to identify the cell types that express ANG in the focal ischemic rat brain. The rat brain ischemia-reperfusion model was produced by a 2 h occlusion of the left middle cerebral artery with a nylon thread followed by reperfusion for 1 day, 3 days, 7 days or 14 days. The expression levels of ANG in the rat brain at each time points were determined by western blotting. The co-staining of ANG with NeuN was observed using double immunofluorescent labeling combined with confocal laser scanning microscope. We found that the expression level of ANG increased significantly in the rat brain 1 day, 3 days, and 7 days after ischemia (Pbrain after ischemia. The upregulated ANG was mostly expressed by neurons.

  10. Valvular heart disease by transthoracic echocardiography is associated with focal brain injury and central neuropsychiatric systemic lupus erythematosus.

    Science.gov (United States)

    Roldan, Carlos A; Gelgand, Erika A; Qualls, Clifford R; Sibbitt, Wilmer L

    2007-01-01

    Previous studies using transesophageal echocardiography (TEE) report an association of valvular heart disease (VHD) with cerebral infarcts and central neuropsychiatric systemic lupus erythematosus (NPSLE). However, TEE cannot be routinely used. To determine if VHD detected by transthoracic echocardiography (TTE) is associated with focal brain injury on magnetic resonance imaging (MRI) and secondarily with central NPSLE. Sixty-nine patients with systemic lupus erythematosus underwent general clinical, neuropsychiatric and laboratory evaluations followed by MRI of the brain and TTE. Forty-one patients (59%) had NPSLE (stroke, transient ischemic attack, cognitive dysfunction, acute confusional state, seizures or psychosis); 46 (67%) had focal brain injury on MRI (cerebral infarcts, white matter lesions or small punctate lesions); 38 (55%) had VHD (vegetations, thickening or regurgitation). VHD was more common in patients with than in those without focal brain injury and NPSLE (all p < 0.05); focal brain lesions were more common in patients with than in those without NPSLE (all p < 0.04); and VHD was an independent predictor of focal brain lesions and NPSLE (both p < 0.04). In patients with systemic lupus erythematosus, VHD detected by TTE is associated with focal brain injury and NPSLE. (c) 2007 S. Karger AG, Basel.

  11. LOTUS overexpression accelerates neuronal plasticity after focal brain ischemia in mice.

    Science.gov (United States)

    Takase, Hajime; Kurihara, Yuji; Yokoyama, Taka-Akira; Kawahara, Nobutaka; Takei, Kohtaro

    2017-01-01

    Nogo receptor-1 (NgR1) and its ligands inhibit neuronal plasticity and limit functional recovery after brain damage such as ischemic stroke. We have previously shown that lateral olfactory tract usher substance (LOTUS) antagonizes NgR1-mediated signaling. Here, we investigated whether LOTUS enhances neuronal plasticity and functional recovery after brain focal ischemia in adult mice. Focal ischemic infarcts were induced in wild-type and LOTUS-overexpressing transgenic mice via middle cerebral artery occlusion. Endogenous LOTUS expression was increased in brain and cervical spinal cord of the contralateral side of ischemia in the chronic phase after brain ischemia. LOTUS overexpression accelerated midline-crossing axonal sprouting from the contralateral side to the ipsilateral side of ischemia in the medullar reticular formation and gray matter of denervated cervical spinal cord. Importantly, LOTUS overexpression improved neurological score highly correlated with laterality ratio of corticoreticular fibers of the medulla oblongata, indicating that LOTUS overexpression may overcome the inhibitory environment induced by NgR1 signaling for damaged motor pathway reconstruction after ischemic stroke. Thus, our data suggest that LOTUS overexpression accelerates neuronal plasticity in the brainstem and cervical spinal cord after stroke and LOTUS administration is useful for future therapeutic strategies.

  12. Value of repeat brain MRI in children with focal epilepsy and negative findings on initial MRI

    Energy Technology Data Exchange (ETDEWEB)

    Jeon, Tae Yeon; Kim, Ji Hye; Lee, Jee Hun; Yoo, So Young; Hwang, Sook Min; Lee, Mun Hyang [Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2017-08-01

    To evaluate the value of repeat brain magnetic resonance imaging (MRI) in identifying potential epileptogenic lesions in children with initial MRI-negative focal epilepsy. Our Institutional Review Board approved this retrospective study and waived the requirement for informed consent. During a 15-year period, 257 children (148 boys and 109 girls) with initial MRI-negative focal epilepsy were included. After re-evaluating both initial and repeat MRIs, positive results at repeat MRI were classified into potential epileptogenic lesions (malformation of cortical development and hippocampal sclerosis) and other abnormalities. Contributing factors for improved lesion conspicuity of the initially overlooked potential epileptogenic lesions were analyzed and classified into lesion factors and imaging factors. Repeat MRI was positive in 21% (55/257) and negative in 79% cases (202/257). Of the positive results, potential epileptogenic lesions comprised 49% (27/55) and other abnormalities comprised 11% of the cases (28/257). Potential epileptogenic lesions included focal cortical dysplasia (n = 11), hippocampal sclerosis (n = 10), polymicrogyria (n = 2), heterotopic gray matter (n = 2), microlissencephaly (n = 1), and cortical tumor (n = 1). Of these, seven patients underwent surgical resection. Contributing factors for new diagnoses were classified as imaging factors alone (n = 6), lesion factors alone (n = 2), both (n = 18), and neither (n = 1). Repeat MRI revealed positive results in 21% of the children with initial MRI-negative focal epilepsy, with 50% of the positive results considered as potential epileptogenic lesions. Enhanced MRI techniques or considering the chronological changes of lesions on MRI may improve the diagnostic yield for identification of potential epileptogenic lesions on repeat MRI.

  13. Pathophysiology and neuroprotection of global and focal perinatal brain injury: lessons from animal models.

    Science.gov (United States)

    Titomanlio, Luigi; Fernández-López, David; Manganozzi, Lucilla; Moretti, Raffaella; Vexler, Zinaida S; Gressens, Pierre

    2015-06-01

    Arterial ischemic stroke occurs more frequently in term newborns than in the elderly, and brain immaturity affects mechanisms of ischemic injury and recovery. The susceptibility to injury of the brain was assumed to be lower in the perinatal period as compared with childhood. This concept was recently challenged by clinical studies showing marked motor disabilities after stroke in neonates, with the severity of motor and cortical sensory deficits similar in both perinatal and childhood ischemic stroke. Our understanding of the triggers and the pathophysiological mechanisms of perinatal stroke has greatly improved in recent years, but many factors remain incompletely understood. In this review, we focus on the pathophysiology of perinatal stroke and on therapeutic strategies that can protect the immature brain from the consequences of stroke by targeting inflammation and brain microenvironment. Studies in neonatal rodent models of cerebral ischemia have suggested a potential role for soluble inflammatory molecules as important modulators of injury and recovery. A great effort is underway to investigate neuroprotective molecules based on our increasing understanding of the pathophysiology. In this review, we provide a comprehensive summary of new insights concerning pathophysiology of focal and global perinatal brain injury and their implications for new therapeutic approaches. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Therapeutic impact of eicosapentaenoic acid on ischemic brain damage following transient focal cerebral ischemia in rats.

    Science.gov (United States)

    Ueda, Masayuki; Inaba, Toshiki; Nito, Chikako; Kamiya, Nobuo; Katayama, Yasuo

    2013-06-26

    Long-chain n-3 polyunsaturated fatty acids, such as eicosapentaenoic acid (EPA), have been shown to reduce ischemic neuronal injury. We investigated the effects of ethyl-EPA (EPA-E) on ischemic brain damage using a rat transient focal cerebral ischemia model. Male Sprague-Dawley rats (n=105) were subjected to 90 min of focal cerebral ischemia. EPA-E (100mg/kg/day) or vehicle was administered once a day for 3, 5 or 7 days prior to ischemia. Different withdrawal intervals of 3, 5, and 7 days prior to ischemia following 7-day pretreatment with EPA-E or vehicle were also examined. In addition, post-ischemic administration of EPA-E was investigated. Pretreatment with EPA-E for 7 and 5 days, but not 3 days, showed significant infarct volume reduction and neurological improvements when compared with vehicle pretreatment. In addition, withdrawal of EPA-E administration for 3 days, but not 5 and 7 days, also demonstrated significant infarct volume reduction and neurological improvements when compared with vehicle treatment. Post-ischemic treatment of EPA-E did not show any neuroprotection. Immunohistochemistry revealed that 7-day pretreatment with EPA-E significantly reduced cortical expression of 8-hydroxydeoxyguanosine (maker for oxidative DNA damage), 4-hydroxy-2-nonenal (maker for lipid peroxidation), phosphorylated adducin (marker for Rho-kinase activation) and von Willebrand factor (endothelial marker) when compared with vehicle pretreatment. In addition, phosphorylated adducin expression co-localized with von Willebrand factor immunoreactivity. The present study established the neuroprotective effect of EPA-E on ischemic brain damage following transient focal cerebral ischemia in rats, which may be involved in the suppression of oxidative stress and endothelial Rho-kinase activation. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. The metabolism of C-glucose by neurons and astrocytes in brain subregions following focal cerebral ischemia in rats.

    Science.gov (United States)

    Thoren, Anna E; Helps, Stephen C; Nilsson, Michael; Sims, Neil R

    2006-05-01

    To provide insights into the effects of temporary focal ischemia on the function of neurons and astrocytes in vivo, we measured the incorporation of radiolabel from [U-14C]glucose into both glutamate and glutamine in brain subregions at 1 h of reperfusion following occlusion of the middle cerebral artery for 2 or 3 h. Under the experimental conditions used, 14C-glutamate is mainly produced in neurons whereas 14C-glutamine is generated in astrocytes from 14C-glutamate of both neuronal and astrocytic origin. Radiolabel incorporation into both amino acids was greatly decreased. The change in 14C-glutamate accumulation provides strong evidence for substantial reductions in neuronal glucose metabolism. The resulting decrease in delivery of 14C-glutamate from the neurons to astrocytes was probably also the major contributor to the change in 14C-glutamine content. These alterations probably result in part from a marked depression of glycolytic activity in the neurons, as suggested by previous studies assessing deoxyglucose utilization. Alterations in 14C-glucose metabolism were not restricted to tissue that would subsequently become infarcted. Thus, these changes did not inevitably lead to death of the affected cells. The ATP : ADP ratio and phosphocreatine content were essentially preserved during recirculation following 2 h of ischemia and showed at most only moderate losses in some subregions following 3 h of ischemia. This retention of energy reserves despite the decreases in 14C-glucose metabolism in neurons suggests that energy needs were substantially reduced in the post-ischemic brain. Marked increases in tissue lactate accumulation during recirculation, particularly following 3 h of ischemia, provided evidence that impaired pyruvate oxidation probably also contributed to the altered 14C-glucose metabolism. These findings indicate the presence of complex changes in energy metabolism that are likely to greatly influence the responses of neurons and astrocytes to

  16. Dichotic listening in children with focal epilepsy: effects of structural brain abnormality and seizure characteristics.

    Science.gov (United States)

    Korkman, Marit; Granström, Marja-Liisa; Berg, Salla

    2004-02-01

    The study examined performance on a dichotic listening test in children with focal epilepsy. The aim of the study was to explore how factors related to brain pathology would affect ear advantage. The effects of lateralization of epileptogenic area, size and localization of structural abnormality on MRI findings, and seizure characteristics were studied. Children treated for focal epileptic seizures took part in the study (N = 35). The dichotic test consisted of pairs of words, nonwords, syllables and vowels. Results demonstrated that large congenital structural abnormality in the left hemisphere altered ear advantage whereas smaller abnormality and right-hemisphere abnormality did not. Further, epileptic seizures of left-hemisphere origin that had started at an early age affected ear advantage whereas seizure frequency at the time of the assessment did not. Children with early onset of seizures of right-hemisphere origin had a strong right-ear advantage. The total score did not differ between the groups. There was a strong negative correlation between the scores for the right-ear and the left-ear. The findings were interpreted to indicate altered functional dominance for perception of auditory, linguistic stimuli following early left-hemisphere pathology rather than unilateral functional suppression.

  17. Magnetic resonance volumetry reveals focal brain atrophy in transient epileptic amnesia.

    Science.gov (United States)

    Butler, Christopher; van Erp, Willemijn; Bhaduri, Amit; Hammers, Alexander; Heckemann, Rolf; Zeman, Adam

    2013-09-01

    Transient epileptic amnesia (TEA) is a recently described epilepsy syndrome characterized by recurrent episodes of isolated memory loss. It is associated with two unusual forms of interictal memory impairment: accelerated long-term forgetting (ALF) and autobiographical amnesia. We investigated the neural basis of TEA using manual volumetry and automated multi-atlas-based segmentation of whole-brain magnetic resonance imaging data from 40 patients with TEA and 20 healthy controls. Both methods confirmed the presence of subtle, bilateral hippocampal atrophy. Additional atrophy was revealed in perirhinal and orbitofrontal cortices. The volumes of these regions correlated with anterograde memory performance. No structural correlates were found for ALF or autobiographical amnesia. The results support the hypothesis that TEA is a focal medial temporal lobe epilepsy syndrome but reveal additional pathology in connected brain regions. The unusual interictal memory deficits of TEA remain unexplained by structural pathology and may reflect physiological disruption of memory networks by subclinical epileptiform activity. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Voxel-based analysis of whole brain FLAIR at 3T detects focal cortical dysplasia.

    Science.gov (United States)

    Focke, Niels K; Symms, Mark R; Burdett, Jane L; Duncan, John S

    2008-05-01

    Focal Cortical Dysplasia (FCD) is an important cause for pharmacoresistant epilepsy that can be treated surgically. The identification of the abnormal cortex on standard MRI can be difficult and computational techniques have been developed to increase sensitivity. In this study we evaluate the potential of a novel whole-brain voxel-based technique using normalized FLAIR signal intensity (nFSI) at 3 Tesla. Twenty-five patients with neuroradiologically reported FCD were included and compared to 25 healthy control subjects using Statistical Parametric Mapping (SPM5). T2 FLAIR scans were intensity normalized and each individual patient was compared against the control group. Each control subject was compared against the remaining control group. SPM correctly identified the FCD in 88% of cases (22/25) with only one false positive finding in the control group. In all but one of these cases the FCD was the most significant finding in the whole brain. All three missing cases could be detected at lower threshold levels but this would give rise to more false positive findings and thus reduce specificity. We present a novel technique that uses standard clinical T2 FLAIR scans to automatically detect FCDs. It can give supplementary information to the established T1-based automated techniques and could be useful for additional screening test, to complement the visual reading and clinical interpretation of MRI scans.

  19. Regulation of brain tumor dispersal by NKCC1 through a novel role in focal adhesion regulation.

    Directory of Open Access Journals (Sweden)

    Tomas Garzon-Muvdi

    Full Text Available Glioblastoma (GB is a highly invasive and lethal brain tumor due to its universal recurrence. Although it has been suggested that the electroneutral Na(+-K(+-Cl(- cotransporter 1 (NKCC1 can play a role in glioma cell migration, the precise mechanism by which this ion transporter contributes to GB aggressiveness remains poorly understood. Here, we focused on the role of NKCC1 in the invasion of human primary glioma cells in vitro and in vivo. NKCC1 expression levels were significantly higher in GB and anaplastic astrocytoma tissues than in grade II glioma and normal cortex. Pharmacological inhibition and shRNA-mediated knockdown of NKCC1 expression led to decreased cell migration and invasion in vitro and in vivo. Surprisingly, knockdown of NKCC1 in glioma cells resulted in the formation of significantly larger focal adhesions and cell traction forces that were approximately 40% lower than control cells. Epidermal growth factor (EGF, which promotes migration of glioma cells, increased the phosphorylation of NKCC1 through a PI3K-dependant mechanism. This finding is potentially related to WNK kinases. Taken together, our findings suggest that NKCC1 modulates migration of glioma cells by two distinct mechanisms: (1 through the regulation of focal adhesion dynamics and cell contractility and (2 through regulation of cell volume through ion transport. Due to the ubiquitous expression of NKCC1 in mammalian tissues, its regulation by WNK kinases may serve as new therapeutic targets for GB aggressiveness and can be exploited by other highly invasive neoplasms.

  20. Brain Network Architecture and Global Intelligence in Children with Focal Epilepsy.

    Science.gov (United States)

    Paldino, M J; Golriz, F; Chapieski, M L; Zhang, W; Chu, Z D

    2017-02-01

    The biologic basis for intelligence rests to a large degree on the capacity for efficient integration of information across the cerebral network. We aimed to measure the relationship between network architecture and intelligence in the pediatric, epileptic brain. Patients were retrospectively identified with the following: 1) focal epilepsy; 2) brain MR imaging at 3T, including resting-state functional MR imaging; and 3) full-scale intelligence quotient measured by a pediatric neuropsychologist. The cerebral cortex was parcellated into approximately 700 gray matter network "nodes." The strength of a connection between 2 nodes was defined by the correlation between their blood oxygen level-dependent time-series. We calculated the following topologic properties: clustering coefficient, transitivity, modularity, path length, and global efficiency. A machine learning algorithm was used to measure the independent contribution of each metric to the intelligence quotient after adjusting for all other metrics. Thirty patients met the criteria (4-18 years of age); 20 patients required anesthesia during MR imaging. After we accounted for age and sex, clustering coefficient and path length were independently associated with full-scale intelligence quotient. Neither motion parameters nor general anesthesia was an important variable with regard to accurate intelligence quotient prediction by the machine learning algorithm. A longer history of epilepsy was associated with shorter path lengths (P = .008), consistent with reorganization of the network on the basis of seizures. Considering only patients receiving anesthesia during machine learning did not alter the patterns of network architecture contributing to global intelligence. These findings support the physiologic relevance of imaging-based metrics of network architecture in the pathologic, developing brain. © 2017 by American Journal of Neuroradiology.

  1. Effects of focal brain cooling on extracellular concentrations of neurotransmitters in patients with epilepsy.

    Science.gov (United States)

    Nomura, Sadahiro; Inoue, Takao; Imoto, Hirochika; Suehiro, Eiichi; Maruta, Yuichi; Hirayama, Yuya; Suzuki, Michiyasu

    2017-04-01

    Brain hypothermia controls epileptic discharge and reduces extracellular concentrations of glutamate (Glu), an excitatory neurotransmitter. We aimed to determine the effects of focal brain cooling (FBC) on levels of γ-aminobutyric acid (GABA), which is a major inhibitory neurotransmitter. The relationship between Glu or GABA concentrations and the severity of epileptic symptoms was also analyzed. Patients with intractable epilepsy underwent FBC at lesionectomized (n = 11) or hippocampectomized (n = 8) regions at 15°C for 30 min using custom-made cooling devices. Concentrations of Glu (n = 18) and GABA (n = 12) were measured in extracellular fluid obtained through microdialysis using high-performance liquid chromatography (HPLC). The reduction rate of neurotransmitter levels and its relationship with electrocorticography (ECoG) signal changes in response to FBC were measured. We found no relationship between the concentrations of Glu or GABA and seizure severity. There was a significant decrease in the concentration of Glu to 66.3% of control levels during the cooling period (p = 0.001). This rate of reduction correlated with ECoG power (r(2) = 0.68). Cortical and hippocampal GABA levels significantly (p = 0.02) and nonsignificantly decreased to 47.7% and 32.4% of control levels, respectively. However, the rate of this reduction did not correlate with ECoG (r(2) = 0.11). Although the decrease in hippocampal GABA levels was not significant due to wide variations in its concentration, the levels of cortical GABA and Glu were decreased following FBC. FBC suppresses epileptic discharge and the release of both excitatory and inhibitory neurotransmitters. The reduction in Glu levels further contributes to the reduction in epileptic discharge. However, the reduction in the levels of GABA has no impact on ECoG. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  2. Focal adhesion kinase as a mechanotransducer during rapid brain growth of the chick embryo.

    Science.gov (United States)

    Desmond, Mary E; Knepper, Janice E; DiBenedetto, Angela J; Malaugh, Elizabeth; Callejo, Sagrario; Carretero, Raquel; Alonso, Maria-Isabel; Gato, Angel

    2014-01-01

    Expansion of the hollow fluid-filled embryonic brain occurs by an increase in intraluminal pressure created by accumulation of cerebrospinal fluid (CSF). Experiments have shown a direct correlation between cavity pressure and cell proliferation within the neuroepithelium. These findings lead us to ask how mechanistically this might come about. Are there perhaps molecules on the luminal surface of the embryonic neuroepithelium, such as focal adhesion kinases (FAKs) known to respond to tension in other epithelial cells? Immunodetection using antibodies to total FAK and p-FAK was performed with subsequent confocal analysis of the pattern of their activation under normal intraluminal pressure and induced chronic pressure. Western analysis was also done to look at the amount of FAK expression, as well as its activation under these same conditions. Using immunolocalization, we have shown that FAK is present and activated on both apical and basolateral surfaces and within the cytoplasm of the neuroepithelial cells. This pattern changed profoundly when the neuroepithelium was under pressure. By Western blot, we have shown that FAK was upregulated and activated in the neuroepithelium of the embryos just after the neural tube becomes a closed pressurized system, with phosphorylation detected on the luminal instead of the basal surface, along with an increase in cell proliferation. Chronic hyper-pressure does not induce an increase in phosphorylation of FAK. In conclusion, here we show that neuroepithelial cells respond to intraluminal pressure via FAK phosphorylation on the luminal surface.

  3. USE OF PROTON MAGNETIC RESONANCE SPECTROSCOPIC IMAGING DATA IN PLANNING FOCAL RADIATION THERAPIES FOR BRAIN TUMORS

    Directory of Open Access Journals (Sweden)

    Edward E Graves

    2011-05-01

    Full Text Available Advances in radiation therapy for malignant neoplasms have produced techniques such as Gamma Knife radiosurgery, capable of delivering an ablative dose to a specific, irregular volume of tissue. However, efficient use of these techniques requires the identification of a target volume that will produce the best therapeutic response while sparing surrounding normal brain tissue. Accomplishing this task using conventional computed tomography (CT and contrast-enhanced magnetic resonance imaging (MRI techniques has proven difficult because of the difficulties in identifying the effective tumor margin. Magnetic resonance spectroscopic imaging (MRSI has been shown to offer a clinically-feasible metabolic assessment of the presence and extent of neoplasm that can complement conventional anatomic imaging. This paper reviews current Gamma Knife protocols and MRSI acquisition, reconstruction, and interpretation techniques, and discusses the motivation for including magnetic resonance spectroscopy findings while planning focal radiation therapies. A treatment selection and planning strategy incorporating MRSI is then proposed, which can be used in the future to assess the efficacy of spectroscopy-based therapy planning.

  4. Magnesium sulfate and nimesulide have synergistic effects on rescuing brain damage after transient focal ischemia.

    Science.gov (United States)

    Wang, Liang-Chao; Huang, Chih-Yuan; Wang, Hao-Kuang; Wu, Ming-Hsiu; Tsai, Kuen-Jer

    2012-05-01

    Magnesium sulfate and nimesulide are commonly used drugs with reported neuroprotective effects. Their combination as stroke treatment has the potential benefits of decreasing individual drug dosage and fewer adverse effects. This study evaluated their synergistic effects and compared a low-dose combination with individual drug alone and placebo. Sprague-Dawley rats underwent 90 min of focal ischemia with intraluminal suture occlusion of the middle cerebral artery followed by reperfusion. The rats were randomly assigned to receive one of the following treatments: placebo, magnesium sulfate (MgSO₄; 45 mg/kg) intravenously immediately after the induction of middle cerebral artery occlusion, nimesulide (6 mg/kg) intraperitoneally before reperfusion, and combined therapy. Three days after the ischemia-reperfusion insult, therapeutic outcome was assessed by 2,3,5-triphenyltetrazolium chloride staining and a 28-point neurological severity scoring system. Cyclooxygenase-2, prostaglandin E₂, myeloperoxidase, and caspase-3 expression after treatment were evaluated using Western blot analyses and immunohistochemical staining, followed by immunoreactive cell analysis using tissue cytometry. Only the combination treatment group showed a significant decrease in infarction volume (10.93±6.54% versus 26.43±7.08%, peffects of each individual drug. MgSO₄ and nimesulide have synergistic effects on ischemia-reperfusion insults. Their combination helps decrease drug dosage and adverse effects. Combined treatment strategies may help to combat stroke-induced brain damage in the future.

  5. Parenchymal cystatin C focal deposits and glial scar formation around brain arteries in Hereditary Cystatin C Amyloid Angiopathy.

    Science.gov (United States)

    Osk Snorradottir, Asbjorg; Isaksson, Helgi J; Kaeser, Stephan A; Skodras, Angelos A; Olafsson, Elias; Palsdottir, Astridur; Thor Bragason, Birkir

    2015-10-05

    Hereditary Cystatin C Amyloid Angiopathy (HCCAA) is an amyloid disorder in Icelandic families caused by an autosomal dominant mutation in the cystatin C gene. Mutant cystatin C forms amyloid deposits in brain arteries and arterioles which are associated with changes in the arterial wall structure, notably deposition of extracellular matrix proteins. In this post-mortem study we examined the neuroinflammatory response relative to the topographical distribution of cystatin C deposition, and associated haemorrhages, in the leptomeninges, cerebrum, cerebellum, thalamus, and midbrain of HCCAA patients. Cystatin C was deposited in all brain areas, grey and white matter alike, most prominently in arteries and arterioles; capillaries and veins were not, or minimally, affected. We also observed perivascular deposits and parenchymal focal deposits proximal to affected arteries. This study shows for the first time, that cystatin C does not exclusively form CAA and perivascular amyloid but also focal deposits in the brain parenchyma. Haemorrhages were observed in all patients and occurred in all brain areas, variable between patients. Microinfarcts were observed in 34.6% of patients. The neuroinflammatory response was limited to the close vicinity of affected arteries and perivascular as well as parenchymal focal deposits. Taken together with previously reported arterial accumulation of extracellular matrix proteins in HCCAA, our results indicate that the central nervous system pathology of HCCAA is characterised by the formation of a glial scar within and around affected arteries. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Identification of Focal Epileptogenic Networks in Generalized Epilepsy Using Brain Functional Connectivity Analysis of Bilateral Intracranial EEG Signals.

    Science.gov (United States)

    Chen, Po-Ching; Castillo, Eduardo M; Baumgartner, James; Seo, Joo Hee; Korostenskaja, Milena; Lee, Ki Hyeong

    2016-09-01

    Simultaneous bilateral onset and bi-synchrony epileptiform discharges in electroencephalogram (EEG) remain hallmarks for generalized seizures. However, the possibility of an epileptogenic focus triggering rapidly generalized epileptiform discharges has been documented in several studies. Previously, a new multi-stage surgical procedure using bilateral intracranial EEG (iEEG) prior to and post complete corpus callosotomy (CC) was developed to uncover seizure focus in non-lateralizing focal epilepsy. Five patients with drug-resistant generalized epilepsy who underwent this procedure were included in the study. Their bilateral iEEG findings prior to complete CC showed generalized epileptiform discharges with no clear lateralization. Nonetheless, the bilateral ictal iEEG findings post complete CC indicated lateralized or localized seizure onset. This study hypothesized that brain functional connectivity analysis, applied to the pre CC bilateral iEEG recordings, could help identify focal epileptogenic networks in generalized epilepsy. The results indicated that despite diffuse epileptiform discharges, focal features can still be observed in apparent generalized seizures through brain connectivity analysis. The seizure onset localization/lateralization from connectivity analysis demonstrated a good agreement with the bilateral iEEG findings post complete CC and final surgical outcomes. Our study supports the role of focal epileptic networks in generalized seizures.

  7. Proprioceptive dysfunction in focal dystonia: from experimental evidence to rehabilitation strategies.

    Directory of Open Access Journals (Sweden)

    Laura eAvanzino

    2014-12-01

    Full Text Available Dystonia has historically been considered a disorder of the basal ganglia, mainly affecting planning and execution of voluntary movements. This notion comes from the observation that most lesions responsible for secondary dystonia involve the basal ganglia. However, what emerges from recent research is that dystonia is linked to the dysfunction of a complex neural network that comprises basal ganglia-thalamic-frontal cortex, but also the inferior parietal cortex and the cerebellum. While dystonia is clearly a motor problem, it turned out that sensory aspects are also fundamental, especially those related to proprioception.We outline experimental evidence for proprioceptive dysfunction in focal dystonia from intrinsic sensory abnormalities to impaired sensorimotor integration, that is the process by which sensory information is used to plan and execute volitional movements. Particularly, we will focus on proprioceptive aspects of dystonia, including: i processing of vibratory input, ii temporal discrimination of two passive movements, iii multimodal integration of visual-tactile and proprioceptive inputs and, iv motor control in the absence of visual feedback. We suggest that these investigations contribute not only to a better understanding of dystonia pathophysiology, but also to develop rehabilitation strategies aimed at facilitating the processing of proprioceptive input.

  8. Alcohol Exposure after Mild Focal Traumatic Brain Injury Impairs Neurological Recovery and Exacerbates Localized Neuroinflammation

    Science.gov (United States)

    Teng, Sophie X; Katz, Paige S; Maxi, John K; Mayeux, Jacques P; Gilpin, Nicholas W; Molina, Patricia E

    2014-01-01

    Traumatic brain injury (TBI) represents a leading cause of morbidity and mortality among young individuals. Alcohol abuse is a risk factor associated with increased TBI incidence. In addition, up to 26% of TBI patients engage in alcohol consumption after TBI. Limited preclinical studies have examined the impact of post-injury alcohol exposure on TBI recovery. The aim of this study was to determine the isolated and combined effects of TBI and alcohol on cognitive, behavioral, and physical recovery, as well as on associated neuroinflammatory changes. Male Sprague-Dawley rats (~300 g) were subjected to a mild focal TBI by lateral fluid percussion (~30 PSI, ~25 ms) under isoflurane anesthesia. On day 4 after TBI, animals were exposed to either sub-chronic intermittent alcohol vapor (95% ethanol 14h on /10h off; BAL~200 mg/dL) or room air for 10 days. TBI induced neurological dysfunction reflected by an increased neurological severity score (NSS) showed progressive improvement in injured animals exposed to room air (TBI/air). In contrast, TBI animals exposed to alcohol vapor (TBI/alcohol) showed impaired NSS recovery throughout the 10-day period of alcohol exposure. Open-field exploration test revealed an increased anxiety-like behavior in TBI/alcohol group compared to TBI/air group. Additionally, alcohol-exposed animals showed decreased locomotion and impaired novel object recognition. Immunofluorescence showed enhanced reactive astrocytes, microglial activation, and HMGB1 expression localized to the injured cortex of TBI/alcohol as compared to TBI/air animals. The expression of neuroinflammatory markers showed significant positive correlation with NSS. These findings indicated a close relationship between accentuated neuroinflammation and impaired neurological recovery from post-TBI alcohol exposure. The clinical implications of long-term consequences in TBI patients exposed to alcohol during recovery warrant further investigation. PMID:25489880

  9. Focal neurological deficits

    Science.gov (United States)

    ... or head Electromyogram (EMG), nerve conduction velocities (NCV) MRI of the back, neck, or head Spinal tap Alternative Names Neurological deficits - focal Images Brain References Daroff RB, Jankovic ...

  10. {sup 1}H MR spectroscopy evidence for the varied nature of asymptomatic focal brain lesions in neurofibromatosis type 1

    Energy Technology Data Exchange (ETDEWEB)

    Jones, A.P. [North Western Medical Physics, Royal Preston Hospital (United Kingdom); Gunawardena, W.J.; Coutinho, C.M.A. [Dept. of Clinical Radiology, Royal Preston Hospital (United Kingdom)

    2001-01-01

    We present the MRI and {sup 1}H MR spectroscopy findings in six patients with neurofibromatosis type 1 (NF1) and asymptomatic focal brain lesions. Variations in imaging appearances were seen, including regression of a previously identified lesion. MR spectra for the lesions and corresponding areas of normal brain show significant differences. The lesions could be separated into two groups, one demonstrating only slight metabolite ratio changes relative to normal brain and the other group showing significant increase in choline and decrease in N-acetyl aspartate. The lesion which regressed fell into the second group. These findings are not in agreement with those previously reported and provide evidence for the varied and possibly transient nature of these asymptomatic lesions. The spectroscopy findings suggest that metabolite changes may be present without visible changes on MRI. (orig.)

  11. Prevalence, and Intellectual Outcome of Unilateral Focal Cortical Brain Damage as a Function of Age, Sex and Aetiology

    Directory of Open Access Journals (Sweden)

    C. M. J. Braun

    2002-01-01

    Full Text Available Neurologists and neuropsychologists are aware that aging men are more at risk than women for brain damage, principally because of the well known male-predominant risk for cardiovascular disease and related cerebrovascular accidents. However, a disproportion in prevalence of brain damage between the sexes in childhood may be less suspected. Furthermore, sex-specific risk for other aetiologies of brain damage may be little known, whether in the pediatric or adult populations. Proposals of a sex difference in cognitive recovery from brain damage have also been controversial. Six hundred and thirty five “consecutive” cases with cortical focal lesions including cases of all ages and both sexes were reviewed. Aetiology of the lesion was determined for each case as was postlesion IQ. Risk was highly male prevalent in all age groups, with a predominance of cardiovascular aetiology explaining much of the adult male prevalence. However, several other aetiological categories were significantly male prevalent in juveniles (mitotic, traumatic, dysplasic and adults (mitotic, traumatic. There was no sex difference in outcome (i.e., postlesion IQ of these cortical brain lesions for the cohort as a whole, after statistical removal of the influence of lesion extent, aetiology and presence of epilepsy. Mechanisms potentially responsible for sex differences in prevalence, aetiology of brain damage, and recovery, are reviewed and discussed.

  12. Metallothionein-1+2 protect the CNS after a focal brain injury

    DEFF Research Database (Denmark)

    Giralt, Mercedes; Penkowa, Milena; Lago, Natalia

    2002-01-01

    We have evaluated the physiological relevance of metallothionein-1+2 (MT-1+2) in the CNS following damage caused by a focal cryolesion onto the cortex. In comparison to normal mice, transgenic mice overexpressing the MT-1 isoform (TgMTI* mice) showed a significant decrease of the number of activa...

  13. The effects of early exercise on brain damage and recovery after focal cerebral infarction in rats.

    Science.gov (United States)

    Matsuda, F; Sakakima, H; Yoshida, Y

    2011-02-01

    Exercise can be used to enhance neuroplasticity and facilitate motor recovery after a stroke in rats. We investigated whether treadmill running could reduce brain damage and enhance the expression of midkine (MK) and nerve growth factor (NGF), increase angiogenesis and decrease the expression of caspase-3. Seventy-seven Wistar rats were split into three experimental groups (ischaemia-control: 36, ischaemia-exercise: 36, sham-exercise: 5). Stroke was induced by 90-min left middle cerebral artery occlusion using an intraluminal filament. Beginning on the following day, the rats were made to run on a treadmill for 20 min once a day for a maximum of 28 consecutive days. Functional recovery after ischaemia was assessed using the beamwalking test and a neurological evaluation scale in all rats. Infarct volume, and the expression of MK, NGF, anti-platelet-endothelial cell adhesion molecule (PECAM-1), and caspase-3 were evaluated at 1, 3, 5, 7, 14 and 28 days after the induction of ischaemia. Over time motor coordination and neurological deficits improved more in the exercised group than in the non-exercised group. The infarct volume in the exercised group (12.4 ± 0.8%) subjected to treadmill running for 28 days was significantly decreased compared with that in the control group (19.8 ± 4.2%, P exercised rats. Our findings show that treadmill exercise improves motor behaviour and reduces neurological deficits and infarct volume, suggesting that it may aid recovery from central nervous system injury.

  14. Experimental deep brain stimulation in animal models.

    Science.gov (United States)

    Tan, Sonny Kh; Vlamings, Rinske; Lim, Leewei; Sesia, Thibault; Janssen, Marcus Lf; Steinbusch, Harry Wm; Visser-Vandewalle, Veerle; Temel, Yasin

    2010-10-01

    DEEP BRAIN STIMULATION (DBS) as a therapy in neurological and psychiatric disorders is widely applied in the field of functional and stereotactic neurosurgery. In this respect, experimental DBS in animal models is performed to evaluate new indications and new technology. In this article, we review our experience with the concept of experimental DBS, including its development and validation. An electrode construction was developed using clinical principles to perform DBS unilaterally or bilaterally in freely moving rats. The stimulation parameters were adjusted for the rat using current density calculations. We performed validation studies in 2 animal models: a rat model of Parkinson's disease (bilateral 6-hydroxydopamine infusion in the striatum) and a rat model of Huntington's disease (transgenic rats). The effects of DBS were evaluated in different behavioral tasks measuring motor and cognitive functions. The electrode construction developed allows experimental DBS to be performed in freely moving rats. With the current setup, electrodes are placed in the target in 70% to 95% of the cases. Using a rat model, we showed that bilateral DBS of the subthalamic nucleus improves parkinsonian motor disability, but can induce behavioral side effects, similar to the clinical situation. In addition, we showed that DBS of the globus pallidus can improve motor and cognitive symptoms in a rat model of Huntington's disease. Nevertheless, during the process of the development and validation of experimental DBS, we encountered specific problems. These are discussed in detail. Experimental DBS in freely moving animals is an adequate tool to explore new indications for DBS and to refine DBS technology.

  15. La biopsia estereotáctica en el diagnóstico de las lesiones cerebrales focales en sida Stereotactic brain biopsy in the diagnosis of focal brain lesions in AIDS

    Directory of Open Access Journals (Sweden)

    Marcelo Corti

    2008-08-01

    Full Text Available Las lesiones cerebrales focales constituyen una complicación frecuente en los pacientes con infección por el virus de la inmunodeficiencia humana (HIV y síndrome de inmunodeficiencia adquirida (sida. Durante el período comprendido entre enero de 1999 y mayo de 2007 se realizaron un total de 83 biopsias en pacientes con sida y lesiones cerebrales. Se incluyeron aquellos pacientes que no hubiesen respondido al algoritmo habitual de enfoque diagnóstico-terapéutico de estas lesiones. Todas las muestras obtenidas fueron sometidas a evaluación intraoperatoria para asegurar la obtención de material patológico y posterior análisis histopatológico y exámenes microbiológicos. De los 41 pacientes con lesiones cerebrales múltiples, 62 tenían localización supratentorial, en 4 eran infratentoriales y 17 mostraron ambas localizaciones. Cincuenta y un lesiones seleccionadas como blanco estereotáctico tuvieron refuerzo periférico del contraste. Se obtuvo material histopatológico en el 100% de los procedimientos. El diagnóstico más frecuente fue el de leucoencefalopatía multifocal progresiva (LEMP con 24 casos (29%, seguido del linfoma primario del sistema nervioso central (LPSNC con 19 diagnósticos (23% y de toxoplasmosis en 13 pacientes (15.7%. Se comprobó una relación significativa entre los diagnósticos histopatológicos y la localización de las lesiones y entre los diagnósticos histopatológicos y el comportamiento de las imágenes luego de la administración de la sustancia de contraste. El rédito diagnóstico alcanzó el 90.3% (75 biopsias. La morbiletalidad en esta serie fue de 2.4%. La biopsia cerebral estereotáctica permitió alcanzar el diagnóstico etiológico y adecuar el enfoque terapéutico en la mayoría de los pacientes de esta serie.Focal brain lesions are frequent complications among HIV/AIDS patients. Between January 1999 and May 2007, 83 procedures of stereotactic brain biopsies in HIV/AIDS patients with focal

  16. The Effects of Antecedent Exercise on Motor Function Recovery and Brain-derived Neurotrophic Factor Expression after Focal Cerebral Ischemia in Rats

    OpenAIRE

    KIM, GYEYEOP; Kim, Eunjung

    2013-01-01

    [Purpose] In the present study, we investigated the effect of antecedent exercise on functional recovery and brain-derived neurotrophic factor (BDNF) expression following focal cerebral ischemia injury. [Subjects] The rat middle cerebral artery occlusion (MCAO) model was employed. Adult male Sprague-Dawley rats were randomly divided into 4 groups. Group I included untreated normal rats (n=10); Group II included untreated rats with focal cerebral ischemia (n=10); Group III included rats that p...

  17. [Brain metastases: Focal treatment (surgery and radiation therapy) and cognitive consequences].

    Science.gov (United States)

    Reygagne, Emmanuelle; Du Boisgueheneuc, Foucaud; Berger, Antoine

    2017-04-01

    Brain metastases represent the first cause of malignant brain tumor. Without radiation therapy, prognosis was poor with fast neurological deterioration, and a median overall survival of one month. Nowadays, therapeutic options depend on brain metastases presentation, extra brain disease, performance status and estimated prognostic (DS GPA). Therefore, for oligometastatic brain patients with a better prognosis, this therapeutic modality is controversial. In fact, whole-brain radiation therapy improves neurological outcomes, but it can also induce late neuro-cognitive sequelae for long-term survivors of brain metastases. Thus, in this strategy for preserving good cognitive functions, stereotactic radiation therapy is a promising treatment. Delivering precisely targeted radiation in few high-doses in one to four brain metastases, allows to reduce radiation damage to normal tissues and it should allow to decrease radiation-induced cognitive decline. In this paper, we will discuss about therapeutic strategies (radiation therapy and surgery) with their neuro-cognitive consequences for brain metastases patients and future concerning preservation of cognitive functions. Copyright © 2016 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  18. In-vivo measurements of human brain tissue conductivity using focal electrical current injection through intracerebral multicontact electrodes.

    Science.gov (United States)

    Koessler, Laurent; Colnat-Coulbois, Sophie; Cecchin, Thierry; Hofmanis, Janis; Dmochowski, Jacek P; Norcia, Anthony M; Maillard, Louis G

    2017-02-01

    In-vivo measurements of human brain tissue conductivity at body temperature were conducted using focal electrical currents injected through intracerebral multicontact electrodes. A total of 1,421 measurements in 15 epileptic patients (age: 28 ± 10) using a radiofrequency generator (50 kHz current injection) were analyzed. Each contact pair was classified as being from healthy (gray matter, n = 696; white matter, n = 530) or pathological (epileptogenic zone, n = 195) tissue using neuroimaging analysis of the local tissue environment and intracerebral EEG recordings. Brain tissue conductivities were obtained using numerical simulations based on conductivity estimates that accounted for the current flow in the local brain volume around the contact pairs (a cube with a side length of 13 mm). Conductivity values were 0.26 S/m for gray matter and 0.17 S/m for white matter. Healthy gray and white matter had statistically different median impedances (P Brain Mapp 38:974-986, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  19. Diffuse optical systems and methods to image physiological changes of the brain in response to focal TBI (Conference Presentation)

    Science.gov (United States)

    Abookasis, David; Volkov, Boris; Kofman, Itamar

    2017-02-01

    During the last four decades, various optical techniques have been proposed and intensively used for biomedical diagnosis and therapy both in animal model and in human. These techniques have several advantages over the traditional existing methods: simplicity in structure, low-cost, easy to handle, portable, can be used repeatedly over time near the patient bedside for continues monitoring, and offer high spatiotemporal resolution. In this work, we demonstrate the use of two optical imaging modalities namely, spatially modulated illumination and dual-wavelength laser speckle to image the changes in brain tissue chromophores, morphology, and metabolic before, during, and after the onset of focal traumatic brain injury in intact mouse head (n=15). Injury was applied in anesthetized mice by weight-drop apparatus using 50gram metal rod striking the mouse's head. Following data analysis, we show a series of hemodynamic and structural changes over time including higher deoxyhemoglobin, reduction in oxygen saturation and blood flow, cell swelling, etc., in comparison with baseline measurements. In addition, to validate the monitoring of cerebral blood flow by the imaging system, measurements with laser Doppler flowmetry were also performed (n=5), which confirmed reduction in blood flow following injury. Overall, our result demonstrates the capability of diffuse optical modalities to monitor and map brain tissue optical and physiological properties following brain trauma.

  20. Glucocorticoid receptor expression in the cortex of the neonatal rat brain with and without focal cerebral ischemia.

    Science.gov (United States)

    Lee, Ben H; Wen, Tong-Chun; Rogido, Marta; Sola, Augusto

    2007-01-01

    Glucocorticoid receptors (GR) mediate cellular processes which may be neuroprotective and/or neurotoxic to the neonatal rat brain. Our aim was to describe GR ontogeny in the developing rat brain cortex and changes in GR expression after permanent neonatal focal cerebral ischemia (FCI). GR Western blots and immunohistochemical stains were performed on neonatal rat cortices on P1, P3, P7, P10, P15, and P30 and on P7 at 1 h, 3 h, 6 h, 12 h, 24 h, and 72 h after FCI or sham-operation (S-O), 8 per group. Nissl staining was performed on FCI or S-O P7 cortical samples. Cortical GR expression was increased by 65.2% at P7, 110.1% at P15, and 87.0% at P30, compared to P1. On P7, GR expression decreased in the ischemic cortex after 6 h and in the non-ischemic cortex after 24 h of FCI (p cortex after 6 h and in the non-ischemic cortex after 24 h of FCI. Thus, cortical GR may play important roles in normal brain development and neonatal brain injury responses.

  1. Protective Effect of Angiopoietin-1 on the Blood Brain Barrier after Focal Cerebral IschemiaReperfusion Injury in Rats

    Directory of Open Access Journals (Sweden)

    Xuan GAO

    2015-03-01

    Full Text Available Objective: To observe the protective effect of angiopoietin-1 (Ang-1 on the blood brain barrier (BBB after focal cerebral ischemia-reperfusion injury (CIRI in rats. Methods: Forty male healthy Wister rats were selected. The focal CIRI models were established using middle cerebral artery occlusion and 30 rats were divided into sham-operation group (n=10, normal saline group (NS group (n=10 and Ang-1 treatment group (n=10. The rats were killed 48 h after reperfusion, and brain water content, BBB permeability, cerebral infarction volume and neurological severity scores in rats were detected respectively. Results: 48 h after reperfusion, both the brain water content and Evans blue (EB content in Ang-1 treatment group were significantly lower than in NS control [(68.69±4.46 % vs. (79.08±4.12 %, P<0.001; (98.60±10.56 μg/g vs. (379.90±21.64 μg/g, P<0.001], and there was no statistical significance by comparison to those in sham-operation group [(65.37±3.28 %; (89.62±8.65 μg/g, P>0.05]. The cerebral infarction volume in Ang-1 treatment group was markedly smaller than in NS group [(0.119±0.022 cm3 vs. (0.407±0.036 cm3, P<0.001], and no significant difference was presented when compared with sham-operation group [(0.104±0.011 cm3, P>0.05]. Besides, the neurological severity scores in Ang-1 treatment group were notably lower than in NS group [(1.83±0.29 points vs. (2.87±0.34 points, P<0.001], but higher than in sham-operation group [(0.79±0.11 points, P<0.001]. Conclusion: Ang-1 can decrease BBB permeability after focal CIRI in rats, so it has a protective effect on CIRI.

  2. Astrocyte-targeted expression of IL-6 protects the CNS against a focal brain injury

    DEFF Research Database (Denmark)

    Penkowa, Milena; Giralt, Mercedes; Lago, Natalia

    2003-01-01

    The effect of CNS-targeted IL-6 gene expression has been thoroughly investigated in the otherwise nonperturbed brain but not following brain injury. Here we examined the impact of astrocyte-targeted IL-6 production in a traumatic brain injury (cryolesion) model using GFAP-IL6 transgenic mice....... This study demonstrated that transgenic IL-6 production significantly increased wound healing following the cryolesion. Thus, at 20 days postlesion (dpl) the GFAP-IL6 mice showed almost complete wound healing compared to litter mate nontransgenic controls. It seems likely that a reduced inflammatory response...... neuropathological insult such as following traumatic injury, a clear neuroprotective role is evident....

  3. Mania secondary to focal brain lesions: implications for understanding the functional neuroanatomy of bipolar disorder.

    Science.gov (United States)

    Satzer, David; Bond, David J

    2016-05-01

    Approximately 3.5 million Americans will experience a manic episode during their lifetimes. The most common causes are psychiatric illnesses such as bipolar I disorder and schizoaffective disorder, but mania can also occur secondary to neurological illnesses, brain injury, or neurosurgical procedures. For this narrative review, we searched Medline for articles on the association of mania with stroke, brain tumors, traumatic brain injury, multiple sclerosis, neurodegenerative disorders, epilepsy, and neurosurgical interventions. We discuss the epidemiology, features, and treatment of these cases. We also review the anatomy of the lesions, in light of what is known about the neurobiology of bipolar disorder. The prevalence of mania in patients with brain lesions varies widely by condition, from bipolar disorder, and first manic episodes after the age of 40 years. Treatment with antimanic medications, along with specific treatment for the underlying neurologic condition, is typically required. Typical lesion locations fit with current models of bipolar disorder, which implicate hyperactivity of left-hemisphere reward-processing brain areas and hypoactivity of bilateral prefrontal emotion-modulating regions. Lesion studies complement these models by suggesting that right-hemisphere limbic-brain hypoactivity, or a left/right imbalance, may be relevant to the pathophysiology of mania. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. In vivo optical reflectance imaging of spreading depression waves in rat brain with and without focal cerebral ischemia.

    Science.gov (United States)

    Chen, Shangbin; Feng, Zhe; Li, Pengcheng; Jacques, Steven L; Zeng, Shaoqun; Luo, Qingming

    2006-01-01

    Spreading depression (SD) waves occur in focal cerebral ischemia of the brain. Optical reflectance imaging at 550 +/- 10-nm wavelength using a charge-coupled device (CCD) camera, called optical intrinsic signal imaging (OISI) in the neuroscience community, provides high resolution imaging of SD waves based on changes in blood perfusion. We present optical images of SD waves in normal rat brain induced by a pinprick, and the spontaneous SD waves that follow middle cerebral artery occlusion (MCAO). The images of change in reflectance are calculated as A = (I-I(o))I(o), where I is pixel intensity as some timepoint and I(o) is the initial intensity just prior to an SD wave. Difference images B = [I(i)-I(i-1)]I(o), where I(i) is the image at time i and I(i-1) is the previous image at time i-1 (a 6.4-s interval), significantly sharpen the boundaries between leading and trailing edges of the SD wave. Maximum rate-of-change images C = max(B) display the maximum pixel value of B within the duration of a single SD wave, and provide an image that visualizes the entire penumbra. The penumbra appear bright due to a rapid drop in perfusion, while the normal brain and infarct area appear dark.

  5. Laser Acupuncture at GV20 Improves Brain Damage and Oxidative Stress in Animal Model of Focal Ischemic Stroke.

    Science.gov (United States)

    Jittiwat, Jinatta

    2017-10-01

    The burden of stroke is high and is continually increasing due to a dramatic growth in the world's elderly population. Novel therapeutic strategies are therefore required. The present study sought to determine the effect of laser acupuncture at GV20 on brain damage, oxidative-status markers in the cerebral cortex, and superoxide dismutase in the mitochondria of an animal model of focal ischemic stroke. Wistar rats, weighing 300-350 g, were divided into the following four groups: (1) control; (2) permanent occlusion of the right middle cerebral artery (Rt.MCAO) alone; (3) Rt.MCAO plus sham laser acupuncture; and (4) Rt.MCAO plus laser-acupuncture groups. Sham laser acupuncture or laser acupuncture was performed once daily at the GV20 (Baihui) acupoint for 14 days following Rt.MCAO. Half of the rats in each group were examined by 2,3,5-triphenyltetrazolium chloride staining to determine the brain infarct volume, while the other half were examined by biochemical assays to determine the malondialdehyde level, and the glutathione peroxidase, catalase, and superoxide-dismutase activities in the brain-cortex mitochondria. The results showed that laser acupuncture at GV20 significantly decreased the brain infarct volume and malondialdehyde level, and increased the catalase, glutathione peroxidase, and superoxide-dismutase activities in cerebral ischemic rats. In conclusion, laser acupuncture at GV20 decreases the brain infarct volume in cerebral ischemic rats, at least in part due to decreased oxidative stress. Further study is warranted to investigate other possible underlying mechanisms. Copyright © 2017. Published by Elsevier B.V.

  6. Investigating Focal Connectivity Deficits in Alzheimer's Disease Using Directional Brain Networks Derived from Resting-State fMRI

    Directory of Open Access Journals (Sweden)

    Sinan Zhao

    2017-07-01

    Full Text Available Connectivity analysis of resting-state fMRI has been widely used to identify biomarkers of Alzheimer's disease (AD based on brain network aberrations. However, it is not straightforward to interpret such connectivity results since our understanding of brain functioning relies on regional properties (activations and morphometric changes more than connections. Further, from an interventional standpoint, it is easier to modulate the activity of regions (using brain stimulation, neurofeedback, etc. rather than connections. Therefore, we employed a novel approach for identifying focal directed connectivity deficits in AD compared to healthy controls. In brief, we present a model of directed connectivity (using Granger causality that characterizes the coupling among different regions in healthy controls and Alzheimer's disease. We then characterized group differences using a (between-subject generative model of pathology, which generates latent connectivity variables that best explain the (within-subject directed connectivity. Crucially, our generative model at the second (between-subject level explains connectivity in terms of local or regionally specific abnormalities. This allows one to explain disconnections among multiple regions in terms of regionally specific pathology; thereby offering a target for therapeutic intervention. Two foci were identified, locus coeruleus in the brain stem and right orbitofrontal cortex. Corresponding disrupted connectivity network associated with the foci showed that the brainstem is the critical focus of disruption in AD. We further partitioned the aberrant connectomic network into four unique sub-networks, which likely leads to symptoms commonly observed in AD. Our findings suggest that fMRI studies of AD, which have been largely cortico-centric, could in future investigate the role of brain stem in AD.

  7. Netrin-1 hyperexpression in mouse brain promotes angiogenesis and long-term neurological recovery after transient focal ischemia.

    Science.gov (United States)

    Lu, Haiyan; Wang, Yongting; He, Xiaosong; Yuan, Falei; Lin, Xiaojie; Xie, Bohua; Tang, Guanghui; Huang, Jun; Tang, Yaohui; Jin, Kunlin; Chen, Shengdi; Yang, Guo-Yuan

    2012-03-01

    Netrin-1 (NT-1) stimulates endothelial cell proliferation and migration in vitro and promotes focal neovascularization in the adult brain in vivo. This in vivo study in mice investigated the effect of NT-1 hyperexpression on focal angiogenesis and long-term functional outcome after transient middle cerebral artery occlusion (tMCAO). Adeno-associated viral vectors carrying either the NT-1 gene (AAV-NT-1) or GFP (AAV-GFP) were generated and injected into the brains of separate groups of 93 mice. Seven days later, tMCAO followed by 7-28 days of reperfusion were carried out. Histological outcomes and behavioral deficits were quantified 7-28 days after tMCAO. Small cerebral vessel network and angiogenesis were assessed 28 days after tMCAO, using synchrotron radiation microangiography and immunohistochemistry. Western blot and immunohistochemistry showed that on the day of tMCAO, NT-1 hyperexpression had been achieved in both normal and ischemic hemispheres. Immunofluorescence imaging showed that NT-1 expression was primarily in neurons and astrocytes. Ischemia-induced infarction in the NT-1 hyperexpression group was attenuated in comparison to saline or AAV-GFP-treated groups (PAAV-NT-1-treated mice compared with mice in saline or AAV-GFP-treated groups (PAAV-NT-1-treated mice compared with the other 2 groups (PAAV-NT-1-treated mice than in other groups. AAV-NT-1 induced NT-1 hyperexpression before tMCAO reduced infarct size, enhanced neovascularization, and improved long-term functional recovery.

  8. MicroRNA responses to focal cerebral ischemia in male and female mouse brain

    Directory of Open Access Journals (Sweden)

    Theresa Ann Lusardi

    2014-02-01

    Full Text Available Stroke occurs with greater frequency in men than in women across diverse ethnic backgrounds and nationalities. Work from our lab and others have revealed a sex-specific sensitivity to cerebral ischemia whereby males exhibit a larger extent of brain damage resulting from an ischemic event compared to females. Previous studies revealed that microRNA (miRNA expression is regulated by cerebral ischemia in males; however, no studies to date have examined the effect of ischemia on miRNA responses in females. Thus, we examined miRNA responses in male and female brain in response to cerebral ischemia using miRNA arrays. These studies revealed that in male and female brains, ischemia leads to both a universal miRNA response as well as a sexually distinct response to challenge. Target prediction analysis of the miRNAs increased in male or female ischemic brain reveal sex-specific differences in gene targets and protein pathways. These data support that the mechanisms underlying sexually dimorphic responses to cerebral ischemia includes distinct changes in miRNAs in male and female brain, in addition to a miRNA signature response to ischemia that is common to both.

  9. Neuroprotective role of a brain-enriched tyrosine phosphatase, STEP, in focal cerebral ischemia.

    Science.gov (United States)

    Deb, Ishani; Manhas, Namratta; Poddar, Ranjana; Rajagopal, Sathyanarayanan; Allan, Andrea M; Lombroso, Paul J; Rosenberg, Gary A; Candelario-Jalil, Eduardo; Paul, Surojit

    2013-11-06

    The striatal-enriched phosphatase (STEP) is a component of the NMDA-receptor-mediated excitotoxic signaling pathway, which plays a key role in ischemic brain injury. Using neuronal cultures and a rat model of ischemic stroke, we show that STEP plays an initial role in neuroprotection, during the insult, by disrupting the p38 MAPK pathway. Degradation of active STEP during reperfusion precedes ischemic brain damage and is associated with secondary activation of p38 MAPK. Application of a cell-permeable STEP-derived peptide that is resistant to degradation and binds to p38 MAPK protects cultured neurons from hypoxia-reoxygenation injury and reduces ischemic brain damage when injected up to 6 h after the insult. Conversely, genetic deletion of STEP in mice leads to sustained p38 MAPK activation and exacerbates brain injury and neurological deficits after ischemia. Administration of the STEP-derived peptide at the onset of reperfusion not only prevents the sustained p38 MAPK activation but also reduces ischemic brain damage in STEP KO mice. The findings indicate a neuroprotective role of STEP and suggest a potential role of the STEP-derived peptide in stroke therapy.

  10. Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia

    DEFF Research Database (Denmark)

    Inácio, Ana R; Liu, Yawei; Clausen, Bettina H

    2015-01-01

    modified mouse lines, lacking either IFN-β or its receptor, the IFN-α/β receptor. Subsets of inflammatory and immune cells isolated from the brain, blood, and spleen were studied using flow cytometry. Sensorimotor deficits were assessed by a modified composite neuroscore, the rotating pole and grip...

  11. Three-dimensional visualization of rat brain microvasculature following permanent focal ischaemia by synchrotron radiation.

    Science.gov (United States)

    Zhang, M Q; Sun, D N; Xie, Y Y; Peng, G Y; Xia, J; Long, H Y; Xiao, B

    2014-06-01

    Identifying morphological changes that occur in microvessels under both normal and ischaemic conditions is crucial for understanding and treating stroke. However, conventional imaging techniques are not able to detect microvessels on a micron or sub-micron scale without angiography. In the present study, synchrotron radiation (SR)-based X-ray in-line phase contrast imaging (ILPCI) was used to acquire high-resolution and high-contrast images of rat brain tissues in both normal and ischaemic states. ILPCI was performed at the Shanghai Synchrotron Radiation Facility, Shanghai, China, without the use of contrast agents. CT slices were reformatted and then converted into three-dimensional (3D) reconstruction images to analyse subtle details of the cerebral microvascular network. By using ILPCI, brain vessels up to 11.8 μm in diameter were resolved. The number of cortical and penetrating arteries detected were found to undergo a remarkable decrease within the infarct area. 3 days after permanent ischaemia, vascular masses were also observed in the peripheral region of the infarcts. SR-based ILPCI-CT can serve as a powerful tool to accurately visualize brain microvasculature. The morphological parameters of blood vessels in both CT slices and 3D reconstructions were determined, and this approach has great potential for providing an effective diagnosis and evaluation for rehabilitation therapy for stroke. In the absence of contrast agent, the 3D morphologies of the brain microvasculature in normal and stroke rats were obtained using SR-based ILPCI. SR imaging is a sensitive and promising method which can be used to explore primary brain function.

  12. Mechanisms of blast induced brain injuries, experimental studies in rats.

    Science.gov (United States)

    Risling, M; Plantman, S; Angeria, M; Rostami, E; Bellander, B-M; Kirkegaard, M; Arborelius, U; Davidsson, J

    2011-01-01

    Traumatic brain injuries (TBI) potentially induced by blast waves from detonations result in significant diagnostic problems. It may be assumed that several mechanisms contribute to the injury. This study is an attempt to characterize the presumed components of the blast induced TBI. Our experimental models include a blast tube in which an anesthetized rat can be exposed to controlled detonations of explosives that result in a pressure wave with a magnitude between 130 and 260 kPa. In this model, the animal is fixed with a metal net to avoid head acceleration forces. The second model is a controlled penetration of a 2mm thick needle. In the third model the animal is subjected to a high-speed sagittal rotation angular acceleration. Immunohistochemical labeling for amyloid precursor protein revealed signs of diffuse axonal injury (DAI) in the penetration and rotation models. Signs of punctuate inflammation were observed after focal and rotation injury. Exposure in the blast tube did not induce DAI or detectable cell death, but functional changes. Affymetrix Gene arrays showed changes in the expression in a large number of gene families including cell death, inflammation and neurotransmitters in the hippocampus after both acceleration and penetration injuries. Exposure to the primary blast wave induced limited shifts in gene expression in the hippocampus. The most interesting findings were a downregulation of genes involved in neurogenesis and synaptic transmission. These experiments indicate that rotational acceleration may be a critical factor for DAI and other acute changes after blast TBI. The further exploration of the mechanisms of blast TBI will have to include a search for long-term effects. Copyright © 2010 Elsevier Inc. All rights reserved.

  13. Focal experimental injury leads to widespread gene expression and histologic changes in equine flexor tendons.

    Directory of Open Access Journals (Sweden)

    Else Jacobson

    Full Text Available It is not known how extensively a localised flexor tendon injury affects the entire tendon. This study examined the extent of and relationship between histopathologic and gene expression changes in equine superficial digital flexor tendon after a surgical injury. One forelimb tendon was hemi-transected in six horses, and in three other horses, one tendon underwent a sham operation. After euthanasia at six weeks, transected and control (sham and non-operated contralateral tendons were regionally sampled (medial and lateral halves each divided into six 3 cm regions for histologic (scoring and immunohistochemistry and gene expression (real time PCR analysis of extracellular matrix changes. The histopathology score was significantly higher in transected tendons compared to control tendons in all regions except for the most distal (P ≤ 0.03 with no differences between overstressed (medial and stress-deprived (lateral tendon halves. Proteoglycan scores were increased by transection in all but the most proximal region (P < 0.02, with increased immunostaining for aggrecan, biglycan and versican. After correcting for location within the tendon, gene expression for aggrecan, versican, biglycan, lumican, collagen types I, II and III, MMP14 and TIMP1 was increased in transected tendons compared with control tendons (P < 0.02 and decreased for ADAMTS4, MMP3 and TIMP3 (P < 0.001. Aggrecan, biglycan, fibromodulin, and collagen types I and III expression positively correlated with all histopathology scores (P < 0.001, whereas lumican, ADAMTS4 and MMP14 expression positively correlated only with collagen fiber malalignment (P < 0.001. In summary, histologic and associated gene expression changes were significant and widespread six weeks after injury to the equine SDFT, suggesting rapid and active development of tendinopathy throughout the entire length of the tendon. These extensive changes distant to the focal injury may contribute to poor functional outcomes

  14. Multiple cystic and focal encephalomalacia in infancy and childhood with brain stem damage.

    Science.gov (United States)

    Smith, J F; Rodeck, C

    1975-07-01

    Two cases are described in which damage to the brain stem was associated with extensive necrosis of the cerebral hemisphere. In the first case--a monochorionic twin--there was clear evidence that injury of an ischaemic or hypoxic type had occurred during fetal life and some evidence that an inadequate share of the placental circulation was an important aetiological factor. In the second case death occurred 4 yr after an asphyxial episode at birth. The lesions in the hemispheres and brain stem were extensive, although less than in the first example. The lesions are discussed in the context of our knowledge of the anatomy and physiology of the developing nervous system. Although they cannot as yet be fitted into the concepts of "critical periods" and "vulnerable periods" of development, this is perhaps because observations on human cases are scanty in comparison with the extensive animal studies which have been reported. The lesions are contrasted and compared with those seen in animals.

  15. Elevated global SUMOylation in Ubc9 transgenic mice protects their brains against focal cerebral ischemic damage.

    Directory of Open Access Journals (Sweden)

    Yang-Ja Lee

    Full Text Available We have previously shown that a massive increase in global SUMOylation occurs during torpor in ground squirrels, and that overexpression of Ubc9 and/or SUMO-1 in cell lines and cortical neurons protects against oxygen and glucose deprivation. To examine whether increased global SUMOylation protects against ischemic brain damage, we have generated transgenic mice in which Ubc9 is expressed strongly in all tissues under the chicken β-actin promoter. Ubc9 expression levels in 10 founder lines ranged from 2 to 30 times the endogenous level, and lines that expressed Ubc9 at modestly increased levels showed robust resistance to brain ischemia compared to wild type mice. The infarction size was inversely correlated with the Ubc9 expression levels for up to five times the endogenous level. Although further increases showed no additional benefit, the Ubc9 expression level was highly correlated with global SUMO-1 conjugation levels (and SUMO-2,3 levels to a lesser extent up to a five-fold Ubc9 increase. Most importantly, there were striking reciprocal relationships between SUMO-1 (and SUMO-2,3 conjugation levels and cerebral infarction volumes among all tested animals, suggesting that the limit in cytoprotection by global SUMOylation remains undefined. These results support efforts to further augment global protein SUMOylation in brain ischemia.

  16. Elevated global SUMOylation in Ubc9 transgenic mice protects their brains against focal cerebral ischemic damage.

    Science.gov (United States)

    Lee, Yang-Ja; Mou, Yongshan; Maric, Dragan; Klimanis, Dace; Auh, Sungyoung; Hallenbeck, John M

    2011-01-01

    We have previously shown that a massive increase in global SUMOylation occurs during torpor in ground squirrels, and that overexpression of Ubc9 and/or SUMO-1 in cell lines and cortical neurons protects against oxygen and glucose deprivation. To examine whether increased global SUMOylation protects against ischemic brain damage, we have generated transgenic mice in which Ubc9 is expressed strongly in all tissues under the chicken β-actin promoter. Ubc9 expression levels in 10 founder lines ranged from 2 to 30 times the endogenous level, and lines that expressed Ubc9 at modestly increased levels showed robust resistance to brain ischemia compared to wild type mice. The infarction size was inversely correlated with the Ubc9 expression levels for up to five times the endogenous level. Although further increases showed no additional benefit, the Ubc9 expression level was highly correlated with global SUMO-1 conjugation levels (and SUMO-2,3 levels to a lesser extent) up to a five-fold Ubc9 increase. Most importantly, there were striking reciprocal relationships between SUMO-1 (and SUMO-2,3) conjugation levels and cerebral infarction volumes among all tested animals, suggesting that the limit in cytoprotection by global SUMOylation remains undefined. These results support efforts to further augment global protein SUMOylation in brain ischemia.

  17. Cilostazol, a phosphodiesterase inhibitor, attenuates photothrombotic focal ischemic brain injury in hypertensive rats.

    Science.gov (United States)

    Ito, Hideki; Hashimoto, Ayako; Matsumoto, Yutaka; Yao, Hiroshi; Miyakoda, Goro

    2010-02-01

    The aim of this study was to evaluate and compare the effects of anti-platelet agents with different modes of action (cilostazol, aspirin, and clopidogrel) on brain infarction produced by photothrombotic middle-cerebral-artery (MCA) occlusion in male, spontaneously hypertensive rats. Cerebral blood flow (CBF) was measured with laser-Doppler flowmetry in the penumbral cortex. Infarct size was evaluated 24 h after MCA occlusion. The effects of these drugs on infarct size were examined by pretreatment of rats undergoing MCA occlusion. Pretreatment with cilostazol (100 mg/kg) significantly reduced infarct size. In contrast, aspirin (10 mg/kg) and clopidogrel (3 mg/kg) failed to mitigate infarct size, regardless of their apparent inhibitory effects on platelet aggregation. Post-treatment with cilostazol also significantly attenuated the infarct size, associated with improved CBF in the penumbral region. In support of this effect, cilostazol increased nitric oxide (NO) production and prostaglandin-I(2) (PGI(2)) release in cultured human brain microvascular endothelial cells. Cilostazol-induced NO production and PGI(2) release were completely abolished by an NO synthase inhibitor and aspirin, respectively. These findings show that cilostazol reduced brain infarct size due to an improvement in penumbral CBF possibly in association with increased endothelial NO and PGI(2) production.

  18. Individual Assessment of Brain Tissue Changes in MS and the Effect of Focal Lesions on Short-Term Focal Atrophy Development in MS: A Voxel-Guided Morphometry Study

    Directory of Open Access Journals (Sweden)

    Jan Fox

    2016-04-01

    Full Text Available We performed voxel-guided morphometry (VGM investigating the mechanisms of brain atrophy in multiple sclerosis (MS related to focal lesions. VGM maps detect regional brain changes when comparing 2 time points on high resolution T1-weighted (T1w magnetic resonace imaging (MRI. Two T1w MR datasets from 92 relapsing-remitting MS patients obtained 12 months apart were analysed with VGM. New lesions and volume changes of focal MS lesions as well as in the surrounding tissue were identified by visual inspection on colour coded VGM maps. Lesions were dichotomized in active and inactive lesions. Active lesions, defined by either new lesions (NL (volume increase > 5% in VGM, chronic enlarging lesions (CEL (pre-existent T1w lesions with volume increase > 5%, or chronic shrinking lesions (CSL (pre-existent T1w lesions with volume reduction > 5% in VGM, were accompanied by tissue shrinkage in surrounding and/or functionally related regions. Volume loss within the corpus callosum was highly correlated with the number of lesions in its close proximity. Volume loss in the lateral geniculate nucleus was correlated with lesions along the optic radiation. VGM analysis provides strong evidence that all active lesion types (NL, CEL, and CSL contribute to brain volume reduction in the vicinity of lesions and/or in anatomically and functionally related areas of the brain.

  19. Role of nitric oxide synthases in early blood-brain barrier disruption following transient focal cerebral ischemia.

    Directory of Open Access Journals (Sweden)

    Zheng Jiang

    Full Text Available The role of nitric oxide synthases (NOSs in early blood-brain barrier (BBB disruption was determined using a new mouse model of transient focal cerebral ischemia. Ischemia was induced by ligating the middle cerebral artery (MCA at its M2 segment and reperfusion was induced by releasing the ligation. The diameter alteration of the MCA, arterial anastomoses and collateral arteries were imaged and measured in real time. BBB disruption was assessed by Evans Blue (EB and sodium fluorescein (Na-F extravasation at 3 hours of reperfusion. The reperfusion produced an extensive vasodilation and a sustained hyperemia. Although expression of NOSs was not altered at 3 hours of reperfusion, L-NAME (a non-specific NOS inhibitor abolished reperfusion-induced vasodilation/hyperemia and significantly reduced EB and Na-F extravasation. L-NIO (an endothelial NOS (eNOS inhibitor significantly attenuated cerebral vasodilation but not BBB disruption, whereas L-NPA and 7-NI (neuronal NOS (nNOS inhibitors significantly reduced BBB disruption but not cerebral vasodilation. In contrast, aminoguanidine (AG (an inducible NOS (iNOS inhibitor had less effect on either cerebral vasodilation or BBB disruption. On the other hand, papaverine (PV not only increased the vasodilation/hyperemia but also significantly reduced BBB disruption. Combined treatment with L-NAME and PV preserved the vasodilation/hyperemia and significantly reduced BBB disruption. Our findings suggest that nNOS may play a major role in early BBB disruption following transient focal cerebral ischemia via a hyperemia-independent mechanism.

  20. Microglial involvement in neuroplastic changes following focal brain ischemia in rats.

    Directory of Open Access Journals (Sweden)

    Alexandre Madinier

    2009-12-01

    Full Text Available The pathogenesis of ischemic stroke is a complex sequence of events including inflammatory reaction, for which the microglia appears to be a major cellular contributor. However, whether post-ischemic activation of microglial cells has beneficial or detrimental effects remains to be elucidated, in particular on long term brain plasticity events. The objective of our study was to determine, through modulation of post-stroke inflammatory response, to what extent microglial cells are involved in some specific events of neuronal plasticity, neurite outgrowth and synaptogenesis. Since microglia is a source of neurotrophic factors, the identification of the brain-derived neurophic factor (BDNF as possible molecular actor involved in these events was also attempted. As a means of down-regulating the microglial response induced by ischemia, 3-aminobenzamide (3-AB, 90 mg/kg, i.p. was used to inhibit the poly(ADP-ribose polymerase-1 (PARP-1. Indeed, PARP-1 contributes to the activation of the transcription factor NF-kB, which is essential to the upregulation of proinflammatory genes, in particular responsible for microglial activation/proliferation. Experiments were conducted in rats subjected to photothrombotic ischemia which leads to a strong and early microglial cells activation/proliferation followed by an infiltration of macrophages within the cortical lesion, events evaluated at serial time points up to 1 month post-ictus by immunostaining for OX-42 and ED-1. Our most striking finding was that the decrease in acute microglial activation induced by 3-AB was associated with a long term down-regulation of two neuronal plasticity proteins expression, synaptophysin (marker of synaptogenesis and GAP-43 (marker of neuritogenesis as well as to a significant decrease in tissue BDNF production. Thus, our data argue in favour of a supportive role for microglia in brain neuroplasticity stimulation possibly through BDNF production, suggesting that a targeted

  1. Interleukin-6 mediates enhanced thrombus development in cerebral arterioles following a brief period of focal brain ischemia

    Science.gov (United States)

    Tang, Ya Hui; Vital, Shantel; Russell, Janice; Seifert, Hilary; Granger, D. Neil

    2015-01-01

    Objective The cerebral microvasculature is rendered more vulnerable to thrombus formation following a brief (5.0 min) period of focal ischemia. This study examined the contribution of interleukin-6 (IL-6), a neuroprotective and prothrombotic cytokine produced by the brain, to transient ischemia-induced thrombosis in cerebral arterioles. Approach & results The middle cerebral artery of C57BL/6J mice was occluded for 5 minutes, followed by 24 hrs of reperfusion (MCAo/R). Intravital fluorescence microscopy was used to monitor thrombus development in cerebral arterioles induced by light/dye photoactivation. Thrombosis was quantified as the time of onset of platelet aggregation on the vessel wall and the time for complete blood flow cessation. MCAo/R in wild type (WT) mice yielded an acceleration of thrombus formation that was accompanied by increased IL-6 levels in plasma and in post-ischemic brain tissue. The exaggerated thrombosis response to MCAo/R was blunted in WT mice receiving an IL-6 receptor-blocking antibody and in IL-6 deficient (IL-6−/−) mice. Bone marrow chimeras, produced by transplanting IL-6−/− marrow into WT recipients, did not exhibit protection against MCAo/R-induced thrombosis. Conclusions The increased vulnerability of the cerebral vasculature to thrombus development after MCAo/R is mediated by IL-6, which is likely derived from brain cells rather than circulating blood cells. These findings suggest that anti-IL-6 therapy may reduce the likelihood of cerebral thrombus development after a transient ischemic attack. PMID:26054883

  2. Human-derived physiological heat shock protein 27 complex protects brain after focal cerebral ischemia in mice.

    Directory of Open Access Journals (Sweden)

    Shinichiro Teramoto

    Full Text Available Although challenging, neuroprotective therapies for ischemic stroke remain an interesting strategy for countering ischemic injury and suppressing brain tissue damage. Among potential neuroprotective molecules, heat shock protein 27 (HSP27 is a strong cell death suppressor. To assess the neuroprotective effects of HSP27 in a mouse model of transient middle cerebral artery occlusion, we purified a "physiological" HSP27 (hHSP27 from normal human lymphocytes. hHSP27 differed from recombinant HSP27 in that it formed dimeric, tetrameric, and multimeric complexes, was phosphorylated, and contained small amounts of αβ-crystallin and HSP20. Mice received intravenous injections of hHSP27 following focal cerebral ischemia. Infarct volume, neurological deficit scores, physiological parameters, and immunohistochemical analyses were evaluated 24 h after reperfusion. Intravenous injections of hHSP27 1 h after reperfusion significantly reduced infarct size and improved neurological deficits. Injected hHSP27 was localized in neurons on the ischemic side of the brain. hHSP27 suppressed neuronal cell death resulting from cytochrome c-mediated caspase activation, oxidative stress, and inflammatory responses. Recombinant HSP27 (rHSP27, which was artificially expressed and purified from Escherichia coli, and dephosphorylated hHSP27 did not have brain protective effects, suggesting that the phosphorylation of hHSP27 may be important for neuroprotection after ischemic insults. The present study suggests that hHSP27 with posttranslational modifications provided neuroprotection against ischemia/reperfusion injury and that the protection was mediated through the inhibition of apoptosis, oxidative stress, and inflammation. Intravenously injected human HSP27 should be explored for the treatment of acute ischemic strokes.

  3. Atypical focal non-neoplastic brain changes in neurofibromatosis type 1: mass effect and contrast enhancement

    Energy Technology Data Exchange (ETDEWEB)

    Raininko, R. [Dept. of Oncology, Radiology and Clinical Immunology, Section of Radiology, Uppsala University (Sweden); Thelin, L. [Dept. of Pediatrics, Gaevle County Hospital (Sweden); Eeg-Olofsson, O. [Dept. of Women' s and Children' s Health, Section of Pediatrics, Uppsala University (Sweden)

    2001-07-01

    Abstract Children and young adults with neurofibromatosis type 1 often have small high-signal foci on T2-weighted images of the brain. We describe follow-up of two patients in whom one of the foci had atypical features, commonly regarded as signs of a neoplasm. In the first, one lesion showed temporary contrast enhancement and decreasing mass effect. The second developed an expanding lesion that increased minimally in size over 4.5 year's follow-up. The borderline between neoplastic and non-neoplastic lesions seems to be indistinct. (orig.)

  4. The neuroprotective effects of preconditioning exercise on brain damage and neurotrophic factors after focal brain ischemia in rats.

    Science.gov (United States)

    Otsuka, Shotaro; Sakakima, Harutoshi; Sumizono, Megumi; Takada, Seiya; Terashi, Takuto; Yoshida, Yoshihiro

    2016-04-15

    Preconditioning exercise can exert neuroprotective effects after stroke. However, the mechanism underlying these neuroprotective effects by preconditioning exercise remains unclear. We investigated the neuroprotective effects of preconditioning exercise on brain damage and the expression levels of the midkine (MK) and brain-derived neurotrophic factor (BDNF) after brain ischemia. Animals were assigned to one of 4 groups: exercise and ischemia (Ex), no exercise and ischemia (No-Ex), exercise and no ischemia (Ex-only), and no exercise and intact (Control). Rats ran on a treadmill for 30 min once a day at a speed of 25 m/min for 5 days a week for 3 weeks. After the exercise program, stroke was induced by a 60 min left middle cerebral artery occlusion using an intraluminal filament. The infarct volume, motor function, neurological deficits, and the cellular expressions levels of MK, BDNF, GFAP, PECAM-1, caspase 3, and nitrotyrosine (NT) were evaluated 48 h after the induction of ischemia. The infarct volume, neurological deficits and motor function in the Ex group were significantly improved compared to that of the No-Ex group. The expression levels of MK, BDNF, GFAP, and PECAM-1 were enhanced in the Ex group compared to the expression levels in the No-Ex group after brain ischemia, while the expression levels of activated caspase 3 and NT were reduced in the area surrounding the necrotic lesion. Our findings suggest that preconditioning exercise reduced the infract volume and ameliorated motor function, enhanced expression levels of MK and BDNF, increased astrocyte proliferation, increased angiogenesis, and reduced neuronal apoptosis and oxidative stress. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. YiQiFuMai powder injection ameliorates blood–brain barrier dysfunction and brain edema after focal cerebral ischemia–reperfusion injury in mice

    Directory of Open Access Journals (Sweden)

    Cao GS

    2016-01-01

    Full Text Available Guosheng Cao, Xinyi Ye, Yingqiong Xu, Mingzhu Yin, Honglin Chen, Junping Kou, Boyang Yu Jiangsu Key Laboratory of TCM Evaluation and Translational Research, Department of Complex Prescription of TCM, China Pharmaceutical University, Nanjing, People’s Republic of China Abstract: YiQiFuMai powder injection (YQFM is a modern preparation derived from the traditional Chinese medicine Sheng-Mai-San. YQFM is widely used in clinical practice in the People’s Republic of China, mainly for the treatment of microcirculatory disturbance-related diseases. However, little is known about its role in animals with ischemic stroke. The aim of this study was to examine the effect of YQFM on brain edema and blood–brain barrier (BBB dysfunction induced by cerebral ischemia–reperfusion (I/R injury. Male C57BL/6J mice underwent right middle cerebral artery occlusion for 1 hour with a subsequent 24-hour reperfusion to produce I/R injury. YQFM (three doses: 0.336, 0.671, and 1.342 g/kg was then given intraperitoneally (IP. The results demonstrated that YQFM significantly decreased infarct size, improved neurological deficits, reduced brain water content, and increased cerebral blood flow after I/R injury. 18F-fluorodeoxyglucose micro-positron emission tomography imaging and hematoxylin and eosin staining results indicated that YQFM is able to ameliorate brain metabolism and histopathological damage after I/R. Moreover, YQFM administration reduced BBB leakage and upregulated the expression of zona occludens-1 (ZO-1 and occludin, which was confirmed by Evans Blue extravasation, Western blotting, and immunofluorescence assay. Our findings suggest that YQFM provides protection against focal cerebral I/R injury in mice, possibly by improving BBB dysfunction via upregulation of the expression of tight junction proteins. Keywords: YiQiFuMai powder injection, YQFM, ischemic stroke, blood–brain barrier, microvascular permeability, tight junctions

  6. [Utility of diffusion-weighted magnetic resonance imaging in severe focal traumatic brain injuries].

    Science.gov (United States)

    Prieto-Valderrey, F; Muñiz-Montes, J R; López-García, J A; Villegas-Del Ojo, J; Málaga-Gil, J; Galván-García, R

    2013-01-01

    To describe the apparent diffusion coefficient (ADC) in a series of severe traumatic brain injuries, their clinical and outcome features, and possible implications. A descriptive, observational case-series study was carried out. Patients with severe traumatic brain injuries (TBIs) admitted to the ICU were subjected to MRI study using a 1.5 T scanner. Diffusion-weighted images (DWMR) were obtained using the following echo-planar pulse sequence: TR 10000 ms, TE 126.9 ms, with b values 1000 s/mm2 in the three spatial dimensions. Combining the three sets of images, an isotropic image conforming a map of the mean ADCs was obtained. DWMR was performed in 23 patients with severe TBI admitted to the ICU between 2001 and 2004. In the MR images we selected 26 regions of interest (ROIs) where ADC was recorded. We observed a clear increase in diffusion in non-treated space-occupying lesions versus other types of injuries and the normal values. A poorer outcome was recorded in patients with lower ADC values. Mean ADC in the lesions was greater than the normal values and greater in contusions than in other types of injuries, as an expression of extracellular edema. ADCs were decreased in patients with a poor outcome, suggesting an association between ischemia and the patient prognosis. Copyright © 2011 Elsevier España, S.L. and SEMICYUC. All rights reserved.

  7. Focal Brain Injury Associated with a Model of Severe Hypoxic-Ischemic Encephalopathy in Nonhuman Primates.

    Science.gov (United States)

    McAdams, Ryan M; McPherson, Ronald J; Kapur, Raj P; Juul, Sandra E

    2017-01-01

    Worldwide, hypoxic-ischemic encephalopathy (HIE) is a major cause of neonatal mortality and morbidity. To better understand the mechanisms contributing to brain injury and improve outcomes in neonates with HIE, better preclinical animal models that mimic the clinical situation following birth asphyxia in term newborns are needed. In an effort to achieve this goal, we modified our nonhuman primate model of HIE induced by in utero umbilical cord occlusion (UCO) to include postnatal hypoxic episodes, in order to simulate apneic events in human neonates with HIE. We describe a cohort of 4 near-term fetal Macaca nemestrina that underwent 18 min of in utero UCO, followed by cesarean section delivery, resuscitation, and subsequent postnatal mechanical ventilation, with exposure to intermittent daily hypoxia (3 min, 8% O2 3-8 times daily for 3 days). After delivery, all animals demonstrated severe metabolic acidosis (pH 7 ± 0.12; mean ± SD) and low APGAR scores (neonates after severe, abrupt hypoxic-ischemic insults. The UCO model permits timely detection of biomarkers associated with specific patterns of neonatal brain injury, and it may ultimately be useful for validating therapeutic strategies to treat neonatal HIE. © 2017 S. Karger AG, Basel.

  8. [Cerebral activation during Stroop's test in a case of early focal brain injury].

    Science.gov (United States)

    Salgado-Pineda, P; Román, F; Sánchez-Navarro, J P; López-Hernández, F; Bargalló, N; Falcón, C; Ramírez-Ruiz, B; Caldú-Ferrús, X; Martínez-Lage, J

    Functional magnetic resonance imaging (fMRI) offers an important advantage over other functional neuroimaging techniques used with children because of its harmlessness. Previous studies conducted with adults with alexia suggested two ways the brain can reorganise reading after a brain injury affecting the left hemisphere, one contralateral and the other ipsilateral. We describe a study carried out using fMRI of a 10 year old girl with an injury to the left hemisphere caused by a fishing harpoon when she was 6 years old. As a result of the accident the girl presented a right hemiparesia. The girl s parents and teachers also reported difficulties in the acquisition of reading writing and arithmetic, as well as a certain degree of attentional deficit. An fMRI exploration was performed while the girl was doing the Stroop test. The structural MR images showed left hemisphere cortical lesions in the orbital and angular gyrus regions, in addition to the caudate and putamen nuclei, and in the inferior longitudinal bundle. The fRMI revealed a strong overactivation of the right dorsolateral frontal cortex, in the evaluation of interference, and activations of the right angular and bilateral supramarginal gyri, in the evaluation of word reading. The functional study suggests the existence of a reorganisation of reading that is both intra and inter hemispheric.

  9. Left hemisphere regions are critical for language in the face of early left focal brain injury.

    Science.gov (United States)

    Raja Beharelle, Anjali; Dick, Anthony Steven; Josse, Goulven; Solodkin, Ana; Huttenlocher, Peter R; Levine, Susan C; Small, Steven L

    2010-06-01

    A predominant theory regarding early stroke and its effect on language development, is that early left hemisphere lesions trigger compensatory processes that allow the right hemisphere to assume dominant language functions, and this is thought to underlie the near normal language development observed after early stroke. To test this theory, we used functional magnetic resonance imaging to examine brain activity during category fluency in participants who had sustained pre- or perinatal left hemisphere stroke (n = 25) and in neurologically normal siblings (n = 27). In typically developing children, performance of a category fluency task elicits strong involvement of left frontal and lateral temporal regions and a lesser involvement of right hemisphere structures. In our cohort of atypically developing participants with early stroke, expressive and receptive language skills correlated with activity in the same left inferior frontal regions that support language processing in neurologically normal children. This was true independent of either the amount of brain injury or the extent that the injury was located in classical cortical language processing areas. Participants with bilateral activation in left and right superior temporal-inferior parietal regions had better language function than those with either predominantly left- or right-sided unilateral activation. The advantage conferred by left inferior frontal and bilateral temporal involvement demonstrated in our study supports a strong predisposition for typical neural language organization, despite an intervening injury, and argues against models suggesting that the right hemisphere fully accommodates language function following early injury.

  10. Increased expression of neurotrophin 4 following focal cerebral ischemia in adult rat brain with treadmill exercise.

    Directory of Open Access Journals (Sweden)

    Jin-Young Chung

    Full Text Available Neurotrophin 4 (NT-4 belongs to the family of neurotrophic factors, and it interacts with the tyrosine kinase B (trkB receptor. NT-4 has neuroprotective effects following cerebral ischemia. Its role might be similar to brain-derived neurotrophic factor (BDNF, because both interact with trkB. Exercise also improves neural function by increasing neurotrophic factors. However, expression profiles of NT-4 in the brain during exercise are unknown. Here, we assessed the expressions of NT-4 and its receptor, trkB, following cerebral ischemia and hypothesized that exercise changes the expressions of NT-4 and trkB. Results showed that in a permanent middle cerebral artery occlusion rat model, ischemia decreased NT-4 and trkB expression. Immunohistochemistry showed their immunoreactivities around the region of the ischemic area. Treadmill exercise changed the expression of NT-4, which increased in the contralateral hemisphere in rats with ischemic injury. TrkB also showed similar patterns to its neurotophins. The change in NT-4 suggested that exercise might have primed NT4 production so that further injury causes slightly greater increases in NT4 compared with non-exercise controls.

  11. The Effects of Antecedent Exercise on Motor Function Recovery and Brain-derived Neurotrophic Factor Expression after Focal Cerebral Ischemia in Rats.

    Science.gov (United States)

    Kim, Gyeyeop; Kim, Eunjung

    2013-05-01

    [Purpose] In the present study, we investigated the effect of antecedent exercise on functional recovery and brain-derived neurotrophic factor (BDNF) expression following focal cerebral ischemia injury. [Subjects] The rat middle cerebral artery occlusion (MCAO) model was employed. Adult male Sprague-Dawley rats were randomly divided into 4 groups. Group I included untreated normal rats (n=10); Group II included untreated rats with focal cerebral ischemia (n=10); Group III included rats that performed treadmill exercise (20 m/min) training after focal cerebral ischemia (n=10); and Group IV included rats that performed antecedent treadmill exercise (20 m/min) training before focal cerebral ischemia (n=10) as well as treadmill exercise after ischemia. At different time points (1, 7, 14, and 21 days) Garcia's score, and the hippocampal expressions level of BDNF were examined. [Results] In the antecedent exercise group, improvements in the motor behavior index (Garcia's score) were observed and hippocampal BDNF protein expression levels increased. [Conclusion] These results indicate that antecedent treadmill exercise, before permanent brain ischemia exerts a neuroprotective effect against ischemia brain injury by improving motor performance and increasing the level of BDNF expression. Furthermore, the antecedent treadmill exercise of appropriate intensity is critical for post-stroke rehabilitation.

  12. Tumor histology and location predict deep nuclei toxicity: Implications for late effects from focal brain irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Plaga, Alexis; Shields, Lisa B.E. [Norton Neuroscience Institute, Louisville, KY (United States); Sun, David A.; Vitaz, Todd W. [Norton Neuroscience Institute, Louisville, KY (United States); Brain Tumor Center, Norton Healthcare, Louisville, KY (United States); Spalding, Aaron C., E-mail: acspalding1@gmail.com [Brain Tumor Center, Norton Healthcare, Louisville, KY (United States); Norton Cancer Institute, Radiation Center, Kosair Children' s Hospital, Louisville, KY (United States)

    2012-10-01

    Normal tissue toxicity resulting from both disease and treatment is an adverse side effect in the management of patients with central nervous system malignancies. We tested the hypothesis that despite these improvements, certain tumors place patients at risk for neurocognitive, neuroendocrine, and neurosensory late effects. Defining patient groups at risk for these effects could allow for development of preventive strategies. Fifty patients with primary brain tumors underwent radiation planning with magnetic resonance imaging scan and computed tomography datasets. Organs at risk (OAR) responsible for neurocognitive, neuroendocrine, and neurosensory function were defined. Inverse-planned intensity-modulated radiation therapy was optimized with priority given to target coverage while penalties were assigned to exceeding normal tissue tolerances. Tumor laterality, location, and histology were compared with OAR doses, and analysis of variance was performed to determine the significance of any observed correlation. The ipsilateral hippocampus exceeded dose limits in frontal (74%), temporal (94%), and parietal (100%) lobe tumor locations. The contralateral hippocampus was at risk in the following tumor locations: frontal (53%), temporal (83%), or parietal (50%) lobe. Patients with high-grade glioma were at risk for ipsilateral (88%) and contralateral (73%) hippocampal damage (P <0.05 compared with other histologies). The pituitary gland and hypothalamus exceeded dose tolerances in patients with pituitary tumors (both 100%) and high-grade gliomas (50% and 75%, P <0.05 compared with other histologies), respectively. Despite application of modern radiation therapy, certain tumor locations and histologies continue to place patients at risk for morbidity. Patients with high-grade gliomas or tumors located in the frontal, temporal, or parietal lobes are at risk for neurocognitive decline, likely because of larger target volumes and higher radiation doses. Data from this study

  13. PI3K/AKT pathway mutations cause a spectrum of brain malformations from megalencephaly to focal cortical dysplasia

    National Research Council Canada - National Science Library

    Jansen, Laura A; Mirzaa, Ghayda M; Ishak, Gisele E; O'Roak, Brian J; Hiatt, Joseph B; Roden, William H; Gunter, Sonya A; Christian, Susan L; Collins, Sarah; Adams, Carissa; Rivière, Jean-Baptiste; St-Onge, Judith; Ojemann, Jeffrey G; Shendure, Jay; Hevner, Robert F; Dobyns, William B

    2015-01-01

    Malformations of cortical development containing dysplastic neuronal and glial elements, including hemimegalencephaly and focal cortical dysplasia, are common causes of intractable paediatric epilepsy...

  14. The effect of focal brain injury on beta-amyloid plaque deposition, inflammation and synapses in the APP/PS1 mouse model of Alzheimer's disease.

    Science.gov (United States)

    Collins, Jessica M; King, Anna E; Woodhouse, Adele; Kirkcaldie, Matthew T K; Vickers, James C

    2015-05-01

    Traumatic brain injury is a risk factor for Alzheimer's disease (AD), however the effect of such neural damage on the onset and progression of beta-amyloid (Aβ) plaque pathology is not well understood. This study utilized an in vivo model of focal brain injury to examine how localized damage may acutely affect the onset and progression of Aβ plaque deposition as well as inflammatory and synaptic changes, in the APP/PS1 (APPSWE, PSEN1dE9) transgenic model of AD relative to wild-type (Wt) mice. Acute focal brain injury in 3- and 9-month-old APP/PS1 and Wt mice was induced by insertion of a needle into the somatosensory neocortex, as compared to sham surgery, and examined at 24h and 7d post-injury (PI). Focal brain injury did not induce thioflavine-S stained or (pan-Aβ antibody) MOAB-2-labeled plaques at either 24h or 7d PI in 3-month-old APP/PS1 mice or Wt mice. Nine-month-old APP/PS1 mice demonstrate cortical Aβ plaques but focal injury had no statistically significant (p>0.05) effect on thioflavine-S or MOAB-2 plaque load surrounding the injury site at 24h PI or 7d PI. There was a significant (p0.05). For both Wt and APP/PS1 mice alike, synaptophysin puncta near the injury site were significantly reduced 24h PI (compared to sites distant to the injury and the corresponding area in sham mice; p0.05). There was no significant effect of genotype on this response (p>0.05). These results indicate that focal brain injury and the associated microglial response do not acutely alter Aβ plaque deposition in the APP/PS1 mouse model. Furthermore the current study demonstrated that the brains of both Wt and APP/PS1 mice are capable of recovering lost synaptophysin immunoreactivity post-injury, the latter in the presence of Aβ plaque pathology that causes synaptic degeneration. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Willed-movement training reduces brain damage and enhances synaptic plasticity related proteins synthesis after focal ischemia.

    Science.gov (United States)

    Nie, Jingjing; Yang, Xiaosu; Tang, Qingping; Shen, Qin; Li, Simin

    2016-01-01

    It has been wildly accepted that willed movement(WM) training promotes neurological rehabilitation in patients with stroke. However, it was not clear whether the effect of WM is better than other forms of exercise. The purpose of this study is to assess different effects of WM and other forms of exercise on rats with focal ischemia. The subjects are all had right middle cerebral artery occlusion (MCAO) surgery and randomly allocated to three groups of training and one control group with no training. Infarct volume by 2,3,5-triphenyltetrazolium chloride (TTC) dye, expression of PICK1 and synaptophysin in cerebral cortex and striatum of injured side by western blotting and immunofluorescence performed are analyzed. Exercise has done respectively on rats in each group for 15 days and 30 days. Compared with the control group, the brain damage is reduced in other groups after 15 days exercise. The protein expressions levels of synaptophysin and PICK1 are upregulated after exercise. Concentration of PICK1 protein in WM is greater than other exercise groups, and the expression of synaptophysin in WM and SM groups are higher than EM groups. The number of PICK1 positive cells, synaptophysin and PICK1 co-positive cells are increased by exercise. Synaptophysin is widely distributed in cortex surrounding the injury area in WM and EM. It is indicated in our result that willed-movement training is the most effective intervention in enhancing the PICK1-mediated synaptic plasticity in the area adjacent to the damage region of ischemic rats. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Is the motor system necessary for processing action and abstract emotion words? Evidence from focal brain lesions

    Directory of Open Access Journals (Sweden)

    Felix R. Dreyer

    2015-11-01

    Full Text Available Neuroimaging and neuropsychological experiments suggest that modality-preferential cortices, including motor- and somatosensory areas contribute to the semantic processing of action related concrete words. In contrast, a possible role of modality-preferential – including sensorimotor – areas in processing abstract meaning remains under debate. However, recent fMRI studies indicate an involvement of the left sensorimotor cortex in the processing of abstract-emotional words (e.g. love. But are these areas indeed necessary for processing action-related and abstract words? The current study now investigates word processing in two patients suffering from focal brain lesion in the left frontocentral motor system. A speeded lexical decision task (LDT on meticulously matched word groups showed that the recognition of nouns from different semantic categories – related to food, animals, tools and abstract-emotional concepts – was differentially affected. Whereas patient HS with a lesion in dorsolateral central sensorimotor cortex next to the hand area showed a category-specific deficit in recognizing tool words, patient CA suffering from lesion centered in the left SMA was primarily impaired in abstract-emotional word processing. These results point to a causal role of the motor cortex in the semantic processing of both action-related object concepts and abstract-emotional concepts and therefore suggest that the motor areas previously found active in action-related and abstract word processing can serve a meaning-specific necessary role in word recognition. The category-specific nature of the observed dissociations is difficult to reconcile with the idea that sensorimotor systems are somehow peripheral or ‘epiphenomenal’ to meaning and concept processing. Rather, our results are consistent with the claim that cognition is grounded in action and perception and based on distributed action perception circuits reaching into sensorimotor areas.

  17. Application of Entropy Measures on Intrinsic Mode Functions for the Automated Identification of Focal Electroencephalogram Signals

    Directory of Open Access Journals (Sweden)

    Rajeev Sharma

    2015-02-01

    Full Text Available The brain is a complex structure made up of interconnected neurons, and its electrical activities can be evaluated using electroencephalogram (EEG signals. The characteristics of the brain area affected by partial epilepsy can be studied using focal and non-focal EEG signals. In this work, a method for the classification of focal and non-focal EEG signals is presented using entropy measures. These entropy measures can be useful in assessing the nonlinear interrelation and complexity of focal and non-focal EEG signals. These EEG signals are first decomposed using the empirical mode decomposition (EMD method to extract intrinsic mode functions (IMFs. The entropy features, namely, average Shannon entropy (ShEnAvg, average Renyi’s entropy (RenEnAvg , average approximate entropy (ApEnAvg, average sample entropy (SpEnAvg and average phase entropies (S1Avg and S2Avg, are computed from different IMFs of focal and non-focal EEG signals. These entropies are used as the input feature set for the least squares support vector machine (LS-SVM classifier to classify into focal and non-focal EEG signals. Experimental results show that our proposed method is able to differentiate the focal and non-focal EEG signals with an average classification accuracy of 87% correct.

  18. Neuromorphological and wiring pattern alterations effects on brain function: a mixed experimental and computational approach.

    Directory of Open Access Journals (Sweden)

    Linus Manubens-Gil

    2015-04-01

    In addition, the study of fixed intact brains (by means of the state of the art CLARITY technique brings us closer to biologically and medically relevant situations, allowing not only to confirm whether the functional links in neuronal cultures are also present in vivo, but also enabling the introduction of functional information (like behavioral studies and functional imaging and another layer of structural alterations such as brain region morphology, neuronal density, and long-range connectivity. Taking together the experimental information from these systems we want to feed self-developed computational models that allow us to understand what are the fundamental characteristics of the observed connectivity patterns and the impact of each of the alterations on neuronal network function. These models will also provide a framework able to account for the emergent properties that bridge the gap between spontaneous electrical activity arousal/transmission and higher order information processing and memory storage capacities in the brain. As an additional part of the project we are now working on the application of the clearing, labeling and imaging protocols to human biopsy samples. Our aim is to obtain neuronal architecture and connectivity information from focal cortical dysplasia microcircuits using samples from intractable temporal lobe epilepsy patients that undergo deep-brain electrode recording diagnosis and posterior surgical extraction of the tissue. Our computational models can allow us to discern the contributions of the observed abnormalities to neuronal hyperactivity and epileptic seizure generation.

  19. Cross-brain neurofeedback: scientific concept and experimental platform.

    Directory of Open Access Journals (Sweden)

    Lian Duan

    Full Text Available The present study described a new type of multi-person neurofeedback with the neural synchronization between two participants as the direct regulating target, termed as "cross-brain neurofeedback." As a first step to implement this concept, an experimental platform was built on the basis of functional near-infrared spectroscopy, and was validated with a two-person neurofeedback experiment. This novel concept as well as the experimental platform established a framework for investigation of the relationship between multiple participants' cross-brain neural synchronization and their social behaviors, which could provide new insight into the neural substrate of human social interactions.

  20. Cross-brain neurofeedback: scientific concept and experimental platform.

    Science.gov (United States)

    Duan, Lian; Liu, Wei-Jie; Dai, Rui-Na; Li, Rui; Lu, Chun-Ming; Huang, Yu-Xia; Zhu, Chao-Zhe

    2013-01-01

    The present study described a new type of multi-person neurofeedback with the neural synchronization between two participants as the direct regulating target, termed as "cross-brain neurofeedback." As a first step to implement this concept, an experimental platform was built on the basis of functional near-infrared spectroscopy, and was validated with a two-person neurofeedback experiment. This novel concept as well as the experimental platform established a framework for investigation of the relationship between multiple participants' cross-brain neural synchronization and their social behaviors, which could provide new insight into the neural substrate of human social interactions.

  1. Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

    Directory of Open Access Journals (Sweden)

    Haveman Jaap

    2007-09-01

    Full Text Available Abstract Background High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models– high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a stereotactic brachytherapy mouse model for high-dose focal irradiation of experimental intracerebral (orthotopic brain tumors. Methods Twenty-one nude mice received a hollow guide-screw implanted in the skull. After three weeks, 5 × 105 U251-NG2 human glioblastoma cells were injected. Five days later, a 2 mCi iodine-125 brachytherapy seed was inserted through the guide-screw in 11 randomly selected mice; 10 mice received a sham seed. Mice were euthanized when severe neurological or physical symptoms occurred. The cumulative irradiation dose 5 mm below the active iodine-125 seeds was 23.0 Gy after 13 weeks (BEDtumor = 30.6 Gy. Results In the sham group, 9/10 animals (90% showed signs of lethal tumor progression within 6 weeks. In the experimental group, 2/11 mice (18% died of tumor progression within 13 weeks. Acute side effects in terms of weight loss or neurological symptoms were not observed in the irradiated animals. Conclusion The intracerebral implantation of an iodine-125 brachytherapy seed through a stereotactic guide-screw in the skull of mice with implanted brain tumors resulted in a significantly prolonged survival, caused by high-dose irradiation of the brain tumor that is biologically comparable to high-dose fractionated radiotherapy– without fatal irradiation toxicity. This is an excellent mouse model for testing orthotopic brain tumor therapies in combination with radiation therapy.

  2. Evans blue staining reveals vascular leakage associated with focal areas of host-parasite interaction in brains of pigs infected with Taenia solium.

    Science.gov (United States)

    Marzal, Miguel; Guerra-Giraldez, Cristina; Paredes, Adriana; Cangalaya, Carla; Rivera, Andrea; Gonzalez, Armando E; Mahanty, Siddhartha; Garcia, Hector H; Nash, Theodore E

    2014-01-01

    Cysticidal drug treatment of viable Taenia solium brain parenchymal cysts leads to an acute pericystic host inflammatory response and blood brain barrier breakdown (BBB), commonly resulting in seizures. Naturally infected pigs, untreated or treated one time with praziquantel were sacrificed at 48 hr and 120 hr following the injection of Evans blue (EB) to assess the effect of treatment on larval parasites and surrounding tissue. Examination of harvested non encapsulated muscle cysts unexpectedly revealed one or more small, focal round region(s) of Evans blue dye infiltration (REBI) on the surface of otherwise non dye-stained muscle cysts. Histopathological analysis of REBI revealed focal areas of eosinophil-rich inflammatory infiltrates that migrated from the capsule into the tegument and internal structures of the parasite. In addition some encapsulated brain cysts, in which the presence of REBI could not be directly assessed, showed histopathology identical to that of the REBI. Muscle cysts with REBI were more frequent in pigs that had received praziquantel (6.6% of 3736 cysts; n = 6 pigs) than in those that were untreated (0.2% of 3172 cysts; n = 2 pigs). Similar results were found in the brain, where 20.7% of 29 cysts showed histopathology identical to muscle REBI cysts in praziquantel-treated pigs compared to the 4.3% of 47 cysts in untreated pigs. Closer examination of REBI infiltrates showed that EB was taken up only by eosinophils, a major component of the cellular infiltrates, which likely explains persistence of EB in the REBI. REBI likely represent early damaging host responses to T. solium cysts and highlight the focal nature of this initial host response and the importance of eosinophils at sites of host-parasite interaction. These findings suggest new avenues for immunomodulation to reduce inflammatory side effects of anthelmintic therapy.

  3. Failure of intravenous or intracardiac delivery of mesenchymal stromal cells to improve outcomes after focal traumatic brain injury in the female rat.

    Science.gov (United States)

    Turtzo, L Christine; Budde, Matthew D; Dean, Dana D; Gold, Eric M; Lewis, Bobbi K; Janes, Lindsay; Lescher, Jacob; Coppola, Tiziana; Yarnell, Angela; Grunberg, Neil E; Frank, Joseph A

    2015-01-01

    Mesenchymal stromal cells secrete a variety of anti-inflammatory factors and may provide a regenerative medicine option for the treatment of traumatic brain injury. The present study investigates the efficacy of multiple intravenous or intracardiac administrations of rat mesenchymal stromal cells or human mesenchymal stromal cells in female rats after controlled cortical impact by in vivo MRI, neurobehavior, and histopathology evaluation. Neither intravenous nor intracardiac administration of mesenchymal stromal cells derived from either rats or humans improved MRI measures of lesion volume or neurobehavioral outcome compared to saline treatment. Few mesenchymal stromal cells (brain at 30 or 56 days post-injury. These findings suggest that non-autologous mesenchymal stromal cells therapy via intravenous or intracardiac administration is not a promising treatment after focal contusion traumatic brain injury in this female rodent model.

  4. Expression of Neurotrophin-3 and trkC following Focal Cerebral Ischemia in Adult Rat Brain with Treadmill Exercise

    Directory of Open Access Journals (Sweden)

    Jin-Young Chung

    2017-01-01

    Full Text Available Neurotrophin-3 (NT-3 is a neurotrophic factor that mainly binds to the tyrosine kinase C (trkC receptor. NT-3 has been shown to have neuroprotective effects in focal cerebral ischemia. Exercise also has ability to induce functional recovery in focal cerebral ischemia. However, the relationship between NT-3, its receptor trkC, and exercise has not been revealed. In this study, we assessed the expressions of NT-3 and trkC in focal cerebral ischemia. We also assessed the expression of NT-3 and trkC with treadmill exercise in focal cerebral ischemia. The results showed that, in a permanent middle cerebral artery occlusion rat model, exercise increased NT-3 and trkC expression. However, the patterns of expression of NT-3 and trkC at different time points varied. These results suggest that exercise-induced functional recovery in focal cerebral ischemia was related to NT-3 and trkC, but the role on times of NT-3 and trkC differed, although trkC is the receptor kinase for NT-3.

  5. Effects of salidroside pretreatment on expression of tumor necrosis factor-alpha and permeability of blood brain barrier in rat model of focal cerebralischemia-reperfusion injury.

    Science.gov (United States)

    Han, Tian

    2013-02-01

    To observe changes in expression of tumor necrosis factor (TNF)-alpha and permeability of blood brain barrier after salidroside pretreatment in rats with injury induced by focal cerebralischemia-reperfusion. Forty-five male SD rats were randomly divided into three groups (n=15): control group, ischemia-reperfusion (IR) model group, and salidroside pretreatment group. Before the IR model establishment, the rats in the salidroside pretreatment group were intraperitoneally administered with salidroside at a dose of 24 mg/(kg·d) for 7 d. After 30 min post the last administration, the IR model was induced by occlusion of middle cerebral artery with a filament. After 24 h post the operation, the water content and Evens blue content in the ischemia cerebral hemisphere were determined, and the level of TNF-alpha mRNA was detected by the semi-quantitative RT-PCR. Compared with the IR model group, the salidroside pretreatment group had significantly lower (Psalidroside pretreatment alleviated the focal cerebralischemia-reperfusion injury in the rat model, possibly by decreasing the permeability of blood brain barrier, attenuating brain edema and reducing TNF-alpha expression. Copyright © 2013 Hainan Medical College. Published by Elsevier B.V. All rights reserved.

  6. Experimental approbation of a new ultrosound contrast agent based on sulfur geksafluoride in diagnostics of focal liver lesions of inflammatory genesis

    Directory of Open Access Journals (Sweden)

    S. V. Fomina

    2017-01-01

    Full Text Available Purpose of the study. Experimental approbation of a new domestic ultrasound contrast agent (UCA based on sulfur hexafluoride in the diagnosis of focal liver lesions of inflammatory genesis.Materials and methods. The investigated ultrasound contrast agent (UCA was a heterogeneous gas-liquid system consisting of micro bubbles of a sparingly soluble gas of sulfur hexafluoride (SF6 surrounded by a flexible mobile membrane of surfactants. Experimental work was carried out on rabbits. The study group included rabbits of males and females with focal liver lesion of inflammatory genesis (n = 12 weighing 1500- 1700 g. UCA was administered to animals in the ear vein. Focal lesions of the liver in animals were created in the experimental laboratory conditions. 14 days after the operation, all animals were subjected to ultrasound examination of the surgical intervention zones by using the Toshiba Aplio 400 scanners (Japan with a 3,5–8 MHz convection sensor. In a natural study, the size, structure and echogenicity of the focus were assessed, the degree of vascularization, the evenness and clarity of the contours were determined. When performing post contrast ultrasound, the time of the onset of contrast enhancement, the total duration of contrast, the changes in the contrast enhancement of the focus in different phases of the study were measured, the dimensions of the focus were measured, and the evenness and acuity of contours were measured. For histological examination, liver fragments and lungs were used. 

  7. Delayed neuromotor recovery and increased memory acquisition dysfunction following experimental brain trauma in mice lacking the DNA repair gene XPA.

    Science.gov (United States)

    Tomasevic, Gregor; Laurer, Helmut L; Mattiasson, Gustav; van Steeg, Harry; Wieloch, Tadeusz; McIntosh, Tracy K

    2012-06-01

    This study investigates the outcome after traumatic brain injury (TBI) in mice lacking the essential DNA repair gene xeroderma pigmentosum group A (XPA). As damage to DNA has been implicated in neuronal cell death in various models, the authors sought to elucidate whether the absence of an essential DNA repair factor would affect the outcome of TBI in an experimental setting. Thirty-seven adult mice of either wild-type (n = 18) or XPA-deficient ("knock-out" [n = 19]) genotype were subjected to controlled cortical impact experimental brain trauma, which produced a focal brain injury. Sham-injured mice of both genotypes were used as controls (9 in each group). The mice were subjected to neurobehavoral tests evaluating learning/acquisition (Morris water maze) and motor dysfunction (Rotarod and composite neuroscore test), pre- and postinjury up to 4 weeks. The mice were killed after 1 or 4 weeks, and cortical lesion volume, as well as hippocampal and thalamic cell loss, was evaluated. Hippocampal staining with doublecortin antibody was used to evaluate neurogenesis after the insult. Brain-injured XPA(-/-) mice exhibited delayed recovery from impairment in neurological motor function, as well as pronounced cognitive dysfunction in a spatial learning task (Morris water maze), compared with injured XPA(+/+) mice (p recovery after TBI, although they do not support the notion that this DNA repair deficiency results in increased cell or tissue death in the posttraumatic brain.

  8. Morphological and histochemical changes in the brain stem in case of experimental hemispheric intracerebral hemorrhage

    Directory of Open Access Journals (Sweden)

    S. I. Tertishniy

    2015-10-01

    Full Text Available Aim. Investigation of the extent of morphological changes and activity of biogenic amines (according to the intensity of luminescence in the neurons of the brain stem in intracerebral hemorrhage (ICH. Methods and results. ICH was designed on 29 white rats of Vistar line by the administration of autologous blood in the cerebral hemisphere. It was revealed that increased luminescence intensity by 18.4±5.5% was registered in monoaminergic neurons in 1–6 hours after experimental ICH. After 12 hours – 1 day development of dislocation syndrome leads to mosaic focal ischemic neuronal injuries with maximum reduction in the level of catecholamines by 29.5±5.0% compared with control cases. Three–6 days after ICH on a background of selective neuronal necrosis in substantial number of neurons in the nuclei of the brainstem the level of catecholamines is significantly reduced. Conclusion. Disclosed observations reflect significant functional pathology of neurons responsible for the regulation of cardiorespiratory function and may underlie disturbances of integrative activity in the brain stem in general.

  9. Distribution of opiate alkaloids in brain tissue of experimental animals

    Science.gov (United States)

    Pilija, Vladimir; Mimica-Dukic, Neda; Budakov, Branislav; Cvjeticanin, Stanko

    2012-01-01

    The present study examined regional distribution of opiate alkaloids from seized heroin in brain regions of experimental animals in order to select parts with the highest content of opiates. Their analysis should contribute to resolve causes of death due to heroin intake. The tests were performed at different time periods (5, 15, 45 and 120 min) after male and female Wistar rats were treated with seized heroin. Opiate alkaloids (codeine, morphine, acetylcodeine, 6-acetylmorphine and 3,6-diacetylmorphine) were quantitatively determined in brain regions known for their high concentration of µ-opiate receptors: cortex, brainstem, amygdala and basal ganglia, by using gas chromatography–mass spectrometry (GC–MS). The highest content of opiate alkaloids in the brain tissue of female animals was found 15 min and in male animals 45 min after treatment. The highest content of opiates was determined in the basal ganglia of the animals of both genders, indicating that this part of brain tissue presents a reliable sample for identifying and assessing contents of opiates after heroin intake. PMID:23554560

  10. Meta-analysis on brain representation of experimental dental pain.

    Science.gov (United States)

    Lin, C-S; Niddam, D M; Hsu, M-L

    2014-02-01

    Functional magnetic resonance imaging (fMRI) has been widely used for investigating the brain representation associated with dental pain evoked by pulpal electrical stimulation. However, because of the heterogeneity of experimental designs and the small sample size of individual studies, the common brain representation regarding dental pain has remained elusive. We used imaging meta-analysis to investigate six dental pain-related fMRI studies (n = 87) and tested 3 hypotheses: (1) Dental pain is associated with the 'core' pain-related network; (2) pain-related brain activation is somatotopically organized in the somatosensory cortex; and (3) dental pain is associated with the cognitive-affective network related to pain. Qualitative and quantitative meta-analyses revealed: (1) common activation of the core pain-related network, including the somatosensory cortex, the insula, and the cingulate cortex; (2) inconsistency in somatotopically organized activation of the primary somatosensory cortex; and (3) common activation in the dorsolateral prefrontal cortex, suggesting a role of re-appraisal and coping in the experience of dental pain. In conclusion, fMRI combined with pulpal stimulation can effectively evoke activity in the pain-related network. The dental pain-related brain representation disclosed the mechanisms of how sensory and cognitive-affective factors shape dental pain, which will help in the development of more effective customized methods for central pain control.

  11. The effects of neck flexion on cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in related sensory cortices.

    Science.gov (United States)

    Fujiwara, Katsuo; Kunita, Kenji; Kiyota, Naoe; Mammadova, Aida; Irei, Mariko

    2012-12-03

    A flexed neck posture leads to non-specific activation of the brain. Sensory evoked cerebral potentials and focal brain blood flow have been used to evaluate the activation of the sensory cortex. We investigated the effects of a flexed neck posture on the cerebral potentials evoked by visual, auditory and somatosensory stimuli and focal brain blood flow in the related sensory cortices. Twelve healthy young adults received right visual hemi-field, binaural auditory and left median nerve stimuli while sitting with the neck in a resting and flexed (20° flexion) position. Sensory evoked potentials were recorded from the right occipital region, Cz in accordance with the international 10-20 system, and 2 cm posterior from C4, during visual, auditory and somatosensory stimulations. The oxidative-hemoglobin concentration was measured in the respective sensory cortex using near-infrared spectroscopy. Latencies of the late component of all sensory evoked potentials significantly shortened, and the amplitude of auditory evoked potentials increased when the neck was in a flexed position. Oxidative-hemoglobin concentrations in the left and right visual cortices were higher during visual stimulation in the flexed neck position. The left visual cortex is responsible for receiving the visual information. In addition, oxidative-hemoglobin concentrations in the bilateral auditory cortex during auditory stimulation, and in the right somatosensory cortex during somatosensory stimulation, were higher in the flexed neck position. Visual, auditory and somatosensory pathways were activated by neck flexion. The sensory cortices were selectively activated, reflecting the modalities in sensory projection to the cerebral cortex and inter-hemispheric connections.

  12. Glutamate Metabolism in Brain Structures in Experimental Hemorrhagic Shock

    Directory of Open Access Journals (Sweden)

    V. N. Jakovlev

    2017-01-01

    Full Text Available Purpose. To study glutamate metabolism characteristics in phylogenetically different parts of the mammalian brain in experimentally induced hemorrhagic shock (HS in cats.Material and methods. Experiments were performed on 76 cats. HS was induced by intermittent bloodletting from femoral artery at a rate of 10ml/kg•10 minutes, with the average volume of 24±0.8 ml/kg. The bloodletting was discontinued after arterial pressure (BP drop to 60.0±1.5 mmHg. We studied ammonia, glutamate (Gt, and α-ketoglutarate (α-KG levels and glutaminase (GS and glutamate dehydrogenase (GDG activity in specimens harvested from phylogenetically different parts of the brain (cortex, limbic system, diencephalon, and medulla oblongata.Results. In intact animals, the peak GDG activity was found in the medulla oblongata (phylogenetically the oldest part of the brain and the peak GS activity was registered in the sensorimotor cortex (phylogenetically the youngest part of the brain; the glutaminase activity did not depend on the phylogenetic age of brain structures.In the case of HS, Gt metabolism changes began in the sensorimotor cortex manifested by decreased GS activity, which progresses by the 70th minute of the post%hemorrhagic period (PHP accompanied by delayed increase in the GDG and glutaminase activity, as well as Gt accumulation. In the limbic system and diencephalon the Gt metabolism was changing (impaired glutamine synthesis, stimuled Gt synthesis with glutamine desamidization and α%KG amination when developed by the 70th minute of the PHP. Similarly to sensorimotor cortex, changes were associated with Gt accumulation. During the agony, α%KG deficiency developed in all parts of the brain as a result of its increased contribution to Gt synthesis. At the same period of time, in the sensorimotor cortex, limbic system and diencephalon the Gt synthesis from glutamine was stimulated, however, the Gt contribution tothe formation of glutamine was decreased. The

  13. Quantitative MRI analysis of the brain after twenty-two years of neuromyelitis optica indicates focal tissue damage

    DEFF Research Database (Denmark)

    Aradi, Mihaly; Koszegi, Edit; Orsi, Gergely

    2013-01-01

    BACKGROUND: The long-term effect of neuromyelitis optica (NMO) on the brain is not well established. METHODS: After 22 years of NMO, a patient's brain was examined by quantitative T1- and T2-weighted mono- and biexponential diffusion and proton spectroscopy. It was compared to 3 cases with short......, and they were also not quantitatively different from the controls. CONCLUSION: After NMO of 22-year duration, metabolic changes, altered diffusivity and magnetic resonance relaxation features of patchy brain areas may suggest tissue damage in NAWM that persist for at least 6 months....

  14. Array Focal Cortical Stimulation Enhances Motor Function Recovery and Brain Remodeling in a Rat Model of Ischemia.

    Science.gov (United States)

    Yang, Jing; Liu, Lu; Li, Tao; Li, Chengyan

    2017-03-01

    Using a new microelectrode array implanted into the cranial window employing a new stimulation protocol, we investigated the effects of the implanted electrode arrays on both motor map plasticity and neural regeneration in a rodent model of stroke. Rats were pretrained on single-pellet retrieval task, then received focal ischemic infarction and microelectrode arrays implantation. Rats in the cortical stimulation (CS) group received daily electrical stimulation (1 hour each day) for 14 days whereas animals in the no stimulation (NS) group did not receive electrical stimulation and only underwent motor mapping. Behavior data and residual electrophysiological mapping on stimulation days 2, 5, 8, 11, and 14 were statistically compared. Neural reorganization in pathological with glial fibrillary acidic protein and microtubule-associated protein-2 was performed. Rats in CS group showed greater increases in reaching accuracy and significantly decreased in motor threshold than rats in NS group. Immunohistochemical study has shown that array focal CS suppressed inflammatory response, and enhanced dendritic sprouting in the peri-infarction cortex. The present findings support the viability of epidural CS with microelectrode arrays for enhancing motor function after stroke and monitoring the neural reorganization of residual electrophysiological mapping after motor cortex injury. Copyright © 2017 National Stroke Association. Published by Elsevier Inc. All rights reserved.

  15. Failure of intravenous or intracardiac delivery of mesenchymal stromal cells to improve outcomes after focal traumatic brain injury in the female rat.

    Directory of Open Access Journals (Sweden)

    L Christine Turtzo

    Full Text Available Mesenchymal stromal cells secrete a variety of anti-inflammatory factors and may provide a regenerative medicine option for the treatment of traumatic brain injury. The present study investigates the efficacy of multiple intravenous or intracardiac administrations of rat mesenchymal stromal cells or human mesenchymal stromal cells in female rats after controlled cortical impact by in vivo MRI, neurobehavior, and histopathology evaluation. Neither intravenous nor intracardiac administration of mesenchymal stromal cells derived from either rats or humans improved MRI measures of lesion volume or neurobehavioral outcome compared to saline treatment. Few mesenchymal stromal cells (<0.0005% of injected dose were found within 3 days of last dosage at the site of injury after either delivery route, with no mesenchymal stromal cells being detectable in brain at 30 or 56 days post-injury. These findings suggest that non-autologous mesenchymal stromal cells therapy via intravenous or intracardiac administration is not a promising treatment after focal contusion traumatic brain injury in this female rodent model.

  16. Protection of ischemic post conditioning against transient focal ischemia-induced brain damage is associated with inhibition of neuroinflammation via modulation of TLR2 and TLR4 pathways.

    Science.gov (United States)

    Wang, Ying; Ge, Pengfei; Yang, Li; Wu, Chunyun; Zha, Hao; Luo, Tianfei; Zhu, Yuhong

    2014-01-24

    Ischemic postconditioning has been demonstrated to be a protective procedure to brain damage caused by transient focal ischemia/reperfusion. However, it is elusive whether the protection of postconditioning against brain damage and neuroinflammation is via regulating TLR2 and TLR4 pathways. In the present study, we examined the protection of ischemic postconditioning performed immediately prior to the recovery of cerebral blood supply on brain damage caused by various duration of ischemia and tested the hypothesis that its protection is via inhibition of neuroinflammation by modulating TLR2/TLR4 pathways. Brain damage in rats was induced by using the middle cerebral artery occlusion (MCAO) model. Ischemic postconditioning consisting of fivecycles of ten seconds of ischemia and reperfusion was performed immediately following theischemic episode Theduration of administration of ischemic postconditioning was examined by comparing its effects on infarction volume, cerebral edema and neurological function in 2, 3, 4, 4.5and 6 hour ischemia groups. The protective mechanism of ischemic postconditioning was investigated by comparing its effects on apoptosis, production of the neurotoxic cytokine IL-1β and the transcription and expression of TLR2, TLR4 and IRAK4 in the 2 and 4.5 hour ischemia groups. Ischemic postconditioning significantly attenuated cerebral infarction, cerebral edema and neurological dysfunction in ischemia groups of up to 4 hours duration, but not in 4.5and 6 hour ischemia groups. It also inhibited apoptosis, production of IL-1β, abnormal transcription and expression of TLR2, TLR4 and IRAK4 in the 2 hour ischemia group, but not in the 4.5 hour ischemia group. Ischemic postconditioning protected brain damage caused by 2, 3 and 4 hours of ischemia, but not by 4.5 and 6 hours of ischemia. The protection of ischemic postconditioning is associated with its inhibition of neuroinflammation via inhibition of TLR2 and TLR4 pathways.

  17. Differences in visual vs. verbal memory impairments as a result of focal temporal lobe damage in patients with traumatic brain injury.

    Science.gov (United States)

    Ariza, Mar; Pueyo, Roser; Junqué, Carme; Mataró, María; Poca, María Antonia; Mena, Maria Pau; Sahuquillo, Juan

    2006-09-01

    The aim of the present study was to determine whether the type of lesion in a sample of moderate and severe traumatic brain injury (TBI) was related to material-specific memory impairment. Fifty-nine patients with TBI were classified into three groups according to whether the site of the lesion was right temporal, left temporal or diffuse. Six-months post-injury, visual (Warrington's Facial Recognition Memory Test and Rey's Complex Figure Test) and verbal (Rey's Auditory Verbal Learning Test) memories were assessed. Visual memory deficits assessed by facial memory were associated with right temporal lobe lesion, whereas verbal memory performance assessed with a list of words was related to left temporal lobe lesion. The group with diffuse injury showed both verbal and visual memory impairment. These results suggest a material-specific memory impairment in moderate and severe TBI after focal temporal lesions and a non-specific memory impairment after diffuse damage.

  18. P300-based brain computer interface experimental setup.

    Science.gov (United States)

    Arboleda, Carolina; Garcia, Eliana; Posada, Alejandro; Torres, Robinson

    2009-01-01

    A Brain-Computer interface (BCI) is a communication system that enables the generation of a control signal from brain signals such as sensorymotor rhythms and evoked potentials; therefore, it constitutes a novel communication option for people with severe motor disabilities (such as Amyotrophic Lateral Sclerosis patients). This paper presents the development of a P300-based BCI. This prototype uses a homemade six-channel electroencephalograph for the acquisition of the signals, and a visual stimulation matrix; since this matrix contains letters of the alphabet as well as images associated to them, it permits word-writing and the elaboration of messages with the images. To process the signals the software BCI2000 and MATLAB 7.0 were used. The latter was used to program three linear translation algorithms (Stepwise Linear Discriminant Analysis, Lineal Discriminant Analysis and Least Squares) to convert the brain signals into communication signals. These algorithms had a classification accuracy of 90.73 %, 95.75 % and 89.45 % respectively, when using raw data; and of 90.78%, 49.48 % and 53.9 %, when data was previously common-average filtered. The experimental setup was tested in ten healthy volunteers; 5 of them got a 100% success, 1 a 90% success, 2 an around 70% success and 2 a 50% success, in the online free-spelling tests.

  19. Selective Activation of Resting-State Networks following Focal Stimulation in a Connectome-Based Network Model of the Human Brain.

    Science.gov (United States)

    Spiegler, Andreas; Hansen, Enrique C A; Bernard, Christophe; McIntosh, Anthony R; Jirsa, Viktor K

    2016-01-01

    When the brain is stimulated, for example, by sensory inputs or goal-oriented tasks, the brain initially responds with activities in specific areas. The subsequent pattern formation of functional networks is constrained by the structural connectivity (SC) of the brain. The extent to which information is processed over short- or long-range SC is unclear. Whole-brain models based on long-range axonal connections, for example, can partly describe measured functional connectivity dynamics at rest. Here, we study the effect of SC on the network response to stimulation. We use a human whole-brain network model comprising long- and short-range connections. We systematically activate each cortical or thalamic area, and investigate the network response as a function of its short- and long-range SC. We show that when the brain is operating at the edge of criticality, stimulation causes a cascade of network recruitments, collapsing onto a smaller space that is partly constrained by SC. We found both short- and long-range SC essential to reproduce experimental results. In particular, the stimulation of specific areas results in the activation of one or more resting-state networks. We suggest that the stimulus-induced brain activity, which may indicate information and cognitive processing, follows specific routes imposed by structural networks explaining the emergence of functional networks. We provide a lookup table linking stimulation targets and functional network activations, which potentially can be useful in diagnostics and treatments with brain stimulation.

  20. Porcine focal symmetrical poliomyelomalacia.

    Science.gov (United States)

    Wilson, T M; Drake, T R

    1982-04-01

    An acute afebrile paretic condition was diagnosed in 16 of 100 feeder pigs between eight to ten weeks of age. Nine pigs died acutely and seven pigs were euthanized. Macroscopic lesions in the ventral horns of the cervical, thoracic, lumbar and sacral segments of the spinal cord consisted of focal, bilateral, grey depressed areas. There was a bilateral symmetrical focal poliomyelomalacia histopathologically characterized by microcavitation, endothelial and glial cell proliferation and infiltration of eosinophils. Clinical and pathological findings resemble spontaneous and experimental lesions associated with acute nicotinamide deficiency and selenium toxicosis in swine.

  1. Propagation of alpha-synuclein pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

    Science.gov (United States)

    Uchihara, Toshiki; Giasson, Benoit I

    2016-01-01

    Progressive aggregation of alpha-synuclein (αS) through formation of amorphous pale bodies to mature Lewy bodies or in neuronal processes as Lewy neurites may be the consequence of conformational protein changes and accumulations, which structurally represents "molecular template". Focal initiation and subsequent spread along anatomically connected structures embody "structural template". To investigate the hypothesis that both processes might be closely associated and involved in the progression of αS pathology, which can be observed in human brains, αS amyloidogenic precursors termed "seeds" were experimentally injected into the brain or peripheral nervous system of animals. Although these studies showed that αS amyloidogenic seeds can induce αS pathology, which can spread in the nervous system, the findings are still not unequivocal in demonstrating predominant transsynaptic or intraneuronal spreads either in anterograde or retrograde directions. Interpretation of some of these studies is further complicated by other concurrent aberrant processes including neuroimmune activation, injury responses and/or general perturbation of proteostasis. In human brain, αS deposition and neuronal degeneration are accentuated in distal axon/synapse. Hyperbranching of axons is an anatomical commonality of Lewy-prone systems, providing a structural basis for abundance in distal axons and synaptic terminals. This neuroanatomical feature also can contribute to such distal accentuation of vulnerability in neuronal demise and the formation of αS inclusion pathology. Although retrograde progression of αS aggregation in hyperbranching axons may be a consistent feature of Lewy pathology, the regional distribution and gradient of Lewy pathology are not necessarily compatible with a predictable pattern such as upward progression from lower brainstem to cerebral cortex. Furthermore, "focal Lewy body disease" with the specific isolated involvement of autonomic, olfactory or cardiac

  2. Correlation between lactate and neuronal cell damage in the rat brain after focal ischemia: An in vivo 1H magnetic resonance spectroscopic (1H-MRS) study.

    Science.gov (United States)

    Woo, Chul-Woong; Lee, Byong Sop; Kim, Sang Tae; Kim, Ki-Soo

    2010-04-01

    Increased levels of lactate are observed by (1)H magnetic resonance spectroscopy ((1)H-MRS) in rat brains after stroke. However, it is not known whether the changes in lactate levels are predictive of the degree of neuronal damage. To investigate the correlation between changes in lactate and lipid levels measured by (1)H-MRS and neuronal cell damage in the rat brain. A middle cerebral artery occlusion (MCAO) model was used to evaluate focal ischemia in rats (n=36). After MCAO for 90 min T2-weighted images (T2WIs), diffusion-weighted images (DWIs), and (1)H-MRS data were obtained from brains immediately, 6 hours, 9 hours, 12 hours, 18 hours, 24 hours, 3 days, and 7 days after reperfusion. Infarct volumes were measured in T2WIs obtained 4 weeks after reperfusion. The degree of neuronal damage was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining in three rats from each group at the same time as brain images were collected. Creatine (Cr)-normalized lactate + lipid levels ([Lac+Lip]/Cr) were negatively correlated with Cr-normalized N-acetyl-L-aspartate levels (NAA/Cr) and positively correlated with TUNEL-positive cell numbers up to 24 hours after reperfusion. (Lac+Lip)/Cr at 6 hours and 9 hours was significantly correlated with NAA/Cr at 7 days, but there was no significant correlation between (Lac+Lip)/Cr during the first 24 hours and infarct volume at 4 weeks. Up to 24 hours after reperfusion, (Lac+Lip)/Cr was strongly negatively correlated with NAA/Cr, and was a good predictor of neuronal damage at 7 days; however, it was not predictive of final infarct volume at 4 weeks.

  3. Combination of early and delayed ischemic postconditioning enhances brain-derived neurotrophic factor production by upregulating the ERK-CREB pathway in rats with focal ischemia.

    Science.gov (United States)

    Wu, Hui; Yang, Shao-Feng; Dai, Jiong; Qiu, Yong-Ming; Miao, Yi-Feng; Zhang, Xiao-Hua

    2015-11-01

    cortex, following focal ischemia. The results of the present study suggest that the combination of early and delayed ischemic postconditioning may further reduce brain ischemic reperfusion injury following focal ischemia, compared with either treatment alone. In addition, it induces the production of BDNF in neurons and astrocytes. Furthermore, the effects of combinative ischemic postconditioning may be mediated by the activation of ERK1/2 and CREB.

  4. A quantitative brain map of experimental cerebral malaria pathology.

    Science.gov (United States)

    Strangward, Patrick; Haley, Michael J; Shaw, Tovah N; Schwartz, Jean-Marc; Greig, Rachel; Mironov, Aleksandr; de Souza, J Brian; Cruickshank, Sheena M; Craig, Alister G; Milner, Danny A; Allan, Stuart M; Couper, Kevin N

    2017-03-01

    The murine model of experimental cerebral malaria (ECM) has been utilised extensively in recent years to study the pathogenesis of human cerebral malaria (HCM). However, it has been proposed that the aetiologies of ECM and HCM are distinct, and, consequently, no useful mechanistic insights into the pathogenesis of HCM can be obtained from studying the ECM model. Therefore, in order to determine the similarities and differences in the pathology of ECM and HCM, we have performed the first spatial and quantitative histopathological assessment of the ECM syndrome. We demonstrate that the accumulation of parasitised red blood cells (pRBCs) in brain capillaries is a specific feature of ECM that is not observed during mild murine malaria infections. Critically, we show that individual pRBCs appear to occlude murine brain capillaries during ECM. As pRBC-mediated congestion of brain microvessels is a hallmark of HCM, this suggests that the impact of parasite accumulation on cerebral blood flow may ultimately be similar in mice and humans during ECM and HCM, respectively. Additionally, we demonstrate that cerebrovascular CD8+ T-cells appear to co-localise with accumulated pRBCs, an event that corresponds with development of widespread vascular leakage. As in HCM, we show that vascular leakage is not dependent on extensive vascular destruction. Instead, we show that vascular leakage is associated with alterations in transcellular and paracellular transport mechanisms. Finally, as in HCM, we observed axonal injury and demyelination in ECM adjacent to diverse vasculopathies. Collectively, our data therefore shows that, despite very different presentation, and apparently distinct mechanisms, of parasite accumulation, there appear to be a number of comparable features of cerebral pathology in mice and in humans during ECM and HCM, respectively. Thus, when used appropriately, the ECM model may be useful for studying specific pathological features of HCM.

  5. The role of dynamic susceptibility contrast-enhanced perfusion MR imaging in differentiating between infectious and neoplastic focal brain lesions: results from a cohort of 100 consecutive patients.

    Directory of Open Access Journals (Sweden)

    Valdeci Hélio Floriano

    Full Text Available BACKGROUND AND PURPOSE: Differentiating between infectious and neoplastic focal brain lesions that are detected by conventional structural magnetic resonance imaging (MRI may be a challenge in routine practice. Brain perfusion-weighted MRI (PWI may be employed as a complementary non-invasive tool, providing relevant data on hemodynamic parameters, such as the degree of angiogenesis of lesions. We aimed to employ dynamic susceptibility contrast-enhanced perfusion MR imaging (DSC-MRI to differentiate between infectious and neoplastic brain lesions by investigating brain microcirculation changes. MATERIALS AND METHODS: DSC-MRI perfusion studies of one hundred consecutive patients with non-cortical neoplastic (n = 54 and infectious (n = 46 lesions were retrospectively assessed. MRI examinations were performed using a 1.5-T scanner. A preload of paramagnetic contrast agent (gadolinium was administered 30 seconds before acquisition of dynamic images, followed by a standard dose 10 seconds after starting imaging acquisitions. The relative cerebral blood volume (rCBV values were determined by calculating the regional cerebral blood volume in the solid areas of lesions, normalized to that of the contralateral normal-appearing white matter. Discriminant analyses were performed to determine the cutoff point of rCBV values that would allow the differentiation of neoplastic from infectious lesions and to assess the corresponding diagnostic performance of rCBV when using this cutoff value. RESULTS: Neoplastic lesions had higher rCBV values (4.28±2.11 than infectious lesions (0.63±0.49 (p<0.001. When using an rCBV value <1.3 as the parameter to define infectious lesions, the sensitivity of the method was 97.8% and the specificity was 92.6%, with a positive predictive value of 91.8%, a negative predictive value of 98.0%, and an accuracy of 95.0%. CONCLUSION: PWI is a useful complementary tool in distinguishing between infectious and neoplastic brain

  6. The effect of right vagus nerve stimulation on focal cerebral ischemia: an experimental study in the rat

    Science.gov (United States)

    Sun, Zhenghui; Baker, Wesley; Hiraki, Teruyuki; Greenberg, Joel H.

    2011-01-01

    Background The aim of this study was to determine the effect of vagus nerve stimulation (VNS) on infarct size after transient and after permanent focal cerebral ischemia in rats and to test the hypothesis that VNS-induced neuroprotection is due to changes in cerebral blood flow. Methods Ischemia was produced by either temporary proximal middle cerebral artery occlusion (TMCAO) or permanent distal middle cerebral artery occlusion (PMCAO). Stimulating electrodes were implanted on the cervical part of the right vagus nerve, and electrical stimulation was initiated 30 minutes after the induction of ischemia and delivered for 30 seconds every 5 minutes for 1 hour. All the procedures were duplicated but no stimulus was delivered in control groups. Cerebral blood flow in the MCA territory was continuously monitored with laser speckle contrast imaging. A neurological evaluation was undertaken after 24 hours of ischemia, and animals were euthanized and neuronal damage evaluated. Results Ischemic lesion volume was smaller in VNS-treated animals in both the temporary and permanent ischemic groups (p<0.01). VNS-treated animals in TMCAO had better functional scores at 24 h as compared with control animals (p<0.01), but there were no statistically significant differences in the neurobehavioral scores in PMCAO (p=0.089). CBF changes in the MCA territory during ischemia did not differ between the VNS-treated animals and control animals in either group. Conclusion VNS offers neuroprotection against stroke in both temporary and permanent ischemia. Although the precise mechanism of this effect remains to be determined, alterations in cerebral blood flow do not appear to play a role. VNS could readily be translated to clinical practice. PMID:22037134

  7. The inflammatory molecules IL-1β and HMGB1 can rapidly enhance focal seizure generation in a brain slice model of temporal lobe epilepsy

    Directory of Open Access Journals (Sweden)

    Angela eChiavegato

    2014-06-01

    Full Text Available Epilepsy is a neurological disorder characterized by a hyperexcitable brain tissue and unpredictable seizures, i.e., aberrant firing discharges in large neuronal populations. It is well established that proinflammatory cytokines, in addition to their canonical involvement in the immune response, have a crucial role in the mechanism of seizure generation. The purpose of the present study was to investigate the role of interleukin-1β (IL-1β and high mobility group B1 (HMGB1 in the generation of seizure-like discharges using two models of focal epilepsy in a rat entorhinal cortex slice preparation. Seizure like-discharges were evoked by either slice perfusion with low Mg2+ and picrotoxin or with a double NMDA local stimulation in the presence of the proconvulsant 4-amino-pyridine. The effects of IL-1β or HMGB1 were evaluated by monitoring seizure discharge generation through laser scanning microscope imaging of Ca2+ signals from neurons and astrocytes. In the picrotoxin model, we revealed that both cytokines increased the mean frequency of spontaneous ictal-like discharges, whereas only IL-1β reduced the latency and prolonged the duration of the first ictal-like event. In the second model, a single NMDA pulse, per se ineffective, became successful when it was performed after IL-β or HMGB1 local applications. These findings demonstrate that both IL-1β and HMGB1 can rapidly lower focal ictal event threshold and strengthen the possibility that targeting these inflammatory pathways may represent an effective therapeutic strategy to prevent seizures.

  8. Elucidating opportunities and pitfalls in the treatment of experimental traumatic brain injury to optimize and facilitate clinical translation.

    Science.gov (United States)

    de la Tremblaye, Patricia B; O'Neil, Darik A; LaPorte, Megan J; Cheng, Jeffrey P; Beitchman, Joshua A; Thomas, Theresa Currier; Bondi, Corina O; Kline, Anthony E

    2017-05-30

    The aim of this review is to discuss the research presented in a symposium entitled "Current progress in characterizing therapeutic strategies and challenges in experimental CNS injury" which was presented at the 2016 International Behavioral Neuroscience Society annual meeting. Herein we discuss diffuse and focal traumatic brain injury (TBI) and ensuing chronic behavioral deficits as well as potential rehabilitative approaches. We also discuss the effects of stress on executive function after TBI as well as the response of the endocrine system and regulatory feedback mechanisms. The role of the endocannabinoids after CNS injury is also discussed. Finally, we conclude with a discussion of antipsychotic and antiepileptic drugs, which are provided to control TBI-induced agitation and seizures, respectively. The review consists predominantly of published data. Copyright © 2017 Elsevier Ltd. All rights reserved.

  9. Experimental evidence for sex-specific plasticity in adult brain.

    Science.gov (United States)

    Herczeg, Gábor; Gonda, Abigél; Balázs, Gergely; Noreikiene, Kristina; Merilä, Juha

    2015-01-01

    Plasticity in brain size and the size of different brain regions during early ontogeny is known from many vertebrate taxa, but less is known about plasticity in the brains of adults. In contrast to mammals and birds, most parts of a fish's brain continue to undergo neurogenesis throughout adulthood, making lifelong plasticity in brain size possible. We tested whether maturing adult three-spined sticklebacks (Gasterosteus aculeatus) reared in a stimulus-poor environment exhibited brain plasticity in response to environmental enrichment, and whether these responses were sex-specific, thus altering the degree of sexual size dimorphism in the brain. Relative sizes of total brain and bulbus olfactorius showed sex-specific responses to treatment: males developed larger brains but smaller bulbi olfactorii than females in the enriched treatment. Hence, the degree of sexual size dimorphism (SSD) in relative brain size and the relative size of the bulbus olfactorius was found to be environment-dependent. Furthermore, the enriched treatment induced development of smaller tecta optica in both sexes. These results demonstrate that adult fish can alter the size of their brain (or brain regions) in response to environmental stimuli, and these responses can be sex-specific. Hence, the degree of SSD in brain size can be environment-dependent, and our results hint at the possibility of a large plastic component to SSD in stickleback brains. Apart from contributing to our understanding of the processes shaping and explaining variation in brain size and the size of different brain regions in the wild, the results show that provision of structural complexity in captive environments can influence brain development. Assuming that the observed plasticity influences fish behaviour, these findings may also have relevance for fish stocking, both for economical and conservational purposes.

  10. Mice Lacking the β2 Adrenergic Receptor Have a Unique Genetic Profile before and after Focal Brain Ischaemia

    Directory of Open Access Journals (Sweden)

    Robin E White

    2012-08-01

    Full Text Available The role of the β2AR (β2 adrenergic receptor after stroke is unclear as pharmacological manipulations of the β2AR have produced contradictory results. We previously showed that mice deficient in the β2AR (β2KO had smaller infarcts compared with WT (wild-type mice (FVB after MCAO (middle cerebral artery occlusion, a model of stroke. To elucidate mechanisms of this neuroprotection, we evaluated changes in gene expression using microarrays comparing differences before and after MCAO, and differences between genotypes. Genes associated with inflammation and cell deaths were enriched after MCAO in both genotypes, and we identified several genes not previously shown to increase following ischaemia (Ccl9, Gem and Prg4. In addition to networks that were similar between genotypes, one network with a central core of GPCR (G-protein-coupled receptor and including biological functions such as carbohydrate metabolism, small molecule biochemistry and inflammation was identified in FVB mice but not in β2KO mice. Analysis of differences between genotypes revealed 11 genes differentially expressed by genotype both before and after ischaemia. We demonstrate greater Glo1 protein levels and lower Pmaip/Noxa mRNA levels in β2KO mice in both sham and MCAO conditions. As both genes are implicated in NF-κB (nuclear factor κB signalling, we measured p65 activity and TNFα (tumour necrosis factor α levels 24 h after MCAO. MCAO-induced p65 activation and post-ischaemic TNFα production were both greater in FVB compared with β2KO mice. These results suggest that loss of β2AR signaling results in a neuroprotective phenotype in part due to decreased NF-κB signalling, decreased inflammation and decreased apoptotic signalling in the brain.

  11. Experimental human endotoxemia enhances brain activity during social cognition.

    Science.gov (United States)

    Kullmann, Jennifer S; Grigoleit, Jan-Sebastian; Wolf, Oliver T; Engler, Harald; Oberbeck, Reiner; Elsenbruch, Sigrid; Forsting, Michael; Schedlowski, Manfred; Gizewski, Elke R

    2014-06-01

    Acute peripheral inflammation with corresponding increases in peripheral cytokines affects neuropsychological functions and induces depression-like symptoms. However, possible effects of increased immune responses on social cognition remain unknown. Therefore, this study investigated the effects of experimentally induced acute inflammation on performance and neural responses during a social cognition task assessing Theory of Mind (ToM) ability. In this double-blind randomized crossover functional magnetic resonance imaging study, 18 healthy right-handed male volunteers received an injection of bacterial lipopolysaccharide (LPS; 0.4 ng/kg) or saline, respectively. Plasma levels of pro- and anti-inflammatory cytokines as well as mood ratings were analyzed together with brain activation during a validated ToM task (i.e. Reading the Mind in the Eyes Test). LPS administration induced pronounced transient increases in pro- (IL-6, TNF-α) and anti-inflammatory (IL-10, IL-1ra) cytokines as well as decreases in mood. Social cognition performance was not affected by acute inflammation. However, altered neural activity was observed during the ToM task after LPS administration, reflected by increased responses in the fusiform gyrus, temporo-parietal junction, superior temporal gyrus and precuneus. The increased task-related neural responses in the LPS condition may reflect a compensatory strategy or a greater social cognitive processing as a function of sickness. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  12. P300-based brain computer interface experimental setup

    NARCIS (Netherlands)

    Arboleda, C.; Garcia Cossio, E.; Posada, A.; Torres, R.

    2009-01-01

    A Brain-Computer interface (BCI) is a communication system that enables the generation of a control signal from brain signals such as sensorymotor rhythms and evoked potentials; therefore, it constitutes a novel communication option for people with severe motor disabilities (such as Amyotrophic

  13. Brain-derived neurotrophic factor ameliorates brain stem cardiovascular dysregulation during experimental temporal lobe status epilepticus.

    Directory of Open Access Journals (Sweden)

    Ching-Yi Tsai

    Full Text Available BACKGROUND: Status epilepticus (SE is an acute, prolonged epileptic crisis with a mortality rate of 20-30%; the underlying mechanism is not completely understood. We assessed the hypothesis that brain stem cardiovascular dysregulation occurs during SE because of oxidative stress in rostral ventrolateral medulla (RVLM, a key nucleus of the baroreflex loop; to be ameliorated by brain-derived neurotrophic factor (BDNF via an antioxidant action. METHODOLOGY/PRINCIPAL FINDINGS: In a clinically relevant experimental model of temporal lobe SE (TLSE using Sprague-Dawley rats, sustained hippocampal seizure activity was accompanied by progressive hypotension that was preceded by a reduction in baroreflex-mediated sympathetic vasomotor tone; heart rate and baroreflex-mediated cardiac responses remained unaltered. Biochemical experiments further showed concurrent augmentation of superoxide anion, phosphorylated p47(phox subunit of NADPH oxidase and mRNA or protein levels of BDNF, tropomyosin receptor kinase B (TrkB, angiotensin AT1 receptor subtype (AT1R, nitric oxide synthase II (NOS II or peroxynitrite in RVLM. Whereas pretreatment by microinjection bilaterally into RVLM of a superoxide dismutase mimetic (tempol, a specific antagonist of NADPH oxidase (apocynin or an AT1R antagonist (losartan blunted significantly the augmented superoxide anion or phosphorylated p47(phox subunit in RVLM, hypotension and the reduced baroreflex-mediated sympathetic vasomotor tone during experimental TLSE, pretreatment with a recombinant human TrkB-Fc fusion protein or an antisense bdnf oligonucleotide significantly potentiated all those events, alongside peroxynitrite. However, none of the pretreatments affected the insignificant changes in heart rate and baroreflex-mediated cardiac responses. CONCLUSIONS/SIGNIFICANCE: We conclude that formation of peroxynitrite by a reaction between superoxide anion generated by NADPH oxidase in RVLM on activation by AT1R and NOS II

  14. Brain infection following experimental Staphylococcus aureus sepsis in pigs

    DEFF Research Database (Denmark)

    Astrup, Lærke Boye; Iburg, Tine Moesgaard; Nielsen, Ole Lerberg

    2010-01-01

    Introduction: Sepsis is a major problem in humans and both the incidence and mortality is increasing. Multiple microabcesses can be found in the brain of septic patients. Staphylococcus aureus is one of the most common causes of sepsis and brain abscesses. S. aureus is also a frequent cause...... pigs were kept as controls. The pigs were euthanized in groups of four at either 6, 12, 24 or 48 h post infection. The brain was collected from all the animals and examined histologically. Results: All the inoculated pigs developed sepsis and 7 out of 12 animals had microabscesses in the prosencephalon...

  15. Sumoylation of hypoxia-inducible factor-1α ameliorates failure of brain stem cardiovascular regulation in experimental brain death.

    Directory of Open Access Journals (Sweden)

    Julie Y H Chan

    2011-03-01

    Full Text Available One aspect of brain death is cardiovascular deregulation because asystole invariably occurs shortly after its diagnosis. A suitable neural substrate for mechanistic delineation of this aspect of brain death resides in the rostral ventrolateral medulla (RVLM. RVLM is the origin of a life-and-death signal that our laboratory detected from blood pressure of comatose patients that disappears before brain death ensues. At the same time, transcriptional upregulation of heme oxygenase-1 in RVLM by hypoxia-inducible factor-1α (HIF-1α plays a pro-life role in experimental brain death, and HIF-1α is subject to sumoylation activated by transient cerebral ischemia. It follows that sumoylation of HIF-1α in RVLM in response to hypoxia may play a modulatory role on brain stem cardiovascular regulation during experimental brain death.A clinically relevant animal model that employed mevinphos as the experimental insult in Sprague-Dawley rat was used. Biochemical changes in RVLM during distinct phenotypes in systemic arterial pressure spectrum that reflect maintained or defunct brain stem cardiovascular regulation were studied. Western blot analysis, EMSA, ELISA, confocal microscopy and immunoprecipitation demonstrated that drastic tissue hypoxia, elevated levels of proteins conjugated by small ubiquitin-related modifier-1 (SUMO-1, Ubc9 (the only known conjugating enzyme for the sumoylation pathway or HIF-1α, augmented sumoylation of HIF-1α, nucleus-bound translocation and enhanced transcriptional activity of HIF-1α in RVLM neurons took place preferentially during the pro-life phase of experimental brain death. Furthermore, loss-of-function manipulations by immunoneutralization of SUMO-1, Ubc9 or HIF-1α in RVLM blunted the upregulated nitric oxide synthase I/protein kinase G signaling cascade, which sustains the brain stem cardiovascular regulatory machinery during the pro-life phase.We conclude that sumoylation of HIF-1α in RVLM ameliorates brain stem

  16. Focal choroidal excavation associated with focal retinochoroiditis.

    Science.gov (United States)

    Ohki, Tetsutaro; Sakai, Tsutomu; Tsuneoka, Hiroshi

    2015-01-01

    To describe detailed spectral-domain optical coherence tomography (OCT) findings for two patients with focal choroidal excavation (FCE) associated with focal retinochoroiditis. Three eyes from two patients with FCE associated with focal retinochoroiditis were evaluated by funduscopy, fluorescence angiography, indocyanine green angiography, and spectral-domain OCT during follow-up. Both patients with focal retinochoroiditis developed new FCE after oral steroid treatment and two eyes showed regression of the FCE during the follow-up. Both eyes from one patient transformed from the conforming to the nonconforming type and neither of the eyes were stable during the follow-up. Ultimately, all eyes exhibited the conforming-type FCE. Focal choroidal excavation can be seen as a tomographic phenotype after the treatment of focal retinochoroiditis. Spectral-domain OCT was useful for detecting the development of FCE after the treatment and for observing FCE regression.

  17. Systemic focal epileptogenesis

    Energy Technology Data Exchange (ETDEWEB)

    Remler, M.P.; Marcussen, W.H.

    1986-01-01

    Rats that receive radiation to 0.25 cc of one cerebral hemisphere are clinically and electroencephalographically normal until there is a breakdown of the blood-brain barrier (BBB) at 3 to 6 months postradiation. This BBB lesion can be detected by transient focal seizure activity produced by the BBB-excluded systemic convulsant bicuculline methiodide. In two rats the seizure activity induced by this one injection was self-sustaining. In seven of 15 other rats tested, the subsequent administration of repeated 2 mg/kg injections created a chronic focus that continued to spike with great frequency for 3 weeks or more without further administration of any convulsant. In three of eight other rats, implanted minipumps delivering 180 micrograms/h of bicuculline methiodide produced self-sustaining epileptic activity.

  18. Arginine-Vasopressin Receptor Blocker Conivaptan Reduces Brain Edema and Blood-Brain Barrier Disruption after Experimental Stroke in Mice.

    Directory of Open Access Journals (Sweden)

    Emil Zeynalov

    Full Text Available Stroke is a major cause of morbidity and mortality. Stroke is complicated by brain edema and blood-brain barrier (BBB disruption, and is often accompanied by increased release of arginine-vasopressin (AVP. AVP acts through V1a and V2 receptors to trigger hyponatremia, vasospasm, and platelet aggregation which can exacerbate brain edema. The AVP receptor blockers conivaptan (V1a and V2 and tolvaptan (V2 are used to correct hyponatremia, but their effect on post-ischemic brain edema and BBB disruption remains to be elucidated. Therefore, we conducted this study to investigate if these drugs can prevent brain edema and BBB disruption in mice after stroke.Experimental mice underwent the filament model of middle cerebral artery occlusion (MCAO with reperfusion. Mice were treated with conivaptan, tolvaptan, or vehicle. Treatments were initiated immediately at reperfusion and administered IV (conivaptan or orally (tolvaptan for 48 hours. Physiological variables, neurological deficit scores (NDS, plasma and urine sodium and osmolality were recorded. Brain water content (BWC and Evans Blue (EB extravasation index were evaluated at the end point.Both conivaptan and tolvaptan produced aquaresis as indicated by changes in plasma and urine sodium levels. However plasma and urine osmolality was changed only by conivaptan. Unlike tolvaptan, conivaptan improved NDS and reduced BWC in the ipsilateral hemisphere: from 81.66 ± 0.43% (vehicle to 78.28 ± 0.48% (conivaptan, 0.2 mg, p < 0.05 vs vehicle. Conivaptan also attenuated the EB extravasation from 1.22 ± 0.08 (vehicle to 1.01 ± 0.02 (conivaptan, 0.2 mg, p < 0.05.Continuous IV infusion with conivaptan for 48 hours after experimental stroke reduces brain edema, and BBB disruption. Conivaptan but not tolvaptan may potentially be used in patients to prevent brain edema after stroke.

  19. Xenon neuroprotection in experimental stroke: interactions with hypothermia and intracerebral hemorrhage

    National Research Council Canada - National Science Library

    Sheng, Siyuan P; Lei, Beilei; James, Michael L; Lascola, Christopher D; Venkatraman, Talaignair N; Jung, Jin Yong; Maze, Mervyn; Franks, Nicholas P; Pearlstein, Robert D; Sheng, Huaxin; Warner, David S

    2012-01-01

    Xenon has been proven to be neuroprotective in experimental brain injury. The authors hypothesized that xenon would improve outcome from focal cerebral ischemia with a delayed treatment onset and prolonged recovery interval...

  20. Experimental Injury Biomechanics of the Pediatric Head and Brain

    Science.gov (United States)

    Margulies, Susan; Coats, Brittany

    Traumatic brain injury (TBI) is a leading cause of death and disability among children and young adults in the United States and results in over 2,500 childhood deaths, 37,000 hospitalizations, and 435,000 emergency department visits each year (Langlois et al. 2004). Computational models of the head have proven to be powerful tools to help us understand mechanisms of adult TBI and to determine load thresholds for injuries specific to adult TBI. Similar models need to be developed for children and young adults to identify age-specific mechanisms and injury tolerances appropriate for children and young adults. The reliability of these tools, however, depends heavily on the availability of pediatric tissue material property data. To date the majority of material and structural properties used in pediatric computer models have been scaled from adult human data. Studies have shown significant age-related differences in brain and skull properties (Prange and Margulies 2002; Coats and Margulies 2006a, b), indicating that the pediatric head cannot be modeled as a miniature adult head, and pediatric computer models incorporating age-specific data are necessary to accurately mimic the pediatric head response to impact or rotation. This chapter details the developmental changes of the pediatric head and summarizes human pediatric properties currently available in the literature. Because there is a paucity of human pediatric data, material properties derived from animal tissue are also presented to demonstrate possible age-related differences in the heterogeneity and rate dependence of tissue properties. The chapter is divided into three main sections: (1) brain, meninges, and cerebral spinal fluid (CSF); (2) skull; and (3) scalp.

  1. Metallic gold reduces TNFalpha expression, oxidative DNA damage and pro-apoptotic signals after experimental brain injury

    DEFF Research Database (Denmark)

    Pedersen, Mie Ostergaard; Larsen, Agnete; Pedersen, Dan Sonne

    2009-01-01

    -45 microm in size or the vehicle (placebo) were implanted in the cortical tissue followed by a cortical freeze-lesioning. At 1-2 weeks post-injury, brains were analyzed by using immunohistochemistry and markers of inflammation, oxidative stress and apoptosis. This study shows that gold treatment......Brain injury represents a major health problem and may result in chronic inflammation and neurodegeneration. Due to antiinflammatory effects of gold, we have investigated the cerebral effects of metallic gold particles following a focal brain injury (freeze-lesion) in mice. Gold particles 20...

  2. Focal Choroidal Excavation.

    Science.gov (United States)

    Cebeci, Zafer; Bayraktar, Şerife; Oray, Merih; Kır, Nur

    2016-12-01

    Focal choroidal excavation is a choroidal pit that can be detected by optical coherence tomography. Central serous chorioretinopathy, choroidal neovascularization and polypoidal choroidal vasculopathy are pathologies associated with focal choroidal excavation. In this article, we present the follow-up and treatment outcomes of three eyes of two patients with focal choroidal excavation.

  3. Focal femoral condyle resurfacing.

    LENUS (Irish Health Repository)

    Brennan, S A

    2013-03-01

    Focal femoral inlay resurfacing has been developed for the treatment of full-thickness chondral defects of the knee. This technique involves implanting a defect-sized metallic or ceramic cap that is anchored to the subchondral bone through a screw or pin. The use of these experimental caps has been advocated in middle-aged patients who have failed non-operative methods or biological repair techniques and are deemed unsuitable for conventional arthroplasty because of their age. This paper outlines the implant design, surgical technique and biomechanical principles underlying their use. Outcomes following implantation in both animal and human studies are also reviewed. Cite this article: Bone Joint J 2013;95-B:301-4.

  4. Crise epiléptica focal ipsilateral a tumor cerebral: relato de caso Focal epileptic seizures ipsilateral to the tumor: case report

    Directory of Open Access Journals (Sweden)

    Sebastião Silva Gusmão

    2002-06-01

    Full Text Available Descreve-se um caso de crise focal somatosensorial ipsilateral a tumor cerebral e revê-se a literatura. Trata-se de ocorrência excepcional, tendo sido descritos apenas seis casos. Vários mecanismos fisiopatológicos foram propostos para explicar a crise focal somatosensorial ipsilateral. A proximidade das lesões da convexidade cerebral baixa (perisilviana sugere o comprometimento da área somatosensorial secundária e parece comprovar os achados experimentais de crises somatosensoriais originadas desta área.Focal somatosensory epileptic seizures ipsilateral to a brain tumor is reported and the literature reviewed. It is an exceptional occurrence, having been described only six cases, with several mechanisms being proposed. The proximity of the lesions with the low cerebral convexity (perisylvian suggests the compromising of the secondary somatosensorial area, seeming to prove the experimental observation of somatosensorial crises originating in this area.

  5. Dynamics of the brain: Mathematical models and non-invasive experimental studies

    Science.gov (United States)

    Toronov, V.; Myllylä, T.; Kiviniemi, V.; Tuchin, V. V.

    2013-10-01

    Dynamics is an essential aspect of the brain function. In this article we review theoretical models of neural and haemodynamic processes in the human brain and experimental non-invasive techniques developed to study brain functions and to measure dynamic characteristics, such as neurodynamics, neurovascular coupling, haemodynamic changes due to brain activity and autoregulation, and cerebral metabolic rate of oxygen. We focus on emerging theoretical biophysical models and experimental functional neuroimaging results, obtained mostly by functional magnetic resonance imaging (fMRI) and near-infrared spectroscopy (NIRS). We also included our current results on the effects of blood pressure variations on cerebral haemodynamics and simultaneous measurements of fast processes in the brain by near-infrared spectroscopy and a very novel functional MRI technique called magnetic resonance encephalography. Based on a rapid progress in theoretical and experimental techniques and due to the growing computational capacities and combined use of rapidly improving and emerging neuroimaging techniques we anticipate during next decade great achievements in the overall knowledge of the human brain.

  6. Proper Measurement of the Prostate Volume by Transrectal Ultrasound: Experimental Study about the Prostate with Focal Intravesical Protrusion of the Enlarged Central Gland

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Sung Kyoung; Kim, Hyoung Jung; Lim, Joo Won; Lee, Dong Ho; Ko, Young Tae [Kyung Hee University Hospital, Seoul (Korea, Republic of)

    2008-06-15

    To evaluate the proper volume measurement of prostate with focal intravesical protrusion of enlarged central gland by comparison between methods using craniocaudal length from top of protruded central gland and from prostate base near bladder neck to prostate apex. We made 20 prostate models with focal intravesical protrusion (volume range: 20{approx}50 mL, height of protrusion: about 1 cm) using devil's tongue jelly. Two radiologists measured volume of models 3 times by two kinds of methods using craniocaudal length from top of protruded central gland (method 1) and from prostate base near bladder neck (method 2) by transrectal ultrasound. The accuracy of volume measurement of models was evaluated statistically by comparing their average volume to true volume. Intra- and interobserver agreement was also evaluated. Average true volume of models was 31.05 mL. Each average volume using method 1 by two observers was 37.07 mL and 38.56 mL. Each average volume using method 2 was 30.69 mL and 31.55 mL. Volume measurement using method 2 was approximated to true volume of prostate statistically (p = .654, .823). There was no significant inter- and intra-observer variation in both methods. To measure the accurate volume of prostate with focal intravesical protrusion of enlarged central gland, its craniocaudal length should be measured from prostate base near bladder neck

  7. [Neuroprotective and antiamnesic effects of GK-2h dipeptide HNGF mimetic on a model of experimental ischemic stroke of brain cortex prefrontal areas].

    Science.gov (United States)

    Gudasheva, T A; Romanova, G A; Shakova, F M; Kotel'nikova, S O; Barskov, I V; Stel'mashuk, E V; Seredenin, S B

    2012-01-01

    Neuroprotective and antiamnesic effects of human nerve growth factor (HNGF) synthetic dipeptide mimetic bis-(N-monosuccinyl-glycyl-lysine)hexamethylenediamide (GK-2h) has been studied on a model of bilateral photochemically induced focal ischemical brain injury in prefrontal cortex of rats. It is established that a single intraperitoneal injection of GK-2h (0.1 mg/kg) 1 h or 4 h after operation, followed by injections on the 2nd, 4th and 8th days after operation, results (on the 9th day) in reduction of the cortical infarction volume by 47 or 65%, and leads to restoration of the passive avoidance reflex (acquired before experimental ischemic insult) by 42 and 60%, respectively. It is concluded that GK-2h possesses significant neuroprotective properties.

  8. Gold ions bio-released from metallic gold particles reduce inflammation and apoptosis and increase the regenerative responses in focal brain injury

    DEFF Research Database (Denmark)

    Larsen, Agnete; Kolind, Kristian; Pedersen, Dan Sonne

    2008-01-01

    Traumatic brain injury results in loss of neurons caused as much by the resulting neuroinflammation as by the injury. Gold salts are known to be immunosuppressive, but their use are limited by nephrotoxicity. However, as we have proven that implants of pure metallic gold release gold ions which d...... a completely new medical concept that bypasses the blood-brain-barrier and allows direct drug delivery to inflamed brain tissue....

  9. A quantitative MRI method for imaging blood-brain barrier leakage in experimental traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available Blood-brain barrier (BBB disruption is common following traumatic brain injury (TBI. Dynamic contrast enhanced (DCE MRI can longitudinally measure the transport coefficient Ktrans which reflects BBB permeability. Ktrans measurements however are not widely used in TBI research because it is generally considered to be noisy and possesses low spatial resolution. We improved spatiotemporal resolution and signal sensitivity of Ktrans MRI in rats by using a high-sensitivity surface transceiver coil. To overcome the signal drop off profile of the surface coil, a pre-scan module was used to map the flip angle (B1 field and magnetization (M0 distributions. A series of T1-weighted gradient echo images were acquired and fitted to the extended Kety model with reversible or irreversible leakage, and the best model was selected using F-statistics. We applied this method to study the rat brain one hour following controlled cortical impact (mild to moderate TBI, and observed clear depiction of the BBB damage around the impact regions, which matched that outlined by Evans Blue extravasation. Unlike the relatively uniform T2 contrast showing cerebral edema, Ktrans shows a pronounced heterogeneous spatial profile in and around the impact regions, displaying a nonlinear relationship with T2. This improved Ktrans MRI method is also compatible with the use of high-sensitivity surface coil and the high-contrast two-coil arterial spin-labeling method for cerebral blood flow measurement, enabling more comprehensive investigation of the pathophysiology in TBI.

  10. Brain metabolic pattern analysis using a magnetic resonance spectra classification software in experimental stroke.

    Science.gov (United States)

    Jiménez-Xarrié, Elena; Davila, Myriam; Candiota, Ana Paula; Delgado-Mederos, Raquel; Ortega-Martorell, Sandra; Julià-Sapé, Margarida; Arús, Carles; Martí-Fàbregas, Joan

    2017-01-13

    Magnetic resonance spectroscopy (MRS) provides non-invasive information about the metabolic pattern of the brain parenchyma in vivo. The SpectraClassifier software performs MRS pattern-recognition by determining the spectral features (metabolites) which can be used objectively to classify spectra. Our aim was to develop an Infarct Evolution Classifier and a Brain Regions Classifier in a rat model of focal ischemic stroke using SpectraClassifier. A total of 164 single-voxel proton spectra obtained with a 7 Tesla magnet at an echo time of 12 ms from non-infarcted parenchyma, subventricular zones and infarcted parenchyma were analyzed with SpectraClassifier ( http://gabrmn.uab.es/?q=sc ). The spectra corresponded to Sprague-Dawley rats (healthy rats, n = 7) and stroke rats at day 1 post-stroke (acute phase, n = 6 rats) and at days 7 ± 1 post-stroke (subacute phase, n = 14). In the Infarct Evolution Classifier, spectral features contributed by lactate + mobile lipids (1.33 ppm), total creatine (3.05 ppm) and mobile lipids (0.85 ppm) distinguished among non-infarcted parenchyma (100% sensitivity and 100% specificity), acute phase of infarct (100% sensitivity and 95% specificity) and subacute phase of infarct (78% sensitivity and 100% specificity). In the Brain Regions Classifier, spectral features contributed by myoinositol (3.62 ppm) and total creatine (3.04/3.05 ppm) distinguished among infarcted parenchyma (100% sensitivity and 98% specificity), non-infarcted parenchyma (84% sensitivity and 84% specificity) and subventricular zones (76% sensitivity and 93% specificity). SpectraClassifier identified candidate biomarkers for infarct evolution (mobile lipids accumulation) and different brain regions (myoinositol content).

  11. Cerebral transplantation of encapsulated mesenchymal stem cells improves cellular pathology after experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Heile, Anna M B; Wallrapp, Christine; Klinge, Petra M

    2009-01-01

    PURPOSE: "Naked" human mesenchymal stem cells (MSC) are neuro-protective in experimental brain injury (TBI). In a controlled cortical impact (CCI) rat model, we investigated whether encapsulated MSC (eMSC) act similarly, and whether efficacy is augmented using cells transfected to produce the neuro...

  12. Technical and experimental features of Magnetic Resonance Spectroscopy of brain glycogen metabolism.

    Science.gov (United States)

    Soares, Ana Francisca; Gruetter, Rolf; Lei, Hongxia

    2017-07-15

    In the brain, glycogen is a source of glucose not only in emergency situations but also during normal brain activity. Altered brain glycogen metabolism is associated with energetic dysregulation in pathological conditions, such as diabetes or epilepsy. Both in humans and animals, brain glycogen levels have been assessed non-invasively by Carbon-13 Magnetic Resonance Spectroscopy (13C-MRS) in vivo. With this approach, glycogen synthesis and degradation may be followed in real time, thereby providing valuable insights into brain glycogen dynamics. However, compared to the liver and muscle, where glycogen is abundant, the sensitivity for detection of brain glycogen by 13C-MRS is inherently low. In this review we focus on strategies used to optimize the sensitivity for 13C-MRS detection of glycogen. Namely, we explore several technical perspectives, such as magnetic field strength, field homogeneity, coil design, decoupling, and localization methods. Furthermore, we also address basic principles underlying the use of 13C-labeled precursors to enhance the detectable glycogen signal, emphasizing specific experimental aspects relevant for obtaining kinetic information on brain glycogen. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Idiopathic focal epilepsies: the "lost tribe".

    Science.gov (United States)

    Pal, Deb K; Ferrie, Colin; Addis, Laura; Akiyama, Tomoyuki; Capovilla, Giuseppe; Caraballo, Roberto; de Saint-Martin, Anne; Fejerman, Natalio; Guerrini, Renzo; Hamandi, Khalid; Helbig, Ingo; Ioannides, Andreas A; Kobayashi, Katsuhiro; Lal, Dennis; Lesca, Gaetan; Muhle, Hiltrud; Neubauer, Bernd A; Pisano, Tiziana; Rudolf, Gabrielle; Seegmuller, Caroline; Shibata, Takashi; Smith, Anna; Striano, Pasquale; Strug, Lisa J; Szepetowski, Pierre; Valeta, Thalia; Yoshinaga, Harumi; Koutroumanidis, Michalis

    2016-09-01

    The term idiopathic focal epilepsies of childhood (IFE) is not formally recognised by the ILAE in its 2010 revision (Berg et al., 2010), nor are its members and boundaries precisely delineated. The IFEs are amongst the most commonly encountered epilepsy syndromes affecting children. They are fascinating disorders that hold many "treats" for both clinicians and researchers. For example, the IFEs pose many of the most interesting questions central to epileptology: how are functional brain networks involved in the manifestation of epilepsy? What are the shared mechanisms of comorbidity between epilepsy and neurodevelopmental disorders? How do focal EEG discharges impact cognitive functioning? What explains the age-related expression of these syndromes? Why are EEG discharges and seizures so tightly locked to slow-wave sleep? In the last few decades, the clinical symptomatology and the respective courses of many IFEs have been described, although they are still not widely appreciated beyond the specialist community. Most neurologists would recognise the core syndromes of IFE to comprise: benign epilepsy of childhood with centro-temporal spikes or Rolandic epilepsy (BECTS/RE); Panayiotopoulos syndrome; and the idiopathic occipital epilepsies (Gastaut and photosensitive types). The Landau-Kleffner syndrome and the related (idiopathic) epilepsy with continuous spikes and waves in sleep (CSWS or ESES) are also often included, both as a consequence of the shared morphology of the interictal discharges and their potential evolution from core syndromes, for example, CSWS from BECTS. Atypical benign focal epilepsy of childhood also has shared electro-clinical features warranting inclusion. In addition, a number of less well-defined syndromes of IFE have been proposed, including benign childhood seizures with affective symptoms, benign childhood epilepsy with parietal spikes, benign childhood seizures with frontal or midline spikes, and benign focal seizures of adolescence. The

  14. Imaging experimental cerebral malaria in vivo: significant role of ischemic brain edema.

    Science.gov (United States)

    Penet, Marie-France; Viola, Angèle; Confort-Gouny, Sylviane; Le Fur, Yann; Duhamel, Guillaume; Kober, Frank; Ibarrola, Danielle; Izquierdo, Marguerite; Coltel, Nicolas; Gharib, Bouchra; Grau, Georges E; Cozzone, Patrick J

    2005-08-10

    The first in vivo magnetic resonance study of experimental cerebral malaria is presented. Cerebral involvement is a lethal complication of malaria. To explore the brain of susceptible mice infected with Plasmodium berghei ANKA, multimodal magnetic resonance techniques were applied (imaging, diffusion, perfusion, angiography, spectroscopy). They reveal vascular damage including blood-brain barrier disruption and hemorrhages attributable to inflammatory processes. We provide the first in vivo demonstration for blood-brain barrier breakdown in cerebral malaria. Major edema formation as well as reduced brain perfusion was detected and is accompanied by an ischemic metabolic profile with reduction of high-energy phosphates and elevated brain lactate. In addition, angiography supplies compelling evidence for major hemodynamics dysfunction. Actually, edema further worsens ischemia by compressing cerebral arteries, which subsequently leads to a collapse of the blood flow that ultimately represents the cause of death. These findings demonstrate the coexistence of inflammatory and ischemic lesions and prove the preponderant role of edema in the fatal outcome of experimental cerebral malaria. They improve our understanding of the pathogenesis of cerebral malaria and may provide the necessary noninvasive surrogate markers for quantitative monitoring of treatment.

  15. Propagation of Aß pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

    Science.gov (United States)

    Eisele, Yvonne S; Duyckaerts, Charles

    2016-01-01

    In brains of patients with Alzheimer's disease (AD), Aβ peptides accumulate in parenchyma and, almost invariably, also in the vascular walls. Although Aβ aggregation is, by definition, present in AD, its impact is only incompletely understood. It occurs in a stereotypical spatiotemporal distribution within neuronal networks in the course of the disease. This suggests a role for synaptic connections in propagating Aβ pathology, and possibly of axonal transport in an antero- or retrograde way-although, there is also evidence for passive, extracellular diffusion. Striking, in AD, is the conjunction of tau and Aβ pathology. Tau pathology in the cell body of neurons precedes Aβ deposition in their synaptic endings in several circuits such as the entorhino-dentate, cortico-striatal or subiculo-mammillary connections. However, genetic evidence suggests that Aβ accumulation is the first step in AD pathogenesis. To model the complexity and consequences of Aβ aggregation in vivo, various transgenic (tg) rodents have been generated. In rodents tg for the human Aβ precursor protein, focal injections of preformed Aβ aggregates can induce Aβ deposits in the vicinity of the injection site, and over time in more distant regions of the brain. This suggests that Aβ shares with α-synuclein, tau and other proteins the property to misfold and aggregate homotypic molecules. We propose to group those proteins under the term "propagons". Propagons may lack the infectivity of prions. We review findings from neuropathological examinations of human brains in different stages of AD and from studies in rodent models of Aβ aggregation and discuss putative mechanisms underlying the initiation and spread of Aβ pathology.

  16. EXPERIMENTAL AND THEORETICAL FOUNDATIONS AND PRACTICAL IMPLEMENTATION OF TECHNOLOGY BRAIN-COMPUTER INTERFACE

    Directory of Open Access Journals (Sweden)

    A. Ya. Kaplan

    2013-01-01

    Full Text Available Technology brain-computer interface (BCI allow saperson to learn how to control external devices via thevoluntary regulation of own EEG directly from the brain without the involvement in the process of nerves and muscles. At the beginning the main goal of BCI was to replace or restore motor function to people disabled by neuromuscular disorders. Currently, the task of designing the BCI increased significantly, more capturing different aspects of life a healthy person. This article discusses the theoretical, experimental and technological base of BCI development and systematized critical fields of real implementation of these technologies.

  17. Focal cerebral ischemia induces increased myelin basic protein and growth-associated protein-43 gene transcription in peri-infarct areas in the rat brain

    DEFF Research Database (Denmark)

    Gregersen, R; Christensen, Thomas; Lehrmann, E

    2001-01-01

    Although oligodendrocytes are vulnerable to focal cerebral ischemia, remyelination of denuded or regenerating axons in the peri-infarct area has been observed in the central nervous system. We studied the expression of myelin basic protein (MBP), a major component of central nervous system myelin...... messenger RNA (mRNA) had disappeared by 24 h, whereas myelin protein, identified by MBP and myelin oligodendrocyte glycoprotein (MOG) immunohistochemistry, appeared structurally intact until day 3. Peri-infarct oligodendrocytes increased their expression of MBP mRNA from 24 h to maximal levels at day 7...... showed that increased expression of GAP-43 mRNA in neurons was concomitant to MBP mRNA upregulation in oligodendrocytes. While the mechanisms regulating oligodendrocyte survival and myelination signals are not clear at this point, axonal sprouting could putatively serve as a stimulus for the upregulation...

  18. Cortical spreading depression causes a long-lasting decrease in cerebral blood flow and induces tolerance to permanent focal ischemia in rat brain.

    Science.gov (United States)

    Otori, Tatsuo; Greenberg, Joel H; Welsh, Frank A

    2003-01-01

    Cortical spreading depression (CSD) has previously been shown to induce tolerance to a subsequent episode of transient cerebral ischemia. The objective of the present study was to determine whether CSD also induces tolerance to permanent focal ischemia and, if so, whether tolerance may be mediated by alterations in cerebral blood flow (CBF). Sprague-Dawley rats were preconditioned by applying potassium chloride to one hemisphere for 2 hours, evoking 19 +/- 5 episodes of CSD (mean +/- SD, n = 19). Three days later, the middle cerebral artery (MCA) was permanently occluded using an intraluminal suture. In a subset of animals, laser Doppler blood flow (LDF) was monitored over the parietal cortex before and during the first 2 hours of MCA occlusion. Preconditioning with CSD reduced the hemispheric volume of infarction from 248 +/- 115 mm3 (n = 18) in sham-conditioned animals to 161 +/- 81 mm3 (n = 19, P< 0.02). Similarly, CSD reduced the neocortical volume of infarction from 126 +/- 82 mm3 to 60 +/- 61 mm3 (P < 0.01). Moreover, preconditioning with CSD significantly improved LDF during MCA occlusion from 21% +/- 7% (n = 9) of preischemic baseline in sham-conditioned animals to 29% +/- 9% (n = 7, P< 0.02). Preconditioning with CSD therefore preserved relative levels of CBF during focal ischemia and reduced the extent of infarction resulting from permanent MCA occlusion. To determine whether CSD may have altered preischemic baseline CBF, [14 C]iodoantipyrine was used in additional animals to measure CBF 3 days after CSD conditioning or sham conditioning. CSD, but not sham conditioning, significantly reduced baseline CBF in the ipsilateral neocortex to values 67% to 75% of those in the contralateral cortex. Therefore, CSD causes a long-lasting decrease in baseline CBF that is most likely related to a reduction in metabolic rate. A reduction in the rate of metabolism may contribute to the induction of tolerance to ischemia after preconditioning with CSD.

  19. Experimental investigation of the mechanical properties of brain simulants used for cranial gunshot simulation.

    Science.gov (United States)

    Lazarjan, Milad Soltanipour; Geoghegan, Patrick Henry; Jermy, Mark Christopher; Taylor, Michael

    2014-06-01

    The mechanical properties of the human brain at high strain rate were investigated to analyse the mechanisms that cause backspatter when a cranial gunshot wound occurs. Different concentrations of gelatine and a new material (M1) developed in this work were tested and compared to bovine brain samples. Kinetic energy absorption and expansion rate of the samples caused by the impact of a bullet from .22 air rifle (AR) (average velocity (uav) of 290m/s) and .22 long rifle (LR) (average velocity (uav) of 330m/s) were analysed using a high speed camera (24,000fps). The AR projectile had, in the region of interest, an average kinetic energy (Ek) of 42±1.3J. On average, the bovine brain absorbed 50±5% of Ek, and the simulants 46-58±5%. The Ek of the .22 LR was 141±3.7J. The bovine brain absorbed 27% of the .22LR Ek and the simulants 15-29%. The expansion of the sample, after penetration, was measured. The bovine brain experienced significant plastic deformation whereas the gelatine solution exhibited a principally elastic response. The permanent damage patterns in the M1 material were much closer to those in brain tissue, than were the damage patterns in the gelatine. The results provide a first step to developing a realistic experimental simulant for the human brain which can produce the same blood backspatter patterns as a human brain during a cranial gunshot. These results can also be used to improve the 3D models of human heads used in car crash and blast trauma injury research. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  20. Effects of experimentally-induced maternal hypothyroidism on crucial offspring rat brain enzyme activities.

    Science.gov (United States)

    Koromilas, Christos; Liapi, Charis; Zarros, Apostolos; Stolakis, Vasileios; Tsagianni, Anastasia; Skandali, Nikolina; Al-Humadi, Hussam; Tsakiris, Stylianos

    2014-06-01

    Hypothyroidism is known to exert significant structural and functional changes to the developing central nervous system, and can lead to the establishment of serious mental retardation and neurological problems. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil-induced experimental hypothyroidism on crucial brain enzyme activities of Wistar rat offspring, at two time-points of their lives: at birth (day-1) and at 21 days of age (end of lactation). Under all studied experimental conditions, offspring brain acetylcholinesterase (AChE) activity was found to be significantly decreased due to maternal hypothyroidism, in contrast to the two studied adenosinetriphosphatase (Na(+),K(+)-ATPase and Mg(2+)-ATPase) activities that were only found to be significantly altered right after birth (increased and decreased, respectively, following an exposure to gestational maternal hypothyroidism) and were restored to control levels by the end of lactation. As our findings regarding the pattern of effects that maternal hypothyroidism has on the above-mentioned crucial offspring brain enzyme activities are compared to those reported in the literature, several differences are revealed that could be attributed to both the mode of the experimental simulation approach followed as well as to the time-frames examined. These findings could provide the basis for a debate on the need of a more consistent experimental approach to hypothyroidism during neurodevelopment as well as for a further evaluation of the herein presented and discussed neurochemical (and, ultimately, neurodevelopmental) effects of experimentally-induced maternal hypothyroidism, in a brain region-specific manner. Copyright © 2014 ISDN. Published by Elsevier Ltd. All rights reserved.

  1. Influence of a brief episode of anesthesia during the induction of experimental brain trauma on secondary brain damage and inflammation.

    Directory of Open Access Journals (Sweden)

    Clara Luh

    Full Text Available It is unclear whether a single, brief, 15-minute episode of background anesthesia already modulates delayed secondary processes after experimental brain injury. Therefore, this study was designed to characterize three anesthesia protocols for their effect on molecular and histological study endpoints. Mice were randomly separated into groups that received sevoflurane (sevo, isoflurane (iso or an intraperitoneal anesthetic combination (midazolam, fentanyl and medetomidine; comb prior to traumatic brain injury (controlled cortical impact, CCI; 8 m/s, 1 mm impact depth, 3 mm diameter. Twenty-four hours after insult, histological brain damage, neurological function (via neurological severity score, cerebral inflammation (via real-time RT-PCR for IL6, COX-2, iNOS and microglia (via immunohistochemical staining for Iba1 were determined. Fifteen minutes after CCI, the brain contusion volume did not differ between the anesthetic regimens (sevo = 17.9±5.5 mm(3; iso = 20.5±3.7 mm(3; comb = 19.5±4.6 mm(3. Within 24 hours after injury, lesion size increased in all groups (sevo = 45.3±9.0 mm(3; iso = 31.5±4.0 mm(3; comb = 44.2±6.2 mm(3. Sevo and comb anesthesia resulted in a significantly larger contusion compared to iso, which was in line with the significantly better neurological function with iso (sevo = 4.6±1.3 pts.; iso = 3.9±0.8 pts.; comb = 5.1±1.6 pts.. The expression of inflammatory marker genes was not significantly different at 15 minutes and 24 hours after CCI. In contrast, significantly more Iba1-positive cells were present in the pericontusional region after sevo compared to comb anesthesia (sevo = 181±48/mm(3; iso = 150±36/mm(3; comb = 113±40/mm(3. A brief episode of anesthesia, which is sufficient for surgical preparations of mice for procedures such as delivering traumatic brain injury, already has a significant impact on the extent of secondary brain damage.

  2. [Changes in the morphometric indices of the microvascular bed of the brain in experimental hypertension].

    Science.gov (United States)

    Aleksandrova, T B; Rodionov, I M; Shinkarenko, V S

    1984-09-01

    Brain stem microvessels up to 15 microns in diameter of spontaneously hypertensive rats and rats with experimental renal hypertension were investigated in histological sections with the aid of a texture analysis system. Hypertensive animals showed a reduction in the vascular diameter per unit volume of cerebral tissue, in the mean vascular diameter as well as in the area occupied by the vessels, thus attesting to the lessened density of brain vascularization. The proportion of the vessels measuring from 6 to 15 microns in diameter per unit volume of cerebral tissue decreased whereas the proportion of the vessels measuring up to 5 microns in diameter remained unchanged. The characteristics under study demonstrated the same line of changes in both spontaneous and experimental renal hypertension.

  3. Anatomopathological study in BALB/c mice brains experimentally infected with Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Marcos Gontijo da Silva

    Full Text Available Toxoplasmosis is one of the most important diseases of the nervous central system, leading to severe symptoms and, many times, irreversible sequelae. This work demonstrated the main anatomopathological lesions caused by Toxoplasma gondii in brains from experimentally infected BALB/c mice. We analyzed 51 cases of mice that developed toxoplasmosis after experimental infection by intraperitoneal inoculation of blood, amniotic liquid and cerebrospinal fluid from fetuses, newly born children and pregnant women with clinical and laboratory signals of toxoplasmosis. In all experiments where we detected the parasite in mice we also detected pathological lesions in the animal brains with great polymorphism between experiments. Edema was the most found lesion in all cases. Besides, it was possible to demonstrate the inflammatory process in 82.4% of cases and necrosis in 64.7% of cases, in agreement with the literature that describes severe neurological damage in its hosts.

  4. Regional distribution of opiate alkaloids in experimental animals' brain tissue and blood

    Directory of Open Access Journals (Sweden)

    Đurendić-Brenesel Maja

    2012-01-01

    Full Text Available The aim of this study was to examine the regional distribution of opiate alkaloids from seized heroin in experimental animals' brain regions and blood. Results could be used in the examination of opiate alkaloids' distribution in human biological samples in order to contribute to the solution of the causes of death due to heroin intake. Experimental animals (Wistar rats were treated with seized heroin, and were sacrificed at different time periods: 5, 15, 45 and 120 min after treatment. Opiate alkaloids' (codeine, morphine, acetylcodeine, 6- acetylmorphine and 3,6-diacetylmorphine content was determined in the brain regions (cortex, brainstem, amygdala and basal ganglia and blood of animals using gas chromatography-mass spectrometry (GC-MS method. The highest content of opiate alkaloids in the blood was measured 15 min, and in the brain tissue 45 min after the treatment with heroin. The maximal concentration of opiates was determined in the basal ganglia. The obtained results offer the possibility of selecting this part of the brain tissue as a representative sample for identifying and assessing the content of opiates.

  5. Repetitive ischemic preconditioning attenuates inflammatory reaction and brain damage after focal cerebral ischemia in rats: involvement of PI3K/Akt and ERK1/2 signaling pathway.

    Science.gov (United States)

    Tu, Xian-kun; Yang, Wei-zhong; Chen, Jian-ping; Chen, Yan; Chen, Quan; Chen, Ping-ping; Shi, Song-sheng

    2015-04-01

    Ischemic preconditioning (IPC) has been demonstrated to provide a neuroprotection against brain damage produced by focal cerebral ischemia. However, it is elusive whether ischemic preconditioning attenuates ischemic brain damage through modulating phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathway. In the present study, we first explored the best scheme of repetitive ischemic preconditioning (RIPC) to protect rat brain against ischemic damage and then further investigated the underlying mechanisms in RIPC's neuroprotection. Adult male Sprague-Dawley rats underwent ischemic preconditioning or (and) middle cerebral artery occlusion (MCAO). LY294002 or (and) PD98059 were injected intracerebroventricularly to selectively inhibit the activation of PI3K/Akt or ERK1/2. Neurological deficit scores, cerebral infarct volume, and morphological characteristic were detected at corresponding time after cerebral ischemia. The enzymatic activity of myeloperoxidase (MPO) was measured 24 h after cerebral ischemia. Expressions of p-Akt, t-Akt, p-ERK1/2, t-ERK1/2, nuclear factor-kappa B (NF-κB) p65, and cyclooxygenase-2 (COX-2) in ischemic brain were determined by Western blot. The release of tumor necrosis factor-α (TNF-α) in blood was examined by ELISA. In the various schemes of RIPC, IPC2 × 5 min causes less neuronal damage in the cortex and subcortex of ischemic brain and provides an obvious alleviation of cerebral infarction and neurological deficit after lethal ischemia. IPC2 × 5 min significantly reduces cerebral infarct volume, neurological deficit scores, and MPO activity; all of which were diminished by LY294002 or (and) PD98059. IPC2 × 5 min significantly upregulates the expressions of p-Akt and p-ERK1/2, which were inhibited by LY294002 or (and) PD98059. IPC2 × 5 min significantly downregulates the expressions of NF-κB p65 and COX-2 and attenuates the release of TNF-α; all of

  6. Anatomical landmarks for registration of experimental image data to volumetric rodent brain atlasing templates.

    Science.gov (United States)

    Sergejeva, Marina; Papp, Eszter A; Bakker, Rembrandt; Gaudnek, Manuel A; Okamura-Oho, Yuko; Boline, Jyl; Bjaalie, Jan G; Hess, Andreas

    2015-01-30

    Assignment of anatomical reference is a key step in integration of the rapidly expanding collection of rodent brain data. Landmark-based registration facilitates spatial anchoring of diverse types of data not suitable for automated methods operating on voxel-based image information. Here we propose a standardized set of anatomical landmarks for registration of whole brain imaging datasets from the mouse and rat brain, and in particular for integration of experimental image data in Waxholm Space (WHS). Sixteen internal landmarks of the C57BL/6J mouse brain have been reliably identified: by different individuals, independent of their experience in anatomy; across different MRI contrasts (T1, T2, T2(*)) and other modalities (Nissl histology and block-face anatomy); in different specimens; in different slice acquisition angles; and in different image resolutions. We present a registration example between T1-weighted MRI and the mouse WHS template using these landmarks and reaching fairly high accuracy. Landmark positions identified in the mouse WHS template are shared through the Scalable Brain Atlas, accompanied by graphical and textual guidelines for locating each landmark. We identified 14 of the 16 landmarks in the WHS template for the Sprague Dawley rat. This landmark set can withstand substantial differences in acquisition angle, imaging modality, and is less vulnerable to subjectivity. This facilitates registration of multimodal 3D brain data to standard coordinate spaces for mouse and rat brain taking a step toward the creation of a common rodent reference system; raising data sharing to a qualitatively higher level. Copyright © 2014 Elsevier B.V. All rights reserved.

  7. Azadirachta indica ethanolic extract protects neurons from apoptosis and mitigates brain swelling in experimental cerebral malaria.

    Science.gov (United States)

    Bedri, Selma; Khalil, Eltahir A; Khalid, Sami A; Alzohairy, Mohammad A; Mohieldein, Abdlmarouf; Aldebasi, Yousef H; Seke Etet, Paul Faustin; Farahna, Mohammed

    2013-08-29

    Cerebral malaria is a rapidly developing encephalopathy caused by the apicomplexan parasite Plasmodium falciparum. Drugs currently in use are associated with poor outcome in an increasing number of cases and new drugs are urgently needed. The potential of the medicinal plant Azadirachta indica (Neem) for the treatment of experimental cerebral malaria was evaluated in mice. Experimental cerebral malaria was induced in mice by infection with Plasmodium berghei ANKA. Infected mice were administered with Azadirachta indica ethanolic extract at doses of 300, 500, or 1000 mg/kg intraperitoneally (i.p.) in experimental groups, or with the anti-malarial drugs chloroquine (12 mg/kg, i.p.) or artemether (1.6 mg/kg, i.p.), in the positive control groups. Treatment was initiated at the onset of signs of brain involvement and pursued for five days on a daily basis. Mice brains were dissected out and processed for the study of the effects of the extract on pyramidal cells' fate and on markers of neuroinflammation and apoptosis, in the medial temporal lobe. Azadirachta indica ethanolic extract mitigated neuroinflammation, decreased the severity of brain oedema, and protected pyramidal neurons from apoptosis, particularly at the highest dose used, comparable to chloroquine and artemether. The present findings suggest that Azadirachta indica ethanolic extract has protective effects on neuronal populations in the inflamed central nervous system, and justify at least in part its use in African and Asian folk medicine and practices.

  8. Ginsenoside Rd promotes neurogenesis in rat brain after transient focal cerebral ischemia via activation of PI3K/Akt pathway.

    Science.gov (United States)

    Liu, Xin-yu; Zhou, Xin-yu; Hou, Jin-cai; Zhu, Hua; Wang, Zhong; Liu, Jian-xun; Zheng, Yong-qiu

    2015-04-01

    To investigate the effects of ginsenoside Rd (Rd) on neurogenesis in rat brain after ischemia/reperfusion injury (IRI). Male SD rats were subjected to transient middle cerebral artery occlusion (MCAO) followed by reperfusion. The rats were injected with Rd (1, 2.5, and 5 mg·kg(-1)·d(-1), ip) from d 1 to d 3 after MCAO, and with BrdU (50 mg·kg(-1)·d(-1), ip) from d 3 to d 6, then sacrificed on 7 d. The infarct size and neurological scores were assessed. Neurogenesis in the brains was detected by BrdU, DCX, Nestin, and GFAP immunohistochemistry staining. PC12 cells subjected to OGD/reperfusion were used as an in vitro model of brain ischemia. VEGF and BDNF levels were assessed with ELISA, and Akt and ERK phosphorylation was measured using Western blotting. Rd administration dose-dependently decreased the infarct size and neurological scores in the rats with IRI. The high dose of Rd 5 (mg·kg(-1)·d(-1)) significantly increased Akt phosphorylation in ipsilateral hemisphere, and markedly increased the number of BrdU/DCX and Nestin/GFAP double-positive cells in ischemic area, which was partially blocked by co-administration of the PI3 kinase inhibitor LY294002. Treatment with Rd (25, 50, and 100 μmol/L) during reperfusion significantly increased the expression of VEGF and BDNF in PC12 cells with IRI. Furthermore, treatment with Rd dose-dependently increased the phosphorylation of Akt and ERK, and significantly decreased PC12 cell apoptosis, which were blocked by co-application of LY294002. Rd not only attenuates ischemia/reperfusion injury in rat brain, but also promotes neurogenesis via increasing VEGF and BDNF expression and activating the PI3K/Akt and ERK1/2 pathways.

  9. Imaging mass spectrometry detection of gangliosides species in the mouse brain following transient focal cerebral ischemia and long-term recovery.

    Directory of Open Access Journals (Sweden)

    Shawn N Whitehead

    Full Text Available Gangliosides, a member of the glycosphingolipid family, are heterogeneously expressed in biological membranes and are particularly enriched within the central nervous system. Gangliosides consist of mono- or poly-sialylated oligosaccharide chains of variable lengths attached to a ceramide unit and are found to be intimately involved in brain disease development. The purpose of this study is to examine the spatial profile of ganglioside species using matrix-assisted laser desorption/ionization (MALDI imaging (IMS following middle cerebral artery occlusion (MCAO reperfusion injury in the mouse. IMS is a powerful method to not only discriminate gangliosides by their oligosaccharide components, but also by their carbon length within their sphingosine base. Mice were subjected to a 30 min unilateral MCAO followed by long-term survival (up to 28 days of reperfusion. Brain sections were sprayed with the matrix 5-Chloro-2-mercaptobenzothiazole, scanned and analyzed for a series of ganglioside molecules using an Applied Biosystems 4800 MALDI TOF/TOF. Traditional histological and immunofluorescence techniques were performed to assess brain tissue damage and verification of the expression of gangliosides of interest. Results revealed a unique anatomical profile of GM1, GD1 and GT1b (d18:1, d20:1 as well as other members of the glycosphingolipid family. There was marked variability in the ratio of expression between ipsilateral and contralateral cortices for the various detected ganglioside species following MCAO-reperfusion injury. Most interestingly, MCAO resulted in the transient induction of both GM2 and GM3 signals within the ipsilateral hemisphere; at the border of the infarcted tissue. Taken together, the data suggest that brain region specific expression of gangliosides, particularly with respect to hydrocarbon length, may play a role in neuronal responses to injury.

  10. [Morphological study of neuroprotective properties of dipeptide mimetic of nerve growth factor (GK-2h) in focal ischemic damage of rat brain prefrontal cortex].

    Science.gov (United States)

    Barskov, I V; Stelmashuk, E V; Romanova, G A; Khaspekov, L G

    2013-01-01

    The neuroprotective effects of dipeptide GK-2h, a mimetic of nerve growth factor, in bifocal photoinduced ischemia in rat brain prefrontal cortex was studied. It was shown that GK-2h, injected intraperitonealy in dose 0.1 mg/kg in 1 h or 4 h after operation and then on 2nd, 4th and 8th days, prevented significantly on 9th day from increasing volume of cortical infarction.

  11. Porcine focal symmetrical poliomyelomalacia.

    OpenAIRE

    Wilson, T.M.; Drake, T R

    1982-01-01

    An acute afebrile paretic condition was diagnosed in 16 of 100 feeder pigs between eight to ten weeks of age. Nine pigs died acutely and seven pigs were euthanized. Macroscopic lesions in the ventral horns of the cervical, thoracic, lumbar and sacral segments of the spinal cord consisted of focal, bilateral, grey depressed areas. There was a bilateral symmetrical focal poliomyelomalacia histopathologically characterized by microcavitation, endothelial and glial cell proliferation and infiltra...

  12. Mutations in DEPDC5 cause familial focal epilepsy with variable foci

    NARCIS (Netherlands)

    Dibbens, Leanne M.; de Vries, Boukje; Donatello, Simona; Heron, Sarah E.; Hodgson, Bree L.; Chintawar, Satyan; Crompton, Douglas E.; Hughes, James N.; Bellows, Susannah T.; Klein, Karl Martin; Callenbach, Petra M. C.; Corbett, Mark A.; Gardner, Alison E.; Kivity, Sara; Iona, Xenia; Regan, Brigid M.; Weller, Claudia M.; Crimmins, Denis; O'Brien, Terence J.; Guerrero-Lopez, Rosa; Mulley, John C.; Dubeau, Francois; Licchetta, Laura; Bisulli, Francesca; Cossette, Patrick; Thomas, Paul Q.; Gecz, Jozef; Serratosa, Jose; Brouwer, Oebele F.; Andermann, Frederick; Andermann, Eva; van den Maagdenberg, Arn M. J. M.; Pandolfo, Massimo; Berkovic, Samuel F.; Scheffer, Ingrid E.

    The majority of epilepsies are focal in origin, with seizures emanating from one brain region. Although focal epilepsies often arise from structural brain lesions, many affected individuals have normal brain imaging. The etiology is unknown in the majority of individuals, although genetic factors

  13. Pharmacological response of systemically derived focal epileptic lesions

    Energy Technology Data Exchange (ETDEWEB)

    Remler, M.P.; Sigvardt, K.; Marcussen, W.H.

    1986-11-01

    Focal epileptic lesions were made in rats by systemic focal epileptogenesis. In this method, a focal lesion of the blood-brain barrier (BBB) is produced by focal alpha irradiation followed by repeated systemic injection of a convulsant drug that cannot cross the normal BBB, resulting in a chronic epileptic focus. Changes in the spike frequency of these foci in response to various drugs was recorded. The controls, saline and chlorpromazine, produced no change. Phenytoin, phenobarbital, chlordiazepoxide, and valproic acid produced the expected decrease in spike frequency. Pentobarbital and diazepam produced a paradoxical increase in spike frequency.

  14. SSVEP-based Experimental Procedure for Brain-Robot Interaction with Humanoid Robots.

    Science.gov (United States)

    Zhao, Jing; Li, Wei; Mao, Xiaoqian; Li, Mengfan

    2015-11-24

    Brain-Robot Interaction (BRI), which provides an innovative communication pathway between human and a robotic device via brain signals, is prospective in helping the disabled in their daily lives. The overall goal of our method is to establish an SSVEP-based experimental procedure by integrating multiple software programs, such as OpenViBE, Choregraph, and Central software as well as user developed programs written in C++ and MATLAB, to enable the study of brain-robot interaction with humanoid robots. This is achieved by first placing EEG electrodes on a human subject to measure the brain responses through an EEG data acquisition system. A user interface is used to elicit SSVEP responses and to display video feedback in the closed-loop control experiments. The second step is to record the EEG signals of first-time subjects, to analyze their SSVEP features offline, and to train the classifier for each subject. Next, the Online Signal Processor and the Robot Controller are configured for the online control of a humanoid robot. As the final step, the subject completes three specific closed-loop control experiments within different environments to evaluate the brain-robot interaction performance. The advantage of this approach is its reliability and flexibility because it is developed by integrating multiple software programs. The results show that using this approach, the subject is capable of interacting with the humanoid robot via brain signals. This allows the mind-controlled humanoid robot to perform typical tasks that are popular in robotic research and are helpful in assisting the disabled.

  15. Malnutrition and brain function: experimental studies using the phenomenon of cortical spreading depression.

    Science.gov (United States)

    Guedes, R C; Monteiro, J S; Teodósio, N R

    1996-12-01

    Depending on its intensity and duration, nutritional deficiency can disrupt the structure and function of the nervous system of humans and other mammals, with consequences more or less devastating for the whole organism, particularly in the early postnatal life, when body growth is very rapid and the need for proteins, calories and other nutrients is greatest. In this review, electrophysiological data are presented regarding the use of the phenomenon of cortical spreading depression (CSD) to study effects of malnutrition on the brain. Several conditions of clinical importance and that are known to alter brain function are shown also to influence CSD features in experimental animals. Some of these conditions, (e.g., pharmacological manipulation of neurotransmitter systems, dietary treatment with Lithium, acute hyperglycemia, hypothyroidism, aging and environmental stimulation) decrease CSD susceptibility, while other conditions increase it, as, for example, systemic reduction of extracellular chloride levels, deprivation of REM-sleep, acute hypoglycemia, treatment with diazepam, consumption of ethanol and malnutrition. Particular emphasis is laid on the effect of early environmental enrichment on CSD in normal and malnourished animals. Our results suggest that such effect is more evident in the malnourished brain, as compared to the well-nourished one. The data also show that malnutrition alters the brain responsivity to some CSD-facilitatory or inhibitory agents. The underlying mechanisms to explain the observed effects are discussed.

  16. Found in translation: understanding the biology and behavior of experimental traumatic brain injury

    Science.gov (United States)

    Bondi, Corina O.; Semple, Bridgette D.; Noble-Haeusslein, Linda J.; Osier, Nicole D.; Carlson, Shaun W.; Dixon, C. Edward; Giza, Christopher C.; Kline, Anthony E.

    2014-01-01

    BONDI, C.O., B.D. Semple, L.J. Noble-Haeusslein, N.D. Osier, S.W. Carlson, C.E. Dixon, C.C. Giza and A.E. Kline. Found in translation: understanding the biology and behavior of experimental traumatic brain injury. NEUROSCI BIOBEHAV REV. The aim of this review is to discuss in greater detail the topics covered in the recent symposium entitled “Traumatic brain injury: laboratory and clinical perspectives,” presented at the 2014 International Behavioral Neuroscience Society annual meeting. Herein we review contemporary laboratory models of traumatic brain injury (TBI) including common assays for sensorimotor and cognitive behavior. New modalities to evaluate social behavior after injury to the developing brain, as well as the attentional set-shifting test (AST) as a measure of executive function in TBI, will be highlighted. Environmental enrichment (EE) will be discussed as a preclinical model of neurorehabilitation, and finally, an evidence-based approach to sports-related concussion will be considered. The review consists predominantly of published data, but some discussion of ongoing or future directions is provided. PMID:25496906

  17. Vitamins and nutrients as primary treatments in experimental brain injury: Clinical implications for nutraceutical therapies.

    Science.gov (United States)

    Vonder Haar, Cole; Peterson, Todd C; Martens, Kris M; Hoane, Michael R

    2016-06-01

    With the numerous failures of pharmaceuticals to treat traumatic brain injury in humans, more researchers have become interested in combination therapies. This is largely due to the multimodal nature of damage from injury, which causes excitotoxicity, oxidative stress, edema, neuroinflammation and cell death. Polydrug treatments have the potential to target multiple aspects of the secondary injury cascade, while many previous therapies focused on one particular aspect. Of specific note are vitamins, minerals and nutrients that can be utilized to supplement other therapies. Many of these have low toxicity, are already FDA approved and have minimal interactions with other drugs, making them attractive targets for therapeutics. Over the past 20 years, interest in supplementation and supraphysiologic dosing of nutrients for brain injury has increased and indeed many vitamins and nutrients now have a considerable body of the literature backing their use. Here, we review several of the prominent therapies in the category of nutraceutical treatment for brain injury in experimental models, including vitamins (B2, B3, B6, B9, C, D, E), herbs and traditional medicines (ginseng, Gingko biloba), flavonoids, and other nutrients (magnesium, zinc, carnitine, omega-3 fatty acids). While there is still much work to be done, several of these have strong potential for clinical therapies, particularly with regard to polydrug regimens. This article is part of a Special Issue entitled SI:Brain injury and recovery. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. GM-CSF is not essential for experimental autoimmune encephalomyelitis but promotes brain-targeted disease.

    Science.gov (United States)

    Pierson, Emily R; Goverman, Joan M

    2017-04-06

    Experimental autoimmune encephalomyelitis (EAE) has been used as an animal model of multiple sclerosis to identify pathogenic cytokines that could be therapeutic targets. Granulocyte-macrophage colony-stimulating factor (GM-CSF) is the only cytokine reported to be essential for EAE. We investigated the role of GM-CSF in EAE in C3HeB/FeJ mice that uniquely exhibit extensive brain and spinal cord inflammation. Unexpectedly, GM-CSF-deficient C3HeB/FeJ mice were fully susceptible to EAE because IL-17 activity compensated for the loss of GM-CSF during induction of spinal cord-targeted disease. In contrast, both GM-CSF and IL-17 were needed to fully overcome the inhibitory influence of IFN-γ on the induction of inflammation in the brain. Both GM-CSF and IL-17 independently promoted neutrophil accumulation in the brain, which was essential for brain-targeted disease. These results identify a GM-CSF/IL-17/IFN-γ axis that regulates inflammation in the central nervous system and suggest that a combination of cytokine-neutralizing therapies may be needed to dampen central nervous system autoimmunity.

  19. Persistence of viral RNA in the brain of experimentally infected mice with coxsackievirus B5

    Directory of Open Access Journals (Sweden)

    Sobotova Z.

    2011-04-01

    Full Text Available The aim of our study was to follow the persistence of viral RNA in selected organs of experimentally infected with coxsackievirus (CV B5 strains from different sources such as a patient’s sample, an environmental sample and a prototype virus strain. Methods . CD-1 mice were infected with CVB5 strain Faulkner the prototype, CVB5 – isolate from treated sewage waste and isolate from patient’s stool sample both identified as CVB5. The viral RNA was detected by RT-PCR using enterovirus primers specific for the non-coding 5' region. Results . We observed presence of RNA in the brain and heart of mice infected with isolate from patient’s stool at day 45 post infection (p. i.. Conclusion. We conclude that CVB5 persists in the brain and heart after oral infection of CD1 mice. The relevance of viral persistence maybe related viral origin and the genetics

  20. Focal brainstem gliomas

    Science.gov (United States)

    Sabbagh, Abdulrahman J.; Alaqeel, Ahmed M.

    2015-01-01

    Improved neuronavigation guidance as well as intraoperative imaging and neurophysiologic monitoring technologies have enhanced the ability of neurosurgeons to resect focal brainstem gliomas. In contrast, diffuse brainstem gliomas are considered to be inoperable lesions. This article is a continuation of an article that discussed brainstem glioma diagnostics, imaging, and classification. Here, we address open surgical treatment of and approaches to focal, dorsally exophytic, and cervicomedullary brainstem gliomas. Intraoperative neuronavigation, intraoperative neurophysiologic monitoring, as well as intraoperative imaging are discussed as adjunctive measures to help render these procedures safer, more acute, and closer to achieving surgical goals. PMID:25864061

  1. Vitelliform focal choroidal excavation.

    Science.gov (United States)

    Or, Chris; Forooghian, Farzin

    2014-05-30

    Focal choroidal excavations (FCE) are characterized by foveal or perifoveal choroid excavations seen on optical coherence tomography (OCT). The authors report a case of FCE associated with a vitelliform lesion within the excavation. A case of FCE associated with a small vitelliform lesion has been described previously, but the larger extent of the vitelliform lesion observed in the current case has not been previously reported. This may represent a novel category of FCE, vitelliform focal choroidal excavation, in which deposition of vitelliform material is associated with its development. Copyright 2014, SLACK Incorporated.

  2. SNAP focal plane

    Energy Technology Data Exchange (ETDEWEB)

    Lampton, Michael L.; Kim, A.; Akerlof, C.W.; Aldering, G.; Amanullah, R.; Astier, P.; Barrelet, E.; Bebek, C.; Bergstrom, L.; Berkovitz, J.; Bernstein, G.; Bester, M.; Bonissent, A.; Bower, C.; Carithers Jr., W.C.; Commins, E.D.; Day, C.; Deustua, S.E.; DiGennaro,R.; Ealet, A.; Ellis, R.S.; Eriksson, M.; Fruchter, A.; Genat, J.-F.; Goldhaber, G.; Goobar, A.; Groom, D.; Harris, S.E.; Harvey, P.R.; Heetderks, H.D.; Holland, S.E.; Huterer, D.; Karcher, A.; Kolbe, W.; Krieger, B.; Lafever, R.; Lamoureux, J.; Levi, M.E.; Levin, D.S.; Linder,E.V.; Loken, S.C.; Malina, R.; Massey, R.; McKay, T.; McKee, S.P.; Miquel, R.; Mortsell, E.; Mostek, N.; Mufson, S.; Musser, J.; Nugent, P.; Oluseyi, H.; Pain, R.; Palaio, N.; Pankow, D.; Perlmutter, S.; Pratt, R.; Prieto, E.; Refregier, A.; Rhodes, J.; Robinson, K.; Roe, N.; Sholl, M.; Schubnell, M.; Smadja, G.; Smoot, G.; Spadafora, A.; Tarle, G.; Tomasch,A.; von der Lippe, H.; Vincent, R.; Walder, J.-P.; Wang, G.

    2002-07-29

    The proposed SuperNova/Acceleration Probe (SNAP) mission will have a two-meter class telescope delivering diffraction-limited images to an instrumented 0.7 square-degree field sensitive in the visible and near-infrared wavelength regime. We describe the requirements for the instrument suite and the evolution of the focal plane design to the present concept in which all the instrumentation--visible and near-infrared imagers, spectrograph, and star guiders--share one common focal plane.

  3. Selective preservation of a lexical category in aphasia: dissociations in comprehension of body parts and geographical place names following focal brain lesion.

    Science.gov (United States)

    Goodglass, H; Wingfield, A

    1993-12-01

    The selective dissociation of memory for proper names is discussed in the context of a review of dissociations involving broadly defined vs narrowly defined semantic categories in brain damaged adults. Two narrowly defined categories for which dissociations have been reported are body parts (selectively impaired in comprehension) and geographical place names (selectively preserved in comprehension). In this study, 167 aphasic patients were tested for their ability to correctly identify body parts and map locations from spoken names, relative to a baseline for correct responses on general word discrimination (object identification). Wernicke's aphasics and Global aphasics both had significantly more success in pointing to named map locations and significantly worse performance in pointing to named body parts than they had in selecting other objects from multiple choice. Anomic aphasics showed precisely the opposite pattern of results. Other aphasic subgroups (Broca's aphasics, Mixed Nonfluent aphasics, Conduction aphasics, Transcortical Motor and Transcortical Sensory aphasics, and Mixed Fluent aphasics) did not show significant deviations in either direction. We suggest that the selective preservation for place names may be related to their status as proper names.

  4. Upregulated expression of Nogo-A and NgR in an experimental model of focal microgyria regulates the migration, proliferation and self-renewal of subventricular zone neural progenitors

    Energy Technology Data Exchange (ETDEWEB)

    Yu, Sixun; Shu, Haifeng; Yang, Tao; Huang, Haidong [Department of Neurosurgery, General Hospital of the People' s Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083 (China); Li, Song [Department of Neurosurgery, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037 (China); Zhao, Ziyi [Central Laboratory, Teaching Hospital of Chengdu University of Traditional Chinese Medicine, 610075 (China); Kuang, Yongqin, E-mail: kuangyongqin@163.com [Department of Neurosurgery, General Hospital of the People' s Liberation Army Chengdu Military Region, Chengdu, Sichuan, 610083 (China)

    2016-04-29

    Nogo-A and its receptor (NgR) were first described as myelin-associated inhibitors of neuronal regeneration in response to injury. In recent years, knowledge about the important role of the Nogo-A protein in several neuronal pathologies has grown considerably. Here, we employed a neonatal cortex freeze-lesion (NFL) model in neonatal rats and measured the expression of Nogo-A and NgR in the resulting cerebrocortical microdysgenesis 5–75 days after freezing injury. We observed marked upregulation of Nogo-A and NgR in protein levels. Furthermore, the migration of neural precursor cells (NPCs) derived from the subventricular zone (SVZ) toward the sits of injury was perturbed by treatment of NgR antagonist peptide NEP1-40. In vitro analysis showed that the knockdown of NgR by lentivirus-delivered siRNA promoted in axonal regeneration and SVZ-derived neural stem cell/progenitor cell (SVZ-NPCs) adhesion and migration, findings which were similar to the effects of NEP1-40. Taken together, our results indicate an important role for NgR in regulating the physiological processes of SVZ-NPCs. The observation of upregulated Nogo-A/NgR in lesion sites in the NFL model suggest that the effects of the perturbed Nogo-A are a key feature during the development and/or the progression of cortical malformation. - Highlights: • NFL model is an accurate experimental reproduction of focal microgyria of FCD. • The increase of the Nogo-A Levels occurs in response to freeze-induced focal lesioning. • Nogo-A/NgR may play a critical role for in the pathologic progression of FCD. • Nogo-A is associated with the migration, proliferation and self-renewal of SVZ-NPCs.

  5. On high b diffusion imaging in the human brain: ruminations and experimental insights✩

    Science.gov (United States)

    Mulkern, Robert V.; Haker, Steven J.; Maier, Stephan E.

    2010-01-01

    Interest in the manner in which brain tissue signal decays with b factor in diffusion imaging schemes has grown in recent years following the observation that the decay curves depart from purely monoexponential decay behavior. Regardless of the model or fitting function proposed for characterizing sufficiently sampled decay curves (vide infra), the departure from monoexponentiality spells increased tissue characterization potential. The degree to which this potential can be harnessed to improve specificity, sensitivity and spatial localization of diseases in brain, and other tissues, largely remains to be explored. Furthermore, the degree to which currently popular diffusion tensor imaging methods, including visually impressive white matter fiber “tractography” results, have almost completely ignored the nonmonoexponential nature of the basic signal decay with b factor is worthy of communal introspection. Here we limit our attention to a review of the basic experimental features associated with brain water signal diffusion decay curves as measured over extended b-factor ranges, the simple few parameter fitting functions that have been proposed to characterize these decays and the more involved models, e.g.,“ruminations,” which have been proposed to account for the nonmonoexponentiality to date. PMID:19520535

  6. On high b diffusion imaging in the human brain: ruminations and experimental insights.

    Science.gov (United States)

    Mulkern, Robert V; Haker, Steven J; Maier, Stephan E

    2009-10-01

    Interest in the manner in which brain tissue signal decays with b factor in diffusion imaging schemes has grown in recent years following the observation that the decay curves depart from purely monoexponential decay behavior. Regardless of the model or fitting function proposed for characterizing sufficiently sampled decay curves (vide infra), the departure from monoexponentiality spells increased tissue characterization potential. The degree to which this potential can be harnessed to improve specificity, sensitivity and spatial localization of diseases in brain, and other tissues, largely remains to be explored. Furthermore, the degree to which currently popular diffusion tensor imaging methods, including visually impressive white matter fiber "tractography" results, have almost completely ignored the nonmonoexponential nature of the basic signal decay with b factor is worthy of communal introspection. Here we limit our attention to a review of the basic experimental features associated with brain water signal diffusion decay curves as measured over extended b-factor ranges, the simple few parameter fitting functions that have been proposed to characterize these decays and the more involved models, e.g.,"ruminations," which have been proposed to account for the nonmonoexponentiality to date.

  7. Voluntary Exercise Preconditioning Activates Multiple Antiapoptotic Mechanisms and Improves Neurological Recovery after Experimental Traumatic Brain Injury.

    Science.gov (United States)

    Zhao, Zaorui; Sabirzhanov, Boris; Wu, Junfang; Faden, Alan I; Stoica, Bogdan A

    2015-09-01

    Physical activity can attenuate neuronal loss, reduce neuroinflammation, and facilitate recovery after brain injury. However, little is known about the mechanisms of exercise-induced neuroprotection after traumatic brain injury (TBI) or its modulation of post-traumatic neuronal cell death. Voluntary exercise, using a running wheel, was conducted for 4 weeks immediately preceding (preconditioning) moderate-level controlled cortical impact (CCI), a well-established experimental TBI model in mice. Compared to nonexercised controls, exercise preconditioning (pre-exercise) improved recovery of sensorimotor performance in the beam walk task, as well as cognitive/affective functions in the Morris water maze, novel object recognition, and tail-suspension tests. Further, pre-exercise reduced lesion size, attenuated neuronal loss in the hippocampus, cortex, and thalamus, and decreased microglial activation in the cortex. In addition, exercise preconditioning activated the brain-derived neurotrophic factor pathway before trauma and amplified the injury-dependent increase in heat shock protein 70 expression, thus attenuating key apoptotic pathways. The latter include reduction in CCI-induced up-regulation of proapoptotic B-cell lymphoma 2 (Bcl-2)-homology 3-only Bcl-2 family molecules (Bid, Puma), decreased mitochondria permeabilization with attenuated release of cytochrome c and apoptosis-inducing factor (AIF), reduced AIF translocation to the nucleus, and attenuated caspase activation. Given these neuroprotective actions, voluntary physical exercise may serve to limit the consequences of TBI.

  8. Protective Effects of Angiotensin II AT1 Receptors Blockade against Brain Injury in Experimental Model of Stroke in Rat

    Directory of Open Access Journals (Sweden)

    Hamdollah Panahpour

    2014-06-01

    Full Text Available Background & objectives: Ischemic stroke remains the third leading cause of invalidism and death in industrialized countries. It is suggested that renin–angiotensin system (RAS may contribute in stroke related pathogenic mechanisms and involve in the ischemic brain damage. This study designed to investigate the role of angiotensin II (Ang II in conjunction with AT1 receptors in treatment of the brain injuries following transient focal cerebral ischemia in rats.   Methods: Forty eight male Sprague-Dawley rats were studied in four groups. Sham group, ischemic control group and two ischemic groups that received candesartan (0.1mg/kg, or 0.5mg/kg at the beginning of reperfusion period. Transient focal cerebral ischemia was induced by 60 minutes occlusion of the middle cerebral artery, followed by 24 hours reperfusion. At the end of the reperfusion period, neurological deficit score (NDS was performed. Total cortical and striatal infarct volumes were determined using triphenyltetrazolium chloride (TTC staining technique.   Results: Animals in sham operated group had normal motor function and no ischemic lesions were observed in cortical or striatal regions. Occurring ischemia in ischemic control group that received vehicle produced considerable infarction in cortex (253±15mm3 and striatum (92±7mm3, as well as these animals had sever impaired motor dysfunctions. Blocking of AT1 receptors with candesartan (0.1mg/kg or 0.5mg/kg improved neurological outcome and significantly lowered cortical and striatal infarct volumes relative to ischemic control group.   Conclusion: The findings of the present study indicated that stimulation of AT1 receptors by Ang II involved in ischemia/reperfusion injuries and blocking of AT1 receptors can decrease ischemic brain injury and improve neurological outcome.

  9. In vivo magnetic resonance imaging investigating the development of experimental brain metastases due to triple negative breast cancer.

    Science.gov (United States)

    Hamilton, Amanda M; Foster, Paula J

    2017-02-01

    Triple negative breast cancer (TNBC), when associated with poor outcome, is aggressive in nature with a high incidence of brain metastasis and the shortest median overall patient survival after brain metastasis development compared to all other breast cancer subtypes. As therapies that control primary cancer and extracranial metastatic sites improve, the incidence of brain metastases is increasing and the management of patients with breast cancer brain metastases continues to be a significant clinical challenge. Mouse models have been developed to permit in depth evaluation of breast cancer metastasis to the brain. In this study, we compare the efficiency and metastatic potential of two experimental mouse models of TNBC. Longitudinal MRI analysis and end point histology were used to quantify initial cell arrest as well as the number and volume of metastases that developed in mouse brain over time. We showed significant differences in MRI appearance, tumor progression and model efficiency between the syngeneic 4T1-BR5 model and the xenogeneic 231-BR model. Since TNBC does not respond to many standard breast cancer treatments and TNBC brain metastases lack effective targeted therapies, these preclinical TNBC models represent invaluable tools for the assessment of novel systemic therapeutic approaches. Further pursuits of therapeutics designed to bypass the blood tumor barrier and permit access to the brain parenchyma and metastatic cells within the brain will be paramount in the fight to control and treat lethal metastatic cancer.

  10. High-speed documented experimental gunshot to a skull-brain model and radiologic virtual autopsy.

    Science.gov (United States)

    Thali, Michael J; Kneubuehl, Beat P; Vock, Peter; Allmen, Gabriel v; Dirnhofer, Richard

    2002-09-01

    The authors documented and evaluated experimental gunshots to a skull-brain model with high-speed photography and subsequent radiographic examination for comparison of the morphologic findings in the model. The artificial skull was a polyurethane ball constructed in layers, with a porous diploe sandwiched between a tabula externa and a tabula interna. The brain itself was simulated with gelatin 10% at 4 degrees C, a material well known in wound ballistics. Gunshots were fired at the model from a distance of 10 m and documented with high-speed photography (up to 50 million frames/sec). Subsequently, a complete examination of the artificial skull was performed, including spiral computed tomography (with two-dimensional and three-dimensional reconstructions) and classic skull autopsy. The high-speed photographs clearly showed the dynamic development of the skull fracture system from an external perspective. The subsequent radiographic examination of the entire head volume created two-dimensional reformations in any plane and three-dimensional reconstructions of the gunshot injury of the polyurethane skull-brain model, especially the wound channel and the fracture system. Thanks to the model and high-speed photographs, the dynamic development of the morphology of a gunshot wound could be documented and studied. The data from computed tomography, using two-dimensional and three-dimensional postprocessing with a perspective view, were very similar to those from classic head autopsy, but derived in a hands-off and nondestructive manner. This examination method leads the way to radiographic digital autopsy or virtual autopsy.

  11. Resveratrol defends blood-brain barrier integrity in experimental autoimmune encephalomyelitis mice.

    Science.gov (United States)

    Wang, Dong; Li, Shi-Ping; Fu, Jin-Sheng; Zhang, Sheng; Bai, Lin; Guo, Li

    2016-11-01

    The mouse autoimmune encephalomyelitis (EAE), an experimental model of multiple sclerosis (MS), is primarily characterized as dysfunction of the blood-brain barrier (BBB). Resveratrol exhibits anti-inflammatory, antioxidative, and neuroprotective activities. We investigated the beneficial effects of resveratrol in protecting the integrity of the BBB in EAE mice and observed improved clinical outcome in the EAE mice after resveratrol treatment. Evans blue (EB) extravasation was used to detect the disruption of BBB. Western blot were used to detected the tight junction proteins and adhesion molecules zonula occludens-1 (ZO-1), occludin, ICAM-1, and VCAM-1. Inflammatory factors inducible nitric oxide synthase (iNOS), IL-1β, and arginase 1 were evaluated by quantitative RT-PCR (qPCR) and IL-10 by ELISA. NADPH oxidase (NOX) levels were evaluated by qPCR, and its activity was analyzed by lucigenin-derived chemiluminescence. Resveratrol at doses of 25 and 50 mg/kg produced a dose-dependent decrease in EAE paralysis and EB leakage, ameliorated EAE-induced loss of tight junction proteins ZO-1, occludin, and claudin-5, as well as repressed the EAE-induced increase in adhesion proteins ICAM-1 and VCAM-1. In addition, resveratrol suppressed the EAE-induced overexpression of proinflammatory transcripts iNOS and IL-1β and upregulated the expression of anti-inflammatory transcripts arginase 1 and IL-10 cytokine in the brain. Furthermore, resveratrol downregulated the overexpressed NOX2 and NOX4 in the brain and suppressed NADPH activity. Resveratrol ameliorates the clinical severity of MS through maintaining the BBB integrity in EAE mice. Copyright © 2016 the American Physiological Society.

  12. Pyruvate treatment attenuates cerebral metabolic depression and neuronal loss after experimental traumatic brain injury.

    Science.gov (United States)

    Moro, Nobuhiro; Ghavim, Sima S; Harris, Neil G; Hovda, David A; Sutton, Richard L

    2016-07-01

    Experimental traumatic brain injury (TBI) is known to produce an acute increase in cerebral glucose utilization, followed rapidly by a generalized cerebral metabolic depression. The current studies determined effects of single or multiple treatments with sodium pyruvate (SP; 1000mg/kg, i.p.) or ethyl pyruvate (EP; 40mg/kg, i.p.) on cerebral glucose metabolism and neuronal injury in rats with unilateral controlled cortical impact (CCI) injury. In Experiment 1 a single treatment was given immediately after CCI. SP significantly improved glucose metabolism in 3 of 13 brain regions while EP improved metabolism in 7 regions compared to saline-treated controls at 24h post-injury. Both SP and EP produced equivalent and significant reductions in dead/dying neurons in cortex and hippocampus at 24h post-CCI. In Experiment 2 SP or EP were administered immediately (time 0) and at 1, 3 and 6h post-CCI. Multiple SP treatments also significantly attenuated TBI-induced reductions in cerebral glucose metabolism (in 4 brain regions) 24h post-CCI, as did multiple injections of EP (in 4 regions). The four pyruvate treatments produced significant neuroprotection in cortex and hippocampus 1day after CCI, similar to that found with a single SP or EP treatment. Thus, early administration of pyruvate compounds enhanced cerebral glucose metabolism and neuronal survival, with 40mg/kg of EP being as effective as 1000mg/kg of SP, and multiple treatments within 6h of injury did not improve upon outcomes seen following a single treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  13. Numerical modeling of an experimental shock tube for traumatic brain injury studies

    Science.gov (United States)

    Phillips, Michael; Regele, Jonathan D.

    2015-11-01

    Unfortunately, Improvised Explosive Devices (IEDs) are encountered commonly by both civilians and military soldiers throughout the world. Over a decade of medical history suggests that traumatic brain injury (TBI) may result from exposure to the blast waves created by these explosions, even if the person does not experience any immediate injury or lose consciousness. Medical researchers study the exposure of mice and rats to blast waves created in specially designed shock tubes to understand the effect on brain tissue. A newly developed table-top shock tube with a short driver section has been developed for mice experiments to reduce the time necessary to administer the blast radiation and increase the amount of statistical information available. In this study, numerical simulations of this shock tube are performed to assess how the blast wave takes its shape. The pressure profiles obtained from the numerical results are compared with the pressure histories from the experimental pressure transducers. The results show differences in behavior from what was expected, but the blast wave may still be an effective means of studying TBI.

  14. Phonological memory and vocabulary learning in children with focal lesions.

    Science.gov (United States)

    Gupta, Prahlad; MacWhinney, Brian; Feldman, Heidi M; Sacco, Kelley

    2003-11-01

    Eleven children with early focal lesions were compared with 70 age-matched controls to assess their performance in repeating non-words, in learning new words, and in immediate serial recall, a triad of abilities that are believed to share a dependence on serial ordering mechanisms (e.g.,; ). Results for the experimental group were also compared with other assessments previously reported for the same children by. The children with brain injury showed substantial impairment relative to controls in the experimental tasks, in contrast with relatively unimpaired performance on measures of vocabulary and non-verbal intelligence. The relationships between word learning, non-word repetition, and immediate serial recall were similar to those observed in several other populations. These results support previous reports that there are persistent processing impairments following early brain injury, despite developmental plasticity. They also suggest that word learning, non-word repetition, and immediate serial recall may be relatively demanding tasks, and that their relationship is a fundamental aspect of the cognitive system.

  15. Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis.

    Science.gov (United States)

    Tsang, S W; Auyeung, K K W; Bian, Z X; Ko, J K S

    2016-01-01

    Although the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease. Causal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future therapeutic approaches of IBS will be discussed. When signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and consequently contributing to the development of IBS. Interference of the brain-gut axis can be modulated by various psychological and environmental factors. Although there is no existing animal experiment that can represent this complex multifactorial disease, these in vivo models are clinically relevant readouts of gastrointestinal functions being essential to the identification of effective treatments of IBS symptoms as well as their molecular targets. Understanding the brain-gut axis is essential in developing the effective therapy for IBS. Therapies include improvement of GI motor functions, relief of visceral hypersensitivity and pain, attenuation of autonomic dysfunctions and suppression of mucosal immune activation. Target-oriented therapies that provide symptomatic, psychological and physiological benefits could surely help to improve the quality of life of IBS patients.

  16. [The focal renal lesions].

    Science.gov (United States)

    Tuma, Jan

    2013-06-05

    The focal renal lesions are altogether common. Most frequently are found Columna Bertini hypertrophies (so called pseudotumors) and simple renal cysts. The role of sonography in the practice is to distinguish pseudotumors from real renal tumors, and simple renal cysts from complex cysts. The differentiation of complex renal cysts is possible with the help of the CEUS (= contrast enhanced ultrasound) and other imaging modalities such as CT or MRI. In these cases, the CEUS imaging agent has clear advantages over CT and MRI, because it is composed of gas bubbles, which are only slightly smaller than red blood cells and remains exclusively intravascularly while the CT and MRI contrast agents diffuse into the interstitial space without any real perfusion. The real tumors can be differentiated from certain focal non-tumorous changes based on the ultrasound and clinic. The further differentiation of individual kidney tumors and metastases using ultrasound, MRI, CT and CEUS is only partly possible. In all uncertain or unclear cases, therefore, an open or ultrasound-guided biopsy is useful.

  17. Restricted expression of Borna disease virus glycoprotein in brains of experimentally infected Lewis rats.

    Science.gov (United States)

    Werner-Keiss, N; Garten, W; Richt, J A; Porombka, D; Algermissen, D; Herzog, S; Baumgärtner, W; Herden, C

    2008-12-01

    Borna disease virus (BDV) induces a persistent infection in the central nervous system (CNS) accompanied by a non-purulent meningoencephalitis. BDV-infection of Lewis rats provides an important model to investigate basic principles of neurotropism, viral persistence and resulting dysfunctions. To date, the in vivo strategies of BDV to persist in the CNS are not fully understood. Viral glycoproteins are main targets of the antiviral defence implicating a controlled expression in case of persistent infections. Therefore, we analysed the expression profiles of the BDV-glycoprotein (BDV-GP) and corresponding BDV-intron II RNA in experimentally infected rat brains, focusing on their spatio-temporal occurrence, regional, cellular and intracellular locations. This was carried out by immunohistochemistry and in situ hybridization. The expression pattern of the most abundantly expressed BDV-nucleoprotein (BDV-N) served as a reference. BDV-N mRNA was detected preferentially in the cytoplasm of neurones, whereas BDV-intron II mRNA was found predominantly in the nucleus of brain cells. The genomic RNA was restricted to the nucleus. Expression of BDV-GP was significantly lower than BDV-N expression and mainly limited to cerebral cortex, hippocampus, amygdala and thalamus. BDV-GP was restricted to larger neurones; BDV-N occurred also in astrocytes, oligodendrocytes and ependymal cells. The expression profiles of BDV-GP, BDV-N and their mRNAs are significantly different, indicating that BDV-GP expression is regulated in vivo. This might be achieved by restricted nuclear export and/or maturation of BDV-intron II mRNA or limited translation as a viral mechanism to escape from the immune response and enable persistence in the CNS.

  18. Partial (focal) seizure

    Science.gov (United States)

    ... look at the brain and nervous system. An EEG (electroencephalogram) will be done to check the electrical ... ed. Philadelphia, PA: Elsevier Saunders; 2016:chap 403. Review Date 2/27/2016 Updated by: Amit M. ...

  19. Mechanics of blast loading on the head models in the study of traumatic brain injury using experimental and computational approaches.

    Science.gov (United States)

    Ganpule, S; Alai, A; Plougonven, E; Chandra, N

    2013-06-01

    Blast waves generated by improvised explosive devices can cause mild, moderate to severe traumatic brain injury in soldiers and civilians. To understand the interactions of blast waves on the head and brain and to identify the mechanisms of injury, compression-driven air shock tubes are extensively used in laboratory settings to simulate the field conditions. The overall goal of this effort is to understand the mechanics of blast wave-head interactions as the blast wave traverses the head/brain continuum. Toward this goal, surrogate head model is subjected to well-controlled blast wave profile in the shock tube environment, and the results are analyzed using combined experimental and numerical approaches. The validated numerical models are then used to investigate the spatiotemporal distribution of stresses and pressure in the human skull and brain. By detailing the results from a series of careful experiments and numerical simulations, this paper demonstrates that: (1) Geometry of the head governs the flow dynamics around the head which in turn determines the net mechanical load on the head. (2) Biomechanical loading of the brain is governed by direct wave transmission, structural deformations, and wave reflections from tissue-material interfaces. (3) Deformation and stress analysis of the skull and brain show that skull flexure and tissue cavitation are possible mechanisms of blast-induced traumatic brain injury.

  20. The effects of blood pressure and urokinase on brain injuries after experimental cerebral infarction in rats.

    Science.gov (United States)

    Ji, Xunming; Li, Ke; Li, Wenbin; Li, Shuting; Yan, Feng; Gong, Wei; Luo, Yumin

    2009-03-01

    With the proposal of penumbra theory and development of intra-arterial thrombolysis (such as urokinase), the outcome of ischemic cerebrovascular disease is greatly improved. However, the incidence of hemorrhagic transformation (HT) increased concomitantly, and some studies showed a close relationship between blood pressure and HT. The mechanisms of blood pressure and urokinase effect on the incidence of HT are not clear. In this study, we investigated the effects of the different levels of blood pressure and urokinase on the ischemic lesions, the incidence of HT and the expression of matrix metalloproteinase 9 (MMP-9) in the rat ischemia-reperfusion models. Temporary focal ischemia was induced in male Sprague-Dawley rats using the intraluminal vascular occlusion method. The animals were assigned into four groups (n=11 in each group): low blood pressure group (LP), normal blood pressure group (NP), high blood pressure group (HP) and urokinase/high blood pressure group (UKHP). Adnephrin was applied to enhance the mean arterial blood pressure (MABP) at the beginning of reperfusion. MABP was maintained 20 mmHg higher than the baseline for 1 hour. Sodium nitroprusside was used to decrease MABP by 20 mmHg lower than the baseline for 1 hour. Both urokinase and adnephrin were used concomitantly in the UKHP group. Neurological deficit scores were evaluated at 2 hours (R2h) and 24 hours (R24h) after reperfusion. All rats were decapitated, their brains were sliced into 15-mum-thick slices, and the infarct volume and the visible HT were analysed. Three rats in each group were taken for immunohistochemistry and pathological analysis. There was no significant difference in MABP among the groups at the baseline time points (p>0.05), but blood pressure are definitely increased and decreased in the HP, UKHP, and LP groups. Neurological deficit scores showed no significant difference at R2h among the groups (p=0.443). However, neurological deficit scores showed significant

  1. [Expression of c-jun protein after experimental rat brain concussion].

    Science.gov (United States)

    Wang, Feng; Li, Yong-hong

    2010-02-01

    To observe e-jun protein expression after rat brain concussion and explore the forensic pathologic markers following brain concussion. Fifty-five rats were randomly divided into brain concussion group and control group. The expression of c-jun protein was observed by immunohistochemistry. There were weak positive expression of c-jun protein in control group. In brain concussion group, however, some neutrons showed positive expression of c-jun protein at 15 min after brain concussion, and reach to the peak at 3 h after brain concussion. The research results suggest that detection of c-jun protein could be a marker to determine brain concussion and estimate injury time after brain concussion.

  2. Hyperbaric oxygen modalities are differentially effective in distinct brain ischemia models

    Directory of Open Access Journals (Sweden)

    Robert P Ostrowski

    2016-01-01

    Full Text Available The effectiveness and efficacy of hyperbaric oxygen (HBO preconditioning and post-treatment modalities have been demonstrated in experimental models of ischemic cerebrovascular diseases, including global brain ischemia, transient focal and permanent focal cerebral ischemia, and experimental neonatal hypoxia-ischemia encephalopathy. In general, early and repetitive post-treatment of HBO appears to create enhanced protection against brain ischemia whereas delayed HBO treatment after transient focal ischemia may even aggravate brain injury. This review advocates the level of injury reduction upon HBO as an important component for translational evaluation of HBO based treatment modalities. The combined preconditioning and HBO post-treatment that would provide synergistic effects is also worth considering.

  3. Mutations in DEPDC5 cause Familial Focal Epilepsywith Variable Foci and are a common cause of familial non-lesional focal epilepsy

    NARCIS (Netherlands)

    Pandolfo, Massimo; Dibbens, Leanne; De Vries, Boukje; Donatello, Simona; Heron, Sarah; Hodgson, Bree; Chintawar, Satyan; Crompton, Douglas; Hughes, James; Bellows, Susannah; Klein, Karl Martin; Callenbach, Petra; Corbett, Mark; Gardner, Alison; Kivity, Sarah; Iona, Xenia; Regan, Brigid; Weller, Claudia; Crimmins, Denis; O'Brien, Terence; Guerrero-López, Rosa; Mulley, John; Dubeau, Francois; Licchetta, Laura; Bisulli, Francesca; Cossette, Patrick; Thomas, Paul; Gecz, Jozef; Serratosa, Jose; Brouwer, Oebele; Andermann, Frederick; Andermann, Eva; Van Den Maagdenberg, Arn; Berkovic, Samuel; Scheffer, Ingrid

    2013-01-01

    OBJECTIVE: To identify the genetic cause of autosomal dominant Familial Focal Epilepsy with Variable Foci (FFEVF), to investigate the prevalence of mutations in the FFEVF causative gene in familial cases of non-lesional focal epilepsy, to study the expression in the brain and the subcellular

  4. Focal surfaces of hyperbolic cylinders

    Science.gov (United States)

    Georgiev, Georgi Hristov; Pavlov, Milen Dimov

    2017-12-01

    Cylindrical surfaces have many applications in geometric modeling, architecture and other branches of engineering. In this paper, we describe two cylindrical surfaces associated to a given hyperbolic cylinder. The first one is a focal surface which is determined by reciprocal principle curvature of the hyperbolic cylinder. The second one is a generalized focal surface obtained by reciprocal mean curvature of the same hyperbolic cylinder. In particular, we show that each of these surfaces admits three different parametric representations. As consequence, it is proved that the focal and generalized focal surfaces of the hyperbolic cylinder are rational surfaces. An illustrative example is included.

  5. Charging as a Focal Practice

    DEFF Research Database (Denmark)

    Bødker, Mads

    This position paper reflects on Borgmann’s notion of ‘focal things’ and its applicability in the discourse about interaction with technologies in nature. Using the example of a combined cooking burner and thermoelectric 5W smartphone charger (a BioLite cook stove), this position paper gives...... an example of how a mundance “device” turns focal once it is connected to a contextual infrastructure (the ‘wild’), and reflects on the applicability of the notion of focality. The guiding question is how the notion of ‘focal things and practices’ drawn from Borgmann might help us think about the (strained...

  6. Endothelin-1 Mediates Brain Microvascular Dysfunction Leading to Long-Term Cognitive Impairment in a Model of Experimental Cerebral Malaria.

    Directory of Open Access Journals (Sweden)

    Brandi D Freeman

    2016-03-01

    Full Text Available Plasmodium falciparum infection causes a wide spectrum of diseases, including cerebral malaria, a potentially life-threatening encephalopathy. Vasculopathy is thought to contribute to cerebral malaria pathogenesis. The vasoactive compound endothelin-1, a key participant in many inflammatory processes, likely mediates vascular and cognitive dysfunctions in cerebral malaria. We previously demonstrated that C57BL6 mice infected with P. berghei ANKA, our fatal experimental cerebral malaria model, sustained memory loss. Herein, we demonstrate that an endothelin type A receptor (ETA antagonist prevented experimental cerebral malaria-induced neurocognitive impairments and improved survival. ETA antagonism prevented blood-brain barrier disruption and cerebral vasoconstriction during experimental cerebral malaria, and reduced brain endothelial activation, diminishing brain microvascular congestion. Furthermore, exogenous endothelin-1 administration to P. berghei NK65-infected mice, a model generally regarded as a non-cerebral malaria negative control for P. berghei ANKA infection, led to experimental cerebral malaria-like memory deficits. Our data indicate that endothelin-1 is critical in the development of cerebrovascular and cognitive impairments with experimental cerebral malaria. This vasoactive peptide may thus serve as a potential target for adjunctive therapy in the management of cerebral malaria.

  7. Quantitative MRI predicts long-term structural and functional outcome after experimental traumatic brain injury.

    Science.gov (United States)

    Immonen, Riikka J; Kharatishvili, Irina; Gröhn, Heidi; Pitkänen, Asla; Gröhn, Olli H J

    2009-03-01

    In traumatic brain injury (TBI) the initial impact causes both immediate damage and also launches a cascade of slowly progressive secondary damage. The chronic outcome disabilities vary greatly and can occur several years later. The aim of this study was to find predictive factors for the long-term outcome using multiparametric, non-invasive magnetic resonance imaging (MRI) methodology and a clinically relevant rat model of fluid percussion induced TBI. Our results demonstrated that the multiparametric quantitative MRI (T(2), T(1rho), trace of the diffusion tensor D(av), the extent of hyperintense lesion and intracerebral hemorrhage) acquired during acute and sub acute phases 3 h, 3 days, 9 days and 23 days post-injury has potential to predict the functional and histopathological outcome 6 to 12 months later. The acute D(av) changes in the ipsilateral hippocampus correlated with the chronic spatial learning and memory impairment evaluated using the Morris water maze (phelp to predict the long-term outcome after experimental TBI.

  8. Experimental Cerebral Malaria Pathogenesis—Hemodynamics at the Blood Brain Barrier

    Science.gov (United States)

    Nacer, Adéla; Movila, Alexandru; Sohet, Fabien; Girgis, Natasha M.; Gundra, Uma Mahesh; Loke, P'ng; Daneman, Richard; Frevert, Ute

    2014-01-01

    Cerebral malaria claims the lives of over 600,000 African children every year. To better understand the pathogenesis of this devastating disease, we compared the cellular dynamics in the cortical microvasculature between two infection models, Plasmodium berghei ANKA (PbA) infected CBA/CaJ mice, which develop experimental cerebral malaria (ECM), and P. yoelii 17XL (PyXL) infected mice, which succumb to malarial hyperparasitemia without neurological impairment. Using a combination of intravital imaging and flow cytometry, we show that significantly more CD8+ T cells, neutrophils, and macrophages are recruited to postcapillary venules during ECM compared to hyperparasitemia. ECM correlated with ICAM-1 upregulation on macrophages, while vascular endothelia upregulated ICAM-1 during ECM and hyperparasitemia. The arrest of large numbers of leukocytes in postcapillary and larger venules caused microrheological alterations that significantly restricted the venous blood flow. Treatment with FTY720, which inhibits vascular leakage, neurological signs, and death from ECM, prevented the recruitment of a subpopulation of CD45hi CD8+ T cells, ICAM-1+ macrophages, and neutrophils to postcapillary venules. FTY720 had no effect on the ECM-associated expression of the pattern recognition receptor CD14 in postcapillary venules suggesting that endothelial activation is insufficient to cause vascular pathology. Expression of the endothelial tight junction proteins claudin-5, occludin, and ZO-1 in the cerebral cortex and cerebellum of PbA-infected mice with ECM was unaltered compared to FTY720-treated PbA-infected mice or PyXL-infected mice with hyperparasitemia. Thus, blood brain barrier opening does not involve endothelial injury and is likely reversible, consistent with the rapid recovery of many patients with CM. We conclude that the ECM-associated recruitment of large numbers of activated leukocytes, in particular CD8+ T cells and ICAM+ macrophages, causes a severe restriction in

  9. Focused ultrasound delivery of Raman nanoparticles across the blood-brain barrier: Potential for targeting experimental brain tumors

    Science.gov (United States)

    Diaz, Roberto Jose; McVeigh, Patrick Z.; O’Reilly, Meaghan A.; Burrell, Kelly; Bebenek, Matthew; Smith, Christian; Etame, Arnold; Zadeh, Gelareh; Hynynen, Kullervo; Wilson, Brian C.; Rutka, James T.

    2014-01-01

    Spectral mapping of nanoparticles with surface enhanced Raman scattering (SERS) capability in the near-infrared range is an emerging molecular imaging technique. We used magnetic resonance image-guided transcranial focused ultrasound (TcMRgFUS) to reversibly disrupt the blood-brain barrier (BBB) adjacent to brain tumor margins in rats. Glioma cells were found to internalize SERS capable nanoparticles of 50 nm or 120 nm physical diameter. Surface coating with anti-epidermal growth factor receptor antibody or non-specific human immunoglobulin G, resulted in enhanced cell uptake of nanoparticles in-vitro compared to nanoparticles with methyl terminated 12-unit polyethylene glycol surface. BBB disruption permitted the delivery of SERS capable spherical 50 or 120 nm gold nanoparticles to the tumor margins. Thus, nanoparticles with SERS imaging capability can be delivered across the BBB non-invasively using TcMRgFUS and have the potential to be used as optical tracking agents at the invasive front of malignant brain tumors. PMID:24374363

  10. Focal midbrain tumors in children

    NARCIS (Netherlands)

    Vandertop, W. P.; Hoffman, H. J.; Drake, J. M.; Humphreys, R. P.; Rutka, J. T.; Amstrong, D. C.; Becker, L. E.

    1992-01-01

    The clinical and neuroradiological features of focal midbrain tumors in 12 children are described, and the results of their surgical management are presented. Patients with a focal midbrain tumor usually exhibit either symptoms and signs of raised intracranial pressure caused by an obstructive

  11. Mosaic Focal Plane Development

    Science.gov (United States)

    Mason, D.; Horner, S.; Aamodt, E.

    Advances in manufacturing and applied sciences have enabled the development of large ground and spaced based astronomical instruments having a Field of View (FOV) large enough to capture a large portion of the universe in a single image. A large FOV can be accomplished using light weighted optics, improved structures, and the development of mosaic Focal Plane Assemblies (mFPAs). A mFPA comprises multiple Charged Coupled Devices (CCD) mounted onto a single baseplate integrated at the focus plane of the instrument. Examples of current, or proposed, missions utilizing mFPA technology include FAME, GEST, Kepler, GAIA, LSST, and SNAP. The development of a mFPA mandates tight control on the design trades of component development, CCD definition and characterization, component integration, and performance verification testing. This paper addresses the results of the Lockheed Martin Space Systems Company (LMSSC), Advanced Technology Center (ATC) developed mFPA. The design trades and performance characterization are services provided by the LMSSC ATC but not detailed in this paper.

  12. Prostaglandin E2 Indicates Therapeutic Efficacy of Mesenchymal Stem Cells in Experimental Traumatic Brain Injury.

    Science.gov (United States)

    Kota, Daniel J; Prabhakara, Karthik S; Toledano-Furman, Naama; Bhattarai, Deepa; Chen, Qingzheng; DiCarlo, Bryan; Smith, Philippa; Triolo, Fabio; Wenzel, Pamela L; Cox, Charles S; Olson, Scott D

    2017-05-01

    Traumatic brain injury (TBI) is soon predicted to become the third leading cause of death and disability worldwide. After the primary injury, a complex set of secondary injuries develops hours and days later with prolonged neuroinflammation playing a key role. TBI and other inflammatory conditions are currently being treated in preclinical and clinical trials by a number of cellular therapies. Mesenchymal stem cells (MSC) are of great interest due to their widespread usage, safety, and relative ease to isolate and culture. However, there has been a wide range in efficacy reported using MSC clinically and in preclinical models, likely due to differences in cell preparations and a significant amount of donor variability. In this study, we seek to find a correlation between in vitro activity and in vivo efficacy. We designed assays to explore the responsiveness of MSC to immunological cues to address the immunomodulatory properties of MSC, one of their primary modes of therapeutic activity in TBI. Our results showed intrinsic differences in the immunomodulatory capacity of MSC preparations from different bone marrow and amniotic fluid donors. This difference mirrored the therapeutic capacity of the MSC in an experimental model of TBI, an effect confirmed using siRNA knockdown of COX2 followed by overexpressing COX2. Among the immunomodulatory factors assessed, the therapeutic benefit correlated with the secretion of prostaglandin E2 (PGE2 ) by MSC prior to treatment, suggesting that measurement of PGE2 could be a very useful potency marker to create an index of predicted efficacy for preparations of MSC to treat TBI. Stem Cells 2017;35:1416-1430. © 2017 AlphaMed Press.

  13. Effect of Pregabalin in Preventing Secondary Damage in Traumatic Brain Injury: An Experimental Study

    Science.gov (United States)

    Calikoglu, Cagatay; Aytekin, Hikmet; Akgül, Osman; Akgül, Mehmet Hüseyin; Gezen, Ahmet Ferruh; Akyuz, Feyzullah; Cakir, Murteza

    2015-01-01

    Background In this study we aimed to explore the effects of pregabalin on a traumatic brain injury model in rats. Material/Methods This study included 40 adult male Sprague-Dawley rats randomized into 4 groups, each of which contained equal numbers of animals. The control group had no head trauma and thus was not treated. The trauma group had head trauma but was not treated. The pregabalin group had no head trauma but was treated by pregabalin. The trauma + pregabalin group had head trauma treated with pregabalin. The biopsy samples taken from the study animals were histopathologically examined for the presence of edema, inflammation, and neuronal damage. Results All animals in the trauma group had edema, inflammation, and neuronal damage. Four subjects in the control group, 6 in the pregabalin group, and 4 in the trauma + pregabalin group had edema; inflammation was present in 1 subject in the control group, 3 subjects in the pregabalin group, and 3 subjects in the trauma + pregabalin group; neuronal damage existed in 1 subject in the control group, 1 subject in the pregabalin group, and 6 subjects in the trauma + pregabalin group. The trauma group had significantly higher edema and neuronal damage scores than the other groups. Similarly, inflammation was significantly more prevalent in the trauma group than the control and trauma + pregabalin groups. Conclusions The results of the present study indicated anti-edema, anti-inflammatory, and neuroprotective effects of pregabalin in an experimental head trauma model in rats. Pregabalin may thus be beneficial in humans with acute TBI by relieving concomitant edema and inflammation. PMID:25785578

  14. Effects of the Rabdosia rubescens total flavonoids on focal cerebral ischemia reperfusion model in rats.

    Science.gov (United States)

    Miao, Mingsan; Yan, Xiaoli; Guo, Lin; Shao, Shuai

    2017-05-01

    The effect of the Rabdosia rubescens total flavonoids on focal cerebral ischemia reperfusion model in rats was observed. The model group, nimodipine group, cerebral collateral group, and large, medium and small dose group of the Rabdosia rubescens total flavonoids were administered with corresponding drugs but sham operation group and model group were administered the same volume of 0.5%CMC, 1 times a day, continuous administration of 7 d. After 1 h at 7 d to medicine, left incision in the middle of the neck of rats after anesthesia, we can firstly expose and isolate the left common carotid artery (CCA), and then expose external carotid artery (ECA) and internal carotid artery (ICA). The common carotid artery and the external carotid artery are ligated. Then internal carotid artery with arterial clamp is temporarily clipped. Besides, cut the incision of 0.2 mm from 5 cm of the bifurcation of the common carotid artery. A thread Line bolt is inserted with more than 18-20 mm from bifurcation of CCA into the internal carotid artery until there is resistance. Then the entrance of the middle cerebral artery is blocked and internal carotid artery is ligated (the blank group only exposed the left blood vessel without Plugging wire). Finally it is gently pulled out the plug line after 2 h. Results : Compared with the model mice, Rabdosia rubescens total flavonoids can significantly relieve the injury of brain in hippocampus and cortex nerve cells; experimental rat focal cerebral ischemia was to improve again perfusion model of nerve function defect score mortality; significantly reduce brain homogenate NOS activity and no content, MDA, IL-1, TNF-a, ICAM-1 content; increase in brain homogenate SOD and ATPase activity ( P  group of the Rabdosia rubescens total flavonoids has a better Improvement effect on focal cerebral ischemia reperfusion model in rats.

  15. Pathogenesis, Experimental Models and Contemporary Pharmacotherapy of Irritable Bowel Syndrome: Story About the Brain-Gut Axis

    Science.gov (United States)

    Tsang, S.W.; Auyeung, K.K.W.; Bian, Z.X.; Ko, J.K.S.

    2016-01-01

    Background Although the precise pathophysiology of irritable bowel syndrome (IBS) remains unknown, it is generally considered to be a disorder of the brain-gut axis, representing the disruption of communication between the brain and the digestive system. The present review describes advances in understanding the pathophysiology and experimental approaches in studying IBS, as well as providing an update of the therapies targeting brain-gut axis in the treatment of the disease. Methods Causal factors of IBS are reviewed. Following this, the preclinical experimental models of IBS will be introduced. Besides, both current and future therapeutic approaches of IBS will be discussed. Results When signal of the brain-gut axis becomes misinterpreted, it may lead to dysregulation of both central and enteric nervous systems, altered intestinal motility, increased visceral sensitivity and consequently contributing to the development of IBS. Interference of the brain-gut axis can be modulated by various psychological and environmental factors. Although there is no existing animal experiment that can represent this complex multifactorial disease, these in vivo models are clinically relevant readouts of gastrointestinal functions being essential to the identification of effective treatments of IBS symptoms as well as their molecular targets. Understanding the brain-gut axis is essential in developing the effective therapy for IBS. Therapies include improvement of GI motor functions, relief of visceral hypersensitivity and pain, attenuation of autonomic dysfunctions and suppression of mucosal immune activation. Conclusion Target-oriented therapies that provide symptomatic, psychological and physiological benefits could surely help to improve the quality of life of IBS patients. PMID:27009115

  16. The sigma-1 receptor enhances brain plasticity and functional recovery after experimental stroke

    DEFF Research Database (Denmark)

    Ruscher, Karsten; Shamloo, Mehrdad; Rickhag, Karl Mattias

    2011-01-01

    Stroke leads to brain damage with subsequent slow and incomplete recovery of lost brain functions. Enriched housing of stroke-injured rats provides multi-modal sensorimotor stimulation, which improves recovery, although the specific mechanisms involved have not been identified. In rats housed in ...

  17. Starbugs: focal plane fiber positioning technology

    Science.gov (United States)

    Goodwin, Michael; Heijmans, Jeroen; Saunders, Ian; Brzeski, Jurek; Saunders, Will; Muller, Rolf; Haynes, Roger; Gilbert, James

    2010-07-01

    We report on the technological achievements of our latest Starbug prototypes and their implications for smart focal plane fiber positioning applications for wide-field astronomy. The Starbugs are innovative self-motile miniature robotic devices that can simultaneously and independently position fibers or payloads over a field plate located at the telescope's focal plane. The Starbugs concept overcomes many of the limitations associated with the traditional 'pick and place' positioners where a robot places fixed buttons onto the field plate. The new Starbug prototypes use piezoelectric actuators and have the following features: (i) new 'lift-and-step' method (discrete step) for accurate positioning over different surfaces; and (ii) operate in an inverted hanging position underneath a transparent field plate, removing the need for fibercable retractors. In this paper, we present aspects of the Starbug prototypes, including the theoretical model, mechanical design, experimental setup, algorithms, performance and applications for astronomical instrumentation.

  18. White matter integrity and cerebral network topology in focal epilepsy

    NARCIS (Netherlands)

    Otte, W.M.

    2012-01-01

    Worldwide more than fifty million people suffer from recurrent spontaneous seizures. Seizures are considered to be harmful to the brain and may have adverse long-term behavioral and cognitive consequences in particular in people with focal epilepsies that do not respond to pharmacotherapy.

  19. Minocycline up-regulates the expression of brain-derived neurotrophic factor and nerve growth factor in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Chen, Xiaohong; Ma, Lili; Jiang, Ying; Chen, Shaoqiong; Zhu, Cansheng; Liu, Mei; Ma, Xiaomeng; Zhu, Dongliang; Liu, Yingying; Peng, Fuhua; Wang, Qing; Pi, Rongbiao

    2012-07-05

    Previous evidence demonstrated that minocycline could ameliorate clinical severity of experimental autoimmune encephalomyelitis and exhibit several anti-inflammatory and neuroprotective activities. However, few studies have been carried out to assess its effects on the expression of neurotrophins in experimental autoimmune encephalomyelitis or multiple sclerosis. Here we investigated the alteration of brain-derived neurotrophic factor and nerve growth factor in the sera, cerebral cortex, and lumbar spinal cord of experimental autoimmune encephalomyelitis C57 BL/6 mice in vivo as well as the splenocytes culture supernatants in vitro after minocycline administration. Our results demonstrated that minocycline could up-regulate the expression of brain-derived neurotrophic factor and nerve growth factor both in peripheral (sera and splenocytes culture supernatants) and target organs (cerebral cortex and lumber spinal cord) of mice with experimental autoimmune encephalomyelitis. These data suggest that up-regulation of neurotrophins in experimental autoimmune encephalomyelitis may be a novel neuroprotective mechanism of minocycline. Copyright © 2012 Elsevier B.V. All rights reserved.

  20. Focal encephalitis with enterovirus infections.

    Science.gov (United States)

    Modlin, J F; Dagan, R; Berlin, L E; Virshup, D M; Yolken, R H; Menegus, M

    1991-10-01

    We report on four pediatric patients with Enterovirus infections who were admitted to the hospital with signs or symptoms of acute, focal encephalitis. All four experienced focal seizures. Each had a cerebrospinal fluid pleocytosis at the initial lumbar puncture. In all four patients the diagnosis of herpes simplex encephalitis was entertained. Each child improved spontaneously within a few days of admission to the hospital, and only one had residual neurologic abnormalities at the time of discharge. A brief review of these cases, and three additional cases from the literature, indicate that the enteroviruses, particularly the group A Coxsackieviruses, are rare causes of acute focal encephalitis in children and adolescents.

  1. SPECT in Focal Epilepsies

    Directory of Open Access Journals (Sweden)

    Roderick Duncan

    2000-01-01

    Full Text Available Brain perfusion changes during seizures were first observed in the 1930s. Single Photon Emission Computed Tomography (SPECT was developed in the 1970s, and tracers suitable for the imaging of regional cerebral perfusion (rCP became available in the 1980s. The method was first used to study rCP in the interictal phase, and this showed areas of low perfusion in a proportion of cases, mainly in patients with temporal lobe epilepsies. However, the trapping paradigm of tracers such as hexamethyl propyleneamine oxime (HMPAO provided a practicable method of studying changes in rCP during seizures, and a literature was established in the late 1980s and early 1990s showing a typical sequence of changes during and after seizures of mesial temporal lobe origin; the ictal phase was associated with large increases in perfusion throughout the temporal lobe, with first the lateral, then the mesial temporal lobe becoming hypoperfused in the postictal phase. Activation and inhibition of other structures, such as the basal ganglia and frontal cortex, were also seen. Studies of seizures originating elsewhere in the brain have shown a variety of patterns of change, according to the structures involved. These changes have been used practically to aid the process of localisation of the epileptogenic zone so that epilepsy surgery can be planned.

  2. The computed cranial focal point

    NARCIS (Netherlands)

    Jong, G.A. de; Maal, T.J.J.; Delye, H.

    2015-01-01

    INTRODUCTION: Stereophotogrammetry is a radiation-free method for monitoring skull development after craniosynostosis repair. Lack of clear fixed reference points complicate longitudinal comparison of 3D photographs. Therefore we developed the 'computed cranial focal point' (CCFP). METHODS: The CCFP

  3. Effect of Coenzyme Q10 on ischemia and neuronal damage in an experimental traumatic brain-injury model in rats

    Directory of Open Access Journals (Sweden)

    Hanci Volkan

    2011-07-01

    Full Text Available Abstract Background Head trauma is one of the most important clinical issues that not only can be fatal and disabling, requiring long-term treatment and care, but also can cause heavy financial burden. Formation or distribution of free oxygen radicals should be decreased to enable fixing of poor neurological outcomes and to prevent neuronal damage secondary to ischemia after trauma. Coenzyme Q10 (CoQ10, a component of the mitochondrial electron transport chain, is a strong antioxidant that plays a role in membrane stabilization. In this study, the role of CoQ10 in the treatment of head trauma is researched by analyzing the histopathological and biochemical effects of CoQ10 administered after experimental traumatic brain injury in rats. A traumatic brain-injury model was created in all rats. Trauma was inflicted on rats by the free fall of an object of 450 g weight from a height of 70 cm on the frontoparietal midline onto a metal disc fixed between the coronal and the lambdoid sutures after a midline incision was carried out. Results In the biochemical tests, tissue malondialdehyde (MDA levels were significantly higher in the traumatic brain-injury group compared to the sham group (p 10 after trauma was shown to be protective because it significantly lowered the increased MDA levels (p 10 group had SOD levels ranging between those of sham group and traumatic brain-injury group, and no statistically significant increase was detected. Histopathological results showed a statistically significant difference between the CoQ10 and the other trauma-subjected groups with reference to vascular congestion, neuronal loss, nuclear pyknosis, nuclear hyperchromasia, cytoplasmic eosinophilia, and axonal edema (p Conclusion Neuronal degenerative findings and the secondary brain damage and ischemia caused by oxidative stress are decreased by CoQ10 use in rats with traumatic brain injury.

  4. Focal Conic Flower Textures at Curved Interfaces

    Directory of Open Access Journals (Sweden)

    Daniel A. Beller

    2013-12-01

    Full Text Available Focal conic domains (FCDs in smectic-A liquid crystals have drawn much attention, both for their exquisitely structured internal form and for their ability to direct the assembly of micromaterials and nanomaterials in a variety of patterns. A key to directing FCD assembly is control over the eccentricity of the domain. Here, we demonstrate a new paradigm for creating spatially varying FCD eccentricity by confining a hybrid-aligned smectic with curved interfaces. In particular, we manipulate interface behavior with colloidal particles in order to experimentally produce two examples of what has recently been dubbed the flower texture [C. Meyer et al., Focal Conic Stacking in Smectic A Liquid Crystals: Smectic Flower and Apollonius Tiling, Materials 2, 499, 2009MATEG91996-194410.3390/ma2020499], where the focal hyperbolæ diverge radially outward from the center of the texture, rather than inward as in the canonical éventail or fan texture. We explain how this unconventional assembly can arise from appropriately curved interfaces. Finally, we present a model for this system that applies the law of corresponding cones, showing how FCDs may be embedded smoothly within a “background texture” of large FCDs and concentric spherical layers, in a manner consistent with the qualitative features of the smectic flower. Such understanding could potentially lead to disruptive liquid-crystal technologies beyond displays, including patterning, smart surfaces, microlens arrays, sensors, and nanomanufacturing.

  5. [Histopathological and autoradiographical studies of experimental brain tumors after continuous local chemotherapy--acute stage in rat models].

    Science.gov (United States)

    Shimura, T; Teramoto, A; Aihara, K

    1997-04-01

    Continuous local chemotherapy has been evaluated as being an effective administration method and as a possible adjuvant therapy in the sensitivity aspect of the cell cycle for malignant glioma. However, neurotoxicity of anti-cancer agents in the normal brain and non-effective methods for the deeper part of the tumor seem to be the most serious problems. This study was initiated to evaluate histological findings, the uptake distribution, and neurotoxicity of the continuous local administration of isotope labeled anti-cancer agents in the brain tumor of rats. The experimental brain tumor of rats and the method of continuous local chemotherapy were as follows. The tumor was produced by intracerebral inoculation of cultured cells derived from rat brain tumor induced by Rous sarcoma virus (Kumanishi et al. strain). One week later Fluorouracil (5-6-3H) (17.7 Ci/m mol) and methotrexate (L-glutamyl 3-4-3H) (41.0 Ci/m mol) were administered into the brain tumors of rats utilizing a mini osmotic pump (Alzet Model 2001), respectively. We used five rats of various groups. The rats were sacrificed at various time intervals (6 hrs, 12 hrs, 24 hrs, 48 hrs, 72 hrs and 7 days). The tumor tissues for light microscopic autoradiography were fixed in 10% formalin for 24 hours. Sections for the light microscopic autoradiography were cut at 4 mu thick and coated with Sakura NR-M2 drips. Following exposure for one week at 4 degrees C, the sections were stained with Konidol X. Six hours after administration, slight radioactivity was distributed in the subarachnoid space and subpial brain tissue in the vicinity of the inserted tube. Twenty-four hours after administration, high radioactivity was clearly present in many tumor cells and phagocytes at the tube tip, but no radioactivity was observed in the deeper part of the tumor or normal brain tissue. In the vicinity of necrosis foci, acute toxic inflammation was also observed. In conclusion, this experimental study shows that these anti

  6. The effect of electromagnetic radiation on the rat brain: an experimental study.

    Science.gov (United States)

    Eser, Olcay; Songur, Ahmet; Aktas, Cevat; Karavelioglu, Ergun; Caglar, Veli; Aylak, Firdevs; Ozguner, Fehmi; Kanter, Mehmet

    2013-01-01

    The aim of this study is to determine the structural changes of electromagnetic waves in the frontal cortex, brain stem and cerebellum. 24 Wistar Albino adult male rats were randomly divided into four groups: group I consisted of control rats, and groups II-IV comprised electromagnetically irradiated (EMR) with 900, 1800 and 2450 MHz. The heads of the rats were exposed to 900, 1800 and 2450 MHz microwaves irradiation for 1h per day for 2 months. While the histopathological changes in the frontal cortex and brain stem were normal in the control group, there were severe degenerative changes, shrunken cytoplasm and extensively dark pyknotic nuclei in the EMR groups. Biochemical analysis demonstrated that the Total Antioxidative Capacity level was significantly decreased in the EMR groups and also Total Oxidative Capacity and Oxidative Stress Index levels were significantly increased in the frontal cortex, brain stem and cerebellum. IL-1β level was significantly increased in the EMR groups in the brain stem. EMR causes to structural changes in the frontal cortex, brain stem and cerebellum and impair the oxidative stress and inflammatory cytokine system. This deterioration can cause to disease including loss of these areas function and cancer development.

  7. ALTERATIONS IN BRAIN CREATINE CONCENTRATIONS UNDER LONG-TERM SOCIAL ISOLATION (EXPERIMENTAL STUDY).

    Science.gov (United States)

    Koshoridze, N; Kuchukashvili, Z; Menabde, K; Lekiashvili, Sh; Koshoridze, M

    2016-02-01

    Stress represents one of the main problems of modern humanity. This study was done for understanding more clearly alterations in creatine content of the brain under psycho-emotional stress induced by long-term social isolation. It was shown that under 30 days social isolation creatine amount in the brain was arisen, while decreasing concentrations of synthesizing enzymes (AGAT, GAMT) and creatine transporter protein (CrT). Another important point was that such changes were accompanied by down-regulation of creatine kinase (CK), therefore the enzyme's concentration was lowered. In addition, it was observed that content of phosphocreatine (PCr) and ATP were also reduced, thus indicating down-regulation of energy metabolism of brain that is really a crucial point for its normal functioning. To sum up the results it can be underlined that long-term social isolation has negative influence on energy metabolism of brain; and as a result reduce ATP content, while increase of free creatine concentration, supposedly maintaining maximal balance for ATP amount, but here must be also noted that up-regulated oxidative pathways might have impact on blood brain barrier, resulting on its permeability.

  8. The self-regulating brain and neurofeedback: Experimental science and clinical promise.

    Science.gov (United States)

    Thibault, Robert T; Lifshitz, Michael; Raz, Amir

    2016-01-01

    Neurofeedback, one of the primary examples of self-regulation, designates a collection of techniques that train the brain and help to improve its function. Since coming on the scene in the 1960s, electroencephalography-neurofeedback has become a treatment vehicle for a host of mental disorders; however, its clinical effectiveness remains controversial. Modern imaging technologies of the living human brain (e.g., real-time functional magnetic resonance imaging) and increasingly rigorous research protocols that utilize such methodologies begin to shed light on the underlying mechanisms that may facilitate more effective clinical applications. In this paper we focus on recent technological advances in the field of human brain imaging and discuss how these modern methods may influence the field of neurofeedback. Toward this end, we outline the state of the evidence and sketch out future directions to further explore the potential merits of this contentious therapeutic prospect. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Impact of Laser Irradiation on Brain Resistance to Postresuscitative Emotional Stresses (Experimental Study

    Directory of Open Access Journals (Sweden)

    V. V. Moroz

    2009-01-01

    Full Text Available The paper shows how to solve the urgent problem of posthypoxic rat brain resistance to emotional stress. An hour hypovolemic hypotension (mean blood pressure 45 mm Hg served as a model of a terminal condition. The integra-tive activity of the rat brain was evaluated by the elevated cross labyrinth test. Emotional stress was induced by confrontation between the falsely operated and antihypertensive rats within 30 postischemic days. Laser irradiation was carried out an hour after blood reinfusion. Laser irradiation used before emotional stress was shown to increase the resistance of the posthypoxic rat brain to emotional stress and to prevent the development of depression-like states in the late periods after resuscitation. Key words: blood loss, postresuscitative period, emotional stress, laser irradiation.

  10. Experimental evaluation of freezing preparation for the macroscopic inspection in putrefied brain.

    Science.gov (United States)

    Hyodoh, Hideki; Matoba, Kotaro; Murakami, Manabu; Matoba, Tomoko; Saito, Atsuko; Feng, Fei; Jin, Shigeki

    2017-01-01

    To evaluate the usefulness of freezing preparation for macroscopic investigation in advanced putrefied brain. After sealing in individual plastic bags, 10 pig heads were stored at 20°C for 5days allow postmortem change (putrefaction) to progress. After an observation period, they were divided into 2 groups to evaluate the usefulness of the freezing effect in macroscopic investigation. The process over the postmortem period and the freezing process were examined. At day-5, the presence of air density was detected between the inner surface of the cranium and the brain parenchyma. Intra-cranial air accumulation presented on CT in all heads. In the control group, the brain parenchyma leaked out from the hole in the meninges, and the gray-white matter difference was clear in 3/72 (4.2%), moderate in 7/72 (9.7%), ambiguous in 17/72 (23.6%), and poor in 45/72 (62.5%). In the freezing group, the brain parenchyma presented homogeneous low density after more than 14h freezing. On opening the cranium, the entire brains were frozen, and the gray-white matter difference was clear in 33/72 (46.0%), moderate in 17/72 (24.0%), ambiguous in 15/72 (21.0%), and poor in 7/72 (10.0%). The freezing group afforded greater clarity in the gray-white matter inspection (pFreezing preparation was useful for the macroscopic investigation of putrefied brain compared with the ordinary autopsy. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  11. In vitro large-scale experimental and theoretical studies for the realization of bi-directional brain-prostheses

    Directory of Open Access Journals (Sweden)

    Paolo eBonifazi

    2013-03-01

    Full Text Available Brain-machine interfaces (BMI were born to control ‘actions from thoughts’ in order to recover motor capability of patients with impaired functional connectivity between the central and peripheral nervous system. The final goal of our studies is the development of a new proof-of-concept BMI - a neuromorphic chip for brain repair - to reproduce the functional organization of a damaged part of the central nervous system. To reach this ambitious goal, we implemented a multidisciplinary ‘bottom-up’ approach in which in vitro networks are the paradigm for the development of an in silico model to be incorporated into a neuromorphic device. In this paper we present the overall strategy and focus on the different building blocks of our studies: (i the experimental characterization and modeling of ‘finite size networks’ which represent the smallest and most general self-organized circuits capable of generating spontaneous collective dynamics; (ii the induction of lesions in neuronal networks and the whole brain preparation with special attention on the impact on the functional organization of the circuits; (iii the first production of a neuromorphic chip able to implement a real-time model of neuronal networks. A dynamical characterization of the finite size circuits with single cell resolution is provided. A neural network model based on Izhikevich neurons was able to replicate the experimental observations. Changes in the dynamics of the neuronal circuits induced by optical and ischemic lesions are presented respectively for in vitro neuronal networks and for a whole brain preparation. Finally the implementation of a neuromorphic chip reproducing the network dynamics in quasi-real time (10 ns precision is presented.

  12. In vitro large-scale experimental and theoretical studies for the realization of bi-directional brain-prostheses

    Science.gov (United States)

    Bonifazi, Paolo; Difato, Francesco; Massobrio, Paolo; Breschi, Gian L.; Pasquale, Valentina; Levi, Timothée; Goldin, Miri; Bornat, Yannick; Tedesco, Mariateresa; Bisio, Marta; Kanner, Sivan; Galron, Ronit; Tessadori, Jacopo; Taverna, Stefano; Chiappalone, Michela

    2013-01-01

    Brain-machine interfaces (BMI) were born to control “actions from thoughts” in order to recover motor capability of patients with impaired functional connectivity between the central and peripheral nervous system. The final goal of our studies is the development of a new proof-of-concept BMI—a neuromorphic chip for brain repair—to reproduce the functional organization of a damaged part of the central nervous system. To reach this ambitious goal, we implemented a multidisciplinary “bottom-up” approach in which in vitro networks are the paradigm for the development of an in silico model to be incorporated into a neuromorphic device. In this paper we present the overall strategy and focus on the different building blocks of our studies: (i) the experimental characterization and modeling of “finite size networks” which represent the smallest and most general self-organized circuits capable of generating spontaneous collective dynamics; (ii) the induction of lesions in neuronal networks and the whole brain preparation with special attention on the impact on the functional organization of the circuits; (iii) the first production of a neuromorphic chip able to implement a real-time model of neuronal networks. A dynamical characterization of the finite size circuits with single cell resolution is provided. A neural network model based on Izhikevich neurons was able to replicate the experimental observations. Changes in the dynamics of the neuronal circuits induced by optical and ischemic lesions are presented respectively for in vitro neuronal networks and for a whole brain preparation. Finally the implementation of a neuromorphic chip reproducing the network dynamics in quasi-real time (10 ns precision) is presented. PMID:23503997

  13. In vitro large-scale experimental and theoretical studies for the realization of bi-directional brain-prostheses.

    Science.gov (United States)

    Bonifazi, Paolo; Difato, Francesco; Massobrio, Paolo; Breschi, Gian L; Pasquale, Valentina; Levi, Timothée; Goldin, Miri; Bornat, Yannick; Tedesco, Mariateresa; Bisio, Marta; Kanner, Sivan; Galron, Ronit; Tessadori, Jacopo; Taverna, Stefano; Chiappalone, Michela

    2013-01-01

    Brain-machine interfaces (BMI) were born to control "actions from thoughts" in order to recover motor capability of patients with impaired functional connectivity between the central and peripheral nervous system. The final goal of our studies is the development of a new proof-of-concept BMI-a neuromorphic chip for brain repair-to reproduce the functional organization of a damaged part of the central nervous system. To reach this ambitious goal, we implemented a multidisciplinary "bottom-up" approach in which in vitro networks are the paradigm for the development of an in silico model to be incorporated into a neuromorphic device. In this paper we present the overall strategy and focus on the different building blocks of our studies: (i) the experimental characterization and modeling of "finite size networks" which represent the smallest and most general self-organized circuits capable of generating spontaneous collective dynamics; (ii) the induction of lesions in neuronal networks and the whole brain preparation with special attention on the impact on the functional organization of the circuits; (iii) the first production of a neuromorphic chip able to implement a real-time model of neuronal networks. A dynamical characterization of the finite size circuits with single cell resolution is provided. A neural network model based on Izhikevich neurons was able to replicate the experimental observations. Changes in the dynamics of the neuronal circuits induced by optical and ischemic lesions are presented respectively for in vitro neuronal networks and for a whole brain preparation. Finally the implementation of a neuromorphic chip reproducing the network dynamics in quasi-real time (10 ns precision) is presented.

  14. Rod microglia: elongation, alignment, and coupling to form trains across the somatosensory cortex after experimental diffuse brain injury

    Directory of Open Access Journals (Sweden)

    Ziebell Jenna M

    2012-10-01

    Full Text Available Abstract Background Since their discovery, the morphology of microglia has been interpreted to mirror their function, with ramified microglia constantly surveying the micro-environment and rapidly activating when changes occur. In 1899, Franz Nissl discovered what we now recognize as a distinct microglial activation state, microglial rod cells (Stäbchenzellen, which he observed adjacent to neurons. These rod-shaped microglia are typically found in human autopsy cases of paralysis of the insane, a disease of the pre-penicillin era, and best known today from HIV-1-infected brains. Microglial rod cells have been implicated in cortical ‘synaptic stripping’ but their exact role has remained unclear. This is due at least in part to a scarcity of experimental models. Now we have noted these rod microglia after experimental diffuse brain injury in brain regions that have an associated sensory sensitivity. Here, we describe the time course, location, and surrounding architecture associated with rod microglia following experimental diffuse traumatic brain injury (TBI. Methods Rats were subjected to a moderate midline fluid percussion injury (mFPI, which resulted in transient suppression of their righting reflex (6 to 10 min. Multiple immunohistochemistry protocols targeting microglia with Iba1 and other known microglia markers were undertaken to identify the morphological activation of microglia. Additionally, labeling with Iba1 and cell markers for neurons and astrocytes identified the architecture that surrounds these rod cells. Results We identified an abundance of Iba1-positive microglia with rod morphology in the primary sensory barrel fields (S1BF. Although present for at least 4 weeks post mFPI, they developed over the first week, peaking at 7 days post-injury. In the absence of contusion, Iba1-positive microglia appear to elongate with their processes extending from the apical and basal ends. These cells then abut one another and lay adjacent

  15. Experimental modelling of the consequences of brief late gestation asphyxia on newborn lamb behaviour and brain structure.

    Directory of Open Access Journals (Sweden)

    Margie Castillo-Melendez

    Full Text Available Brief but severe asphyxia in late gestation or at the time of birth may lead to neonatal hypoxic ischemic encephalopathy and is associated with long-term neurodevelopmental impairment. We undertook this study to examine the consequences of transient in utero asphyxia in late gestation fetal sheep, on the newborn lamb after birth. Surgery was undertaken at 125 days gestation for implantation of fetal catheters and placement of a silastic cuff around the umbilical cord. At 132 days gestation (0.89 term, the cuff was inflated to induce umbilical cord occlusion (UCO, or sham (control. Fetal arterial blood samples were collected for assessment of fetal wellbeing and the pregnancy continued until birth. At birth, behavioral milestones for newborn lambs were recorded over 24 h, after which the lambs were euthanased for brain collection and histopathology assessments. After birth, UCO lambs displayed significant latencies to (i use all four legs, (ii attain a standing position, (iii find the udder, and (iv successfully suckle--compared to control lambs. Brains of UCO lambs showed widespread pathologies including cell death, white matter disruption, intra-parenchymal hemorrhage and inflammation, which were not observed in full term control brains. UCO resulted in some preterm births, but comparison with age-matched preterm non-UCO control lambs showed that prematurity per se was not responsible for the behavioral delays and brain structural abnormalities resulting from the in utero asphyxia. These results demonstrate that a single, brief fetal asphyxic episode in late gestation results in significant grey and white matter disruption in the developing brain, and causes significant behavioral delay in newborn lambs. These data are consistent with clinical observations that antenatal asphyxia is causal in the development of neonatal encephalopathy and provide an experimental model to advance our understanding of neuroprotective therapies.

  16. Endothelial glycocalyx on brain endothelial cells is lost in experimental cerebral malaria

    DEFF Research Database (Denmark)

    Hempel, Casper; Hyttel, Poul; Kurtzhals, Jørgen Al

    2014-01-01

    electron microscopy and measured circulating glycosaminoglycans by dot blot and ELISA. The glycocalyx was degraded in brain vasculature in cerebral and to a lesser degree uncomplicated malaria. It was affected on both intact and apoptotic endothelial cells. Circulating glycosaminoglycan levels suggested...

  17. The Protective Effect of Omeprazole Against Traumatic Brain Injury: An Experimental Study.

    Science.gov (United States)

    Özay, Rafet; Türkoğlu, Mehmet Erhan; Gürer, Bora; Dolgun, Habibullah; Evirgen, Oya; Ergüder, Berrin İmge; Hayırlı, Nazlı; Gürses, Levent; Şekerci, Zeki

    2017-08-01

    The development of secondary brain injury via oxidative stress after traumatic brain injury (TBI) is a well-known entity. Consequently, the aim of the present study was to evaluate the role of omeprazole (OM) on rat model of TBI. A total of 24 male rats were used and divided into 4 groups as follows; control, trauma, OM, and methylprednisolone (MP). The trauma, OM, and MP groups were subjected to closed-head contusive weight-drop injuries. Rats received treatment with saline, OM, or MP, respectively. All the animals were sacrificed at 24 hours after trauma and brain tissues were extracted. The oxidant/antioxidant parameters (malondialdehyde, glutathione peroxidase, superoxide dismutase, nitric oxide) and caspase-3 in the cerebral tissue were analyzed, and histomorphologic evaluation of the cerebral tissue was performed. Levels of MDA and activity of caspase-3 were significantly reduced in the OM and MP groups compared with the trauma group. Glutathione peroxidase and superoxide dismutase levels were increased both in the OM and MP groups compared with the trauma group. The pathology scores were statistically lower in the OM and MP groups than the trauma group. The results of the present study showed that OM was as effective as MP in protecting brain from oxidative stress, and apoptosis in the early phase of TBI. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. Experimental iodine-125 seed irradiation of intracerebral brain tumors in nude mice

    NARCIS (Netherlands)

    Verhoeff, Joost J. C.; Stalpers, Lukas J. A.; Coumou, Annet W.; Koedooder, Kees; Lavini, Cristina; van Noorden, Cornelis J. F.; Haveman, Jaap; Vandertop, William P.; van Furth, Wouter R.

    2007-01-01

    BACKGROUND: High-dose radiotherapy is standard treatment for patients with brain cancer. However, in preclinical research external beam radiotherapy is limited to heterotopic murine models- high-dose radiotherapy to the murine head is fatal due to radiation toxicity. Therefore, we developed a

  19. Dynamic gadolinium uptake in thermally treated canine brain tissue and experimental cerebral tumors.

    Science.gov (United States)

    Kangasniemi, Marko; Stafford, R Jason; Price, Roger E; Jackson, Edward F; Hazle, John D

    2003-02-01

    Thermal coagulation of cerebral tumors induces reactive changes within adjacent brain tissue, which appear as Gd-DTPA enhancement in MR images. This makes assessment of therapeutic success difficult to establish radiographically because the reactive changes can mimic residual tumor. Dynamic Gd-DTPA uptake curves in reactive tissue and tumor were investigated to assess the utility of contrast enhanced (CE)-dynamic MRI to distinguish reactive changes from residual tumor in a canine model. Cerebral thermal necrosis was induced using a 980 nm laser in 11 dogs with intracerebral transmissible venereal tumors (TVTs). A fast spin-echo T1-weighted imaging sequence was used for CE-dynamic MRI. Gd-DTPA uptake data were acquired with 10-second temporal resolution and for untreated TVTs for reactive tissue using a sigmoidal-exponential model. Characteristic gadolinium uptake curves were measured and characterized for reactive brain tissue, and untreated and treated TVTs. Both early and delayed dynamic responses were significantly different in reactive brain tissue compared with TVT. Reactive thermal changes in otherwise normal brain tissue can be distinguished from residual tumor after cerebral thermal therapy using CE-dynamic MRI.

  20. Characteristics of an explosive blast-induced brain injury in an experimental model.

    Science.gov (United States)

    de Lanerolle, Nihal C; Bandak, Faris; Kang, Dewey; Li, Alexander Y; Du, Fu; Swauger, Peter; Parks, Steven; Ling, Geoffrey; Kim, Jung H

    2011-11-01

    Mild traumatic brain injury resulting from exposure to an explosive blast is associated with significant neurobehavioral outcomes in soldiers. Little is known about the neuropathologic consequences of such an insult to the human brain. This study is an attempt to understand the effects of an explosive blast in a large animal gyrencephalic brain blast injury model. Anesthetized Yorkshire swine were exposed to measured explosive blast levels in 3 operationally relevant scenarios: simulated free field (blast tube), high-mobility multipurpose wheeled vehicle surrogate, and building (4-walled structure). Histologic changes in exposed animals up to 2 weeks after blast were compared to a group of naive and sham controls. The overall pathologic changes in all 3 blast scenarios were limited, with very little neuronal injury, fiber tract demyelination, or intracranial hemorrhage observed. However, there were 2 distinct neuropathologic changes observed: increased astrocyte activation and proliferation and periventricular axonal injury detected with β-amyloid precursor protein immunohistochemistry. We postulate that the increased astrogliosis observed may have a longer-term potential for the exacerbation of brain injury and that the pattern of periventricular axonal injury may be related to a potential for cognitive and mood disorders.

  1. Metallic gold treatment reduces proliferation of inflammatory cells, increases expression of VEGF and FGF, and stimulates cell proliferation in the subventricular zone following experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Pedersen, Mie Østergaard; Larsen, Agnete; Pedersen, Dan Sonne

    2009-01-01

    gold implants reduce inflammation and neuronal apoptosis, while generating an increased neuronal stem cell response following focal brain damage. In this study mice were subjected to a unilateral traumatic cryo-lesion with concomitant injection of 25-45 microm gold particles near the lesion. Placebo......Traumatic brain injury represents a leading cause of morbidity in young individuals and there is an imperative need for neuroprotective treatments limiting the neurologic impairment following such injury. It has recently been demonstrated that bio-liberated gold ions liberated from small metallic......-treated mice subjected to cryo-lesion served as controls. The effects of gold-treatment were investigated by examining gold-induced growth factor expression (VEGF and FGF) in the first two weeks after the insult, and the extent of the neurostimulatory effect of gold was explored by comparing cell proliferation...

  2. Experimental studies on pathogenesis of the brain radiation injury in early stage

    Energy Technology Data Exchange (ETDEWEB)

    Ye Tian [Suzhou Medical Coll., Jiangsu (China). 2nd Affiliated Hospital; Shiyao Bao; Weibo Yin; Chunfeng Liu; Zhilin Zhang

    2000-05-01

    To investigate the pathogenesis of the brain radiation injury in the early stage, a series of experiments were performed as below. The SD rats halfbrain were irradiated by the single dose of 10, 20, and 30 Gy of 4 MeV electron, all those experiments were performed in 1 day to 3 months after radiation. The neurological symptoms, the weight and the skin response inside the field of all the rats were evaluated sequentially. The measurement of regional cerebral blood flow (rCBF) using hydrogen gas generated by electrolysis, the calculation of the brain water content percentage with wet-dry weight formula. The DNA contents and the quantities of bcl-2 protein were analyzed by flow cytometry. The brain histological sections were scanned to assess the present or absence of white matter necrosis in the region of hippocampus, and then the hippocampus region was observed for the morphological changes of the blood vessel, neuroglial, and the neurons. Some of the data were analyzed by the Student t test. Intra-portal alopecia was observed in all rats which received 30 Gy and some rats which received 20 Gy, the abnormal neurological signs were not found in all the rats, but the tend of weight increase was less pronounced in 1-3 months in the irradiated rats than those unirradiated. By comparison the unirradiated hemisphere, the rCBF of the contralateral brain decreased in most of the rats. In 20 Gy and 30 Gy groups, rCBF decreased areas expand gradually along with the prolong of observation time, from the nucleus caudate putamen, to the frontal cortex and then the hippocampus, the rCBF of whole the irradiated hemibrain was reduced significantly at 3 month after radiation. The water content of the irradiated halfbrain increased progressively, it means the brain edema exists in the meantime. By comparison the unirradiation halfbrain, the apoptosis of the hippocampus cells in the irradiated brain increased, and the expression of bcl-2 protein decreased at the meantime, and those

  3. Grupo Focal em Pesquisas Sociais

    OpenAIRE

    Maria Lúcia Silva Servo; Pricila Oliveira Araújo

    2012-01-01

    Este artigo tem como objetivo discutir a técnica de grupo focal em pesquisas sociais. Apresenta-se as concepções sobre grupo focal. Traz-se os postulados de Pichon-Rivière sobre grupo operativo, os instrumentos de planificação, os vetores do campo grupal para nortear a dinâmica e a observação do campo grupal, bem como a organização, a operacionalização e a análise dos dados das sessões de grupo focal. Através desta técnica de coleta de dados em pesquisas sociais, é possível a construção do EC...

  4. Continuously variable focal length lens

    Science.gov (United States)

    Adams, Bernhard W; Chollet, Matthieu C

    2013-12-17

    A material preferably in crystal form having a low atomic number such as beryllium (Z=4) provides for the focusing of x-rays in a continuously variable manner. The material is provided with plural spaced curvilinear, optically matched slots and/or recesses through which an x-ray beam is directed. The focal length of the material may be decreased or increased by increasing or decreasing, respectively, the number of slots (or recesses) through which the x-ray beam is directed, while fine tuning of the focal length is accomplished by rotation of the material so as to change the path length of the x-ray beam through the aligned cylindrical slows. X-ray analysis of a fixed point in a solid material may be performed by scanning the energy of the x-ray beam while rotating the material to maintain the beam's focal point at a fixed point in the specimen undergoing analysis.

  5. C5a induces caspase-dependent apoptosis in brain vascular endothelial cells in experimental lupus.

    Science.gov (United States)

    Mahajan, Supriya D; Tutino, Vincent M; Redae, Yonas; Meng, Hui; Siddiqui, Adnan; Woodruff, Trent M; Jarvis, James N; Hennon, Teresa; Schwartz, Stanley; Quigg, Richard J; Alexander, Jessy J

    2016-08-01

    Blood-brain barrier (BBB) dysfunction complicates central nervous system lupus, an important aspect of systemic lupus erythematosus. To gain insight into the underlying mechanism, vascular corrosion casts of brain were generated from the lupus mouse model, MRL/lpr mice and the MRL/MpJ congenic controls. Scanning electron microscopy of the casts showed loss of vascular endothelial cells in lupus mice compared with controls. Immunostaining revealed a significant increase in caspase 3 expression in the brain vascular endothelial cells, which suggests that apoptosis could be an important mechanism causing cell loss, and thereby loss of BBB integrity. Complement activation occurs in lupus resulting in increased generation of circulating C5a, which caused the endothelial layer to become 'leaky'. In this study, we show that C5a and lupus serum induced apoptosis in cultured human brain microvascular endothelial cells (HBMVECs), whereas selective C5a receptor 1 (C5aR1) antagonist reduced apoptosis in these cells, demonstrating C5a/C5aR1-dependence. Gene expression of initiator caspases, caspase 1 and caspase 8, and pro-apoptotic proteins death-associated protein kinase 1, Fas-associated protein (FADD), cell death-inducing DNA fragmentation factor 45 000 MW subunit A-like effector B (CIDEB) and BCL2-associated X protein were increased in HBMVECs treated with lupus serum or C5a, indicating that both the intrinsic and extrinsic apoptotic pathways could be critical mediators of brain endothelial cell apoptosis in this setting. Overall, our findings suggest that C5a/C5aR1 signalling induces apoptosis through activation of FADD, caspase 8/3 and CIDEB in brain endothelial cells in lupus. Further elucidation of the underlying apoptotic mechanisms mediating the reduced endothelial cell number is important in establishing the potential therapeutic effectiveness of C5aR1 inhibition that could prevent and/or reduce BBB alterations and preserve the physiological function of BBB in

  6. Brain Radiation Information Data Exchange (BRIDE): integration of experimental data from low-dose ionising radiation research for pathway discovery.

    Science.gov (United States)

    Karapiperis, Christos; Kempf, Stefan J; Quintens, Roel; Azimzadeh, Omid; Vidal, Victoria Linares; Pazzaglia, Simonetta; Bazyka, Dimitry; Mastroberardino, Pier G; Scouras, Zacharias G; Tapio, Soile; Benotmane, Mohammed Abderrafi; Ouzounis, Christos A

    2016-05-11

    The underlying molecular processes representing stress responses to low-dose ionising radiation (LDIR) in mammals are just beginning to be understood. In particular, LDIR effects on the brain and their possible association with neurodegenerative disease are currently being explored using omics technologies. We describe a light-weight approach for the storage, analysis and distribution of relevant LDIR omics datasets. The data integration platform, called BRIDE, contains information from the literature as well as experimental information from transcriptomics and proteomics studies. It deploys a hybrid, distributed solution using both local storage and cloud technology. BRIDE can act as a knowledge broker for LDIR researchers, to facilitate molecular research on the systems biology of LDIR response in mammals. Its flexible design can capture a range of experimental information for genomics, epigenomics, transcriptomics, and proteomics. The data collection is available at: .

  7. Model development, testing and experimentation in a CyberWorkstation for Brain-Machine Interface research.

    Science.gov (United States)

    Rattanatamrong, Prapaporn; Matsunaga, Andrea; Raiturkar, Pooja; Mesa, Diego; Zhao, Ming; Mahmoudi, Babak; Digiovanna, Jack; Principe, Jose; Figueiredo, Renato; Sanchez, Justin; Fortes, Jose

    2010-01-01

    The CyberWorkstation (CW) is an advanced cyber-infrastructure for Brain-Machine Interface (BMI) research. It allows the development, configuration and execution of BMI computational models using high-performance computing resources. The CW's concept is implemented using a software structure in which an "experiment engine" is used to coordinate all software modules needed to capture, communicate and process brain signals and motor-control commands. A generic BMI-model template, which specifies a common interface to the CW's experiment engine, and a common communication protocol enable easy addition, removal or replacement of models without disrupting system operation. This paper reviews the essential components of the CW and shows how templates can facilitate the processes of BMI model development, testing and incorporation into the CW. It also discusses the ongoing work towards making this process infrastructure independent.

  8. Effects of DDE on experimentally poisoned free-tailed bats (Tadarida brasiliensis): Lethal brain concentrations

    Science.gov (United States)

    Clark, D.R.; Kroll, J.C.

    1977-01-01

    Adult female free-tailed bats (Tadarida brasiliensis) were collected at Bracken Cave, Texas, and shipped to the Patuxent Wildlife Research Center. Treated mealworms (Tenebrio molitor) containing 107 ppm DDE were fed to 17 bats; five other bats were fed untreated mealworms. After 40 days on dosage, during which one dosed bat was killed accidentally, four dosed bats were frozen and the remaining 17 were starved to death. The objective was to elevate brain levels of DDE to lethality and measure these concentrations. After the feeding period, dosed bats weighed less than controls. After starvation, the body condition of dosed bats was poorer than that of controls even though there was no difference in the amounts of carcass fat. During starvation, dosed bats lost weight faster than controls. Also, four dosed bats exhibited the prolonged tremoring that characterizes DDE poisoning. DDE increased in brains of starving bats as fat was metabolized. The estimated mean brain concentration of DDE diagnostic of death was 519 ppm with a range of 458-564 ppm. These values resemble diagnostic levels known for two species of passerine birds, but they exceed published levels for two free-tailed bats from Carlsbad Caverns, New Mexico.

  9. Shared Immune and Repair Markers During Experimental Toxoplasma Chronic Brain Infection and Schizophrenia.

    Science.gov (United States)

    Tomasik, Jakub; Schultz, Tracey L; Kluge, Wolfgang; Yolken, Robert H; Bahn, Sabine; Carruthers, Vern B

    2016-03-01

    Chronic neurologic infection with Toxoplasma gondii is relatively common in humans and is one of the strongest known risk factors for schizophrenia. Nevertheless, the exact neuropathological mechanisms linking T gondii infection and schizophrenia remain unclear. Here we utilize a mouse model of chronic T gondii infection to identify protein biomarkers that are altered in serum and brain samples at 2 time points during chronic infection. Furthermore, we compare the identified biomarkers to those differing between "postmortem" brain samples from 35 schizophrenia patients and 33 healthy controls. Our findings suggest that T gondii infection causes substantial and widespread immune activation indicative of neural damage and reactive tissue repair in the animal model that partly overlaps with changes observed in the brains of schizophrenia patients. The overlapping changes include increases in C-reactive protein (CRP), interleukin-1 beta (IL-1β), interferon gamma (IFNγ), plasminogen activator inhibitor 1 (PAI-1), tissue inhibitor of metalloproteinases 1 (TIMP-1), and vascular cell adhesion molecule 1 (VCAM-1). Potential roles of these factors in the pathogenesis of schizophrenia and toxoplasmosis are discussed. Identifying a defined set of markers shared within the pathophysiological landscape of these diseases could be a key step towards understanding their specific contributions to pathogenesis. © The Author 2015. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  10. Primary experimental study on safety of deep brain stimulation in RF electromagnetic field.

    Science.gov (United States)

    Jun, Xu; Luming, Li; Hongwei, Hao

    2009-01-01

    With the rapid growth of clinical application of Deep Brain Stimulation, its safety and functional concern in the electromagnetic field, another pollution becoming much more serious, has become more and more significant. Meanwhile, the measuring standards on Electromagnetic Compatibility (EMC) for DBS are still incomplete. Particularly, the knowledge of the electromagnetic field induced signals on the implanted lead is ignorant while some informal reports some side effects. This paper briefly surmised the status of EMC standards on implantable medical devices. Based on the EMC experiments of DBS device we developed, two experiments for measuring the induced voltage of the deep brain stimulator in RF electromagnetic field were reported. The measured data showed that the induced voltage in some frequency was prominent, for example over 2V. As a primary research, we think these results would be significant to cause researcher to pay more attention to the EMC safety problem and biological effects of the induced voltage in deep brain stimulation and other implantable devices.

  11. [LINGO-1 expression of brain tissue in experimental autoimmune encephalomyelitis mouse].

    Science.gov (United States)

    Wang, Chunjuan; Guo, Shougang; Qu, Chuanqiang; Zhang, Jie; Fu, Peicai; Tang, Ronghua

    2014-04-22

    To observe the changes of LINGO-1 expression with time after onset in EAE mouse. C57/BL6 mice were completely randomly divided into EAE model group (n = 15) , adjuvant group (n = 15) and control group (n = 15) .LINGO-1 expression of brain tissue was detected on day 1, 7, 14, 21 and 30 after onset by RT-PCR and Western blot.RhoA and p-RhoA expression of brain tissue was analysed by Western blot. The LINGO-1mRNA levels in EAE model group were markedly higher than control group on day 1, 7and 14 after onset (4.63 ± 0.25, 2.72 ± 0.12, 1.98 ± 0.16, P Lingo-1 mRNA was close to control group.Expression levels of Lingo-1 protein on day 1, 7, 14, 21, 30 were higher than control group (2.11 ± 0.15, 3.15 ± 0.09, 2.45 ± 0.12, 1.89 ± 0.17, 1.21 ± 0.05, P LINGO-1 expression of brain tissue of EAE mouse upregulates and changes with time after onset, which may inhibit myelination by RhoA activation.In clinic, the antagonist of LINGO-1 for MS should be applied as soon as possible.

  12. Characteristics of brain cell proliferation and migration in animals with experimental Alzheimer’s disease undergoing cognitive training

    Directory of Open Access Journals (Sweden)

    Yu. K. Komleva

    2016-01-01

    Full Text Available Aims. Alzheimer’s disease is a multifactorial neurodegenerative disease characterized by the presence of amyloid beta peptide containing plaques, and neurofibrillary tangles. Beta-amyloid is a major risk factor and it plays a central role in the onset and progression of Alzheimer’s disease. However, question of the influence of beta-amyloid on neurogenesis in the hippocampus in the adult brain is still open. The purpose of this paper is to study cognitive functions and their association with proliferation, survival and migration of newly-formed cells in normal adult rat brain and in the experimental Alzheimer’s disease.Materials and methods. Rats (Wistar, males, 7 months were used. Experimental group (Alzheimer’s disease model with the intrahippocampal administration of beta-amyloid 1-42 (5 µl bilaterally in the CA1 area and a control group (sham-operated animals with the intrahippocampal administration of Phosphate buffered salin (5 µl bilaterally in the CA1 have been tested. The study was conducted from February to July. Neurobehavioral test (Morris water maze was used to assess working memory and memory consolidation. The study of cell migration was performed by introducing bromodeoxyuridine (50 mg/kg. Expression of neurogenesis markers in the subgranular zone of the dentate gyrus of the hippocampus was studied has been studied with indirect immunohistochemistry for free-floating sections followed by the confocal microscopy.Results. Modelling of Alzheimer’s disease leads to impaired cognitive function and memory in animals. We found that these events were associated with the suppression of proliferative (р = 0,043 and migratory activity of brain cells (р = 0,031, but not survival of cells (p = 0,985 compared to the control group.Training in Morris water maze of animals with experimental Alzheimer’s disease promotes migration of progenitor cells along the rostral migration way (р = 0,011 compared with the group without

  13. Experimental and clinical evidence of differential effects of magnesium sulfate on neuroprotection and angiogenesis in the fetal brain.

    Science.gov (United States)

    Lecuyer, Matthieu; Rubio, Marina; Chollat, Clément; Lecointre, Maryline; Jégou, Sylvie; Leroux, Philippe; Cleren, Carine; Leroux-Nicollet, Isabelle; Marpeau, Loic; Vivien, Denis; Marret, Stéphane; Gonzalez, Bruno J

    2017-08-01

    Clinical studies showed beneficial effects of magnesium sulfate regarding the risk of cerebral palsy. However, regimen protocols fluctuate worldwide and risks of adverse effects impacting the vascular system have been reported for human neonates, keeping open the question of the optimal dosing. Using clinically relevant concentrations and doses of magnesium sulfate, experiments consisted of characterizing, respectively, ex vivo and in vivo, the effects of magnesium sulfate on the nervous and vascular systems of mouse neonates by targeting neuroprotection, angiogenesis, and hemodynamic factors and in measuring, in human fetuses, the impact of a 4-g neuroprotective loading dose of magnesium sulfate on brain hemodynamic parameters. Preclinical experiments using cultured cortical slices from mouse neonates showed that the lowest and highest tested concentrations of magnesium sulfate were equally potent to prevent excitotoxic-induced cell death, cell edema, cell burst, and intracellular calcium increase, whereas no side effects were found regarding apoptosis. In contrast, in vivo data revealed that magnesium sulfate exerted dose-dependent vascular effects on the fetal brain. In particular, it induced brain hypoperfusion, stabilization of Hif-1α, long-term upregulation of VEGF-R2 expression, impaired endothelial viability, and altered cortical angiogenesis. Clinically, in contrast to 6-g loading doses used in some protocols, a 4-g bolus of magnesium sulfate did not altered fetal brain hemodynamic parameters. In conclusion, these data provide the first mechanistic evidence of double-sword and dose-dependent actions of magnesium sulfate on nervous and vascular systems. They strongly support the clinical use of neuroprotection protocols validated for the lowest (4-g) loading dose of magnesium sulfate. © 2017 The Authors. Pharmacology Research & Perspectives published by John Wiley & Sons Ltd, British Pharmacological Society and American Society for Pharmacology and

  14. Focal therapy in prostate cancer

    NARCIS (Netherlands)

    van den Bos, W.

    2016-01-01

    Interesting developments took place in the treatment of prostate cancer including focal therapy for less aggressive organ-confined prostate cancer. Fortunately, curative treatment is often still an option for patients suffering from the lower staged tumors. In carefully selected patients, the

  15. Focal lesions of the patella

    Energy Technology Data Exchange (ETDEWEB)

    Hedayati, B. [Royal national Orthopaedic Hospital Stanmore, Brockley Hill Stanmore, Department of Radiology, Middlesex (United Kingdom); Lewisham Hospital NHS Trust, Department of Radiology, London (United Kingdom); Saifuddin, A. [Royal national Orthopaedic Hospital Stanmore, Brockley Hill Stanmore, Department of Radiology, Middlesex (United Kingdom)

    2009-08-15

    Focal lesions of the patella may be identified during the investigation of anterior knee pain or as an incidental finding on radiological images. This pictorial review describes the radiographic appearances of a wide range of conditions that have been seen in this sesamoid bone. Where appropriate, computed tomography and magnetic resonance features have been included. (orig.)

  16. Complement peptide C3a stimulates neural plasticity after experimental brain ischaemia.

    Science.gov (United States)

    Stokowska, Anna; Atkins, Alison L; Morán, Javier; Pekny, Tulen; Bulmer, Linda; Pascoe, Michaela C; Barnum, Scott R; Wetsel, Rick A; Nilsson, Jonas A; Dragunow, Mike; Pekna, Marcela

    2017-02-01

    Ischaemic stroke induces endogenous repair processes that include proliferation and differentiation of neural stem cells and extensive rewiring of the remaining neural connections, yet about 50% of stroke survivors live with severe long-term disability. There is an unmet need for drug therapies to improve recovery by promoting brain plasticity in the subacute to chronic phase after ischaemic stroke. We previously showed that complement-derived peptide C3a regulates neural progenitor cell migration and differentiation in vitro and that C3a receptor signalling stimulates neurogenesis in unchallenged adult mice. To determine the role of C3a-C3a receptor signalling in ischaemia-induced neural plasticity, we subjected C3a receptor-deficient mice, GFAP-C3a transgenic mice expressing biologically active C3a in the central nervous system, and their respective wild-type controls to photothrombotic stroke. We found that C3a overexpression increased, whereas C3a receptor deficiency decreased post-stroke expression of GAP43 (P plasticity, in the peri-infarct cortex. To verify the translational potential of these findings, we used a pharmacological approach. Daily intranasal treatment of wild-type mice with C3a beginning 7 days after stroke induction robustly increased synaptic density (P neural plasticity and intranasal treatment with C3a receptor agonists is an attractive approach to improve functional recovery after ischaemic brain injury. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  17. A combination of experimental measurement, constitutive damage model, and diffusion tensor imaging to characterize the mechanical properties of the human brain.

    Science.gov (United States)

    Karimi, Alireza; Rahmati, Seyed Mohammadali; Razaghi, Reza

    2017-09-01

    Understanding the mechanical properties of the human brain is deemed important as it may subject to various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the various types of complex loadings during the Traumatic Brain Injury (TBI). Although many studies so far have been conducted to quantify the mechanical properties of the brain, there is a paucity of knowledge on the mechanical properties of the human brain tissue and the damage of its axon fibers under the frontal lobe of the human brain. The constrained nonlinear minimization method was employed to identify the brain coefficients according to the axial and transversal compressive data. The pseudo-elastic damage model data was also well compared with that of the experimental data and it not only up to the primary loading but also the discontinuous softening could well address the mechanical behavior of the brain tissue.

  18. Effect of Pregabalin in Preventing Secondary Damage in Traumatic Brain Injury: An Experimental Study

    OpenAIRE

    Calikoglu, Cagatay; Aytekin, Hikmet; Akg?l, Osman; Akg?l, Mehmet H?seyin; Gezen, Ahmet Ferruh; Akyuz, Feyzullah; Cakir, Murteza

    2015-01-01

    Background In this study we aimed to explore the effects of pregabalin on a traumatic brain injury model in rats. Material/Methods This study included 40 adult male Sprague-Dawley rats randomized into 4 groups, each of which contained equal numbers of animals. The control group had no head trauma and thus was not treated. The trauma group had head trauma but was not treated. The pregabalin group had no head trauma but was treated by pregabalin. The trauma + pregabalin group had head trauma tr...

  19. Experimental study on the toxicity of povidone-iodine solution in brain tissues of rabbits

    OpenAIRE

    Li, Shu-Hua; Wang, Yu; Gao, Hai-Bin; Zhao, Kun; Hou, Yu-Chen; Sun, Wei

    2015-01-01

    Objective: To determine whether Povidone-iodine was toxic to brain tissues by rinsing the cerebral cortex of New Zealand rabbits with Povidone-iodine Solution of different concentrations. Methods: 12 New Zealand rabbits were randomly divided into 4 groups (Group A, B, C and D, 3 rabbits each group). In each group, the left cerebral cortex of rabbits was rinsed with physiological saline after the craniotomy; in Group A and B, the right cerebral cortex of rabbits was also locally rinsed with Po...

  20. Evidence of oxidative stress in brain and liver of young rats submitted to experimental galactosemia.

    Science.gov (United States)

    Castro, Márcia B; Ferreira, Bruna K; Cararo, José Henrique; Chipindo, Adália E; Magenis, Marina L; Michels, Monique; Danielski, Lucinéia G; de Oliveira, Marcos R; Ferreira, Gustavo C; Streck, Emilio L; Petronilho, Fabricia; Schuck, Patrícia F

    2016-12-01

    Galactosemia is a disorder of galactose metabolism, leading to the accumulation of this carbohydrate. Galactosemic patients present brain and liver damage. For evaluated oxidative stress, 30-day-old males Wistar rats were divided into two groups: galactose group, that received a single injection of this carbohydrate (5 μmol/g), and control group, that received saline 0.9 % in the same conditions. One, twelve or twenty-four hours after the administration, animals were euthanized and cerebral cortex, cerebellum, and liver were isolated. After one hour, it was found a significant increase in TBA-RS levels, nitrate and nitrite and protein carbonyl contents in cerebral cortex, as well as protein carbonyl content in the cerebellum and in hepatic level of TBA-RS, and a significant decrease in nitrate and nitrite contents in cerebellum. TBA-RS levels were also found increased in all studied tissues, as well as nitrate and nitrite contents in cerebral cortex and cerebellum, that also present increased protein carbonyl content and impairments in the activity of antioxidant enzymes of rats euthanized at twelve hours. Finally, animals euthanized after twenty-four hours present an increase of TBA-RS levels in studied tissues, as well as the protein carbonyl content in cerebellum and liver. These animals also present an increased nitrate and nitrite content and impairment of antioxidant enzymes activities. Taken together, our data suggest that acute galactose administration impairs redox homeostasis in brain and liver of rats.

  1. Acquired Immunoglobulin G deficiency in stroke patients and experimental brain ischemia.

    Science.gov (United States)

    Liesz, Arthur; Roth, Stefan; Zorn, Markus; Sun, Li; Hofmann, Kerstin; Veltkamp, Roland

    2015-09-01

    Acute brain injuries induce a systemic immune depression syndrome (SIDS) that predisposes patients to bacterial infections. While cellular compartments of this syndrome have been well characterized, the contribution of humoral immune mechanisms and particularly immunoglobulins to SIDS has not been investigated so far. We determined serum immunoglobulin levels and infectious complications at several time points in 159 ischemic and hemorrhagic stroke patients. Additionally, findings were verified in a transient middle cerebral artery occlusion model. A novel immunoassay was established to analyze the IgG excretion ratio in mice. We identified a transient IgG reduction in patients suffering from substantial ischemic or hemorrhagic brain injuries. The IgG-reduction was associated with subsequent bacterial infections. Similarly, transient hypogammaglobulinemia was detected in a murine stroke model. We then used this animal model to further distinguish the mechanism of the IgG reduction by an IgG transfer paradigm. Excretional loss rather than deficient production of IgG was demonstrated to underlay hypogammaglobulinemia. This is the first report of transient hypogammaglobulinemia after ischemic and hemorrhagic stroke suggesting involvement in infectious complications. These findings pave the road for further studies investigating post-stroke hypogammaglobulinemia as a druggable target for stroke-induced complications. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Hypereosinophilia with Multiple Thromboembolic Cerebral Infarcts and Focal Intracerebral Hemorrhage

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Eun Ju; Lee, Young Jun; Lee, Seung Ro; Park, Dong Woo; Kim, Hyun Young [Hanyang University College of Medicine, Seoul (Korea, Republic of)

    2009-10-15

    We report a case of hypereosinophilia causing multiple areas of cerebral infarcts. A 52-year-old Korean man presented with dysarthria and weakness in both arms. A brain MRI revealed multiple acute infarcts in the distal border zone with focal intracerebral hemorrhage, whereas a cerebral angiogram was not remarkable. The eosinophil count was 5,500/{mu}L and was accompanied by elevated cardiac enzyme levels. The pattern of cerebral infarcts and laboratory results suggest a thromboembolic infarction associated with hypereosinophilia.

  3. Widespread EEG changes precede focal seizures.

    Directory of Open Access Journals (Sweden)

    Piero Perucca

    Full Text Available The process by which the brain transitions into an epileptic seizure is unknown. In this study, we investigated whether the transition to seizure is associated with changes in brain dynamics detectable in the wideband EEG, and whether differences exist across underlying pathologies. Depth electrode ictal EEG recordings from 40 consecutive patients with pharmacoresistant lesional focal epilepsy were low-pass filtered at 500 Hz and sampled at 2,000 Hz. Predefined EEG sections were selected immediately before (immediate preictal, and 30 seconds before the earliest EEG sign suggestive of seizure activity (baseline. Spectral analysis, visual inspection and discrete wavelet transform were used to detect standard (delta, theta, alpha, beta and gamma and high-frequency bands (ripples and fast ripples. At the group level, each EEG frequency band activity increased significantly from baseline to the immediate preictal section, mostly in a progressive manner and independently of any modification in the state of vigilance. Preictal increases in each frequency band activity were widespread, being observed in the seizure-onset zone and lesional tissue, as well as in remote regions. These changes occurred in all the investigated pathologies (mesial temporal atrophy/sclerosis, local/regional cortical atrophy, and malformations of cortical development, but were more pronounced in mesial temporal atrophy/sclerosis. Our findings indicate that a brain state change with distinctive features, in the form of unidirectional changes across the entire EEG bandwidth, occurs immediately prior to seizure onset. We postulate that these changes might reflect a facilitating state of the brain which enables a susceptible region to generate seizures.

  4. Widespread EEG Changes Precede Focal Seizures

    Science.gov (United States)

    Perucca, Piero; Dubeau, François; Gotman, Jean

    2013-01-01

    The process by which the brain transitions into an epileptic seizure is unknown. In this study, we investigated whether the transition to seizure is associated with changes in brain dynamics detectable in the wideband EEG, and whether differences exist across underlying pathologies. Depth electrode ictal EEG recordings from 40 consecutive patients with pharmacoresistant lesional focal epilepsy were low-pass filtered at 500 Hz and sampled at 2,000 Hz. Predefined EEG sections were selected immediately before (immediate preictal), and 30 seconds before the earliest EEG sign suggestive of seizure activity (baseline). Spectral analysis, visual inspection and discrete wavelet transform were used to detect standard (delta, theta, alpha, beta and gamma) and high-frequency bands (ripples and fast ripples). At the group level, each EEG frequency band activity increased significantly from baseline to the immediate preictal section, mostly in a progressive manner and independently of any modification in the state of vigilance. Preictal increases in each frequency band activity were widespread, being observed in the seizure-onset zone and lesional tissue, as well as in remote regions. These changes occurred in all the investigated pathologies (mesial temporal atrophy/sclerosis, local/regional cortical atrophy, and malformations of cortical development), but were more pronounced in mesial temporal atrophy/sclerosis. Our findings indicate that a brain state change with distinctive features, in the form of unidirectional changes across the entire EEG bandwidth, occurs immediately prior to seizure onset. We postulate that these changes might reflect a facilitating state of the brain which enables a susceptible region to generate seizures. PMID:24260523

  5. Intestinal permeability to glucose after experimental traumatic brain injury: effect of gadopentetate dimeglumine administration.

    Science.gov (United States)

    Santos, Alejandro; Gonçalves, Pedro; Araújo, João R; Martel, Fátima

    2008-09-01

    Traumatic injuries are the leading cause of mortality in individuals aged 1-44 years, and brain injury significantly contributes to the outcome in nearly one half of all deaths from trauma. At the intestinal level, traumatic brain injury (TBI) induces profound effects, including gastrointestinal mucosa ischaemia and motility dysfunction. However, nothing is known concerning the effect of TBI on the intestinal absorption of glucose. Hence, the aim of this study was to investigate the effect of TBI on the intestinal absorption of glucose by investigating the effect of TBI on the jejunal mucosal-to-serosal apparent permeability (AP-to-BL P(app)) to two glucose model substrates, (3)H-2-deoxy-D-glucose ((3)H-DG) and (3)H-3-O-methyl-D-glucose ((3)H-OMG), and to (14)C-sorbitol. Additionally, we tested if gadopentetate dimeglumine administration could prevent any of the changes observed after TBI. Traumatic brain injury induced an increase in the AP-to-BL P(app) to (3)H-DG. After a 100-min. perfusion of the jejunum, the AP-to-BL P(app) to (3)H-DG in TBI rats was almost 70% higher than in the control rats. There was no change, however, in the AP-to-BL P(app) to neither (3)H-OMG nor (14)C-sorbitol. Interestingly enough, gadopentetate dimeglumine was able to prevent the increase in the AP-to-BL P(app) to (3)H-DG observed after TBI. Given the differences in transport characteristics between (3)H-DG and (3)H-OMG, our results point to the possibility of the Na(+)-independent glucose transporter 2 (GLUT2) being activated by TBI (as the P(app) to (3)H-DG, a GLUT2 substrate, was increased) and the Na(+)-dependent glucose co-transporter (SGLT1) being inhibited by TBI (as the P(app) to (3)H-OMG, a GLUT2 and SGLT1 substrate, remained unchanged). Moreover, gadopentetate dimeglumine prevented these changes associated with TBI.

  6. [Experimental and therapeutic neuromodulation of emotion and social cognition with non-invasive brain stimulation].

    Science.gov (United States)

    Mielacher, C; Scheele, D; Hurlemann, R

    2015-12-01

    Transcranial magnetic stimulation (TMS) is not only a highly elegant method for basic neuroscientific research that employs transient lesions to explore the relationship between brain structure and function but in a clinical context it is also a very promising approach to augmentation therapy in middle to severe grade depressive episodes. This overview illustrates the methodological basis of TMS and illuminates its neuromodulatory potential with reference to findings from recent studies on emotion regulation and social cognition. Against this empirical background, it becomes clear that preclinical studies on healthy participants are extremely important to develop innovative stimulation protocols and define functionally relevant target regions to be tested in clinical studies for therapeutic efficacy. Finally, the perspectives and limitations of functionally guided, individualized TMS neuronavigation will be explored based on task-independent connectivity and task-dependent activity measurements.

  7. Dimethyl fumarate attenuates neuroinflammation and neurobehavioral deficits induced by experimental traumatic brain injury.

    Science.gov (United States)

    Casili, Giovanna; Campolo, Michela; Paterniti, Irene; Lanza, Marika; Filippone, Alessia; Cuzzocrea, Salvatore; Esposito, Emanuela

    2018-01-23

    TBI is a serious neuropathology that causes secondary injury mechanisms, including dynamic interplay between ischemic, inflammatory and cytotoxic processes. Fumaric acid esters (FAEs) showed beneficial effects in preclinical models of neuroinflammation and toxic oxidative stress, so the aim of the present work was to evaluate the potential beneficial effects of dimethyl fumarate (DMF), the most pharmacologically effective molecules among the FAEs, in a mouse model of TBI induced by controlled cortical impact (CCI). Mice were orally administered with DMF at the doses of 1, 10 and 30 mg/Kg, 1h and 4h after CCI. We performed histological, molecular, and immunohistochemistry analysis on the traumatic penumbral areas of the brain 24 hours after CCI. DMF treatment notably reduced histological damage and behavioral impairments, reducing neurodegeneration as evidenced by assessments of neuronal loss, Fluoro-jade C and TUNEL staining; also, treatment with DMF blocked apoptosis process increasing B-cell lymphoma 2 (Bcl-2) expression in injured cortex. Furthermore, DMF treatment up-regulated antioxidant Kelch-like ECH-associated protein 1/ Nuclear factor erythroid 2- related factor (Keap-1/Nrf-2) pathway, inducing activation of manganese superoxide dismutase (Mn-SOD) and heme-oxygenase-1 (HO-1) and reducing 4-hydroxy-2-nonenal (4-HNE) staining. Also, regulating NF-κB pathway, DMF treatment decreased the severity of inflammation through a modulation of neuronal nitrite oxide synthase (nNOS), interleukin 1 (Il-1β), tumor necrosis factor (TNF-α), cyclooxygenase 2 (COX-2) and myeloperoxidase (MPO) activity, reducing ionized calcium-binding adapter molecule 1 (Iba-1) and glial fibrillary acidic protein (GFAP) expression. Our results support the thesis that DMF may be an effective neuroprotectant after brain trauma and warrants further study.

  8. Moringa oleifera phytochemicals protect the brain against experimental nicotine-induced neurobehavioral disturbances and cerebellar degeneration.

    Science.gov (United States)

    Omotoso, Gabriel Olaiya; Gbadamosi, Ismail Temitayo; Olajide, Olayemi Joseph; Dada-Habeeb, Shakirat Opeyemi; Arogundade, Tolulope Timothy; Yawson, Emmanuel Olusola

    2018-01-04

    Nicotine is a neuro-stimulant that has been implicated in the pathophysiology of many brain diseases. The need to prevent or alleviate the resulting dysfunction is therefore paramount, which has also given way to the use of medicinal plants in the management of brain conditions. This study was designed to determine the histomorphological and neurobehavioural changes in the cerebellum of Wistar rats following nicotine insult and how such injuries respond to Moringa intervention. Twenty-four adult male Wistar rats were divided into 4 groups. Group A and B were orally treated with normal saline and Moringa oleifera respectively for twenty-eight days; Group C was treated with nicotine while group D was treated orally with Moringa oleifera and intraperitoneally with nicotine for twenty-eight days. Animals were subjected to the open field test on the last day of treatment. 24 h after last day treatment, the animals were anesthetized and perfusion fixation was carried out. The cerebellum was excised and post-fixed in 4% paraformaldehyde and thereafter put through routine histological procedures. Results revealed cytoarchitectural distortion and extreme chromatolysis in neuronal cells of the cerebellar cortical layers in the nicotine-treated group. The Purkinje cells of the cerebellum of animals in this group were degenerated. There were also reduced locomotor activities in the group. Moringa was able to prevent the chromatolysis, distortion of the cerebellar cortical cells and neurobehavioural deficit. Our result suggests that Moringa oleifera could prevent nicotine-induced cerebellar injury in Wistar rats, with the possibility of ameliorating the clinical features presented in associated cerebellar pathology. Copyright © 2018 Elsevier B.V. All rights reserved.

  9. Focal length estimation guided with object distribution on FocaLens dataset

    Science.gov (United States)

    Yan, Han; Zhang, Yu; Zhang, Shunli; Zhao, Sicong; Zhang, Li

    2017-05-01

    The focal length information of an image is indispensable for many computer vision tasks. In general, focal length can be obtained via camera calibration using specific planner patterns. However, for images taken by an unknown device, focal length can only be estimated based on the image itself. Currently, most of the single-image focal length estimation methods make use of predefined geometric cues (such as vanishing points or parallel lines) to infer focal length, which constrains their applications mainly on manmade scenes. The machine learning algorithms have demonstrated great performance in many computer vision tasks, but these methods are seldom used in the focal length estimation task, partially due to the shortage of labeled images for training the model. To bridge this gap, we first introduce a large-scale dataset FocaLens, which is especially designed for single-image focal length estimation. Taking advantage of the FocaLens dataset, we also propose a new focal length estimation model, which exploits the multiscale detection architecture to encode object distributions in images to assist focal length estimation. Additionally, an online focal transformation approach is proposed to further promote the model's generalization ability. Experimental results demonstrate that the proposed model trained on FocaLens can not only achieve state-of-the-art results on the scenes with distinct geometric cues but also obtain comparable results on the scenes even without distinct geometric cues.

  10. An Experimental Brain Missile Wound: Ascertaining Pathophysiology and evaluating Treatments to Lower Mortality and Morbidity

    Science.gov (United States)

    1989-04-27

    the Institute of Laboratory Animal Resources, National Research Council (DHEW Publication No. (NIH) 86-23, Revised 1985). The experiments on mechinical ...GROUP I: UNWOUNDED NORMOTENSIVE (7 cats): Cats in this group served as controls. Regional CBFs (rCBFs) were measured 5 times during the 100 min...experimental period according to the following schedule: CBF /I 1, control, 10 min before zero time (the time in which wounded animais were injured). CBFs # 2

  11. Mechanisms by which Stress Affects the Experimental and Clinical Inflammatory Bowel Disease (IBD): Role of Brain-Gut Axis.

    Science.gov (United States)

    Brzozowski, Bartosz; Mazur-Bialy, Agnieszka; Pajdo, Robert; Kwiecien, Slawomir; Bilski, Jan; Zwolinska-Wcislo, Malgorzata; Mach, Tomasz; Brzozowski, Tomasz

    2016-01-01

    Stress of different origin is known to alter so called "braingut axis" and contributes to a broad array of gastrointestinal disorders including inflammatory bowel disease (IBD), irritable bowel syndrome (IBS) and other functional gastrointestinal diseases. The stressful situations and various stressors including psychosocial events, heat, hypo- and hyperthermia may worsen the course of IBD via unknown mechanism. The aims of this paper were to provide an overview of experimental and clinical evidences that stress activates the brain-gut axis which results in a mucosal mast cells activation and an increase in the production of proinflammatory cytokines and other endocrine and humoral mediators. Research and online content related to effects of stress on lower bowel disorders are reviewed and most important mechanisms are delineated. Brain conveys the neural, endocrine and circulatory messages to the gut via brain-gut axis reflecting changes in corticotrophin releasing hormone, mast cells activity, neurotransmission at the autonomic nerves system and intestinal barrier function all affecting the pathogenesis of animal colitis and human IBD. Stress triggers the hypothalamus-pituitary axis and the activation of the autonomic nervous system, an increase in cortisol levels and proinflammatory cytokines such as tumor necrosis factor-alpha, interleukin-8, interleukin-1beta and interleukin-6. The acute or chronic stress enhances the intestinal permeability weakening of the tight junctions and increasing bacterial translocation into the intestinal wall. An increased microbial load in the colonic tissue, excessive cytokine release and a partially blunted immune reactivity in response to stress result in its negative impact on IBD.

  12. Experimental infection by Yersinia ruckeri O1 biotype 2 induces brain lesions and neurological signs in rainbow trout (Oncorhynchus mykiss).

    Science.gov (United States)

    Strøm, H K; Ohtani, M; Nowak, B; Boutrup, T S; Jones, B; Raida, M K; Bojesen, A M

    2017-11-17

    Pathological manifestations in rainbow trout (Oncorhynchus mykiss) following experimental waterborne infection with Yersinia ruckeri serotype O1 biotype 2 (strain 07111224) were investigated. Rainbow trout were exposed to 8 × 107  CFU/ml of Y. ruckeri by bath for 6 hr, and mortality was then monitored for 22 days post-infection (dpi). Organs were sampled at 3 dpi and also from moribund fish showing signs of severe systemic infection such as bleeding, exophthalmia or erratic swimming behaviour. Y. ruckeri was observed in the meninges and diencephalon of the brain, and lamina propria of olfactory organ at 3 dpi. At 12 dpi, Y. ruckeri had spread throughout the brain including cranial connective tissues and ventricles and the infection was associated with haemorrhages and an infiltration with leucocytes. Y. ruckeri infection and associated with leucocyte infiltration were observed at 13 dpi. In conclusion, Y. ruckeri strain 07111224 causes encephalitis in the acute phase of infection, which could explain why Y. ruckeri-affected fish show exophthalmia and erratic swimming known as signs of ERM. © 2017 John Wiley & Sons Ltd.

  13. Large-scale cortico-subcortical functional networks in focal epilepsies: The role of the basal ganglia

    Directory of Open Access Journals (Sweden)

    Eva Výtvarová

    2017-01-01

    Significance: Focal epilepsies affect large-scale brain networks beyond the epileptogenic zones. Cortico-subcortical functional connectivity disturbance was displayed in LTLE, FLE, and POLE. Significant changes in the resting-state functional connectivity between cortical and subcortical structures suggest an important role of the BG and thalamus in focal epilepsies.

  14. Intranasal insulin treatment of an experimental model of moderate traumatic brain injury.

    Science.gov (United States)

    Brabazon, Fiona; Wilson, Colin M; Jaiswal, Shalini; Reed, John; Frey, William H; Byrnes, Kimberly R

    2017-09-01

    Traumatic brain injury (TBI) results in learning and memory dysfunction. Cognitive deficits result from cellular and metabolic dysfunction after injury, including decreased cerebral glucose uptake and inflammation. This study assessed the ability of intranasal insulin to increase cerebral glucose uptake after injury, reduce lesion volume, improve memory and learning function and reduce inflammation. Adult male rats received a controlled cortical impact (CCI) injury followed by intranasal insulin or saline treatment daily for 14 days. PET imaging of [18F]-FDG uptake was performed at baseline and at 48 h and 10 days post-injury and MRI on days three and nine post injury. Motor function was tested with the beam walking test. Memory function was assessed with Morris water maze. Intranasal insulin after CCI significantly improved several outcomes compared to saline. Insulin-treated animals performed better on beam walk and demonstrated significantly improved memory. A significant increase in [18F]-FDG uptake was observed in the hippocampus. Intranasal insulin also resulted in a significant decrease in hippocampus lesion volume and significantly less microglial immunolabeling in the hippocampus. These data show that intranasal insulin improves memory, increases cerebral glucose uptake and decreases neuroinflammation and hippocampal lesion volume, and may therefore be a viable therapy for TBI.

  15. Magnesium Administration after Experimental Traumatic Brain Injury Improves Decision-Making Skills.

    Science.gov (United States)

    Young, Jennica M; Hoane, Michael R

    2018-03-01

    After sustaining a traumatic brain injury (TBI), a person's ability to make daily decisions can be affected. Simple tasks such as, deciding what to wear are no longer effortless choices, but are instead difficult decisions. This study explored the use of a discrimination task with a magnesium treatment in order to examine how decision-making skills are affected after TBI and if the treatment helped to attenuate cognitive and motor impairments. Thirty-one male rats were separated into MAG/TBI, VEH/TBI, or VEH/Sham groups. Pre-TBI, rats were trained to dig in the sand for a reinforcer. After establishment of consistent digging behavior rats received a bilateral frontal cortex injury. Rats received either an i.p. injection of 2 mmol/kg magnesium chloride or control at 4, 24, 72 hours post-surgery. Dig task testing began 7 days post-injury, lasting for 4 weeks. The discriminations included two scent pairings; basil (baited) versus coffee then the reversal and then cocoa (baited) versus cumin then the reversal. The results indicated that the magnesium treatment was successful at attenuating cognitive and motor deficits after TBI. The results also indicated that the dig task is a sufficient operant conditioning task in the assessment of frontal functioning after TBI. Copyright © 2018. Published by Elsevier Inc.

  16. Persistence of viral RNA in the brain of experimentally infected mice with coxsackievirus B5

    OpenAIRE

    Sobotova Z.; Marosova L.; Badurova M.; Sojka M.; Borsanyiova M.; Stipalova D.; Bopegamage S.

    2011-01-01

    The aim of our study was to follow the persistence of viral RNA in selected organs of experimentally infected with coxsackievirus (CV) B5 strains from different sources such as a patient’s sample, an environmental sample and a prototype virus strain. Methods . CD-1 mice were infected with CVB5 strain Faulkner the prototype, CVB5 – isolate from treated sewage waste and isolate from patient’s stool sample both identified as CVB5. The viral RNA was detected by RT-PCR using enterovirus primers sp...

  17. Musicians' social representations of health and illness: a qualitative case study about focal dystonia.

    Science.gov (United States)

    Zosso, Amélie; Schoeb, Veronika

    2012-01-01

    Musicians are artists who use the entire body when playing their instruments. Since over-practicing may lead to physical problems, musicians might encounter focal dystonia, a hand's motor disorder. The cause seems to be the brain's confusion between afferent and efferent information transfer provoking a disharmony with the instrument. Although focal dystonia may have serious consequences for a musician's career, it is unclear how musicians perceive this trouble. This case study describes two musicians with focal dystonia. Qualitative research was used to study their social representations of health and illness. The results show the central role of the hand during music playing, the passion for music and the understanding for focal dystonia as "brain panic". Therapists should account for those specific features inherent to this population in order to better help them in their quest for art through music. Giving a voice to musicians may improve their quality of care.

  18. Therapeutic potential of the novel hybrid molecule JM-20 against focal cortical ischemia in rats

    Directory of Open Access Journals (Sweden)

    Yanier Núñez Figueredo

    2016-08-01

    Full Text Available Context: Despite the great mortality and morbidity of stroke, treatment options remain limited. We previously showed that JM-20, a novel synthetic molecule, possessed a strong neuroprotective effect in rats subjected to transient middle cerebral artery occlusion. However, to verify the robustness of the pre-clinical neuroprotective effects of JM-20 to get good prognosis in the translation to the clinic, it is necessary to use other experimental models of brain ischemia. Aims: To evaluate the neuroprotective effects of JM-20 following the onset of permanent focal cerebral ischemia induced in rats by thermocoagulation of blood into pial blood vessels of cerebral cortices. Methods: Ischemic lesion was induced by thermocoagulation of blood into pial blood vessels of primary motor and somatosensory cortices. Behavioral performance was evaluated by the cylinder testing for a period of 2, 3 and 7 days after surgery, and was followed by histopathological study in brain cortex stained with hematoxylin- eosin. Results: Ischemic injury resulted in impaired function of the forelimb evidenced by high asymmetry punctuation, and caused histopathological alterations indicative of tissue damage at cerebral cortex. JM-20 treatment (4 and 8 mg/kg significantly decreased asymmetry scores and histological alterations with a marked preservation of cortical neurons. Conclusions: The effects of permanent brain ischemia were strongly attenuated by JM-20 administration, which expands and improves the current preclinical data of JM-20 as neuroprotector against cerebral ischemia, and strongly support the examination of its translation to the clinic to treat acute ischemic stroke.

  19. Reduced neuronal cell death after experimental brain injury in mice lacking a functional alternative pathway of complement activation

    Directory of Open Access Journals (Sweden)

    Huber-Lang Markus

    2006-07-01

    Full Text Available Abstract Background Neuroprotective strategies for prevention of the neuropathological sequelae of traumatic brain injury (TBI have largely failed in translation to clinical treatment. Thus, there is a substantial need for further understanding the molecular mechanisms and pathways which lead to secondary neuronal cell death in the injured brain. The intracerebral activation of the complement cascade was shown to mediate inflammation and tissue destruction after TBI. However, the exact pathways of complement activation involved in the induction of posttraumatic neurodegeneration have not yet been assessed. In the present study, we investigated the role of the alternative complement activation pathway in contributing to neuronal cell death, based on a standardized TBI model in mice with targeted deletion of the factor B gene (fB-/-, a "key" component required for activation of the alternative complement pathway. Results After experimental TBI in wild-type (fB+/+ mice, there was a massive time-dependent systemic complement activation, as determined by enhanced C5a serum levels for up to 7 days. In contrast, the extent of systemic complement activation was significantly attenuated in fB-/- mice (P fB-/- vs. fB+/+; t = 4 h, 24 h, and 7 days after TBI. TUNEL histochemistry experiments revealed that posttraumatic neuronal cell death was clearly reduced for up to 7 days in the injured brain hemispheres of fB-/- mice, compared to fB+/+ littermates. Furthermore, a strong upregulation of the anti-apoptotic mediator Bcl-2 and downregulation of the pro-apoptotic Fas receptor was detected in brain homogenates of head-injured fB-/- vs. fB+/+ mice by Western blot analysis. Conclusion The alternative pathway of complement activation appears to play a more crucial role in the pathophysiology of TBI than previously appreciated. This notion is based on the findings of (a the significant attenuation of overall complement activation in head-injured fB-/- mice, as

  20. Magnetoencephalographic Identification of Epileptic Focus in Children With Generalized Electroencephalographic (EEG) Features but Focal Imaging Abnormalities.

    Science.gov (United States)

    Shukla, Garima; Kazutaka, Jin; Gupta, Ajay; Mosher, John; Jones, Stephen; Alexopoulos, Andreas; Burgess, Richard C

    2017-10-01

    Children with generalized seizures are often excluded as epilepsy surgery candidates. This prospective study was conducted to evaluate the utility of magnetoencephalography (MEG) to refine the location of the "irritative zone" in children with single lesions on magnetic resonance imaging (MRI) but with generalized ictal electroencephalographic (EEG) findings. Patients admitted with refractory epilepsy with imaging studies showing focal or hemispheric abnormalities but scalp video EEG showing generalized or multiregional epileptiform abnormalities were included. Patients were encouraged into natural sleep, and simultaneous whole-head MEG/EEG was recorded. Source localization of epileptic spikes on MEG was carried out while blinded to other results. Acceptable dipoles were classified into 3 groups: focal, hemispheric clusters, and single focal cluster with additional widespread dipoles. Nine patients (4 female, 5 males; ages 10 months to 15 years) were included. Two had focal features on clinical semiology, whereas all had generalized or multiregional interictal and ictal EEG. Etiologies included tuberous sclerosis complex (2), postencephalitic sequelae (1), focal cortical dysplasia (1), and unknown (2). Five patients had clear focal lesions on brain MRI whereas the other 2 had focal positron emission tomography (PET) abnormalities. An average of 38 spikes were accepted (average goodness of fit = 85.3%). A single tight cluster of dipoles was identified in 5 patients, 1 had dipoles with propagation from left occipital to right temporal. One patient had 2 distinct dipole clusters. MEG demonstrated focal findings 9 times more often than the simultaneously recorded scalp EEG, and 3 times more often than the associated multiday video EEG recordings. This study shows that neurophysiologic evidence of focal epileptiform abnormalities in patients with focal brain lesions and generalized EEG findings can be strengthened using MEG. Further feasibility of surgical candidacy

  1. Delayed sodium pyruvate treatment improves working memory following experimental traumatic brain injury.

    Science.gov (United States)

    Moro, Nobuhiro; Ghavim, Sima S; Hovda, David A; Sutton, Richard L

    2011-03-17

    Prior work indicates that cerebral glycolysis is impaired following traumatic brain injury (TBI) and that pyruvate treatment acutely after TBI can improve cerebral metabolism and is neuroprotective. Since extracellular levels of glucose decrease during periods of increased cognitive demand and exogenous glucose improves cognitive performance, we hypothesized that pyruvate treatment prior to testing could ameliorate cognitive deficits in rats with TBI. Based on pre-surgical spatial alternation performance in a 4-arm plus-maze, adult male rats were randomized to receive either sham injury or unilateral (left) cortical contusion injury (CCI). On days 4, 9 and 14 after surgery animals received an intraperitoneal injection of either vehicle (Sham-Veh, n=6; CCI-Veh, n=7) or 1000 mg/kg of sodium pyruvate (CCI-SP, n=7). One hour after each injection rats were retested for spatial alternation performance. Animals in the CCI-SP group showed no significant working memory deficits in the spatial alternation task compared to Sham-Veh controls. The percent four/five alternation scores for CCI-Veh rats were significantly decreased from Sham-Veh scores on days 4 and 9 (pglucose and regional cytochrome oxidase activity at day 15 post-injury did not differ between CCI-SP and CCI-Veh groups. These results show that spatial alternation testing can reliably detect temporal deficits and recovery of working memory after TBI and that delayed pyruvate treatment can ameliorate TBI-induced cognitive impairments. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  2. Propagation of tau pathology: hypotheses, discoveries, and yet unresolved questions from experimental and human brain studies.

    Science.gov (United States)

    Lewis, Jada; Dickson, Dennis W

    2016-01-01

    Tau is a microtubule-associated protein and a key regulator of microtubule stabilization as well as the main component of neurofibrillary tangles-a principle neuropathological hallmark of Alzheimer's disease (AD)-as well as pleomorphic neuronal and glial inclusions in neurodegenerative tauopathies. Cross-sectional studies of neurofibrillary pathology in AD reveal a stereotypic spatiotemporal pattern of neuronal vulnerability that correlates with disease severity; however, the relationship of this pattern to disease progression is less certain and exceptions to the typical pattern have been described in a subset of AD patients. The basis for the selective vulnerability of specific populations of neurons to tau pathology and cell death is largely unknown, although there have been a number of hypotheses based upon shared properties of vulnerable neurons (e.g., degree of axonal myelination or synaptic plasticity). A recent hypothesis for selective vulnerability takes into account the emerging science of functional connectivity based upon resting state functional magnetic resonance imaging, where subsets of neurons that fire synchronously define patterns of degeneration similar to specific neurodegenerative disorders, including various tauopathies. In the past 6 years, the concept of tau propagation has emerged from numerous studies in cell and animal models suggesting that tau moves from cell-to-cell and that this may trigger aggregation and region-to-region spread of tau pathology within the brain. How the spread of tau pathology relates to functional connectivity is an area of active investigation. Observations of templated folding and propagation of tau have prompted comparisons of tau to prions, the pathogenic proteins in transmissible spongiform encephalopathies. In this review, we discuss the most compelling studies in the field, discuss their shortcomings and consider their implications with respect to human tauopathies as well as the controversy that

  3. Comparative and Experimental Studies on the Genes Altered by Chronic Hypoxia in Human Brain Microendothelial Cells

    Directory of Open Access Journals (Sweden)

    Eugenia Mata-Greenwood

    2017-05-01

    Full Text Available Background : Hypoxia inducible factor 1 alpha (HIF1A is a master regulator of acute hypoxia; however, with chronic hypoxia, HIF1A levels return to the normoxic levels. Importantly, the genes that are involved in the cell survival and viability under chronic hypoxia are not known. Therefore, we tested the hypothesis that chronic hypoxia leads to the upregulation of a core group of genes with associated changes in the promoter DNA methylation that mediates the cell survival under hypoxia.Results : We examined the effect of chronic hypoxia (3 days; 0.5% oxygen on human brain micro endothelial cells (HBMEC viability and apoptosis. Hypoxia caused a significant reduction in cell viability and an increase in apoptosis. Next, we examined chronic hypoxia associated changes in transcriptome and genome-wide promoter methylation. The data obtained was compared with 16 other microarray studies on chronic hypoxia. Nine genes were altered in response to chronic hypoxia in all 17 studies. Interestingly, HIF1A was not altered with chronic hypoxia in any of the studies. Furthermore, we compared our data to three other studies that identified HIF-responsive genes by various approaches. Only two genes were found to be HIF dependent. We silenced each of these 9 genes using CRISPR/Cas9 system. Downregulation of EGLN3 significantly increased the cell death under chronic hypoxia, whereas downregulation of ERO1L, ENO2, adrenomedullin, and spag4 reduced the cell death under hypoxia.Conclusions : We provide a core group of genes that regulates cellular acclimatization under chronic hypoxic stress, and most of them are HIF independent.

  4. Inhibitory Effect of Matrine on Blood-Brain Barrier Disruption for the Treatment of Experimental Autoimmune Encephalomyelitis

    Directory of Open Access Journals (Sweden)

    Su Zhang

    2013-01-01

    Full Text Available Dysfunction of the blood-brain barrier (BBB is a primary characteristic of experimental autoimmune encephalomyelitis (EAE, an experimental model of multiple sclerosis (MS. Matrine (MAT, a quinolizidine alkaloid derived from the herb Radix Sophorae Flave, has been recently found to suppress clinical EAE and CNS inflammation. However, whether this effect of MAT is through protecting the integrity and function of the BBB is not known. In the present study, we show that MAT treatment had a therapeutic effect comparable to dexamethasone (DEX in EAE rats, with reduced Evans Blue extravasation, increased expression of collagen IV, the major component of the basement membrane, and the structure of tight junction (TJ adaptor protein Zonula occludens-1 (ZO-1. Furthermore, MAT treatment attenuated expression of matrix metalloproteinase-9 and -2 (MMP-9/-2, while it increased the expression of tissue inhibitors of metalloproteinase-1 and -2 (TIMP-1/-2. Our findings demonstrate that MAT reduces BBB leakage by strengthening basement membrane, inhibiting activities of MMP-2 and -9, and upregulating their inhibitors. Taken together, our results identify a novel mechanism underlying the effect of MAT, a natural compound that could be a novel therapy for MS.

  5. Image-based in vivo assessment of targeting accuracy of stereotactic brain surgery in experimental rodent models

    Science.gov (United States)

    Rangarajan, Janaki Raman; Vande Velde, Greetje; van Gent, Friso; de Vloo, Philippe; Dresselaers, Tom; Depypere, Maarten; van Kuyck, Kris; Nuttin, Bart; Himmelreich, Uwe; Maes, Frederik

    2016-11-01

    Stereotactic neurosurgery is used in pre-clinical research of neurological and psychiatric disorders in experimental rat and mouse models to engraft a needle or electrode at a pre-defined location in the brain. However, inaccurate targeting may confound the results of such experiments. In contrast to the clinical practice, inaccurate targeting in rodents remains usually unnoticed until assessed by ex vivo end-point histology. We here propose a workflow for in vivo assessment of stereotactic targeting accuracy in small animal studies based on multi-modal post-operative imaging. The surgical trajectory in each individual animal is reconstructed in 3D from the physical implant imaged in post-operative CT and/or its trace as visible in post-operative MRI. By co-registering post-operative images of individual animals to a common stereotaxic template, targeting accuracy is quantified. Two commonly used neuromodulation regions were used as targets. Target localization errors showed not only variability, but also inaccuracy in targeting. Only about 30% of electrodes were within the subnucleus structure that was targeted and a-specific adverse effects were also noted. Shifting from invasive/subjective 2D histology towards objective in vivo 3D imaging-based assessment of targeting accuracy may benefit a more effective use of the experimental data by excluding off-target cases early in the study.

  6. Effects of the Rabdosia rubescens total flavonoids on focal cerebral ischemia reperfusion model in rats

    Directory of Open Access Journals (Sweden)

    Mingsan Miao

    2017-05-01

    Full Text Available The effect of the Rabdosia rubescens total flavonoids on focal cerebral ischemia reperfusion model in rats was observed. The model group, nimodipine group, cerebral collateral group, and large, medium and small dose group of the Rabdosia rubescens total flavonoids were administered with corresponding drugs but sham operation group and model group were administered the same volume of 0.5%CMC, 1 times a day, continuous administration of 7 d. After 1 h at 7 d to medicine, left incision in the middle of the neck of rats after anesthesia, we can firstly expose and isolate the left common carotid artery (CCA, and then expose external carotid artery (ECA and internal carotid artery (ICA. The common carotid artery and the external carotid artery are ligated. Then internal carotid artery with arterial clamp is temporarily clipped. Besides, cut the incision of 0.2 mm from 5 cm of the bifurcation of the common carotid artery. A thread Line bolt is inserted with more than 18–20 mm from bifurcation of CCA into the internal carotid artery until there is resistance. Then the entrance of the middle cerebral artery is blocked and internal carotid artery is ligated (the blank group only exposed the left blood vessel without Plugging wire. Finally it is gently pulled out the plug line after 2 h. Results: Compared with the model mice, Rabdosia rubescens total flavonoids can significantly relieve the injury of brain in hippocampus and cortex nerve cells; experimental rat focal cerebral ischemia was to improve again perfusion model of nerve function defect score mortality; significantly reduce brain homogenate NOS activity and no content, MDA, IL-1, TNF-a, ICAM-1 content; increase in brain homogenate SOD and ATPase activity (P < 0.05, P < 0.01; and reduce the serum S-100β protein content. Each dose group of the Rabdosia rubescens total flavonoids has a better Improvement effect on focal cerebral ischemia reperfusion model in rats.

  7. Why standard brain-computer interface (BCI) training protocols should be changed: an experimental study

    Science.gov (United States)

    Jeunet, Camille; Jahanpour, Emilie; Lotte, Fabien

    2016-06-01

    Objective. While promising, electroencephaloraphy based brain-computer interfaces (BCIs) are barely used due to their lack of reliability: 15% to 30% of users are unable to control a BCI. Standard training protocols may be partly responsible as they do not satisfy recommendations from psychology. Our main objective was to determine in practice to what extent standard training protocols impact users’ motor imagery based BCI (MI-BCI) control performance. Approach. We performed two experiments. The first consisted in evaluating the efficiency of a standard BCI training protocol for the acquisition of non-BCI related skills in a BCI-free context, which enabled us to rule out the possible impact of BCIs on the training outcome. Thus, participants (N = 54) were asked to perform simple motor tasks. The second experiment was aimed at measuring the correlations between motor tasks and MI-BCI performance. The ten best and ten worst performers of the first study were recruited for an MI-BCI experiment during which they had to learn to perform two MI tasks. We also assessed users’ spatial ability and pre-training μ rhythm amplitude, as both have been related to MI-BCI performance in the literature. Main results. Around 17% of the participants were unable to learn to perform the motor tasks, which is close to the BCI illiteracy rate. This suggests that standard training protocols are suboptimal for skill teaching. No correlation was found between motor tasks and MI-BCI performance. However, spatial ability played an important role in MI-BCI performance. In addition, once the spatial ability covariable had been controlled for, using an ANCOVA, it appeared that participants who faced difficulty during the first experiment improved during the second while the others did not. Significance. These studies suggest that (1) standard MI-BCI training protocols are suboptimal for skill teaching, (2) spatial ability is confirmed as impacting on MI-BCI performance, and (3) when faced

  8. Considerations for Experimental Animal Models of Concussion, Traumatic Brain Injury, and Chronic Traumatic Encephalopathy—These Matters Matter

    Directory of Open Access Journals (Sweden)

    Mark W. Wojnarowicz

    2017-06-01

    Full Text Available Animal models of concussion, traumatic brain injury (TBI, and chronic traumatic encephalopathy (CTE are widely available and routinely deployed in laboratories around the world. Effective animal modeling requires careful consideration of four basic principles. First, animal model use must be guided by clarity of definitions regarding the human disease or condition being modeled. Concussion, TBI, and CTE represent distinct clinical entities that require clear differentiation: concussion is a neurological syndrome, TBI is a neurological event, and CTE is a neurological disease. While these conditions are all associated with head injury, the pathophysiology, clinical course, and medical management of each are distinct. Investigators who use animal models of these conditions must take into account these clinical distinctions to avoid misinterpretation of results and category mistakes. Second, model selection must be grounded by clarity of purpose with respect to experimental questions and frame of reference of the investigation. Distinguishing injury context (“inputs” from injury consequences (“outputs” may be helpful during animal model selection, experimental design and execution, and interpretation of results. Vigilance is required to rout out, or rigorously control for, model artifacts with potential to interfere with primary endpoints. The widespread use of anesthetics in many animal models illustrates the many ways that model artifacts can confound preclinical results. Third, concordance between key features of the animal model and the human disease or condition being modeled is required to confirm model biofidelity. Fourth, experimental results observed in animals must be confirmed in human subjects for model validation. Adherence to these principles serves as a bulwark against flawed interpretation of results, study replication failure, and confusion in the field. Implementing these principles will advance basic science discovery and

  9. Considerations for Experimental Animal Models of Concussion, Traumatic Brain Injury, and Chronic Traumatic Encephalopathy-These Matters Matter.

    Science.gov (United States)

    Wojnarowicz, Mark W; Fisher, Andrew M; Minaeva, Olga; Goldstein, Lee E

    2017-01-01

    Animal models of concussion, traumatic brain injury (TBI), and chronic traumatic encephalopathy (CTE) are widely available and routinely deployed in laboratories around the world. Effective animal modeling requires careful consideration of four basic principles. First, animal model use must be guided by clarity of definitions regarding the human disease or condition being modeled. Concussion, TBI, and CTE represent distinct clinical entities that require clear differentiation: concussion is a neurological syndrome, TBI is a neurological event, and CTE is a neurological disease. While these conditions are all associated with head injury, the pathophysiology, clinical course, and medical management of each are distinct. Investigators who use animal models of these conditions must take into account these clinical distinctions to avoid misinterpretation of results and category mistakes. Second, model selection must be grounded by clarity of purpose with respect to experimental questions and frame of reference of the investigation. Distinguishing injury context ("inputs") from injury consequences ("outputs") may be helpful during animal model selection, experimental design and execution, and interpretation of results. Vigilance is required to rout out, or rigorously control for, model artifacts with potential to interfere with primary endpoints. The widespread use of anesthetics in many animal models illustrates the many ways that model artifacts can confound preclinical results. Third, concordance between key features of the animal model and the human disease or condition being modeled is required to confirm model biofidelity. Fourth, experimental results observed in animals must be confirmed in human subjects for model validation. Adherence to these principles serves as a bulwark against flawed interpretation of results, study replication failure, and confusion in the field. Implementing these principles will advance basic science discovery and accelerate clinical

  10. Considerations for Experimental Animal Models of Concussion, Traumatic Brain Injury, and Chronic Traumatic Encephalopathy—These Matters Matter

    Science.gov (United States)

    Wojnarowicz, Mark W.; Fisher, Andrew M.; Minaeva, Olga; Goldstein, Lee E.

    2017-01-01

    Animal models of concussion, traumatic brain injury (TBI), and chronic traumatic encephalopathy (CTE) are widely available and routinely deployed in laboratories around the world. Effective animal modeling requires careful consideration of four basic principles. First, animal model use must be guided by clarity of definitions regarding the human disease or condition being modeled. Concussion, TBI, and CTE represent distinct clinical entities that require clear differentiation: concussion is a neurological syndrome, TBI is a neurological event, and CTE is a neurological disease. While these conditions are all associated with head injury, the pathophysiology, clinical course, and medical management of each are distinct. Investigators who use animal models of these conditions must take into account these clinical distinctions to avoid misinterpretation of results and category mistakes. Second, model selection must be grounded by clarity of purpose with respect to experimental questions and frame of reference of the investigation. Distinguishing injury context (“inputs”) from injury consequences (“outputs”) may be helpful during animal model selection, experimental design and execution, and interpretation of results. Vigilance is required to rout out, or rigorously control for, model artifacts with potential to interfere with primary endpoints. The widespread use of anesthetics in many animal models illustrates the many ways that model artifacts can confound preclinical results. Third, concordance between key features of the animal model and the human disease or condition being modeled is required to confirm model biofidelity. Fourth, experimental results observed in animals must be confirmed in human subjects for model validation. Adherence to these principles serves as a bulwark against flawed interpretation of results, study replication failure, and confusion in the field. Implementing these principles will advance basic science discovery and accelerate

  11. Homeostatic structural plasticity can account for topology changes following deafferentation and focal stroke.

    Science.gov (United States)

    Butz, Markus; Steenbuck, Ines D; van Ooyen, Arjen

    2014-01-01

    After brain lesions caused by tumors or stroke, or after lasting loss of input (deafferentation), inter- and intra-regional brain networks respond with complex changes in topology. Not only areas directly affected by the lesion but also regions remote from the lesion may alter their connectivity-a phenomenon known as diaschisis. Changes in network topology after brain lesions can lead to cognitive decline and increasing functional disability. However, the principles governing changes in network topology are poorly understood. Here, we investigated whether homeostatic structural plasticity can account for changes in network topology after deafferentation and brain lesions. Homeostatic structural plasticity postulates that neurons aim to maintain a desired level of electrical activity by deleting synapses when neuronal activity is too high and by providing new synaptic contacts when activity is too low. Using our Model of Structural Plasticity, we explored how local changes in connectivity induced by a focal loss of input affected global network topology. In accordance with experimental and clinical data, we found that after partial deafferentation, the network as a whole became more random, although it maintained its small-world topology, while deafferentated neurons increased their betweenness centrality as they rewired and returned to the homeostatic range of activity. Furthermore, deafferentated neurons increased their global but decreased their local efficiency and got longer tailed degree distributions, indicating the emergence of hub neurons. Together, our results suggest that homeostatic structural plasticity may be an important driving force for lesion-induced network reorganization and that the increase in betweenness centrality of deafferentated areas may hold as a biomarker for brain repair.

  12. Infrared lens thermal effect: equivalent focal shift and calculating model

    Science.gov (United States)

    Zhang, Cheng-shuo; Shi, Zelin; Feng, Bin; Xu, Bao-shu

    2014-11-01

    It's well-know that the focal shift of infrared lens is the major factor in degeneration of imaging quality when temperature change. In order to figure out the connection between temperature change and focal shift, partial differential equations of thermal effect on light path are obtained by raytrace method, to begin with. The approximately solution of the PDEs show that focal shift is proportional to temperature change. And a formula to compute the proportional factor is given. In order to understand infrared lens thermal effect deeply, we use defocus by image plane shift at constant temperature to equivalently represent thermal effect on infrared lens. So equivalent focal shift (EFS) is defined and its calculating model is proposed at last. In order to verify EFS and its calculating model, Physical experimental platform including a motorized linear stage with built-in controller, blackbody, target, collimator, IR detector, computer and other devices is developed. The experimental results indicate that EFS make the image plane shift at constant temperature have the same influence on infrared lens as thermal effect and its calculating model is correct.

  13. Implications for a regulated replication of Borna disease virus in brains of experimentally infected Lewis rats.

    Science.gov (United States)

    Porombka, Doris; Baumgärtner, Wolfgang; Eickmann, Markus; Herden, Christiane

    2008-04-01

    The neurotropic Borna disease virus (BDV) causes typically a persistent virus infection of the central nervous system. In order to investigate whether an adapted virus replication contributes to BDV persistence in vivo, a fast and reliable real-time RT-PCR assay was constructed to quantify the amounts of leader-containing (leBDV) as a marker for virus replication, genomic (vBDV) and nucleoprotein-(BDV-N +ssRNA)-specific RNA. Therefore, leBDV, vBDV and BDV-N +ssRNA values were determined in experimentally infected Lewis rats between 14 and 90 days post infection (dpi). Surprisingly low leBDV values were found compared to vBDV and the abundantly expressed BDV-N transcripts. vBDV multiplied only in the acute phase of infection followed by constant expression until 90 dpi. Ratios of vBDV to leBDV were 401:1 at 14 dpi and diminished to 209:1 at 90 dpi, indicating a regulated co-expression of replicative intermediates as a potential prerequisite for viral persistence.

  14. SNAP Satellite Focal Plane Development

    Energy Technology Data Exchange (ETDEWEB)

    Bebek, C.; Akerlof, C.; Aldering, G.; Amanullah, R.; Astier, P.; Baltay, C.; Barrelet, E.; Basa, S.; Bercovitz, J.; Bergstrom, L.; Berstein, G.P.; Bester, M.; Bohlin, R.; Bonissent, A.; Bower, C.; Campbell, M.; Carithers, W.; Commins, E.; Day, C.; Deustua, S.; DiGennaro, R.; Ealet, A.; Ellis, R.; Emmett, W.; Eriksson, M.; Fouchez,D.; Fruchter, A.; Genat, J-F.; Goldhaber, G.; Goobar, A.; Groom, D.; Heetderks, H.; Holland, S.; Huterer, D.; Johnson, W.; Kadel, R.; Karcher,A.; Kim, A.; Kolbe, W.; Lafever, R.; Lamoureaux, J.; Lampton, M.; Lefevre, O.; Levi, M.; Levin, D.; Linder, E.; Loken, S.; Malina, R.; Mazure, A.; McKay, T.; McKee, S.; Miquel, R.; Morgan, N.; Mortsell, E.; Mostek, N.; Mufson, S.; Musser, J.; Roe, N.; Nugent, P.; Oluseyi, H.; Pain, R.; Palaio, N.; Pankow, D.; Perlmutter, S.; Prieto, E.; Rabinowitz,D.; Refregier, A.; Rhodes, J.; Schubnell, M.; Sholl, M.; Smadja, G.; Smith, R.; Smoot, G.; Snyder, J.; Spadafora, A.; Szymkowiak, A.; Tarle,G.; Taylor, K.; Tilquin, A.; Tomasch, A.; Vincent, D.; von der Lippe, H.; Walder, J-P.; Wang, G.

    2003-07-07

    The proposed SuperNova/Acceleration Probe (SNAP) mission will have a two-meter class telescope delivering diffraction-limited images to an instrumented 0.7 square degree field in the visible and near-infrared wavelength regime. The requirements for the instrument suite and the present configuration of the focal plane concept are presented. A two year R&D phase, largely supported by the Department of Energy, is just beginning. We describe the development activities that are taking place to advance our preparedness for mission proposal in the areas of detectors and electronics.

  15. Interferon Induced Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Yusuf Kayar

    2016-01-01

    Full Text Available Behçet’s disease is an inflammatory disease of unknown etiology which involves recurring oral and genital aphthous ulcers and ocular lesions as well as articular, vascular, and nervous system involvement. Focal segmental glomerulosclerosis (FSGS is usually seen in viral infections, immune deficiency syndrome, sickle cell anemia, and hyperfiltration and secondary to interferon therapy. Here, we present a case of FSGS identified with kidney biopsy in a patient who had been diagnosed with Behçet’s disease and received interferon-alpha treatment for uveitis and presented with acute renal failure and nephrotic syndrome associated with interferon.

  16. Evaluación experimental y estadística de un prototipo de interfaz cerebro-computador (ICC) [Experimental and statistical evaluation of a brain-computer interface (BCI) prototype

    NARCIS (Netherlands)

    Arcos Argoty, J.; Garcia Cossio, E.; Torres Villa, R.A.

    2010-01-01

    Abstract: Nowadays, brain-computer interfaces (BCI) are designed to be used in experimental and clinical studies, and their results allow the creation of new assistive technologies for people with motor disabilities. In 2008, a prototype of a BCI was developed in the School of Engineering of

  17. Effects of the Treatment with ‍Nigella sativa Oil on Brain Injury and Edema in Experimental Model of Stroke in Rats

    Directory of Open Access Journals (Sweden)

    H Panahpour

    2015-09-01

    Full Text Available Background & objectives: Stroke is third leading cause of death and disability in the most of human communities. The use of herbs and medicinal plants in different countries is increasing. Today, herbal medicine is used as alternative or complementary therapies with a fewer side effects. Nigella sativa has a rich medical and religious history. Oxidative stress has important role in the pathophysiology of stroke. As Nigella sativa has antioxidant effects, its administration may produce a protective effect against complications of this disease. We examined the effects of the treatment with Nigella sativa oil on the cerebral infarction and edema. Methods: 48 Male Sprague-Dawley rats were divided into three groups, sham, control ischemic and Nigella sativa oil treated (2 ml/kg ischemic groups. Transient focal cerebral ischemia was induced by 90-min-long occlusion of the left middle cerebral artery followed by 24-h-long reperfusion. Neurological deficit score was evaluated at the end of the reperfusion period. Thereafter, the animals were randomly selected and used for two projects: (i Measurement of the infarct volumes and neurological outcome (ii investigation of ischemic brain edema formation using a wet/dry method. Results: Induction of cerebral ischemia in the control group produced considerable brain infarction in conjunction with impaired motor functions and severely brain edema. Treatment with Nigella sativa oil significantly reduced the infarct volume and improved the motor functions. The water content in the left (lesioned hemisphere was considerably elevated in the control ischemic group. Administration of the Nigella sativa oil significantly lowered the water content in the ischemic lesioned hemisphere. Conclusion: Treatment with Nigella sativa oil can noticeably decrease the ischemic brain injury, attenuate edema formation and improve motor disabilities.

  18. Spreading depolarization monitoring in neurocritical care of acute brain injury.

    Science.gov (United States)

    Hartings, Jed A

    2017-04-01

    Spreading depolarizations are unique in being discrete pathologic entities that are well characterized experimentally and also occur commonly in patients with substantial acute brain injury. Here, we review essential concepts in depolarization monitoring, highlighting its clinical significance, interpretation, and future potential. Cortical lesion development in diverse animal models is mediated by tissue waves of mass spreading depolarization that cause the toxic loss of ion homeostasis and limit energy substrate supply through associated vasoconstriction. The signatures of such deterioration are observed in electrocorticographic recordings from perilesional cortex of patients with acute stroke or brain trauma. Experimental work suggests that depolarizations are triggered by energy supply-demand mismatch in focal hotspots of the injury penumbra, and depolarizations are usually observed clinically when other monitoring variables are within recommended ranges. These results suggest that depolarizations are a sensitive measure of relative ischemia and ongoing secondary injury, and may serve as a clinical guide for personalized, mechanistically targeted therapy. Both existing and future candidate therapies offer hope to limit depolarization recurrence. Electrocorticographic monitoring of spreading depolarizations in patients with acute brain injury provides a sensitive measure of relative energy shortage in focal, vulnerable brains regions and indicates ongoing secondary damage. Depolarization monitoring holds potential for targeted clinical trial design and implementation of precision medicine approaches to acute brain injury therapy.

  19. Connectome-Wide Phenotypical and Genotypical Associations in Focal Dystonia.

    Science.gov (United States)

    Fuertinger, Stefan; Simonyan, Kristina

    2017-08-02

    Isolated focal dystonia is a debilitating movement disorder of unknown pathophysiology. Early studies in focal dystonias have pointed to segregated changes in brain activity and connectivity. Only recently has the notion that dystonia pathophysiology may lie in abnormalities of large-scale brain networks appeared in the literature. Here, we outline a novel concept of functional connectome-wide alterations that are linked to dystonia phenotype and genotype. Using a neural community detection strategy and graph theoretical analysis of functional MRI data in human patients with the laryngeal form of dystonia (LD) and healthy controls (both males and females), we identified an abnormally widespread hub formation in LD, which particularly affected the primary sensorimotor and parietal cortices and thalamus. Left thalamic regions formed a delineated functional community that highlighted differences in network topology between LD patients with and without family history of dystonia. Conversely, marked differences in the topological organization of parietal regions were found between phenotypically different forms of LD. The interface between sporadic genotype and adductor phenotype of LD yielded four functional communities that were primarily governed by intramodular hub regions. Conversely, the interface between familial genotype and abductor phenotype was associated with numerous long-range hub nodes and an abnormal integration of left thalamus and basal ganglia. Our findings provide the first comprehensive atlas of functional topology across different phenotypes and genotypes of focal dystonia. As such, this study constitutes an important step toward defining dystonia as a large-scale network disorder, understanding its causative pathophysiology, and identifying disorder-specific markers.SIGNIFICANCE STATEMENT The architecture of the functional connectome in focal dystonia was analyzed in a large population of patients with laryngeal dystonia. Breaking with the

  20. Pathogenetic mechanisms of focal cortical dysplasia.

    Science.gov (United States)

    Marin-Valencia, Isaac; Guerrini, Renzo; Gleeson, Joseph G

    2014-07-01

    Focal cortical dysplasias (FCDs) constitute a prevalent cause of intractable epilepsy in children, and is one of the leading conditions requiring epilepsy surgery. Despite recent advances in the cellular and molecular biology of these conditions, the pathogenetic mechanisms of FCDs remain largely unknown. The purpose if this work is to review the molecular underpinnings of FCDs and to highlight potential therapeutic targets. A systematic review of the literature regarding the histologic, molecular, and electrophysiologic aspects of FCDs was conducted. Disruption of the mammalian target of rapamycin (mTOR) signaling comprises a common pathway underlying the structural and electrical disturbances of some FCDs. Other mechanisms such as viral infections, prematurity, head trauma, and brain tumors are also posited. mTOR inhibitors (i.e., rapamycin) have shown positive results on seizure management in animal models and in a small cohort of patients with FCD. Encouraging progress has been achieved on the molecular and electrophysiologic basis of constitutive cells in the dysplastic tissue. Despite the promising results of mTOR inhibitors, large-scale randomized trials are in need to evaluate their efficacy and side effects, along with additional mechanistic studies for the development of novel, molecular-based diagnostic and therapeutic approaches. Wiley Periodicals, Inc. © 2014 International League Against Epilepsy.

  1. Experimental MR-guided cryotherapy of the brain with almost real-time imaging by radial k-space scanning; Experimentelle MR-gesteuerte Kryotherapie des Gehirns mit nahezu Echtzeitdarstellung durch radiale k-Raum-Abtastung

    Energy Technology Data Exchange (ETDEWEB)

    Tacke, J.; Schorn, R.; Glowinski, A.; Grosskortenhaus, S.; Adam, G.; Guenther, R.W. [Technische Hochschule Aachen (Germany). Klinik fuer Radiologische Diagnostik; Speetzen, R.; Rau, G. [Helmholtz-Institut fuer Biomedizinische Technik, Aachen (Germany); Rasche, V. [Philips GmbH Forschungslaboratorium, Hamburg (Germany)

    1999-02-01

    Purpose: To test radial k-space scanning by MR fluoroscopy to guide and control MR-guided interstitial cryotherapy of the healthy pig brain. Methods: After MR tomographic planning of the approach, an MR-compatible experimental cryotherapy probe of 2.7 mm diameter was introduced through a 5 mm burr hole into the right frontal brain of five healthy pigs. The freeze-thaw cycles were imaged using a T{sub 1}-weighted gradient echo sequence with radial k-space scanning in coronal, sagittal, and axial directions. Results: The high temporal resolution of the chosen sequence permits a continuous representation of the freezing process with good image quality and high contrast between ice and unfrozen brain parenchyma. Because of the interactive conception of the sequence the layer plane could be chosen as desired during the measurement. Ice formation was sharply demarcated, spherically configurated, and was free of signals. Its maximum diameter was 13 mm. Conclusions: With use of the novel, interactively controllable gradient echo sequence with radial k-space scanning, guidance of the intervention under fluoroscopic conditions with the advantages of MRT is possible. MR-guided cryotherapy allows a minimally-invasive, precisely dosable focal tissue ablation. (orig.) [Deutsch] Ziel: Erprobung der radialen k-Raum-Abtastung bei der MR-Fluoroskopie zur Steuerung und Kontrolle MR-gesteuerter interstitieller Kryotherapie des gesunden Schweinegehirns. Methoden: Nach MR-tomographischer Planung des Zugangsweges wurde eine MR-kompatible experimentelle Kryotherapiesonde von 2,7 mm Durchmesser ueber ein 5 mm Bohrloch in das rechte Frontalhirn von fuenf gesunden Schweinen eingebracht. Die Frier-/Tauzyklen wurden anhand einer T{sub 1}-gewichteten Gradientenechosequenz mit radialer k-Raum-Abtastung in koronarer, sagittaler und axialer Schichtfuehrung dargestellt. Ergebnisse: Die hohe zeitliche Aufloesung der gewaehlten Sequenz erlaubte eine kontinuierliche Darstellung des Friervorgangs bei

  2. Experimental chronic cerebral hypoperfusion results in decreased pericyte coverage and increased blood-brain barrier permeability in the corpus callosum.

    Science.gov (United States)

    Liu, Qinghai; Radwanski, Ryan; Babadjouni, Robin; Patel, Arati; Hodis, Drew M; Baumbacher, Peter; Zhao, Zhen; Zlokovic, Berislav; Mack, William J

    2017-01-01

    Murine chronic cerebral hypoperfusion (CCH) results in white matter (WM) injury and behavioral deficits. Pericytes influence blood-brain barrier (BBB) integrity and cerebral blood flow. Under hypoxic conditions, pericytes detach from perivascular locations increasing vessel permeability and neuronal injury. This study characterizes the time course of BBB dysfunction and pericyte coverage following murine experimental CCH secondary to bilateral carotid artery stenosis (BCAS). Mice underwent BCAS or sham operation. On post-procedure days 1, 3, 7 and 30, corpus callosum BBB permeability was characterized using Evans blue (EB) extravasation and IgG staining and pericyte coverage/count was calculated. The BCAS cohort demonstrated increased EB extravasation on postoperative days 1 ( p = 0.003) 3 ( p = 0.002), and 7 ( p = 0.001) when compared to sham mice. Further, EB extravasation was significantly greater ( p = 0.05) at day 3 than at day 30 in BCAS mice. BCAS mice demonstrated a nadir in pericyte coverage and count on post-operative day 3 ( p < 0.05, compared to day 7, day 30 and sham). Decreased pericyte coverage/count and increased BBB permeability are most pronounced on postoperative day 3 following murine CCH. This precedes any notable WM injury or behavioral deficits.

  3. Focal nodular hyperplasia in identical twins.

    Science.gov (United States)

    Mindikoglu, Ayse L; Regev, Arie; Levi, Joe U; Casillas, Javier; Schiff, Eugene R

    2005-07-01

    A unique case of a focal nodular hyperplasia (FNH) in identical twins is presented. The computed tomography (CT) and magnetic resonance imaging (MRI) of the abdomen demonstrated in both twins a mass of identical size in the same segment of their liver. Histopathologic examination of both masses confirmed the diagnosis of focal nodular hyperplasia. This case report strongly supports the theory of a congenital vascular anomaly playing a major role in the etiology of focal nodular hyperplasia.

  4. Periodontitis in patients with focal tuberculosis

    Directory of Open Access Journals (Sweden)

    Alexandrova Е.А.

    2010-12-01

    Full Text Available The research goal is to investigate the mechanisms of formation and peculiarities of periodontitis in patients with focal tuberculosis. Patients with periodontitis and focal tuberculosis are proved to develop local inflammatory reaction with increased infection and activation of proinflammatory cytokines in parodontal pockets fluid. The main risk factor of frequent and durable recurrence of parodontal pathology in case of focal tuberculosis was the development of pathologic process as a cause of disbalance of lipid peroxidation and antioxidant system, endotoxicosis syndrome

  5. RF/Optical Demonstration: Focal Plane Assembly

    Science.gov (United States)

    Hoppe, D. J.; Chung, S.; Kovalik, J.; Gama, E.; Fernandez, M. M.

    2016-11-01

    In this article, we describe the second-generation focal plane optical assembly employed in the RF/optical demonstration at DSS-13. This assembly receives reflected light from the two mirror segments mounted on the RF primary. The focal plane assembly contains a fast steering mirror (FSM) to stabilize the focal plane spot, a pupil camera to aid in aligning the two segments, and several additional cameras for receiving the optical signal prior to as well as after the FSM loop.

  6. Large Format Uncooled Focal Plane Array Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Black Forest Engineering has identified innovative modifications in uncooled focal plane array (UFPA) architecture and processing that allows development of large...

  7. Treatment of experimental human breast cancer and lung cancer brain metastases in mice by macitentan, a dual antagonist of endothelin receptors, combined with paclitaxel.

    Science.gov (United States)

    Lee, Ho Jeong; Hanibuchi, Masaki; Kim, Sun-Jin; Yu, Hyunkyung; Kim, Mark Seungwook; He, Junqin; Langley, Robert R; Lehembre, François; Regenass, Urs; Fidler, Isaiah J

    2016-04-01

    We recently demonstrated that brain endothelial cells and astrocytes protect cancer cells from chemotherapy through an endothelin-dependent signaling mechanism. Here, we evaluated the efficacy of macitentan, a dual endothelin receptor (ETAR and ETBR) antagonist, in the treatment of experimental breast and lung cancer brain metastases. The effect of macitentan on astrocyte- and brain endothelial cell-mediated chemoprotective properties was measured in cytotoxic assays. We compared survival of mice bearing established MDA-MB-231 breast cancer or PC-14 non-small cell lung cancer (NSCLC) brain metastases that were treated with vehicle, macitentan, paclitaxel, or macitentan plus paclitaxel. Cell division, apoptosis, tumor vasculature, and expression of survival-related proteins were assessed by immunofluorescent microscopy. Cancer cells and tumor-associated endothelial cells expressed activated forms of AKT and MAPK in vehicle- and paclitaxel-treated groups in both metastasis models, but these proteins were downregulated in metastases of mice that received macitentan. The survival-related proteins Bcl2L1, Gsta5, and Twist1 that localized to cancer cells and tumor-associated endothelial cells in vehicle- and paclitaxel-treated tumors were suppressed by macitentan. Macitentan or paclitaxel alone had no effect on survival. However, when macitentan was combined with paclitaxel, we noted a significant reduction in cancer cell division and marked apoptosis of both cancer cells and tumor-associated endothelial cells. Moreover, macitentan plus paclitaxel therapy significantly increased overall survival by producing complete responses in 35 of 35 mice harboring brain metastases. Dual antagonism of ETAR and ETBR signaling sensitizes experimental brain metastases to paclitaxel and may represent a new therapeutic option for patients with brain metastases. © The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved

  8. Transcranial Magnetic Stimulation-coil design with improved focality

    Science.gov (United States)

    Rastogi, P.; Lee, E. G.; Hadimani, R. L.; Jiles, D. C.

    2017-05-01

    Transcranial Magnetic Stimulation (TMS) is a technique for neuromodulation that can be used as a non-invasive therapy for various neurological disorders. In TMS, a time varying magnetic field generated from an electromagnetic coil placed on the scalp is used to induce an electric field inside the brain. TMS coil geometry plays an important role in determining the focality and depth of penetration of the induced electric field responsible for stimulation. Clinicians and basic scientists are interested in stimulating a localized area of the brain, while minimizing the stimulation of surrounding neural networks. In this paper, a novel coil has been proposed, namely Quadruple Butterfly Coil (QBC) with an improved focality over the commercial Figure-8 coil. Finite element simulations were conducted with both the QBC and the conventional Figure-8 coil. The two coil's stimulation profiles were assessed with 50 anatomically realistic MRI derived head models. The coils were positioned on the vertex and the scalp over the dorsolateral prefrontal cortex to stimulate the brain. Computer modeling of the coils has been done to determine the parameters of interest-volume of stimulation, maximum electric field, location of maximum electric field and area of stimulation across all 50 head models for both coils.

  9. Treatment with the NK1 antagonist emend reduces blood brain barrier dysfunction and edema formation in an experimental model of brain tumors.

    Directory of Open Access Journals (Sweden)

    Elizabeth Harford-Wright

    Full Text Available The neuropeptide substance P (SP has been implicated in the disruption of the blood-brain barrier (BBB and development of cerebral edema in acute brain injury. Cerebral edema accumulates rapidly around brain tumors and has been linked to several tumor-associated deficits. Currently, the standard treatment for peritumoral edema is the corticosteroid dexamethasone, prolonged use of which is associated with a number of deleterious side effects. As SP is reported to increase in many cancer types, this study examined whether SP plays a role in the genesis of brain peritumoral edema. A-375 human melanoma cells were injected into the right striatum of male Balb/c nude mice to induce brain tumor growth, with culture medium injected in animals serving as controls. At 2, 3 or 4 weeks following tumor cell inoculation, non-treated animals were perfusion fixed for immunohistochemical detection of Albumin, SP and NK1 receptor. A further subgroup of animals was treated with a daily injection of the NK1 antagonist Emend (3 mg/kg, dexamethasone (8 mg/kg or saline vehicle at 3 weeks post-inoculation. Animals were sacrificed a week later to determine BBB permeability using Evan's Blue and brain water content. Non-treated animals demonstrated a significant increase in albumin, SP and NK1 receptor immunoreactivity in the peritumoral area as well as increased perivascular staining in the surrounding brain tissue. Brain water content and BBB permeability was significantly increased in tumor-inoculated animals when compared to controls (p<0.05. Treatment with Emend and dexamethasone reduced BBB permeability and brain water content when compared to vehicle-treated tumor-inoculated mice. The increase in peritumoral staining for both SP and the NK1 receptor, coupled with the reduction in brain water content and BBB permeability seen following treatment with the NK1 antagonist Emend, suggests that SP plays a role in the genesis of peritumoral edema, and thus warrants

  10. Neuroproteomics and Systems Biology Approach to Identify Temporal Biomarker Changes Post Experimental Traumatic Brain Injury in Rats

    Directory of Open Access Journals (Sweden)

    Firas H Kobeissy

    2016-11-01

    Full Text Available Traumatic brain injury (TBI represents a critical health problem of which diagnosis, management and treatment remain challenging. TBI is a contributing factor in approximately 1/3 of all injury-related deaths in the United States. The Centers for Disease Control and Prevention (CDC estimate that 1.7 million TBI people suffer a TBI in the United States annually. Efforts continue to focus on elucidating the complex molecular mechanisms underlying TBI pathophysiology and defining sensitive and specific biomarkers that can aid in improving patient management and care. Recently, the area of neuroproteomics-systems biology is proving to be a prominent tool in biomarker discovery for central nervous system (CNS injury and other neurological diseases. In this work, we employed the controlled cortical impact (CCI model of experimental TBI in rat model to assess the temporal-global proteome changes after acute (1 day and for the first time, subacute (7 days, post-injury time frame using the established CAX-PAGE LC-MS/MS platform for protein separation combined with discrete systems biology analyses to identify temporal biomarker changes related to this rat TBI model. Rather than focusing on any one individual molecular entities, we used in silico systems biology approach to understand the global dynamics that govern proteins that are differentially altered post-injury. In addition, gene ontology analysis of the proteomic data was conducted in order to categorize the proteins by molecular function, biological process, and cellular localization. Results show alterations in several proteins related to inflammatory responses and oxidative stress in both acute (1 day and subacute (7 days periods post TBI. Moreover, results suggest a differential upregulation of neuroprotective proteins at 7-days post-CCI involved in cellular functions such as neurite growth, regeneration, and axonal guidance. Our study is amongst the first to assess temporal neuroproteome

  11. Experimental and theoretical study of Bragg-Fresnel focalizing optical systems engraved on multi layers interferential mirrors adapted to X and X-UV fields; Etude experimentale et theorique d`optiques focalisantes de type Bragg-Fresnel gravees sur des miroirs interferentiels multicouches adaptes aux domaines X et X-UV

    Energy Technology Data Exchange (ETDEWEB)

    Idir, M.

    1995-02-01

    This work concerns the study of a particular type of X-ray focusing optics known as Bragg-Fresnel lenses, formed through ion-etching of multilayered structures. Using the Super-ACO (LURE/Orsay) synchrotron storage ring, we tested several Bragg-Fresnel lenses having either linear or elliptical geometries (producing a line or a point focus, respectively). Diffraction profiles were first obtained for the linear lenses ion-etched on W/Si multilayers of nano-metric period. The experimental results were compared with our theoretical predictions. We next proposed and tested a solution to the problem superposing the different diffraction orders in the focal plane, that of fabricating Bragg-Fresnel lenses with an off-axis configuration, first for the linear and then the elliptical geometry. An experimental application, for an off-axis elliptical lens produced a focused X-ray spot of 5 x 10 microns{sup 2} for the Super-ACO synchrotron source. The same lens also produced a 1/3-size X-ray image of a grid-like object at 1750 eV using the first and third diffraction orders. (author).

  12. [Characteristics of structural injuries in pediatric patients with focal epilepsy in a Honduran hospital].

    Science.gov (United States)

    Ramirez-Izcoa, A; Varela-Gonzalez, D; Fonseca, M I

    2017-08-01

    Epilepsy is the most commonly occurring neurological disorder in the world. The study of structural brain lesions is important to understand the secondary complications. In Honduras there is little information on this topic. To determine the characteristics and proportion of structural brain lesions in paediatric patients with focal epilepsy at the Hospital Escuela Universitario. A descriptive, cross-sectional, retrospective-prospective study. The study population consisted of 162 paediatric patients with focal epilepsy who were treated in the paediatric neurology outpatient department between January 2015 and June 2016. On applying the eligibility and exclusion criteria, the universe of study comprised 102 patients with focal epilepsy. 41% of the patients with focal epilepsy presented a structural lesion. The main locations of the structural lesions were the parietal lobe (12.8%), the occipital lobe (10.8%) and the frontal lobe (10.8%). An association was found between the presence of structural brain lesions and the presence of uncontrolled seizures, with statistical significance. The attributable risk was calculated and it was found that among patients with uncontrolled seizures, 67% had a structural lesion in the imaging study. The presence of uncontrolled seizures is associated to the presence of structural lesions in imaging studies, with a high attributable risk. Leukomalacia and cerebral ischaemia were the main findings that were reported. The predominant structural lesions in paediatric patients with focal epilepsy in the population studied are those related to events that take place during the peripartum period.

  13. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jung Kyu; Cho, Jeong Yeon; Lee, Young Ho; Kim, Ei Jeong; Chun, Yi Kyeong [Samsung Cheil Hospital, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-09-15

    Focal musculoskeletal anomalies are various and may be an isolated finding or may be found in conjunction with numerous associations, including genetic syndromes, Karyotype abnormals, central nervous system anomalies and other general musculoskeletal disorders. Early prenatal diagnosis of these focal musculoskeletal anomalies nor only affects prenatal care and postnatal outcome but also helps in approaching other numerous associated anomalies.

  14. Focal-plane sensor-processor chips

    CERN Document Server

    Zarándy, Ákos

    2011-01-01

    Focal-Plane Sensor-Processor Chips explores both the implementation and application of state-of-the-art vision chips. Presenting an overview of focal plane chip technology, the text discusses smart imagers and cellular wave computers, along with numerous examples of current vision chips.

  15. Intravenous xenotransplantation of human placental mesenchymal stem cells to rats: comparative analysis of homing in rat brain in two models of experimental ischemic stroke.

    Science.gov (United States)

    Kholodenko, I V; Yarygin, K N; Gubsky, L V; Konieva, A A; Tairova, R T; Povarova, O V; Kholodenko, R V; Burunova, V V; Yarygin, V N; Skvortsova, V I

    2012-11-01

    Mesenchymal stem cells from human placenta obtained after term natural delivery were cultured and labeled with vital dye Dil of magnetic fluorescing microparticles. The labeled cells were transplanted intravenously to rats with occlusion of the median cerebral artery. Penetration of cells through the brain-blood barrier and their distribution in the brain of experimental animals were studied on serial cryostat sections. Two models of cerebral artery occlusion associated with different traumatic consequences were used. The efficiency of crossing the blood-brain barrier by transplanted cells, the number of mesenchymal cells attaining the ischemic focus and neurogenic zones, and the time of death of transplanted cells largely depended on the degree and nature of injury to the central nervous system, which should be taken into account when planning the experiments for evaluation of the effects of cell therapy on the models of neurological diseases and in clinical studies in the field of regenerative neurology.

  16. Focal therapy for prostate cancer. Alternative treatment.

    Science.gov (United States)

    Gómez-Veiga, F; Martínez-Breijo, S; Solsona-Narbón, E; Hernández, C; Ciudin, A; Ribal, M J; Dickinson, L; Moore, C; Ahmed, H; Rodríguez Antolín, A; Breda, A; Gaya, J; Portela-Pereira, P; Emberton, M

    2014-09-01

    The great controversy surrounding the treatment of localized prostate cancer is related with its possibilities of radical treatment or active surveillance. The objective of this paper is to analyze the rationale selection among current focal therapy modalities regarding tumor and patient selection. Current articles about advantages and disadvantages on the treatment of localized prostate cancer as well as information about focal therapy regarding tumour selection, characteristics and indications cited in MEDLINE search were reviewed. Focal therapy standardized criteria must be: low risk tumors, PSA15. Focal therapy is an alternative for localized prostate cancer treatment. However, some aspects of their diagnosis and selection criteria should be defined by prospective studies which should provide knowledge about the indication for focal therapy. Copyright © 2013 AEU. Published by Elsevier Espana. All rights reserved.

  17. Research and implementation of the integrated cooling system for focal plate

    Science.gov (United States)

    Wang, Jianping; Cheng, Lixuan; Chu, Jiaru; Hu, Hongzhuan; Zhou, Zengxiang

    2016-07-01

    With the rapid development of multi-objective astronomical survey telescope technology, the heat of focal plate which high-density optical fiber positioners were mounted in has become the key factor of system precision. The new integrated cooling system designed multi curved composite grooves on the surface of focal plate for forced convection was proposed. Meanwhile, the manufacturing process, sealing structure and heat dissipation performance of the system were analyzed and tested with detail in the paper. The experimental results suggested that the new integrated cooling system of focal plate has a fast response speed and good heat dissipation performance.

  18. Germline and somatic mutations in the MTOR gene in focal cortical dysplasia and epilepsy

    DEFF Research Database (Denmark)

    Møller, Rikke S; Weckhuysen, Sarah; Chipaux, Mathilde

    2016-01-01

    OBJECTIVE: To assess the prevalence of somatic MTOR mutations in focal cortical dysplasia (FCD) and of germline MTOR mutations in a broad range of epilepsies. METHODS: We collected 20 blood-brain paired samples from patients with FCD and searched for somatic variants using deep-targeted gene panel...... sequencing. Germline mutations in MTOR were assessed in a French research cohort of 93 probands with focal epilepsies and in a diagnostic Danish cohort of 245 patients with a broad range of epilepsies. Data sharing among collaborators allowed us to ascertain additional germline variants in MTOR. RESULTS: We...... frontal lobe epilepsy. CONCLUSIONS: Our data illustrate the increasingly important role of somatic mutations of the MTOR gene in FCD and germline mutations in the pathogenesis of focal epilepsy syndromes with and without brain malformation or macrocephaly....

  19. The Effects of Experimental Fresh Water Drowning on the Organ Weights of the Lungs Livers Brains Hearts and Kidneys of Rats

    Directory of Open Access Journals (Sweden)

    Gülşin Canoğulları Kul

    2011-04-01

    Full Text Available This study was aimed to compare the organ weights in experimentally drowned and post-mortem immersed rats. The experimentations were conducted on 50 rats divided into 5 groups including 10 rats with the consent of Faculty Ethical Committee. The autopsies were done in a total of 50 Wistar Albino adult rats that sacrificed by an anesthetics overdose and subsequently dissected (Group 1: control group, experimental drowned (Group 2, anesthetized and sacrificed with ante-mortem open wounds, immersed for 24 hours (Group 3, sacrificed with an overdose of anesthetics and then immersed for 24 hours (Group 4 and 72 hours (Group 5. The weights of organs obtained during the autopsies were compared among experimentation groups. Whereas lung, liver, brain and right kidney weights decreased in the 72 hours post-mortem immersion group compared to the 24 hours post-mortem immersion group, the mean organ weights for the lung, liver, brain and right kidney increased (with mean increases of 55.1%, 24.3 %, 14.9 % and 10.5 % respectively in the experimental drowning group compared to 24 hours post-mortem immersion group. Only the mean heart weight was not statistically different among the groups. The amount of fluid influx into the alveoli due to hydrostatic pressure is not as much as exogenous water inhaled into the lungs during experimental drowning. The decrease of lung, liver, brain and kidney weights in the 72 hours immersion group might be associated with the effects of putrefaction compared to the 24 hours post-mortem immersion group. Key words: Drowning, post-mortem changes, organ weight.

  20. In vitro and in vivo effects of a novel dimeric inhibitor of PSD-95 on excitotoxicity and functional recovery after experimental traumatic brain injury

    DEFF Research Database (Denmark)

    Sommer, Jens Bak; Bach, Anders; Rytter, Hana Malá

    2017-01-01

    PSD-95 inhibitors have been shown to be neuroprotective in stroke, but have only to a very limited extent been evaluated in the treatment of traumatic brain injury (TBI) that has pathophysiological mechanisms in common with stroke. The aims of the current study were to assess the effects of a nov...... studies taking important experimental factors such as timing of treatment, dosage, and anesthesia into consideration....

  1. Suggestions to Reduce Clinical Fibromyalgia Pain and Experimentally Induced Pain Produce Parallel Effects on Perceived Pain but Divergent Functional MRI-Based Brain Activity.

    Science.gov (United States)

    Derbyshire, Stuart W G; Whalley, Matthew G; Seah, Stanley T H; Oakley, David A

    Hypnotic suggestion is an empirically validated form of pain control; however, the underlying mechanism remains unclear. Thirteen fibromyalgia patients received suggestions to alter their clinical pain, and 15 healthy controls received suggestions to alter experimental heat pain. Suggestions were delivered before and after hypnotic induction with blood oxygen level-dependent (BOLD) activity measured concurrently. Across groups, suggestion produced substantial changes in pain report (main effect of suggestion, F2, 312 = 585.8; p pain report in regions previously associated with pain, including thalamus and anterior cingulate cortex. In controls, BOLD response decreased with pain report. All changes were greater after induction. Region-of-interest analysis revealed largely linear patient responses with increasing pain report. Control responses, however, were higher after suggestion to increase or decrease pain from baseline. Based on behavioral report alone, the mechanism of suggestion could be interpreted as largely similar regardless of the induction or type of pain experience. The functional magnetic resonance imaging data, however, demonstrated larger changes in brain activity after induction and a radically different pattern of brain activity for clinical pain compared with experimental pain. These findings imply that induction has an important effect on underlying neural activity mediating the effects of suggestion, and the mechanism of suggestion in patients altering clinical pain differs from that in controls altering experimental pain. Patient responses imply that suggestions altered pain experience via corresponding changes in pain-related brain regions, whereas control responses imply suggestion engaged cognitive control.

  2. Left Hippocampal Pathology Is Associated with Atypical Language Lateralization in Patients with Focal Epilepsy

    Science.gov (United States)

    Weber, Bernd; Wellmer, Jorg; Reuber, Markus; Mormann, Florian; Weis, Susanne; Urbach, Horst; Ruhlmann, Jurgen; Elger, Christian E.; Fernandez, Guillen

    2006-01-01

    It is well recognized that the incidence of atypical language lateralization is increased in patients with focal epilepsy. The hypothesis that shifts in language dominance are particularly likely when epileptic lesions are located in close vicinity to the so-called language-eloquent areas rather than in more remote brain regions such as the…

  3. Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat

    NARCIS (Netherlands)

    Buttini, M; Appel, K; Sauter, A; GebickeHaerter, PJ; Boddeke, HWGM

    Induction of tumor necrosis factor alpha was studied in the brain of rats after focal cerebral ischaemia by occlusion of the left middle cerebral artery. Using a specific antisense riboprobe for in situ hybridization histochemistry, cells positive for tumor necrosis factor alpha messenger RNA were

  4. Germline and somatic mutations in the MTOR gene in focal cortical dysplasia and epilepsy

    Science.gov (United States)

    Møller, Rikke S.; Weckhuysen, Sarah; Chipaux, Mathilde; Marsan, Elise; Taly, Valerie; Bebin, E. Martina; Hiatt, Susan M.; Prokop, Jeremy W.; Bowling, Kevin M.; Mei, Davide; Conti, Valerio; de la Grange, Pierre; Ferrand-Sorbets, Sarah; Dorfmüller, Georg; Lambrecq, Virginie; Larsen, Line H.G.; Leguern, Eric; Guerrini, Renzo; Rubboli, Guido; Cooper, Gregory M.

    2016-01-01

    Objective: To assess the prevalence of somatic MTOR mutations in focal cortical dysplasia (FCD) and of germline MTOR mutations in a broad range of epilepsies. Methods: We collected 20 blood-brain paired samples from patients with FCD and searched for somatic variants using deep-targeted gene panel sequencing. Germline mutations in MTOR were assessed in a French research cohort of 93 probands with focal epilepsies and in a diagnostic Danish cohort of 245 patients with a broad range of epilepsies. Data sharing among collaborators allowed us to ascertain additional germline variants in MTOR. Results: We detected recurrent somatic variants (p.Ser2215Phe, p.Ser2215Tyr, and p.Leu1460Pro) in the MTOR gene in 37% of participants with FCD II and showed histologic evidence for activation of the mTORC1 signaling cascade in brain tissue. We further identified 5 novel de novo germline missense MTOR variants in 6 individuals with a variable phenotype from focal, and less frequently generalized, epilepsies without brain malformations, to macrocephaly, with or without moderate intellectual disability. In addition, an inherited variant was found in a mother–daughter pair with nonlesional autosomal dominant nocturnal frontal lobe epilepsy. Conclusions: Our data illustrate the increasingly important role of somatic mutations of the MTOR gene in FCD and germline mutations in the pathogenesis of focal epilepsy syndromes with and without brain malformation or macrocephaly. PMID:27830187

  5. Induction of interleukin-1β mRNA after focal cerebral ischaemia in the rat

    NARCIS (Netherlands)

    Buttini, M.; Sauter, A.; Boddeke, H.W.G.M.

    1994-01-01

    The expression of interleukin-1β (IL-1β) mRNA in the brain in response to cerebral ischaemia in rats was examined using in situ hybridization histochemistry. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent occlusion of the left middle cerebral artery (MCAO).

  6. INDUCTION OF INTERLEUKIN-1-BETA MESSENGER-RNA AFTER FOCAL CEREBRAL-ISCHEMIA IN THE RAT

    NARCIS (Netherlands)

    BUTTINI, M; SAUTER, A; BODDEKE, HWGM

    The expression of interleukin-1beta (IL-1beta) mRNA in the brain in response to cerebral ischaemia in rats was examined using in situ hybridization histochemistry. Focal cerebral ischaemia was induced in spontaneously hypertensive rats by permanent occlusion of the left middle cerebral artery

  7. Fructose-1,6-bisphosphate supports cerebral energy metabolism in pigs after ischemic brain injury caused by experimental particle embolization.

    Science.gov (United States)

    Kaakinen, Timo; Heikkinen, Janne; Dahlbacka, Sebastian; Alaoja, Hanna; Laurila, Päivi; Kiviluoma, Kai; Salomäki, Timo; Romsi, Pekka; Tuominen, Hannu; Biancari, Fausto; Lepola, Pasi; Nuutinen, Matti; Juvonen, Tatu

    2006-01-01

    Fructose-1,6-bisphosphate (FDP) is a high-energy intermediate that enhances glycolysis, preserves cellular adenosine triphosphate stores, and prevents the increase of intracellular calcium in ischemic tissue. Since it has been shown to provide metabolic support to the brain during ischemia, we planned this study to evaluate whether FDP is neuroprotective in the setting of combining hypothermic circulatory arrest (HCA) and irreversible embolic brain ischemic injury. Twenty pigs were randomly assigned to receive 2 intravenous infusions of either FDP (500 mg/kg) or saline. The first infusion was given just before a 25-minute period of HCA and the second infusion immediately after HCA. Immediately before HCA, the descending aorta was clamped and 200 mg of albumin-coated polystyrene microspheres (250-750 mm in diameter) were injected into the isolated aortic arch in both study groups. There were no significant differences between the study groups in terms of neurological outcome. Brain lactate/pyruvate ratio was significantly lower (P = .015) and brain pyruvate levels (P = .013) were significantly higher in the FDP group compared with controls. Brain lactate levels were significantly higher 8 hours after HCA (P = .049). The administration of FDP before and immediately after HCA combined with embolic brain ischemic injury was associated with significantly lower brain lactate/pyruvate ratio and significantly higher levels of brain pyruvate, as well as lower lactate levels 8 hours after HCA. FDP seems to protect the brain by supporting energy metabolism. The neurological outcome was not improved, most likely resulting from the irreversible nature of the microsphere occlusion.

  8. Rat model of focal cerebral ischemia in the dominant hemisphere.

    Science.gov (United States)

    Zhang, Hua; Shen, Yan; Wang, Wei; Gao, Huanmin

    2015-01-01

    In the human brain, the dominant hemisphere is more complex than the non-dominant hemisphere. Hence, cerebral ischemia of the dominant hemisphere often leads to serious consequences. This study aims to establish a rodent model of focal cerebral ischemia in the dominant hemisphere. The quadruped feeding test was used to screen 70 male Sprague Dawley rats. From this test, 48 rats with right paw preference were selected and randomly assigned numbers. Half were assigned to the dominant hemisphere ischemia (DHI) group, and the other half were assigned to the non-dominant hemisphere ischemia (NDHI) group. The middle cerebral artery was occluded 2 h before reperfusion. Neurological functions were tested. TTC and HE staining were performed. The volume of cerebral infarction was calculated. Rats in the DHI group had significantly worse neurological scores than rats in the NDHI group (P dominant hemisphere than in the non-dominant hemisphere. The dominant hippocampus indicated severe neuronal loss and disorderly cellular arrangement. The volume of cerebral infarction was also greater in the DHI group compared to the NDHI group (P dominant hemisphere, MCA occlusion in the dominant hemisphere caused greater impairment in neurological functions. The proposed rodent model is reliable and has high levels of reproducibility. Therefore, his model can be reliably for investigating the mechanism of focal cerebral ischemia in the dominant hemisphere of human brains.

  9. Scintigraphic imaging of focal hypoxic tissue: development and clinical applications of {sup 123} I-IAZA

    Energy Technology Data Exchange (ETDEWEB)

    Wiebe, Leonard I.; McEwan, Alexander J.B. [Alberta Univ., Edmonton (Canada); Cross Cancer Institute, Edmonton (Canada); E-mail: leonard.wiebe@ualberta.ca

    2002-09-01

    Affected tissues in a number of diseases, including cancer, stroke, cardiac infarction and diabetes, develop focal tissue hypoxia during their progression. Tbe presence of hypoxic tissue may make the disease refractory to therapy, as in the case of solid tumor therapy using low LET ionizing radiation. In other pathologies, the detection of viable but hypoxic tissues may serve as a prodromal indicator of developing disease (e.g. diabetes), or as a prognostic indicator for management of the disease (e.g. stroke). Over the past two decades a number of hypoxia radio imaging agents have been developed and tested clinically. Of these, {sup 18} F-Fm iso and {sup 123} I - IAZA are the most widely used radiotracers for PET and SPECT/planar imaging, respectively. IAZA and Fm iso are a 2-nitroimidazoles that chemically bind to subcellular components of viable hypoxic tissues. They sensitize hypoxic tumor to the killing effects of ionizing radiation via mechanisms that mimic the radiosensitizing effects of oxygen, and are therefore called oxygen mimetic. The oxygen mimetic effect is attributable in large part to the covalent binding of reductively-activated nitroimidazole intermediates to critical cellular macromolecules. Nitroimidazoles labelled with gamma-emitting radionuclides (e.g. {sup 18} F-Fm iso and {sup 123} I -IAZA) have been used as scintigraphic markers of tumour hypoxia, based on the need to identify radioresistant hypoxic tumour cells as part of the radiotherapy planning process. Broader interest in non-invasive, imaging-based identification of focal hypoxia in a number of diseases has extended hypoxia studies to include peripheral vascular disease associated with diabetes, rheumatoid arthritis, stroke, myocardial ischaemia, brain trauma and oxidative stress. In this review, the current status of hypoxia-selective studies with {sup 123} I - IAZA, an experimental diagnostic radiopharmaceutical, is reviewed with respect to its pre-clinical development and clinical

  10. Physical Exercise Attenuates Experimental Autoimmune Encephalomyelitis by Inhibiting Peripheral Immune Response and Blood-Brain Barrier Disruption.

    Science.gov (United States)

    Souza, Priscila S; Gonçalves, Elaine D; Pedroso, Giulia S; Farias, Hemelin R; Junqueira, Stella C; Marcon, Rodrigo; Tuon, Talita; Cola, Maíra; Silveira, Paulo C L; Santos, Adair R; Calixto, João B; Souza, Cláudio T; de Pinho, Ricardo A; Dutra, Rafael C

    2017-08-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system (CNS) caused by demyelination, immune cell infiltration, and axonal damage. Herein, we sought to investigate the influence of physical exercise on mice experimental autoimmune encephalomyelitis (EAE), a reported MS model. Data show that both strength and endurance training protocols consistently prevented clinical signs of EAE and decreased oxidative stress, an effect which was likely due to improving genomic antioxidant defense-nuclear factor erythroid 2-related factor (Nrf2)/antioxidant response elements (ARE) pathway-in the CNS. In addition, physical exercise inhibited the production of pro-inflammatory cytokines interferon (IFN)-γ, interleukin (IL)-17, and IL-1β in the spinal cord of mice with EAE. Of note, spleen cells obtained from strength training group incubated with MOG 35-55 showed a significant upregulation of CD25 and IL-10 levels, with a decrease of IL-6, MCP-1, and tumor necrosis factor (TNF)-α production, mainly, during acute and chronic phase of EAE. Moreover, these immunomodulatory effects of exercise were associated with reduced expression of adhesion molecules, especially of platelet and endothelial cell adhesion molecule 1 (PECAM-1). Finally, physical exercise also restored the expression of tight junctions in spinal cord. Together, these results demonstrate that mild/moderate physical exercise, when performed regularly in mice, consistently attenuates the progression and pathological hallmarks of EAE, thereby representing an important non-pharmacological intervention for the improvement of immune-mediated diseases such as MS. Graphical Abstract Schematic diagram illustrating the beneficial effects of physical exercise during experimental model of MS. Physical exercise, especially strength (ST) and endurance (ET) training protocols, inhibits the development and progression of disease, measured by the mean maximal clinical score (1.5 and 1.0, respectively

  11. Salidroside improves behavioral and histological outcomes and reduces apoptosis via PI3K/Akt signaling after experimental traumatic brain injury.

    Science.gov (United States)

    Chen, Szu-Fu; Tsai, Hsin-Ju; Hung, Tai-Ho; Chen, Chien-Cheng; Lee, Chao Yu; Wu, Chun-Hu; Wang, Pei-Yi; Liao, Nien-Chieh

    2012-01-01

    Traumatic brain injury (TBI) induces a complex sequence of apopototic cascades that contribute to secondary tissue damage. The aim of this study was to investigate the effects of salidroside, a phenolic glycoside with potent anti-apoptotic properties, on behavioral and histological outcomes, brain edema, and apoptosis following experimental TBI and the possible involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K)/Akt signaling pathway. Mice subjected to controlled cortical impact injury received intraperitoneal salidroside (20, or 50 mg/kg) or vehicle injection 10 min after injury. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of PI3K/Akt signaling-related molecules, apoptosis-related proteins, cytochrome C (CytoC), and Smac/DIABLO were also analyzed. LY294002, a PI3K inhibitor, was administered to examine the mechanism of protection. The protective effect of salidroside was also investigated in primary cultured neurons subjected to stretch injury. Treatment with 20 mg/kg salidroside significantly improved functional recovery and reduced brain tissue damage up to post-injury day 28. Salidroside also significantly reduced neuronal death, apoptosis, and brain edema at day 1. These changes were associated with significant decreases in cleaved caspase-3, CytoC, and Smac/DIABLO at days 1 and 3. Salidroside increased phosphorylation of Akt on Ser473 and the mitochondrial Bcl-2/Bax ratio at day 1, and enhanced phosphorylation of Akt on Thr308 at day 3. This beneficial effect was abolished by pre-injection of LY294002. Moreover, delayed administration of salidroside at 3 or 6 h post-injury reduced neuronal damage at day 1. Salidroside treatment also decreased neuronal vulnerability to stretch-induced injury in vitro. Post-injury salidroside improved long-term behavioral and histological outcomes and reduced brain edema and apoptosis following TBI, at least partially via the PI3K/Akt signaling pathway.

  12. Salidroside improves behavioral and histological outcomes and reduces apoptosis via PI3K/Akt signaling after experimental traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Szu-Fu Chen

    Full Text Available Traumatic brain injury (TBI induces a complex sequence of apopototic cascades that contribute to secondary tissue damage. The aim of this study was to investigate the effects of salidroside, a phenolic glycoside with potent anti-apoptotic properties, on behavioral and histological outcomes, brain edema, and apoptosis following experimental TBI and the possible involvement of the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt signaling pathway.Mice subjected to controlled cortical impact injury received intraperitoneal salidroside (20, or 50 mg/kg or vehicle injection 10 min after injury. Behavioral studies, histology analysis and brain water content assessment were performed. Levels of PI3K/Akt signaling-related molecules, apoptosis-related proteins, cytochrome C (CytoC, and Smac/DIABLO were also analyzed. LY294002, a PI3K inhibitor, was administered to examine the mechanism of protection. The protective effect of salidroside was also investigated in primary cultured neurons subjected to stretch injury. Treatment with 20 mg/kg salidroside significantly improved functional recovery and reduced brain tissue damage up to post-injury day 28. Salidroside also significantly reduced neuronal death, apoptosis, and brain edema at day 1. These changes were associated with significant decreases in cleaved caspase-3, CytoC, and Smac/DIABLO at days 1 and 3. Salidroside increased phosphorylation of Akt on Ser473 and the mitochondrial Bcl-2/Bax ratio at day 1, and enhanced phosphorylation of Akt on Thr308 at day 3. This beneficial effect was abolished by pre-injection of LY294002. Moreover, delayed administration of salidroside at 3 or 6 h post-injury reduced neuronal damage at day 1. Salidroside treatment also decreased neuronal vulnerability to stretch-induced injury in vitro.Post-injury salidroside improved long-term behavioral and histological outcomes and reduced brain edema and apoptosis following TBI, at least partially via the PI3K/Akt signaling

  13. Large Format Uncooled Focal Plane Array Project

    Data.gov (United States)

    National Aeronautics and Space Administration — Uncooled focal plane arrays have improved dramatically and array sizes of 320x240 elements in a 50-?m pitch are commercially available at affordable cost. Black...

  14. Heme oxygenase-1 plays a pro-life role in experimental brain stem death via nitric oxide synthase I/protein kinase G signaling at rostral ventrolateral medulla

    Directory of Open Access Journals (Sweden)

    Dai Kuang-Yu

    2010-09-01

    Full Text Available Abstract Background Despite its clinical importance, a dearth of information exists on the cellular and molecular mechanisms that underpin brain stem death. A suitable neural substrate for mechanistic delineation on brain stem death resides in the rostral ventrolateral medulla (RVLM because it is the origin of a life-and-death signal that sequentially increases (pro-life and decreases (pro-death to reflect the advancing central cardiovascular regulatory dysfunction during the progression towards brain stem death in critically ill patients. The present study evaluated the hypothesis that heme oxygnase-1 (HO-1 may play a pro-life role as an interposing signal between hypoxia-inducible factor-1 (HIF-1 and nitric oxide synthase I (NOS I/protein kinase G (PKG cascade in RVLM, which sustains central cardiovascular regulatory functions during brain stem death. Methods We performed cardiovascular, pharmacological, biochemical and confocal microscopy experiments in conjunction with an experimental model of brain stem death that employed microinjection of the organophosphate insecticide mevinphos (Mev; 10 nmol bilaterally into RVLM of adult male Sprague-Dawley rats. Results Western blot analysis coupled with laser scanning confocal microscopy revealed that augmented HO-1 expression that was confined to the cytoplasm of RVLM neurons occurred preferentially during the pro-life phase of experimental brain stem death and was antagonized by immunoneutralization of HIF-1α or HIF-1β in RVLM. On the other hand, the cytoplasmic presence of HO-2 in RVLM neurons manifested insignificant changes during both phases. Furthermore, immunoneutralization of HO-1 or knockdown of ho-1 gene in RVLM blunted the augmented life-and-death signals exhibited during the pro-life phase. Those pretreatments also blocked the upregulated pro-life NOS I/PKG signaling without affecting the pro-death NOS II/peroxynitrite cascade in RVLM. Conclusions We conclude that transcriptional

  15. Expression and cellular distribution of multidrug transporter proteins in two major causes of medically intractable epilepsy: Focal cortical dysplasia and glioneuronal tumors

    NARCIS (Netherlands)

    Aronica, E.; Gorter, J. A.; Jansen, G. H.; van Veelen, C. W. M.; van Rijen, P. C.; Leenstra, S.; Ramkema, M.; Scheffer, G. L.; Scheper, R. J.; Troost, D.

    2003-01-01

    The cell-specific distribution of multidrug resistance extrusion pumps was studied in developmental glioneuronal lesions, including focal cortical dysplasia (15 cases) and ganglioglioma (15 cases) from patients with medically intractable epilepsy. Lesional, perilesional, as well as normal brain

  16. Large Focal Plane Arrays for Future Missions

    OpenAIRE

    Scowen, Paul A.; Nikzad, Shouleh; Hoenk, Michael; Gontijo, Ivair; Shapiro, Andrew; Greer, Frank; Jones, Todd; Seshadri, Suresh; Jacquot, Blake; Monacos, Steve; Lisman, Doug; Dickie, Matthew; Blacksberg, Jordana

    2009-01-01

    We outline the challenges associated with the development and construction of large focal plane arrays for use both on the ground and in space. Using lessons learned from existing JPL-led and ASU/JPL partnership efforts to develop technology for, and design such arrays and imagers for large focal planes, we enumerate here the remaining problems that need to be solved to make such a venture viable. Technologies we consider vital for further development include: (1) architectures, processes, ci...

  17. Hyperinsulinism: molecular aetiology of focal disease.

    Science.gov (United States)

    Ryan, F; Devaney, D; Joyce, C; Nestorowicz, A; Permutt, M A; Glaser, B; Barton, D E; Thornton, P S

    1998-11-01

    Persistent hypoglycaemia in infancy is most commonly caused by hyperinsulinism. A case is reported of the somatic loss of the maternal 11p in an insulin secreting focal adenoma in association with a germline SUR-1 mutation on the paternal allele in a baby boy with hyperinsulinism diagnosed at 49 days old. A reduction to homozygosity of an SUR-1 mutation is proposed as a critical part of the cause of focal hyperinsulinism.

  18. Experimental evaluation of electrical conductivity imaging of anisotropic brain tissues using a combination of diffusion tensor imaging and magnetic resonance electrical impedance tomography

    Directory of Open Access Journals (Sweden)

    Saurav Z. K. Sajib

    2016-06-01

    Full Text Available Anisotropy of biological tissues is a low-frequency phenomenon that is associated with the function and structure of cell membranes. Imaging of anisotropic conductivity has potential for the analysis of interactions between electromagnetic fields and biological systems, such as the prediction of current pathways in electrical stimulation therapy. To improve application to the clinical environment, precise approaches are required to understand the exact responses inside the human body subjected to the stimulated currents. In this study, we experimentally evaluate the anisotropic conductivity tensor distribution of canine brain tissues, using a recently developed diffusion tensor-magnetic resonance electrical impedance tomography method. At low frequency, electrical conductivity of the biological tissues can be expressed as a product of the mobility and concentration of ions in the extracellular space. From diffusion tensor images of the brain, we can obtain directional information on diffusive movements of water molecules, which correspond to the mobility of ions. The position dependent scale factor, which provides information on ion concentration, was successfully calculated from the magnetic flux density, to obtain the equivalent conductivity tensor. By combining the information from both techniques, we can finally reconstruct the anisotropic conductivity tensor images of brain tissues. The reconstructed conductivity images better demonstrate the enhanced signal intensity in strongly anisotropic brain regions, compared with those resulting from previous methods using a global scale factor.

  19. Experimental evaluation of electrical conductivity imaging of anisotropic brain tissues using a combination of diffusion tensor imaging and magnetic resonance electrical impedance tomography

    Energy Technology Data Exchange (ETDEWEB)

    Sajib, Saurav Z. K.; Jeong, Woo Chul; Oh, Tong In; Kim, Hyung Joong, E-mail: bmekim@khu.ac.kr, E-mail: ejwoo@khu.ac.kr; Woo, Eung Je, E-mail: bmekim@khu.ac.kr, E-mail: ejwoo@khu.ac.kr [Department of Biomedical Engineering, Kyung Hee University, Seoul 02447 (Korea, Republic of); Kyung, Eun Jung [Department of Pharmacology, Chung-Ang University, Seoul 06974 (Korea, Republic of); Kim, Hyun Bum [Department of East-West Medical Science, Kyung Hee University, Yongin 17104 (Korea, Republic of); Kwon, Oh In [Department of Mathematics, Konkuk University, Seoul 05029 (Korea, Republic of)

    2016-06-15

    Anisotropy of biological tissues is a low-frequency phenomenon that is associated with the function and structure of cell membranes. Imaging of anisotropic conductivity has potential for the analysis of interactions between electromagnetic fields and biological systems, such as the prediction of current pathways in electrical stimulation therapy. To improve application to the clinical environment, precise approaches are required to understand the exact responses inside the human body subjected to the stimulated currents. In this study, we experimentally evaluate the anisotropic conductivity tensor distribution of canine brain tissues, using a recently developed diffusion tensor-magnetic resonance electrical impedance tomography method. At low frequency, electrical conductivity of the biological tissues can be expressed as a product of the mobility and concentration of ions in the extracellular space. From diffusion tensor images of the brain, we can obtain directional information on diffusive movements of water molecules, which correspond to the mobility of ions. The position dependent scale factor, which provides information on ion concentration, was successfully calculated from the magnetic flux density, to obtain the equivalent conductivity tensor. By combining the information from both techniques, we can finally reconstruct the anisotropic conductivity tensor images of brain tissues. The reconstructed conductivity images better demonstrate the enhanced signal intensity in strongly anisotropic brain regions, compared with those resulting from previous methods using a global scale factor.

  20. Energetic, oxidative and ionic exchange in rat brain and liver mitochondria at experimental audiogenic epilepsy (Krushinsky-Molodkina model).

    Science.gov (United States)

    Venediktova, Natalya I; Gorbacheva, Olga S; Belosludtseva, Natalia V; Fedotova, Irina B; Surina, Natalia M; Poletaeva, Inga I; Kolomytkin, Oleg V; Mironova, Galina D

    2017-04-01

    The role of brain and liver mitochondria at epileptic seizure was studied on Krushinsky-Molodkina (KM) rats which respond to sound with an intensive epileptic seizure (audiogenic epilepsy). We didn't find significant changes in respiration rats of brain and liver mitochondria of KM and control rats; however the efficiency of АТР synthesis in the KM rat mitochondria was 10% lower. In rats with audiogenic epilepsy the concentration of oxidative stress marker malondialdehyde in mitochondria of the brain (but not liver) was 2-fold higher than that in the control rats. The rate of H 2 O 2 generation in brain mitochondria of КМ rats was twofold higher than in the control animals when using NAD-dependent substrates. This difference was less pronounced in liver mitochondria. In KM rats, the activity of mitochondrial ATP-dependent potassium channel was lower than in liver mitochondria of control rats. The comparative study of the mitochondria ability to retain calcium ions revealed that in the case of using the complex I and complex II substrates, permeability transition pore is easier to trigger in brain and liver mitochondria of KM and КМs rats than in the control ones. The role of the changes in the energetic, oxidative, and ionic exchange in the mechanism of audiogenic epilepsy generation in rats and the possible correction of the epilepsy seizures are discussed.

  1. The post-synaptic density of human postmortem brain tissues: an experimental study paradigm for neuropsychiatric illnesses.

    Directory of Open Access Journals (Sweden)

    Chang-Gyu Hahn

    Full Text Available Recent molecular genetics studies have suggested various trans-synaptic processes for pathophysiologic mechanisms of neuropsychiatric illnesses. Examination of pre- and post-synaptic scaffolds in the brains of patients would greatly aid further investigation, yet such an approach in human postmortem tissue has yet to be tested. We have examined three methods using density gradient based purification of synaptosomes followed by detergent extraction (Method 1 and the pH based differential extraction of synaptic membranes (Methods 2 and 3. All three methods separated fractions from human postmortem brains that were highly enriched in typical PSD proteins, almost to the exclusion of pre-synaptic proteins. We examined these fractions using electron microscopy (EM and verified the integrity of the synaptic membrane and PSD fractions derived from human postmortem brain tissues. We analyzed protein composition of the PSD fractions using two dimensional liquid chromatography tandem mass spectrometry (2D LC-MS/MS and observed known PSD proteins by mass spectrometry. Immunoprecipitation and immunoblot studies revealed that expected protein-protein interactions and certain posttranscriptional modulations were maintained in PSD fractions. Our results demonstrate that PSD fractions can be isolated from human postmortem brain tissues with a reasonable degree of integrity. This approach may foster novel postmortem brain research paradigms in which the stoichiometry and protein composition of specific microdomains are examined.

  2. 28 June 2012 - Members of the European Brain Council led by President Mary Baker visiting the LHC tunnel at Point 5 with Technology Department Group Leader L. Bottura and CMS experimental area with Run Coordinator M. Chamizo-Llatas.

    CERN Multimedia

    Jean-Claude Gadmer

    2012-01-01

    28 June 2012 - Members of the European Brain Council led by President Mary Baker visiting the LHC tunnel at Point 5 with Technology Department Group Leader L. Bottura and CMS experimental area with Run Coordinator M. Chamizo-Llatas.

  3. Electric field depth–focality tradeoff in transcranial magnetic stimulation: simulation comparison of 50 coil designs

    Science.gov (United States)

    Deng, Zhi-De; Lisanby, Sarah H.; Peterchev, Angel V.

    2012-01-01

    Background Various transcranial magnetic stimulation (TMS) coil designs are available or have been proposed. However, key coil characteristics such as electric field focality and attenuation in depth have not been adequately compared. Knowledge of the coil focality and depth characteristics can help TMS researchers and clinicians with coil selection and interpretation of TMS studies. Objective To quantify the electric field focality and depth of penetration of various TMS coils. Methods The electric field distributions induced by 50 TMS coils were simulated in a spherical human head model using the finite element method. For each coil design, we quantified the electric field penetration by the half-value depth, d1/2, and focality by the tangential spread, S1/2, defined as the half-value volume (V1/2) divided by the half-value depth, S1/2 = V1/2/d1/2. Results The 50 TMS coils exhibit a wide range of electric field focality and depth, but all followed a depth–focality tradeoff: coils with larger half-value depth cannot be as focal as more superficial coils. The ranges of achievable d1/2 are similar between coils producing circular and figure-8 electric field patterns, ranging 1.0–3.5 cm and 0.9–3.4 cm, respectively. However, figure-8 field coils are more focal, having S1/2 as low as 5 cm2 compared to 34 cm2 for circular field coils. Conclusions For any coil design, the ability to directly stimulate deeper brain structures is obtained at the expense of inducing wider electrical field spread. Novel coil designs should be benchmarked against comparison coils with consistent metrics such as d1/2 and S1/2. PMID:22483681

  4. Preservation of the blood brain barrier and cortical neuronal tissue by liraglutide, a long acting glucagon-like-1 analogue, after experimental traumatic brain injury.

    Directory of Open Access Journals (Sweden)

    Jakob Hakon

    Full Text Available Cerebral edema is a common complication following moderate and severe traumatic brain injury (TBI, and a significant risk factor for development of neuronal death and deterioration of neurological outcome. To this date, medical approaches that effectively alleviate cerebral edema and neuronal death after TBI are not available. Glucagon-like peptide-1 (GLP-1 has anti-inflammatory properties on cerebral endothelium and exerts neuroprotective effects. Here, we investigated the effects of GLP-1 on secondary injury after moderate and severe TBI. Male Sprague Dawley rats were subjected either to TBI by Controlled Cortical Impact (CCI or sham surgery. After surgery, vehicle or a GLP-1 analogue, Liraglutide, were administered subcutaneously twice daily for two days. Treatment with Liraglutide (200 μg/kg significantly reduced cerebral edema in pericontusional regions and improved sensorimotor function 48 hours after CCI. The integrity of the blood-brain barrier was markedly preserved in Liraglutide treated animals, as determined by cerebral extravasation of Evans blue conjugated albumin. Furthermore, Liraglutide reduced cortical tissue loss, but did not affect tissue loss and delayed neuronal death in the thalamus on day 7 post injury. Together, our data suggest that the GLP-1 pathway might be a promising target in the therapy of cerebral edema and cortical neuronal injury after moderate and severe TBI.

  5. Sighting optics including an optical element having a first focal length and a second focal length

    Science.gov (United States)

    Crandall, David Lynn [Idaho Falls, ID

    2011-08-01

    One embodiment of sighting optics according to the teachings provided herein may include a front sight and a rear sight positioned in spaced-apart relation. The rear sight includes an optical element having a first focal length and a second focal length. The first focal length is selected so that it is about equal to a distance separating the optical element and the front sight and the second focal length is selected so that it is about equal to a target distance. The optical element thus brings into simultaneous focus, for a user, images of the front sight and the target.

  6. Origin and consequences of brain Toll-like receptor 4 pathway stimulation in an experimental model of depression

    Directory of Open Access Journals (Sweden)

    Madrigal José LM

    2011-11-01

    Full Text Available Abstract Background There is a pressing need to identify novel pathophysiological pathways relevant to depression that can help to reveal targets for the development of new medications. Toll-like receptor 4 (TLR-4 has a regulatory role in the brain's response to stress. Psychological stress may compromise the intestinal barrier, and increased gastrointestinal permeability with translocation of lipopolysaccharide (LPS from Gram-negative bacteria may play a role in the pathophysiology of major depression. Methods Adult male Sprague-Dawley rats were subjected to chronic mild stress (CMS or CMS+intestinal antibiotic decontamination (CMS+ATB protocols. Levels of components of the TLR-4 signaling pathway, of LPS and of different inflammatory, oxidative/nitrosative and anti-inflammatory mediators were measured by RT-PCR, western blot and/or ELISA in brain prefrontal cortex. Behavioral despair was studied using Porsolt's test. Results CMS increased levels of TLR-4 and its co-receptor MD-2 in brain as well as LPS and LPS-binding protein in plasma. In addition, CMS also increased interleukin (IL-1β, COX-2, PGE2 and lipid peroxidation levels and reduced levels of the anti-inflammatory prostaglandin 15d-PGJ2 in brain tissue. Intestinal decontamination reduced brain levels of the pro-inflammatory parameters and increased 15d-PGJ2, however this did not affect depressive-like behavior induced by CMS. Conclusions Our results suggest that LPS from bacterial translocation is responsible, at least in part, for the TLR-4 activation found in brain after CMS, which leads to release of inflammatory mediators in the CNS. The use of Gram-negative antibiotics offers a potential therapeutic approach for the adjuvant treatment of depression.

  7. Experimental infection by Yersinia ruckeri O1 biotype 2 induces brain lesions and neurological signs in rainbow trout (Oncorhynchus mykiss)

    DEFF Research Database (Denmark)

    Strøm, H. K.; Ohtani, M.; Nowak, B.

    2018-01-01

    was then monitored for 22 days post-infection (dpi). Organs were sampled at 3 dpi and also from moribund fish showing signs of severe systemic infection such as bleeding, exophthalmia or erratic swimming behaviour. Y. ruckeri was observed in the meninges and diencephalon of the brain, and lamina propria of olfactory...... organ at 3 dpi. At 12 dpi, Y. ruckeri had spread throughout the brain including cranial connective tissues and ventricles and the infection was associated with haemorrhages and an infiltration with leucocytes. Y. ruckeri infection and associated with leucocyte infiltration were observed at 13 dpi...

  8. Laser focal profiler based on forward scattering of a nanoparticle

    Science.gov (United States)

    Ota, Taisuke

    2018-03-01

    A laser focal intensity profiling method based on the forward scattering from a nanoparticle is demonstrated for in situ measurements using a laser focusing system with six microscope objective lenses with different numerical apertures ranging from 0.15 to 1.4. The measured profiles showed Airy disc patterns although their rings showed some imperfections due to aberrations and misalignment of the test system. The dipole radiation model revealed that the artefact of this method was much smaller than the influence of the deterioration in the experimental system; a condition where no artefact appears was predicted based on proper selection of measurement angles.

  9. Trypanosoma brucei Invasion and T-Cell Infiltration of the Brain Parenchyma in Experimental Sleeping Sickness: Timing and Correlation with Functional Changes.

    Directory of Open Access Journals (Sweden)

    Claudia Laperchia

    2016-12-01

    Full Text Available The timing of Trypanosoma brucei entry into the brain parenchyma to initiate the second, meningoencephalitic stage of human African trypanosomiasis or sleeping sickness is currently debated and even parasite invasion of the neuropil has been recently questioned. Furthermore, the relationship between neurological features and disease stage are unclear, despite the important diagnostic and therapeutic implications.Using a rat model of chronic Trypanosoma brucei brucei infection we determined the timing of parasite and T-cell neuropil infiltration and its correlation with functional changes. Parasite DNA was detected using trypanosome-specific PCR. Body weight and sleep structure alterations represented by sleep-onset rapid eye movement (SOREM periods, reported in human and experimental African trypanosomiasis, were monitored. The presence of parasites, as well as CD4+ and CD8+ T-cells in the neuropil was assessed over time in the brain of the same animals by immunocytochemistry and quantitative analyses.Trypanosome DNA was present in the brain at day 6 post-infection and increased more than 15-fold by day 21. Parasites and T-cells were observed in the parenchyma from day 9 onwards. Parasites traversing blood vessel walls were observed in the hypothalamus and other brain regions. Body weight gain was reduced from day 7 onwards. SOREM episodes started in most cases early after infection, with an increase in number and duration after parasite neuroinvasion.These findings demonstrate invasion of the neuropil over time, after an initial interval, by parasites and lymphocytes crossing the blood-brain barrier, and show that neurological features can precede this event. The data thus challenge the current clinical and cerebrospinal fluid criteria of disease staging.

  10. Using Drawings of the Brain Cell to Exhibit Expertise in Neuroscience: Exploring the Boundaries of Experimental Culture

    Science.gov (United States)

    Hay, David B.; Williams, Darren; Stahl, Daniel; Wingate, Richard J.

    2013-01-01

    This paper explores the research perspective of neuroscience by documenting the brain cell (neuron) drawings of undergraduates, trainee scientists, and leading neuroscience researchers in a single research-intensive university. Qualitative analysis, drawing-sorting exercises, and hierarchical cluster analysis are used to answer two related…

  11. Effects of DDE and PCB (Aroclor 1260) on experimentally poisoned little brown bats (Myotis lucifugus): Lethal brain concentrations

    Science.gov (United States)

    Clark, D.R.; Stafford, C.J.

    1981-01-01

    Adult female little brown bats (Myotis lucifugus) were collected in a church attic in North East, Cecil County, Md. Mealworms (Tenebrio molitor) containing organochlorine pollutants were fed to the bats as follows: 5 bats were dosed at 480 ppm DDE, 12 at 150 ppm DDE, 5 at 1000 ppm polychlorinated biphenyl (PCB; Aroclor 1260), and 12 at 15 ppm PCB. Seven other bats were fed untreated mealworms. The objective was to elevate brain levels of DDE and PCB to lethality and measure these concentrations. During 40 d of dosage, one DDE-dosed bat and two PCB-dosed bats died after exhibiting the prolonged tremor that characterizes organochlorine poisoning. After dosage, surviving bats were starved to elevate brain levels of toxicants, and three additional DDE-dosed bats had tremors before dying. The mean brain concentration of DDE diagnostic of death was estimated as 603 ppm, range 540-670 ppm. This mean is 16-18% higher than means for Mexican free-tailed bats (Tadarida brasiliensis) and common grackles (Quiscalus quiscula), and may indicate less sensitivity. Lethal brain concentrations of Aroclor 1260 were 1300 and 1500 ppm. Such values appear to be higher than values (Aroclor 1254) for brown-headed cowbirds (Molothrus ater). During starvation, DDE-dosed bats lost weight about 24% faster than controls. If smaller amounts of stored DDE cause increases in metabolic rates of nonfeeding bats, as during hibernation or migration, the result could be premature energy depletion and increased mortality.

  12. Strain relief from the cerebral ventricles during head impact: experimental studies on natural protection of the brain.

    Science.gov (United States)

    Ivarsson, J; Viano, D C; Lövsund, P; Aldman, B

    2000-02-01

    Physical models of the parasagittal human skull/brain have been tested to investigate whether the cerebral ventricles provide natural protection of the brain by relieving strain during head rotation. A sophisticated model included anatomical structures, and a semicircular model consisted of a cylinder divided into two semicircles. Silicone gel simulated the brain and was detached from the vessel by a layer of liquid paraffin simulating the cerebrospinal fluid. Both models were run with and without an elliptical inclusion filled with liquid paraffin simulating a cerebral ventricle. The 2D models were exposed to angular acceleration by a pendulum impact causing 7600 rad/s2 peak rotational acceleration with 6 ms pulse duration. After rotating 100 degrees, the models were decelerated during 30 ms. The trajectory of grid markers was analyzed from high-speed video (1000 frames/s). Rigid-body displacement, shear strain and principal strain were determined from the displacement of three-point sets inferior and superior to the ventricle. For the subventricular (inferior) region in the sophisticated model, approximately 40% lower peak strain values were obtained in the model with ventricle than in the one without. Subcortical displacement was reduced by 12%. Corresponding strain reduction in the subcortical (superior) region was approximately 40% following the acceleration and 25% following the deceleration. Similar but less pronounced effects were found for the semicircular model. The lateral ventricles play an important role as strain relievers and provide natural protection against brain injury.

  13. Brain Radiation Information Data Exchange (BRIDE): Integration of experimental data from low-dose ionising radiation research for pathway discovery

    NARCIS (Netherlands)

    C. Karapiperis (Christos); S.J. Kempf (Stefan J.); R. Quintens (Roel); O. Azimzadeh (Omid); V.L. Vidal (Victoria Linares); S. Pazzaglia; D. Bazyka (Dimitry); P.G. Mastroberardino (Pier); Z.G. Scouras (Zacharias G.); S. Tapio (Soile); M.A. Benotmane (Mohammed Abderrafi); C.A. Ouzounis (Christos A.)

    2016-01-01

    textabstractBackground: The underlying molecular processes representing stress responses to low-dose ionising radiation (LDIR) in mammals are just beginning to be understood. In particular, LDIR effects on the brain and their possible association with neurodegenerative disease are currently being

  14. Arterially perfused neurosphere-derived cells distribute outside the ischemic core in a model of transient focal ischemia and reperfusion in vitro.

    Science.gov (United States)

    Pastori, Chiara; Librizzi, Laura; Breschi, Gian Luca; Regondi, Cristina; Frassoni, Carolina; Panzica, Ferruccio; Frigerio, Simona; Gelati, Maurizio; Parati, Eugenio; De Simoni, Maria Grazia; de Curtis, Marco

    2008-07-23

    Treatment with neural stem cells represents a potential strategy to improve functional recovery of post-ischemic cerebral injury. The potential benefit of such treatment in acute phases of human ischemic stroke depends on the therapeutic viability of a systemic vascular delivery route. In spite of the large number of reports on the beneficial effects of intracerebral stem cells injection in experimental stroke, very few studies demonstrated the effectiveness of the systemic intravenous delivery approach. METODOLOGY/PRINCIPAL FINDINGS: We utilized a novel in vitro model of transient focal ischemia to analyze the brain distribution of neurosphere-derived cells (NCs) in the early 3 hours that follow transient occlusion of the medial cerebral artery (MCA). NCs obtained from newborn C57/BL6 mice are immature cells with self-renewal properties that could differentiate into neurons, astrocytes and oligodendrocytes. MCA occlusion for 30 minutes in the in vitro isolated guinea pig brain preparation was followed by arterial perfusion with 1x10(6) NCs charged with a green fluorescent dye, either immediately or 60 minutes after reperfusion onset. Changes in extracellular pH and K(+) concentration during and after MCAO were measured through ion-sensitive electrodes. It is demonstrated that NCs injected through the vascular system do not accumulate in the ischemic core and preferentially distribute in non-ischemic areas, identified by combined electrophysiological and morphological techniques. Direct measurements of extracellular brain ions during and after MCA occlusion suggest that anoxia-induced tissue changes, such as extracellular acidosis, may prevent NCs from entering the ischemic area in our in vitro model of transitory focal ischemia and reperfusion suggesting a role played by the surrounding microenviroment in driving NCs outside the ischemic core. These findings strongly suggest that the potential beneficial effect of NCs in experimental focal brain ischemia is not

  15. Arterially perfused neurosphere-derived cells distribute outside the ischemic core in a model of transient focal ischemia and reperfusion in vitro.

    Directory of Open Access Journals (Sweden)

    Chiara Pastori

    Full Text Available BACKGROUND: Treatment with neural stem cells represents a potential strategy to improve functional recovery of post-ischemic cerebral injury. The potential benefit of such treatment in acute phases of human ischemic stroke depends on the therapeutic viability of a systemic vascular delivery route. In spite of the large number of reports on the beneficial effects of intracerebral stem cells injection in experimental stroke, very few studies demonstrated the effectiveness of the systemic intravenous delivery approach. METODOLOGY/PRINCIPAL FINDINGS: We utilized a novel in vitro model of transient focal ischemia to analyze the brain distribution of neurosphere-derived cells (NCs in the early 3 hours that follow transient occlusion of the medial cerebral artery (MCA. NCs obtained from newborn C57/BL6 mice are immature cells with self-renewal properties that could differentiate into neurons, astrocytes and oligodendrocytes. MCA occlusion for 30 minutes in the in vitro isolated guinea pig brain preparation was followed by arterial perfusion with 1x10(6 NCs charged with a green fluorescent dye, either immediately or 60 minutes after reperfusion onset. Changes in extracellular pH and K(+ concentration during and after MCAO were measured through ion-sensitive electrodes. CONCLUSION/SIGNIFICANCE: It is demonstrated that NCs injected through the vascular system do not accumulate in the ischemic core and preferentially distribute in non-ischemic areas, identified by combined electrophysiological and morphological techniques. Direct measurements of extracellular brain ions during and after MCA occlusion suggest that anoxia-induced tissue changes, such as extracellular acidosis, may prevent NCs from entering the ischemic area in our in vitro model of transitory focal ischemia and reperfusion suggesting a role played by the surrounding microenviroment in driving NCs outside the ischemic core. These findings strongly suggest that the potential beneficial effect

  16. I Focalize, You Focalize, We All Focalize Together: Audience Participation in Persepolis

    Directory of Open Access Journals (Sweden)

    Lizzie Nixon

    2010-06-01

    Full Text Available

    Abstract (E: This article combines theories of cognition and empathy with focalization theory to examine how and why different forms of audience engagement in fictional worlds are cued. The article argues that critics should examine the differences between engagement that encourages audiences to apply their own frames to the world presented and type engagement cued by means of point-of-view shots and close-ups of facial expressions.

    Abstract (F: Cet article combine les théories de la cognition et de l’empathie avec la théorie de la focalisation afin d’analyser comment et pourquoi certaines œuvres construisent la manière dont le public est invité à s’investir dans des mondes fictionnels. Il défend l

  17. FOCAL EPILEPTIC MYOCLONUS IN KOZHEVNIKOV–RASMUSSEN SYNDROME

    Directory of Open Access Journals (Sweden)

    N. E. Kvaskova

    2016-01-01

    Full Text Available The article presents the clinical, electroencephalographic (EEG and neuroimaging features, as well as the results of treatment of patients with focal epileptic myoclonus (FEM with the Kozhevnikov–Rasmussen syndrome (KRS. FEM in KRS-patients was identified in 11 cases, accounting for 0.9 % of all the cases of epilepsy with the onset of seizures up to 18 years (n = 1261. The age at onset of KRS ranged from 3 to 21 years (average – 9.2 ± 5.7 years. In the active period of the disease of all patients in the clinical picture the active FEM appeared and increasing frequency of the secondary generalized seizures (SGS. In addition SGS and FEM, the clinical picture of the disease in most patients (91 % the focal motor (clonic and the somatosensory focal seizures were observed. As the disease progressed, the FEM became more pronounced in frequency and intensity, seized more muscle groups, localizing mainly in the muscles of the trunk and limbs. The typical EEG pattern of FEM patients with KRS was regional epileptiform activity that occurs in the structure of the continued regional slowing localizing maximum of the fronto-central-temporal region. During the magnetic resonance tomography of the brain in dynamics all the patients observed the increase in total cortical hemiatrophy. In all the cases, the appointment of antiepileptic therapy resulted in a slowing of the FEM, however, a complete remission was reached at none of the patients. Two patients were made surgical treatment of epilepsy. In one case remission of epileptic seizures was observed after right-side hemispherotomy. Our study showed that FEM is very resistant type of epileptic seizures. This fact calls for the identification of the FEM at the early stages of the disease with the purpose to improve the prognosis, as well as for an earlier surgical treatment.

  18. Prenatal sonographic diagnosis of focal musculoskeletal anomalies

    Energy Technology Data Exchange (ETDEWEB)

    Ryu, Jung-Kyu; Cho, Jeong-Yeon; Choi, Jong-Sun [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2003-12-15

    Focal musculoskeletal anomalies vary, and can manifest as part of a syndrome or be accompanied by numerous other conditions such as genetic disorders, karyotype abnormalities, central nervous system anomalies and other skeletal anomalies, lsolated focal musculoskeletal anomaly does, however, also occur; its early prenatal diagnosis is important in deciding prenatal care, and also helps in counseling parents about the postnatal effects of numerous possible associated anomalies. We have encountered 50 cases involving focal musculoskeletal anomalies, including total limb dysplasia [radial ray abnormality (n=3), mesomelic dysplasia (n=1)]; anomalies of the hand [polydactyly (n=8), syndactyly (n=3), ectrodactyly (n=1), clinodactyly (n=6), clenched hand (n=5)]; anomalies of the foot [clubfoot (n=10), rockerbottom foot (n=5), sandal gap deformity (n=1), curly toe (n=2)]; amniotic band syndrome (n=3); and anomalies of the focal spine [block vertebra (n=1), hemivertebra (n=1)]. Among these 50 cases, five [polydactyly (n=1), syndactyly (n=2) and curly toe (n=2) were confirmed by postnatal physical evaluation, two (focal spine anomalies) were diagnosed after postnatal radiologic examination, and the remaining 43 were proven at autopsy. For each condition, we describe the prenatal sonographic findings, and include a brief review.

  19. Neuroprotective and behavioral efficacy of nerve growth factor-transfected hippocampal progenitor cell transplants after experimental traumatic brain injury.

    Science.gov (United States)

    Philips, M F; Mattiasson, G; Wieloch, T; Björklund, A; Johansson, B B; Tomasevic, G; Martínez-Serrano, A; Lenzlinger, P M; Sinson, G; Grady, M S; McIntosh, T K

    2001-05-01

    Immortalized neural progenitor cells derived from embryonic rat hippocampus (HiB5), were transduced ex vivo with the gene for mouse nerve growth factor (NGF) to secrete NGF (NGF-HiB5) at 2 ng/hr/10(5) cells in culture. Fifty-nine male Wistar rats weighing 300 to 370 g each were anesthetized with 60 mg/kg sodium pentobarbital and subjected to lateral fluid-percussion brain injury of moderate severity (2.3-2.4 atm, 34 rats) or sham injury (25 rats). At 24 hours postinjury, 2 microl (150,000 cells/microl) of [3H]thymidine-labeled NGF-HiB5 cells were transplanted stereotactically into three individual sites in the cerebral cortex adjacent to the injury site (14 rats). Separate groups of brain-injured rats received nontransfected (naive [n])-HiB5 cells (12 animals) or cell suspension vehicle (eight animals). One week postinjury, animals underwent neurological evaluation for motor function and cognition (Morris water maze) and were killed for histological, autoradiographic, and immunocytochemical analysis. Viable HiB5 cell grafts were identified in all animals, together with reactive microglia and macrophages located throughout the periinjured parenchyma and grafts (OX-42 immunohistochemistry). Brain-injured animals transplanted with either NGF-HiB5 or n-HiB5 cells displayed significantly improved neuromotor function (p < 0.05) and spatial learning behavior (p < 0.005) compared with brain-injured animals receiving microinjections of vehicle alone. A significant reduction in hippocampal CA3 cell death was observed in brain-injured animals receiving transplants of NGF-HiB5 cells compared with those receiving n-HiB5 cells or vehicle (p < 0.025). This study demonstrates that immortalized neural stem cells that have been retrovirally transduced to produce NGF can markedly improve cognitive and neuromotor function and rescue hippocampal CA3 neurons when transplanted into the injured brain during the acute posttraumatic period.

  20. Focal fatty infiltra- tion and focal fatty sparing of the liver

    African Journals Online (AJOL)

    Enrique

    gations and liver biopsies can be avoided. Introduction. Focal fatty infiltration of the liver is caused by focal ... invasive procedures such as biopsies, and further anxiety on the part of the patient. This diagnostic problem ... subsequently found to have type 2 diabetes, and her pain settled on oral hypoglycaemic agents. Case 2.

  1. Screening of biochemical and molecular mechanisms of secondary injury and repair in the brain after experimental blast-induced traumatic brain injury in rats.

    Science.gov (United States)

    Kochanek, Patrick M; Dixon, C Edward; Shellington, David K; Shin, Samuel S; Bayır, Hülya; Jackson, Edwin K; Kagan, Valerian E; Yan, Hong Q; Swauger, Peter V; Parks, Steven A; Ritzel, David V; Bauman, Richard; Clark, Robert S B; Garman, Robert H; Bandak, Faris; Ling, Geoffrey; Jenkins, Larry W

    2013-06-01

    Abstract Explosive blast-induced traumatic brain injury (TBI) is the signature insult in modern combat casualty care and has been linked to post-traumatic stress disorder, memory loss, and chronic traumatic encephalopathy. In this article we report on blast-induced mild TBI (mTBI) characterized by fiber-tract degeneration and axonal injury revealed by cupric silver staining in adult male rats after head-only exposure to 35 psi in a helium-driven shock tube with head restraint. We now explore pathways of secondary injury and repair using biochemical/molecular strategies. Injury produced ∼25% mortality from apnea. Shams received identical anesthesia exposure. Rats were sacrificed at 2 or 24 h, and brain was sampled in the hippocampus and prefrontal cortex. Hippocampal samples were used to assess gene array (RatRef-12 Expression BeadChip; Illumina, Inc., San Diego, CA) and oxidative stress (OS; ascorbate, glutathione, low-molecular-weight thiols [LMWT], protein thiols, and 4-hydroxynonenal [HNE]). Cortical samples were used to assess neuroinflammation (cytokines, chemokines, and growth factors; Luminex Corporation, Austin, TX) and purines (adenosine triphosphate [ATP], adenosine diphosphate, adenosine, inosine, 2'-AMP [adenosine monophosphate], and 5'-AMP). Gene array revealed marked increases in astrocyte and neuroinflammatory markers at 24 h (glial fibrillary acidic protein, vimentin, and complement component 1) with expression patterns bioinformatically consistent with those noted in Alzheimer's disease and long-term potentiation. Ascorbate, LMWT, and protein thiols were reduced at 2 and 24 h; by 24 h, HNE was increased. At 2 h, multiple cytokines and chemokines (interleukin [IL]-1α, IL-6, IL-10, and macrophage inflammatory protein 1 alpha [MIP-1α]) were increased; by 24 h, only MIP-1α remained elevated. ATP was not depleted, and adenosine correlated with 2'-cyclic AMP (cAMP), and not 5'-cAMP. Our data reveal (1) gene-array alterations similar to disorders of

  2. Proliferation and cell death in an experimental model of brain tissue heterotopia in the lung Proliferação e morte celular na heterotopia encefálica experimental

    Directory of Open Access Journals (Sweden)

    Paulo Roberto Veiga Quemelo

    2010-08-01

    Full Text Available PURPOSE: To investigate the proliferation and neuronal death in brain tissue heterotopia in the lung in an experimental model during both fetal and neonatal periods. METHODS: Twenty four pregnant female Swiss mice were used to induce brain tissue heterotopia on the 15th gestational day. Briefly, the brain of one fetus of each dam was extracted, disaggregated and injected into the right hemithorax of siblings. Six of these fetuses with pulmonary brain tissue implantation (PBI were collected on the 18th gestational day (group E18 and six other on the 8th postnatal day (group P8. Immunohistochemical staining for PCNA and Bcl2 were used to assess proliferation and cell death. RESULTS: PCNA Labelling Index (LI in heterotopic brain tissue was greater in fetal than postnatal period (E18 > P8 (pOBJETIVO: Investigar a proliferação e morte neuronal na heterotopia encefálica pulmonar em modelo experimental durante o período fetal e neonatal. MÉTODOS: Foram utilizados 24 camundongos Swiss fêmeas prenhes para induzir a heterotopia encefálica no pulmão. O tecido encefálico de um feto de cada fêmea prenha foi removido, picotado e injetado no pulmão dos irmãos. Seis fetos com Implantação Encefálica Pulmonar (IEP foram coletados no 18º dia gestacional (grupo E18 e seis outros fetos no 8º dia pós-natal (grupo P8. Foi realizada a reação Imuno-histoquímica para PCNA e Bcl2 para analisar a proliferação e morte celular. RESULTADOS: O índice de marcação (IM para PCNA era maior no período fetal quando comparado com o período pós-natal (E8 > P18 (p<0,05 e a imunomarcação para o anticorpo Bcl2 não apresentou diferença. CONCLUSÃO: A proliferação celular foi mantida no tecido heterotópico encefálico, embora a apoptose também foi observada.

  3. Brain imaging of analgesic and antihyperalgesic effects of cyclooxygenase inhibition in an experimental human pain model: a functional MRI study.

    Science.gov (United States)

    Maihöfner, Christian; Ringler, Ralf; Herrndobler, Franz; Koppert, Wolfgang

    2007-09-01

    One of the most distressing symptoms of many neuropathic pain syndromes is the enhanced pain sensation to tactile or thermal stimulation (hyperalgesia). In the present study we used functional magnetic resonance imaging (fMRI) and explored brain activation patterns during acute impact pain and mechanical hyperalgesia in the human ultraviolet (UV)-B model. To investigate pharmacological modulation, we examined potential differential fMRI correlates of analgesic and antihyperalgesic effects of two intravenous cyclooxygenase inhibitors, i.e. parecoxib and acetylsalicylic acid (ASA). Fourteen healthy volunteers participated in this double-blinded, randomized and placebo-controlled crossover study. Tactile stimuli and mechanical impact hyperalgesia were tested at the site of a UV-B irradiation and acute mechanical pain was tested at a site distant from the irradiated skin. These measurements were conducted before and 30 min after a 5-min intravenous infusion of either saline (placebo), parecoxib 40 mg or ASA 1000 mg. Acute mechanical pain and mechanical hyperalgesia led to widespread activations of brain areas known to comprise the human pain matrix. Analgesic effects were found in primary (S1) and secondary (S2) somatosensory cortices, parietal association cortex (PA), insula, anterior parts of the cingulate cortex and prefrontal cortices. These brain areas were also modulated under antihyperalgesic conditions. However, we observed a greater drug-induced modulation of mainly PA and inferior frontal cortex during mechanical hyperalgesia; during acute mechanical pain there was a greater modulation of mainly bilateral S2. Therefore, the results of the present study suggest that there is a difference in the brain areas modulated by analgesia and antihyperalgesia.

  4. Feasibility and utility of telephone-based psychological support for people with brain tumor: A single-case experimental study

    Directory of Open Access Journals (Sweden)

    Stephanie eJones

    2015-03-01

    Full Text Available Rates of psychological distress are high following diagnosis and treatment of brain tumor. There can be multiple barriers to accessing psychological support, including physical and cognitive impairments and geographical limitations. Tele-based support could provide an effective and more flexible option for delivering psychological interventions. The present study aimed to investigate the feasibility and utility of a telephone-based psychotherapy intervention for people with brain tumor. A single-case multiple-baseline design was employed with a 4-7 week baseline phase, 10-week treatment phase and 5-week maintenance phase including a booster session. Four participants with a benign or malignant brain tumor (3 males & 1 female; aged 34 to 49 years, received 10 sessions of tele-based therapy and a booster session at four weeks post-treatment. Levels of depression, anxiety, and illness cognitions were monitored on a weekly basis throughout each phase whilst measures of quality of life, stress and self-concept were administered at the start and end of each phase. Weekly measures were analysed using a combination of both visual analysis and Tau-U statistics. Of the four participants, two of them demonstrated significant gains in mental health (depression and/or anxiety and a significant decrease in their levels of helplessness (p<.05. The other two participants did not show gains in mental health or change in illness cognitions. All participants reported improvement in quality of life post-treatment. The results of the study provide preliminary support concerning the feasibility and utility of tele-based therapy for some people with brain tumor. Further research examining factors influencing the outcomes of tele-based psychological support is needed.

  5. Effects of Exercise on Physical and Mental Health, and Cognitive and Brain Functions in Schizophrenia: Clinical and Experimental Evidence.

    Science.gov (United States)

    Rimes, Ridson Rosa; de Souza Moura, Antonio Marcos; Lamego, Murilo Khede; de Sá Filho, Alberto Souza; Manochio, João; Paes, Flávia; Carta, Mauro Giovanni; Mura, Gioia; Wegner, Mirko; Budde, Henning; Ferreira Rocha, Nuno Barbosa; Rocha, Joana; Tavares, João Manuel R S; Arias-Carrión, Oscar; Nardi, Antonio Egidio; Yuan, Ti-Fei; Machado, Sergio

    2015-01-01

    Exercise promotes several health benefits, such as cardiovascular, musculoskeletal and cardiorespiratory improvements. It is believed that the practice of exercise in individuals with psychiatric disorders, e.g. schizophrenia, can cause significant changes. Schizophrenic patients have problematic lifestyle habits compared with general population; this may cause a high mortality rate, mainly caused by cardiovascular and metabolic diseases. Thus, the aim of this study is to investigate changes in physical and mental health, cognitive and brain functioning due to the practice of exercise in patients with schizophrenia. Although still little is known about the benefits of exercise on mental health, cognitive and brain functioning of schizophrenic patients, exercise training has been shown to be a beneficial intervention in the control and reduction of disease severity. Type of training, form of execution, duration and intensity need to be better studied as the effects on physical and mental health, cognition and brain activity depend exclusively of interconnected factors, such as the combination of exercise and medication. However, one should understand that exercise is not only an effective nondrug alternative, but also acts as a supporting linking up interventions to promote improvements in process performance optimization. In general, the positive effects on mental health, cognition and brain activity as a result of an exercise program are quite evident. Few studies have been published correlating effects of exercise in patients with schizophrenia, but there is increasing evidence that positive and negative symptoms can be improved. Therefore, it is important that further studies be undertaken to expand the knowledge of physical exercise on mental health in people with schizophrenia, as well as its dose-response and the most effective type of exercise.

  6. Experimental exposure to urban and pink noise affects brain development and song learning in zebra finches (Taenopygia guttata

    Directory of Open Access Journals (Sweden)

    Dominique A. Potvin

    2016-08-01

    Full Text Available Recently, numerous studies have observed changes in bird vocalizations—especially song—in urban habitats. These changes are often interpreted as adaptive, since they increase the active space of the signal in its environment. However, the proximate mechanisms driving cross-generational changes in song are still unknown. We performed a captive experiment to identify whether noise experienced during development affects song learning and the development of song-control brain regions. Zebra finches (Taeniopygia guttata were bred while exposed, or not exposed, to recorded traffic urban noise (Study 1 or pink noise (Study 2. We recorded the songs of male offspring and compared these to fathers’ songs. We also measured baseline corticosterone and measured the size of song-control brain regions when the males reached adulthood (Study 1 only. While male zebra finches tended to copy syllables accurately from tutors regardless of noise environment, syntax (the ordering of syllables within songs was incorrectly copied affected by juveniles exposed to noise. Noise did not affect baseline corticosterone, but did affect the size of brain regions associated with song learning: these regions were smaller in males that had been had been exposed to recorded traffic urban noise in early development. These findings provide a possible mechanism by which noise affects behaviour, leading to potential population differences between wild animals occupying noisier urban environments compared with those in quieter habitats.

  7. Experimental exposure to urban and pink noise affects brain development and song learning in zebra finches (Taenopygia guttata).

    Science.gov (United States)

    Potvin, Dominique A; Curcio, Michael T; Swaddle, John P; MacDougall-Shackleton, Scott A

    2016-01-01

    Recently, numerous studies have observed changes in bird vocalizations-especially song-in urban habitats. These changes are often interpreted as adaptive, since they increase the active space of the signal in its environment. However, the proximate mechanisms driving cross-generational changes in song are still unknown. We performed a captive experiment to identify whether noise experienced during development affects song learning and the development of song-control brain regions. Zebra finches (Taeniopygia guttata) were bred while exposed, or not exposed, to recorded traffic urban noise (Study 1) or pink noise (Study 2). We recorded the songs of male offspring and compared these to fathers' songs. We also measured baseline corticosterone and measured the size of song-control brain regions when the males reached adulthood (Study 1 only). While male zebra finches tended to copy syllables accurately from tutors regardless of noise environment, syntax (the ordering of syllables within songs) was incorrectly copied affected by juveniles exposed to noise. Noise did not affect baseline corticosterone, but did affect the size of brain regions associated with song learning: these regions were smaller in males that had been had been exposed to recorded traffic urban noise in early development. These findings provide a possible mechanism by which noise affects behaviour, leading to potential population differences between wild animals occupying noisier urban environments compared with those in quieter habitats.

  8. Transient blood-brain barrier permeability following profound temporary global ischemia: an experimental study using /sup 14/C-AIB

    Energy Technology Data Exchange (ETDEWEB)

    Dobbin, J.; Crockard, H.A.; Ross-Russell, R.

    1989-02-01

    The influence of reperfusion after profound incomplete forebrain ischemia on blood-brain barrier (BBB) permeability to a small protein tracer was studied in male Sprague-Dawley rats. The mean cortical blood to brain transfer constant (Ki) for /sup 14/C-amino isobutyric acid (AIB) was significantly greater at 3 and 6 h of reperfusion, 2.5 times the mean values of controls (p less than 0.05) (2.5 microliter g-1 min-1 and 1.0 microliters g-1 min-1 respectively), but had returned to control values after reperfusion for 24 h. Analysis of distribution of Ki values showed that following 15 min and 30 min of profound ischemia, there was a significant increase in transfer of AIB across the blood-brain barrier (BBB) after recirculation for up to 6 h, though there was no evidence of protein extravasation as assessed by Evans Blue (EB) dye. After 24 h of reperfusion, the BBB to AIB was restored, and Ki values had returned to control values. It is concluded that following transient global ischemia, the BBB may recover rapidly.

  9. Low-level light emitting diode (LED) therapy suppresses inflammasome-mediated brain damage in experimental ischemic stroke.

    Science.gov (United States)

    Lee, Hae In; Lee, Sae-Won; Kim, Nam Gyun; Park, Kyoung-Jun; Choi, Byung Tae; Shin, Yong-Il; Shin, Hwa Kyoung

    2017-11-01

    Use of photostimulation including low-level light emitting diode (LED) therapy has broadened greatly in recent years because it is compact, portable, and easy to use. Here, the effects of photostimulation by LED (610 nm) therapy on ischemic brain damage was investigated in mice in which treatment started after a stroke in a clinically relevant setting. The mice underwent LED therapy (20 min) twice a day for 3 days, commencing at 4 hours post-ischemia. LED therapy group generated a significantly smaller infarct size and improvements in neurological function based on neurologic test score. LED therapy profoundly reduced neuroinflammatory responses including neutrophil infiltration and microglia activation in the ischemic cortex. LED therapy also decreased cell death and attenuated the NLRP3 inflammasome, in accordance with down-regulation of pro-inflammatory cytokines IL-1β and IL-18 in the ischemic brain. Moreover, the mice with post-ischemic LED therapy showed suppressed TLR-2 levels, MAPK signaling and NF-kB activation. These findings suggest that by suppressing the inflammasome, LED therapy can attenuate neuroinflammatory responses and tissue damage following ischemic stroke. Therapeutic interventions targeting the inflammasome via photostimulation with LED may be a novel approach to ameliorate brain injury following ischemic stroke. Effect of post-ischemic low-level light emitting diode therapy (LED-T) on infarct reduction was mediated by inflammasome suppression. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Neurovascular Unit Dysfunction and Blood–Brain Barrier Hyperpermeability Contribute to Schizophrenia Neurobiology: A Theoretical Integration of Clinical and Experimental Evidence

    Directory of Open Access Journals (Sweden)

    Souhel Najjar

    2017-05-01

    Full Text Available Schizophrenia is a psychotic disorder characterized by delusions, hallucinations, negative symptoms, as well as behavioral and cognitive dysfunction. It is a pathoetiologically heterogeneous disorder involving complex interrelated mechanisms that include oxidative stress and neuroinflammation. Neurovascular endothelial dysfunction and blood–brain barrier (BBB hyperpermeability are established mechanisms in neurological disorders with comorbid psychiatric symptoms such as epilepsy, traumatic brain injury, and Alzheimer’s disease. Schizophrenia is frequently comorbid with medical conditions associated with peripheral vascular endothelial dysfunction, such as metabolic syndrome, cardiovascular disease, and diabetes mellitus. However, the existence and etiological relevance of neurovascular endothelial dysfunction and BBB hyperpermeability in schizophrenia are still not well recognized. Here, we review the growing clinical and experimental evidence, indicating that neurovascular endotheliopathy and BBB hyperpermeability occur in schizophrenia patients. We present a theoretical integration of human and animal data linking oxidative stress and neuroinflammation to neurovascular endotheliopathy and BBB breakdown in schizophrenia. These abnormalities may contribute to the cognitive and behavioral symptoms of schizophrenia via several mechanisms involving reduced cerebral perfusion and impaired homeostatic processes of cerebral microenvironment. Furthermore, BBB disruption can facilitate interactions between brain innate and peripheral adaptive immunity, thereby perpetuating harmful neuroimmune signals and toxic neuroinflammatory responses, which can also contribute to the symptoms of schizophrenia. Taken together, these findings support the “mild encephalitis” hypothesis of schizophrenia. If neurovascular abnormalities prove to be etiologically relevant to the neurobiology of schizophrenia, then targeting these abnormalities may represent a

  11. Focal Cryoablation of Prostate: A Review

    Directory of Open Access Journals (Sweden)

    Duke K. Bahn

    2008-01-01

    Full Text Available Current treatment options for men with early localized prostate cancer are either some form of radical therapy or active surveillance. Radical therapy is usually associated with significant adverse effects that might jeopardize a man's quality of life. Some observers believe that PSA screening has resulted in the over diagnosis and over treatment of prostate cancer. Many men are being diagnosed with an early stage, small volume, unifocal or unilateral prostate cancer but are reluctant to accept watchful waiting or active surveillance. Focal cryoablation is the less than complete ablation of the gland with ice. Based on review of the limited amount of material available in the current literature, focal cryoablation can provide acceptable cancer control while preserving sexual potency and urinary continence. Focal cryoablation may fill a void in the therapeutic options available to patients with unifocal or unilateral prostate cancer who have a strong desire to maintain their quality of life.

  12. Traumatic brain injury: clinical and pathological parameters in an experimental weightdrop model Lesão cerebral traumática: parâmetros clínicos e patológicos em um modelo experimental de queda de peso

    Directory of Open Access Journals (Sweden)

    Danilo dos Santos Silva

    2011-04-01

    Full Text Available PURPOSE: To investigate the function of an experimental cranium trauma model in rats. METHODS: The equipment, already described in the literature and under discreet adaptations, is composed by a platform that produces closed head impact controlled by weight drop with pre-defined and known energy. 25 Wistar male rats (Rattus norvegicus albinus were divided into five equal groups that received different quantities of cranial impact energy: G1, G2, G3 and G4 with 0,234J, 0,5J, 0,762J and 1J respectively and G5 (Sham. Under intense analgesia, each group was evaluated clinically in a sequence of intervals and had their encephalon removed for pathologic analysis. RESULTS: Important clinical alterations (convulsions, bradycardia, bradypnea and abnormal postures and focal pathologic (hematomas and hemorrhages kept proportion with the intensity of the impact. No fracture was observed and the group 4 had 80% mortality rate. CONCLUSION: The experimental cranium trauma animal model by weight drop is an alternative of low cost and easy reproduction that allows evaluating clinical and pathological alterations in accordance with studies in experimental surgery aims for new traumatic brain injury approach in rats.OBJETIVO: Investigar o uso de um modelo de trauma craniano experimental em ratos. MÉTODOS: O equipamento, já descrito na literatura e sob discretas adaptações, contitui-se de uma plataforma para produção de lesão craniana fechada controlada por queda de peso com energia pré-definida e conhecida. 25 ratos Wistar machos (Rattus norvegicus albinus foram divididos em cinco grupos iguais que receberam níveis diferentes de energia de impacto craniano: G1, G2, G3 e G4 com 0,234J, 0,5J, 0, 762J e 1J respectivamente e G5 (Sham. Sob intensa analgesia, cada grupo foi avaliado clinicamente em uma seqüência de intervalos e tiveram seus encéfalos removidos para análise patológica. RESULTADOS: Alterações clínicas importantes (convulsões, bradicardia

  13. Experimental study on the rim-enhancing lesion of rabbit brain abscess : MR imaging and histopathologic correlation

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hee Jung; Suh, Soo Jhi; Kim, Sang Pyo; Joo, Yang Goo; Zeon, Seok Kil; Woo, Seong Ku [Keimyung Univ. School of Medicine, Taegu (Korea, Republic of)

    1996-11-01

    To evaluate on the basis of histopathologic carrelation the MR findings of mature brain abscess in the rabbit, with particular attention to rim-enhancing lesions. The evolution of abscess formation was obtained by the direct inoculation of Staphylococcus aureus into the gray-white matter junctions of the brains of 16 rabbits. The stages of brain abscesses were divided into four : early cerebritis (days 1 to 5 after inoculation of the organism);late cerebritis (days 6 to 14);early capsular (days 16 to 21);and late capsular (days 22 to 28). The available MR images showed 14 cases at the stage of early cerebritis, seven at the late cerebritis stage, three at the early capsular, and one at the late capsular stage. According to the known pathology of brain abscesses and on the basis of both MR imaging and histopathologic findings, the lesions were grouped according to whether they were found in the central necrotic, border, or peripheral zone. We analyzed the patterns of rim-enhancement (completeness of the rim, thickness, and margin) and the signal intensities of the abscess walls on MR images at each stage. Histopathologic correlation was performed in one case of each stage. We evaluated the presence or absence and degree of infiltration by inflammatory granulation tissue, microhemorrhage, reticulin, collagen, and hemosiderin of the abscess walls. Rim-enhancing lesions were present in three of 14 cases at the late cerebritis stage, in all three cases at the early capsular, in one at the late capsular, but in none at the early cerebritis stage. The enhancing pattern of the late cerebritis stage was irregular-margined incomplete rim-enhancement, with irregular thickness of the abscess walls (3/3). The enhancing pattern of the capsular stages was well-defined, complete rim-enhancement with uniform thickness of the abscess walls (3/4). The signal intensities of the abscess walls at the late cerebritis and early capsular stages were variable. The late capsular stage ws

  14. Expansive focal cemento-osseous dysplasia.

    Science.gov (United States)

    Bulut, Emel Uzun; Acikgoz, Aydan; Ozan, Bora; Zengin, Ayse Zeynep; Gunhan, Omer

    2012-01-01

    To present a case of expansive focal cemento-osseous dysplasia and emphasize the importance of differential diagnosis. Cemento-osseous dysplasia is categorized into three subtypes on the basis of the clinical and radiographic features: Periapical, focal and florid. The focal type exhibits a single site of involvement in any tooth-bearing or edentulous area of the jaws. These lesions are usually asymptomatic; therefore, they are frequently diagnosed incidentally during routine radiographic examinations. Lesions are usually benign, show limited growth, and do not require further surgical intervention, but periodic follow-up is recommended because occasionally, this type of dysplasia progresses into florid osseous dysplasia and simple bone cysts are formed. A 24-year-old female patient was referred to our clinic for swelling in the left edentulous mandibular premolarmolar region and felt discomfort when she wore her prosthetics. She had no pain, tenderness or paresthesia. Clinical examination showed that the swelling in the posterior mandible that was firm, nonfluctuant and covered by normal mucosa. On panoramic radiography and computed tomography, a well defined lesion of approximately 1.5 cm in diameter of mixed density was observed. The swelling increased slightly in size over 2 years making it difficult to use prosthetics and, therefore, the lesion was totally excised under local anesthesia, and surgical specimens were submitted for histopathological examination. The histopathological diagnosis was focal cemento-osseous dysplasia. In the present case, because of the increasing size of the swelling making it difficult to use prosthetics, young age of the patient and localization of the lesion, in the initial examination, cemento-ossifying fibroma was suspected, and the lesion was excised surgically; the histopathological diagnosis confirmed it as focal cemento-osseous dysplasia. We present a case of expansive focal cemento-osseous dysplasia. Differential diagnosis

  15. Actinic Granuloma with Focal Segmental Glomerulosclerosis

    Directory of Open Access Journals (Sweden)

    Ruedee Phasukthaworn

    2016-02-01

    Full Text Available Actinic granuloma is an uncommon granulomatous disease, characterized by annular erythematous plaque with central clearing predominately located on sun-damaged skin. The pathogenesis is not well understood, ultraviolet radiation is recognized as precipitating factor. We report a case of a 52-year-old woman who presented with asymptomatic annular erythematous plaques on the forehead and both cheeks persisting for 2 years. The clinical presentation and histopathologic findings support the diagnosis of actinic granuloma. During that period of time, she also developed focal segmental glomerulosclerosis. The association between actinic granuloma and focal segmental glomerulosclerosis needs to be clarified by further studies.

  16. Natural course of symptomatic focal choroidal excavation.

    Science.gov (United States)

    Pierro, Luisa; Casalino, Giuseppe; Introini, Ugo; Gagliardi, Marco; Sergenti, Jessica; Cascavilla, Maria Lucia; Bandello, Francesco

    2015-01-01

    A 32-year-old man was referred to the authors' department for nonspecified macular dystrophy with persistent metamorphopsia in the right eye diagnosed 10 years before and followed using optical coherence tomography. The patient underwent a comprehensive ocular examination, including multimodal imaging evaluation and electrofunctional testing. The diagnosis was consistent with nonconforming focal choroid excavation. Over 10 years, no complications occurred, visual acuity was stable, and optical coherence tomography showed no progression of the lesion during follow-up. In this case, nonconforming symptomatic focal choroid excavation was a nonprogressive condition with good long-term visual outcome. Copyright 2015, SLACK Incorporated.

  17. Ambroxol-induced focal epileptic seizure.

    Science.gov (United States)

    Lapenta, Leonardo; Morano, Alessandra; Fattouch, Jinane; Casciato, Sara; Fanella, Martina; Giallonardo, Anna Teresa; Di Bonaventura, Carlo

    2014-01-01

    It is well known that in epileptic patients some compounds and different drugs used for the treatment of comorbidities can facilitate or provoke seizures, this evidence regarding a wide spectrum of pharmacological categories. The potential facilitating factors usually include direct toxic effects or pharmacological interactions of either active ingredients or excipients. We report the case of a patient with drug-resistant epilepsy who experienced focal epileptic seizures, easily and constantly reproducible, after each administration of a cough syrup. This is, to our knowledge, the first electroencephalogram-documented case of focal epileptic seizures induced by cough syrup containing ambroxol as active ingredient.

  18. Evidence-based review of oral traditional Chinese medicine compound recipe administration for treating weight drop-induced experimental traumatic brain injury.

    Science.gov (United States)

    Yang, Bo; Wang, Zhe; Sheng, Chenxia; Wang, Yang; Zhou, Jing; Xiong, Xin-gui; Peng, Weijun

    2016-03-09

    Recently, a number of studies conducted and published in China have suggested that traditional Chinese medicine compound recipe (TCMCR) may be beneficial in the treatment of experimental traumatic brain injury (TBI). In this study, we conducted a systematic review and meta-analysis of the efficacy of TCMCR in TBI model with weight drop method to provide robust evidence on the effects of TCMCR and to determine whether TCMCR can be recommended for routine treatment or considered as a standard treatment for TBI. We identified eligible studies by searching five electronic databases on April 1, 2014, and pooled the data using the random-effects model. Results were reported in terms of standardized mean difference (SMD). We also calculated statistical heterogeneity, evaluated the studies' methodological quality and investigated the presence of publication bias. Totally, 187 relevant publications were searched from databases, 25 of which met our inclusion criteria. The overall methodological quality of the most studies was poor, and there was evidence of statistical heterogeneity among studies along with small-study effects. Meta-analysis showed statistically significant effects indicating that TCMCR has a beneficial effect on TBI. Despite the limitations, we concluded that TCMCR may reduce brain water content, improve BBB permeability, and decrease TNF-α/NO expression after experimental TBI in terms of overall efficacy. However, our review also indicates that more well-designed and well-reported animal studies are needed.

  19. Systematic instruction of assistive technology for cognition (ATC) in an employment setting following acquired brain injury: A single case, experimental study.

    Science.gov (United States)

    Powell, Laurie E; Glang, Ann; Pinkelman, Sarah; Albin, Richard; Harwick, Robin; Ettel, Deborah; Wild, Michelle R

    2015-01-01

    Assistive technology for cognition (ATC) can be an effective means of compensating for cognitive impairments following acquired brain injury. Systematic instruction is an evidence-based approach to training a variety of skills and strategies, including the use of ATC. This study experimentally evaluated systematic instruction applied to assistive technology for cognition (ATC) in a vocational setting. The study used a single-case, multiple-probe design across behaviors design. The participant was a 50-year old female with cognitive impairments following an acquired brain injury (ABI). As a part-time employee, she was systematically instructed on how to operate and routinely use selected applications (apps) on her iPod Touch to support three work-related skills: (a) recording/recalling the details of work assignments, (b) recording/recalling work-related meetings and conversations, and (c) recording/performing multi-step technology tasks. The experimental intervention was systematic instruction applied to ATC. The dependent measures were: (a) the use of ATC at work as measured by an ATC routine task analysis; and (b) recall of work-related tasks and information. Treatment effects were replicated across the three work-related skills and were maintained up to one year following the completion of intensive training across behaviors with periodic review (booster sessions). Systematic instruction is a critical component to teaching the routine use of ATC to compensate for cognitive impairments following ABI.

  20. Erythromycin pretreatment induces tolerance against focal cerebral ischemia through up-regulation of nNOS but not down-regulation of HIF-1α in rats.

    Science.gov (United States)

    Lu, Wei-Cheng; Li, Guang-Yu; Xie, Hui; Qiu, Bo; Yang, Ri-Miao; Guo, Zong-Ze

    2014-05-01

    The purpose of this study was to determine whether the antibiotic erythromycin induces tolerance against focal cerebral ischemia, and the possible underlying mechanism including the involvement of neuronal nitric oxide synthase (nNOS) and hypoxia-inducible factor-1α (HIF-1α). In rat focal cerebral ischemia models, we found that erythromycin preconditioning could significantly decrease the cerebral infarct volume and brain edema. Meanwhile, the neurological deficits from day 4 through 7 after surgery were also remarkably decreased after erythromycin preconditioning. Moreover, erythromycin preconditioning induced significantly increased nNOS levels and decreased HIF-1α levels in both mRNA and protein expression. This study for the first time indicated that erythromycin preconditioning could induce focal brain ischemic tolerance and attenuate brain injury of subsequent transient focal cerebral ischemia. The potential mechanism may be due to up-regulation of nNOS, but the HIF-1α system was not involved.

  1. Unilateral autoscopic phenomena as a lateralizing sign in focal epilepsy.

    Science.gov (United States)

    Hoepner, Robert; Labudda, Kirsten; Hoppe, Matthias; Schoendienst, Martin; Schulz, Reinhard; Tomka-Hoffmeister, Maria; Woermann, Friedrich G; Ebner, Alois; Bien, Christian G; Brandt, Christian

    2012-03-01

    Positive autoscopic phenomena - autoscopy, heautoscopy and out-of-body experience - may occur in a variety of diseases and also in physiological conditions. They are a rare but probably underreported phenomenon in focal epilepsies. Here, we investigate whether ictal lateralized autoscopic phenomena give lateralizing information about the underlying epileptic focus. We present the cases of seven patients from our center who experienced ictal lateralized autoscopic phenomena and analyzed their focus lateralization and localization of the underlying brain lesion. In addition, we reviewed seven cases published in German and English language literature. In the total group of 14 patients with ictal lateralized autoscopic phenomena, 12 (85.7%) of them had a well-defined epileptic focus contralateral to the side of the autoscopic appearance. Therefore, the data point to an association between ictal lateralized autoscopy and contralateral epileptic focus. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. [Comparison of electrocorticographic patterns with focal cortical dysplasia types in children with epilepsy].

    Science.gov (United States)

    Korsakova, M B; Kozlova, A B; Arkhipova, N A; Shishkina, L V; Vorob'ev, A N; Sorokin, V S; Masherov, E L; Melikyan, A G

    2015-01-01

    the objective of the study was to determine significant differences in electrocorticographic patterns for various types of focal cortical dysplasias. 42 patients diagnosed with drug-resistant focal epilepsy were operated on at the Burdenko Neurosurgical Institute in the period from 2006 to 2013. Patients who were histologically diagnosed with focal cortical dysplasia (FCD) and underwent video-electroencephalography and electrocorticography were analyzed. The classification of epileptiform patterns proposed by Palmini in 1995 was used. The sporadic epileptiform activity pattern was predominant in electrocorticographic studies. The continued pattern was more frequent in the case of type II focal cortical dysplasias (FCDs), both combined and isolated; burst and sporadic activity patterns prevailed in combinations in the case of type III FCDs. A uniform distribution of all pattern types of the epileptiform activity was observed in type I FCDs. The data are statistically significant for groups with sporadic and continued patterns. The continued epileptiform activity pattern is predominant in type II focal cortical dysplasia that corresponds to the most pronounced epileptogenesis processes of brain tissue with the presence of pathological forms of neurons. A uniform pattern distribution is observed for type I FCD. Patterns of the epileptiform activity and sporadic spike bursts are predominant in the case of type III FCDs. The sporadic activity is likely to be non-specific and almost uniformly distributed in all types of cortical dysplasias.

  3. Therapeutic efficacy of Neuro AiD™ (MLC 601), a traditional Chinese medicine, in experimental traumatic brain injury.

    Science.gov (United States)

    Tsai, Ming-Che; Chang, Ching-Ping; Peng, Syue-Wei; Jhuang, Kai-Sheng; Fang, Yi-Hsien; Lin, Mao-Tsun; Tsao, Thomas Chang-Yao

    2015-03-01

    Traumatic brain injury (TBI) causes increased release of several mediators from injured and dead cells and elicits microglial activation. Activated microglia change their morphology, migrate to injury sites, and release tumor necrosis factor-alpha (TNF-α) and others. In this study we used a controlled fluid percussion injury model of TBI in the rat to determine whether early (4 h post-injury) or late (4 days post-injury) treatment with MLC 601, a Traditional Chinese Medicine, would affect microglial activation and improve recovery. MLC 601 was chosen for this study because its herbal component MLC 901 was beneficial in treating TBI in rats. Herein, rats with induced TBI were treated with MLC 601 (0.2-0.8 mg/kg) 1 h (early treatment) or 4 day post-injury (late treatment) and then injected once daily for consecutive 2 days. Acute neurological and motor deficits were assessed in all rats the day before and 4 days after early MLC 601 treatment. An immunofluorescence microscopy method was used to count the numbers of the cells colocalized with neuron- and apoptosis-specific markers, and the cells colocalized with microglia- and TNF-α-specific markers, in the contused brain regions 4 days post-injury. An immunohistochemistry method was used to evaluate both the number and the morphological transformation of microglia in the injured areas. It was found that early treatment with MLC 601 had better effects in reducing TBI-induced cerebral contusion than did the late therapy with MLC 601. Cerebral contusion caused by TBI was associated with neurological motor deficits, brain apoptosis, and activated microglia (e.g., microgliosis, amoeboid microglia, and microglial overexpression of TNF-α), which all were significantly attenuated by MLC 601 therapy. Our data suggest that MLC 601 is a promising agent for treatment of TBI in rats.

  4. Pressure passive cerebral blood flow and breakdown of the blood-brain barrier in experimental fetal asphyxia

    DEFF Research Database (Denmark)

    Lou, H C; Lassen, N A; Tweed, W A

    1979-01-01

    reaching CBF values up to 6 times normal at normal MABP of about 60 to 70 mmHg, and severe ischemia reaching CBF values close to zero in large cortical areas at MABP of 30 mmHg. CVP remained essentially unchanged at 10--15 mmHg. The severe and prolonged asphyxia rendered the blood-brain barrier leaky...... to the albumin tracer Evans blue. In four other fetuses umbilical cord clamping was omitted. However, only in one of these cases was acidosis completely avoided, and CBF autoregulation maintained. The three other fetuses were acidotic at the end of the surgical procedure and had impaired autoregulation....

  5. Experimental inflammation following dural application of complete Freund's adjuvant or inflammatory soup does not alter brain and trigeminal microvascular passage

    DEFF Research Database (Denmark)

    Lundblad, Cornelia; Haanes, Kristian A; Grände, Gustaf

    2015-01-01

    , following dural application of complete Freund's adjuvant (CFA) or inflammatory soup (IS) on brain and trigeminal microvascular passage. METHODS: In order to address this issue, we induced local inflammation in male Sprague-Dawley-rats dura mater by the addition of CFA or IS directly on the dural surface......) in a major way. However, [(51)Cr]-EDTA readily passed the TG by >30 times compared to the CNS. Application of CFA or IS did not show altered transfer constants. CONCLUSIONS: With these experiments we show that dural IS/CFA triggered TG inflammation, did not increase the BBB passage, and that the TG...

  6. An experimental study on acute brain radiation injury: Dynamic changes in proton magnetic resonance spectroscopy and the correlation with histopathology

    Energy Technology Data Exchange (ETDEWEB)

    Li, Hui, E-mail: lihui@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou (China); Li, Jian-peng, E-mail: lijp@sysucc.org.cn [Department of Radiology, Dongguan People' s Hospital, Dongguan City (China); Lin, Cheng-guang, E-mail: linchg@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Department of Radiation Oncology, Cancer Center, Sun Yat-sen University, Guangzhou (China); Liu, Xue-wen, E-mail: liuxw@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou (China); Geng, Zhi-jun, E-mail: gengzhj@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou (China); Mo, Yun-xian, E-mail: moyx@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou (China); Zhang, Rong, E-mail: zhangr@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou (China); Xie, Chuan-miao, E-mail: xchuanm@sysucc.org.cn [State Key Laboratory of Oncology in Southern China, Guangzhou (China); Medical Imaging and Minimally Invasive Interventional Center, Cancer Center, Sun Yat-sen University, Guangzhou (China)

    2012-11-15

    Purpose: To investigate the correlation between the alterations of single-voxel {sup 1}H MRS and the histopathological characteristics of radiation brain injury following radiation. Materials and methods: Twenty-seven rabbits were randomized into nine groups to receive radiation with a single dose of 25 Gy. The observation time points included a pre-radiation and 1, 2, 3, 4, 5, 6, 7, and 8 wk following radiation. Each treatment group underwent conventional MRI and single-voxel {sup 1}H MRS, N-acetyl aspartate (NAA), choline (Cho), and creatine (Cr) were observed over the region of interest, and the presence or absence of lactate (Lac) and lipid (Lip) was detected. Histological specimens of each group were obtained after image acquisition. Results: The values of Cho were significantly increased in the first 3 wk, and decreased over the following 5 wk after radiation. Levels of NAA showed a trend toward a decrease 5 wk after radiation. The levels of Cr were not changed between before and after radiation. The Cho/NAA metabolic ratio was significantly increased in weeks 6, 7, and 8 following irradiation, compared to pre-radiation values. Vascular and glial injury appeared on 2 wk after RT in the histology samples, until 4 wk after RT, necrosis of the oligodendrocytes, neuronal degeneration and demyelination could be observed. Conclusions: MRS is sensitive to detect metabolic changes following radiation, and can be used in the early diagnosis of radiation brain injury.

  7. Brain transcriptomes of honey bees (Apis mellifera experimentally infected by two pathogens: Black queen cell virus and Nosema ceranae

    Directory of Open Access Journals (Sweden)

    Vincent Doublet

    2016-12-01

    Full Text Available Regulation of gene expression in the brain plays an important role in behavioral plasticity and decision making in response to external stimuli. However, both can be severely affected by environmental factors, such as parasites and pathogens. In honey bees, the emergence and re-emergence of pathogens and potential for pathogen co-infection and interaction have been suggested as major components that significantly impaired social behavior and survival. To understand how the honey bee is affected and responds to interacting pathogens, we co-infected workers with two prevalent pathogens of different nature, the positive single strand RNA virus Black queen cell virus (BQCV, and the Microsporidia Nosema ceranae, and explored gene expression changes in brains upon single infections and co-infections. Our data provide an important resource for research on honey bee diseases, and more generally on insect host-pathogen and pathogen-pathogen interactions. Raw and processed data are publicly available in the NCBI/GEO database: (http://www.ncbi.nlm.nih.gov/geo/ under accession number GSE81664.

  8. Brain transcriptomes of honey bees (Apis mellifera) experimentally infected by two pathogens: Black queen cell virus and Nosema ceranae.

    Science.gov (United States)

    Doublet, Vincent; Paxton, Robert J; McDonnell, Cynthia M; Dubois, Emeric; Nidelet, Sabine; Moritz, Robin F A; Alaux, Cédric; Le Conte, Yves

    2016-12-01

    Regulation of gene expression in the brain plays an important role in behavioral plasticity and decision making in response to external stimuli. However, both can be severely affected by environmental factors, such as parasites and pathogens. In honey bees, the emergence and re-emergence of pathogens and potential for pathogen co-infection and interaction have been suggested as major components that significantly impaired social behavior and survival. To understand how the honey bee is affected and responds to interacting pathogens, we co-infected workers with two prevalent pathogens of different nature, the positive single strand RNA virus Black queen cell virus (BQCV), and the Microsporidia Nosema ceranae, and explored gene expression changes in brains upon single infections and co-infections. Our data provide an important resource for research on honey bee diseases, and more generally on insect host-pathogen and pathogen-pathogen interactions. Raw and processed data are publicly available in the NCBI/GEO database: (http://www.ncbi.nlm.nih.gov/geo/) under accession number GSE81664.

  9. Optical interconnections to focal plane arrays

    Energy Technology Data Exchange (ETDEWEB)

    Rienstra, J.L.; Hinckley, M.K.

    2000-11-01

    The authors have successfully demonstrated an optical data interconnection from the output of a focal plane array to the downstream data acquisition electronics. The demonstrated approach included a continuous wave laser beam directed at a multiple quantum well reflectance modulator connected to the focal plane array analog output. The output waveform from the optical interconnect was observed on an oscilloscope to be a replica of the input signal. They fed the output of the optical data link to the same data acquisition system used to characterize focal plane array performance. Measurements of the signal to noise ratio at the input and output of the optical interconnection showed that the signal to noise ratio was reduced by a factor of 10 or more. Analysis of the noise and link gain showed that the primary contributors to the additional noise were laser intensity noise and photodetector receiver noise. Subsequent efforts should be able to reduce these noise sources considerably and should result in substantially improved signal to noise performance. They also observed significant photocurrent generation in the reflectance modulator that imposes a current load on the focal plane array output amplifier. This current loading is an issue with the demonstrated approach because it tends to negate the power saving feature of the reflectance modulator interconnection concept.

  10. Laser Dazzling of Focal Plane Array Cameras

    NARCIS (Netherlands)

    Schleijpen, H.M.A.; Dimmeler, A.; Eberle, B; Heuvel, J.C. van den; Mieremet, A.L.; Bekman, H.H.P.T.; Mellier, B.

    2007-01-01

    Laser countermeasures against infrared focal plane array cameras aim to saturate the full camera image. In this paper we will discuss the results of dazzling experiments performed with MWIR lasers. In the “low energy” pulse regime we observe an increasing saturated area with increasing power. The

  11. Focal dermal hypoplasia: A rare case report

    Directory of Open Access Journals (Sweden)

    Sahana M Srinivas

    2015-01-01

    Full Text Available Focal dermal hypoplasia (Goltz syndrome is a rare genetic multisystem disorder primarily involving the skin, skeletal system, eyes, and face. We report the case of an eight-month-old female child who presented with multiple hypopigmented atrophic macules along the lines of blaschko, skeletal anomalies, umbilical hernia, developmental delay, hypoplastic nails, syndactyly, and lobster claw deformity characteristic of Goltz syndrome.

  12. Cerebral palsy and seizures in a child with tubulinopathy pattern dysgenesis and focal cortical dysplasia

    Directory of Open Access Journals (Sweden)

    Kevin M. Sweet, MS

    2017-06-01

    Full Text Available A 7-year-old boy with a history of spasticity, global developmental delay, and seizures was given the general diagnosis of cerebral palsy at an early age. Chromosomal array analysis performed at an outside center was normal. The patient's family sought neurodevelopmental pediatric care at a new institution following a move out of state. Electroencephalography confirmed abnormal epileptogenic activity. Brain magnetic resonance imaging showed findings consistent with a tubulin gene defect (tubulinopathy and of focal cortical dysplasia, as well as evidence of a remote occipital lobe injury. This case report describes the various brain magnetic resonance findings suggestive of a tubulin gene defect and raises the possibility of focal cortical dysplasia manifesting as a result of tubulin dysfunction.

  13. Cerebral palsy and seizures in a child with tubulinopathy pattern dysgenesis and focal cortical dysplasia.

    Science.gov (United States)

    Sweet, Kevin M; Shaw, Dennis W W; Chapman, Teresa

    2017-06-01

    A 7-year-old boy with a history of spasticity, global developmental delay, and seizures was given the general diagnosis of cerebral palsy at an early age. Chromosomal array analysis performed at an outside center was normal. The patient's family sought neurodevelopmental pediatric care at a new institution following a move out of state. Electroencephalography confirmed abnormal epileptogenic activity. Brain magnetic resonance imaging showed findings consistent with a tubulin gene defect (tubulinopathy) and of focal cortical dysplasia, as well as evidence of a remote occipital lobe injury. This case report describes the various brain magnetic resonance findings suggestive of a tubulin gene defect and raises the possibility of focal cortical dysplasia manifesting as a result of tubulin dysfunction.

  14. A feasible strategy for focal cerebral ischemia-reperfusion injury: remote ischemic postconditioning.

    Science.gov (United States)

    Liu, Qiang; Zhou, Shengnian; Wang, Yaodong; Qi, Fang; Song, Yuan; Long, Siwei

    2014-08-01

    It is difficult to control the degree of ischemic postconditioning in the brain and other ischemia-sensitive organs. Remote ischemic postconditioning could protect some ischemia-sensitive organs through measures on terminal organs. In this study, a focal cerebral ischemia-reperfusion injury model was established using three cycles of remote ischemic postconditioning, each cycle consisted of 10-minute occlusion of the femoral artery and 10-minute opening. The results showed that, remote ischemic postconditioning significantly decreased the percentage of the infarct area and attenuated brain edema. In addition, inflammatory nuclear factor-κB expression was significantly lower, while anti-apoptotic Bcl-2 expression was significantly elevated in the cerebral cortex on the ischemic side. Our findings indicate that remote ischemic postconditioning attenuates focal cerebral ischemia/reperfusion injury, and that the neuroprotective mechanism is mediated by an anti-apoptotic effect and reduction of the inflammatory response.

  15. Imaging modalities in Focal Therapy: Multiparametric Ultrasound.

    Science.gov (United States)

    Wildeboer, R R; Panfilova, A P; Mischi, M; Wijkstra, H

    2016-07-01

    Prostate cancer (PCa) is the most common form of cancer among men in the US and the second most common cause of death. It has been observed that an increasing number of newly diagnosed patients exhibit low-risk features and that over-treatment with radical prostatectomy is a growing problem. The feasibility of focal therapy as an organsparing alternative, however, depends on the reliability of imaging techniques to identify, localize and monitor clinically relevant PCa lesions. The aim of this review is to investigate the potential of multiparametric ultrasound (mpUS) for focal therapy. We briefly introduce the most common focal therapies and thoroughly discuss the ability of available ultrasound modalities to localize PCa and reflect tissue properties. The imaging requirements of the focal therapies are studied to put the performance of the US techniques into perspective. We found that transrectal greyscale echography, Doppler sonography, elastography, contrast-enhanced ultrasonography and computerized ultrasound have been studied for the purpose of prostate imaging. Several of these modalities are already frequently used in current clinical practice; to add to the diagnostic process of PCa, to guide and monitor the application of focal therapy or to perform follow-up after treatment. Despite their capability to detect a large fraction of the PCa lesions, none of these modalities is currently considered sufficiently accurate for stand-alone tumour detection and localization. However, although there are only few studies reporting on a combined use of different ultrasound modalities, the results of an mpUS approach seem promising. Several US modalities have been successfully applied as a viable alternative to monitor tissue destruction during and after treatment. In view of the advantages of US and the promising results of a multiparametric approach in PCa detection and localization, researchers are urged to further investigate mpUS for therapeutic purposes.

  16. New experimental model of acute aqueductal blockage in cats: effects on cerebrospinal fluid pressure and the size of brain ventricles.

    Science.gov (United States)

    Klarica, M; Oresković, D; Bozić, B; Vukić, M; Butković, V; Bulat, M

    2009-02-18

    It is generally assumed that cerebrospinal fluid (CSF) is secreted in the brain ventricles, and so after an acute blockage of the aqueduct of Sylvius an increase in the ventricular CSF pressure and dilation of isolated ventricles may be expected. We have tested this hypothesis in cats. After blocking the aqueduct, we measured the CSF pressure in both isolated ventricles and the cisterna magna, and performed radiographic monitoring of the cross-sectional area of the lateral ventricle. The complete aqueductal blockage was achieved by implanting a plastic cannula into the aqueduct of Sylvius through a small tunnel in the vermis of the cerebellum in the chloralose-anesthetized cats. After the reconstitution of the occipital bone, the CSF pressure was measured in the isolated ventricles via a plastic cannula implanted in the aqueduct of Sylvius and in the cisterna magna via a stainless steel cannula. During the following 2 h, the CSF pressures in the isolated ventricles and cisterna magna were identical to those in control conditions. We also monitored the ventricular cross-sectional area by means of radiography for 2 h after the aqueductal blockage and failed to observe any significant changes. When mock CSF was infused into isolated ventricles to imitate the CSF secretion, the gradient of pressure between the ventricle and cisterna magna developed, and disappeared as soon as the infusion was terminated. However, when mock CSF was infused into the cisterna magna at various rates, the resulting increased subarachnoid CSF pressure was accurately transmitted across the brain parenchyma into the CSF of isolated ventricles. The lack of the increase in the CSF pressure and ventricular dilation during 2 h of aqueductal blockage suggests that aqueductal obstruction by itself does not lead to development of hypertensive acute hydrocephalus in cats.

  17. Role of Oxidative Stress in the Development of Cardiac Depression in Severe Isolated Brain Injury (Experimental Study

    Directory of Open Access Journals (Sweden)

    V. V. Rusakov

    2009-01-01

    Full Text Available Objective: to study the role of oxidative stress in the development of cardiac structural and metabolic disorders in severe isolated brain injury (BI. Materials and methods. The impact of BI on the parameters of serum chemilu-minescence and the contractility of isolated rat hearts were studied in experiments on 66 outbred male albino rats, as described by E. T. Fallen et al. Lipid peroxidation processes were inhibited, by intraperitoneally injecting the antioxidant carnosine (100 mg/kg 1 and 24 hours before or just after BI. Results. The rate of free radical processes rose an hour after severe isolated BI, which was associated with the indirect signs of cardiomyocitic membrane damages, depressed rat heart contractility, and their diminished resistance to hypoxia, reoxygenation, and exercise by high rhythm. Administration of carnosine to the animals favored the normalization of chemluminescent values with the high overall antioxidative capacity of serum. The effect of the agent depended on the time of its use and it was high when carnosine was injected 1 and 24 hours before injury. At the stage of reoxygenation after the hypoxic test, there was a significant increase in evolving pressure, the rate of left ventricular myocardial contraction and relaxation, and a reduction in AsAT activity in all coronary duct tests, as compared with the controls. A negative correlation was found between the burst amplitude and the myocardial relaxation rate in the animals receiving the agent. Conclusion. Improved cardiac contractility and increased capacities of the mechanisms responsible for Ca2+ transport due to the use of the antioxidant carnosine allow one to state that oxidative stress is one of the pathogenetic factors of cardiac depression in severe isolated BI. Key words: brain injury, heart, oxidative stress, carnosine.

  18. Effects of transient unilateral functional brain disruption on global neural network status in rats

    Directory of Open Access Journals (Sweden)

    Willem M Otte

    2014-03-01

    Full Text Available Permanent focal brain damage can have critical effects on the function of nearby as well as remote brain regions. However, the effects of transient disturbances on global brain function are largely unknown. Our goal was to develop an experimental in vivo model to map the impact of transient functional brain impairment on large-scale neural networks in the absence of structural damage.We describe a new rat model of transient functional hemispheric disruption using unilateral focal anesthesia by intracarotid pentobarbital injection. The brain’s functional status was assessed with resting-state fMRI (rs-fMRI and EEG. We performed network analysis to identify and quantify highly connected network hubs, i.e. ‘rich-club organization’, in pre- and postbarbital functional networks.Perfusion MRI data demonstrated that the catheterized carotid artery predominantly supplied the ipsilateral hemisphere, allowing for selective hemispheric brain silencing. The prebarbital baseline network displayed strong functional connectivity within and between hemispheres. Following pentobarbital injection, the disrupted hemisphere revealed increased intrahemispheric functional connectivity with concomitant decrease of interhemispheric connectivity. The bilateral functional network was characterized by a strong positive rich-club effect, which was not affected by ipsilateral disruption. Nevertheless, the rich-club value was significantly decreased in the ipsilateral hemisphere and to a lesser extent contralaterally. Loss of interhemispheric EEG synchronization supported the rs-fMRI findings.Our data support the concept that densely connected rich-club regions play a central role in global brain communication, and show that network hub configurations can be significantly affected by focal temporary functional hemispheric disruption without structural neuronal damage. Further studies with this rat model will provide essential additional insights into network

  19. Phosphorylation of Akt by SC79 Prevents Iron Accumulation and Ameliorates Early Brain Injury in a Model of Experimental Subarachnoid Hemorrhage

    Directory of Open Access Journals (Sweden)

    Shuangying Hao

    2016-03-01

    Full Text Available Previous studies have demonstrated that activation of Akt may alleviate early brain injury (EBI following subarachnoid hemorrhage (SAH. This study is undertaken to determine whether iron metabolism is involved in the beneficial effect of Akt activation after SAH. Therefore, we used a novel molecule, SC79, to activate Akt in an experimental Sprague–Dawley rat model of SAH. Rats were randomly divided into four groups as follows: sham, SAH, SAH + vehicle, SAH + SC79. The results confirmed that SC79 effectively enhanced the defense against oxidative stress and alleviated EBI in the temporal lobe after SAH. Interestingly, we found that phosphorylation of Akt by SC79 reduced cell surface transferrin receptor-mediated iron uptake and promoted ferroportin-mediated iron transport after SAH. As a result, SC79 administration diminished the iron content in the brain tissue. Moreover, the impaired Fe-S cluster biogenesis was recovered and loss of the activities of the Fe-S cluster-containing enzymes were regained, indicating that injured mitochondrial functions are restored to healthy levels. These findings suggest that disrupted iron homeostasis could contribute to EBI and Akt activation may regulate iron metabolism to relieve iron toxicity, further protecting neurons from EBI after SAH.

  20. Impact of experimental hypothyroidism on monoamines level in discrete brain regions and other peripheral tissues of young and adult male rats.

    Science.gov (United States)

    Hassan, Wafaa A; Aly, Mona S; Rahman, Taghride Abdel; Shahat, Asmaa S

    2013-06-01

    The levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats were measured following experimentally induced hypothyroidism. Hypothyroidism induced by daily oral administration of propylthiouracil (PTU, 5mg/kg body wt) caused a significant reduction in DA levels in most of the tissues examined of both young and adult rats after 21 and 28 days, in NE levels after all the time intervals studied in young rats, and after 21 and 28 days in adult rats. 5-HT exhibited a significant reduction in the selected brain regions and blood plasma after 21 and 28 days and in cardiac muscle after all the time intervals in the two age groups of animals. It may be suggested that the changes in monoamine levels induced by hypothyroidism may be due to disturbance in the synthesis and release of these amines through the neurons impairment or may be due to an alteration pattern of their synthesizing and/or degradative enzymes. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

  1. fNIRS-EEG study of focal interictal epileptiform discharges.

    Science.gov (United States)

    Peng, Ke; Nguyen, Dang Khoa; Tayah, Tania; Vannasing, Phetsamone; Tremblay, Julie; Sawan, Mohamad; Lassonde, Maryse; Lesage, Frédéric; Pouliot, Philippe

    2014-03-01

    Functional near-infrared spectroscopy (fNIRS) acquired with electroencephalography (EEG) is a relatively new non-invasive neuroimaging technique with potential for long term monitoring of the epileptic brain. Simultaneous EEG-fNIRS recording allows the spatio-temporal reconstruction of the hemodynamic response in terms of the concentration changes in oxy-hemoglobin (HbO) and deoxy-hemoglobin (HbR) associated with recorded epileptic events such as interictal epileptic discharges (IEDs) or seizures. While most previous studies investigating fNIRS in epilepsy had limitations due to restricted spatial coverage and small sample sizes, this work includes a sufficiently large number of channels to provide an extensive bilateral coverage of the surface of the brain for a sample size of 40 patients with focal epilepsies. Topographic maps of significant activations due to each IED type were generated in four different views (dorsal, frontal, left and right) and were compared with the epileptic focus previously identified by an epileptologist. After excluding 5 patients due to the absence of IEDs and 6 more with mesial temporal foci too deep for fNIRS, we report that significant HbR (respectively HbO) concentration changes corresponding to IEDs were observed in 62% (resp. 38%) of patients with neocortical epilepsies. This HbR/HbO response was most significant in the epileptic focus region among all the activations in 28%/21% of patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  2. The role of astroglia in the epileptic brain

    Directory of Open Access Journals (Sweden)

    Gabriele eLosi

    2012-07-01

    Full Text Available Epilepsies comprise a family of multifactorial neurological disorders that affect at least 50 million people worldwide. Despite a long history of neurobiological and clinical studies the mechanisms that lead the brain network to a hyperexcitable state and to the intense, massive neuronal discharges reflecting a seizure episode are only partially defined. Most epilepsies of genetic origin are related to mutations in ionic channels that cause neuronal hyperexcitability. However, idiopathic epilepsies of unclear origin represent the majority of these brain disorders. A large body of evidence suggests that in the epileptic brain neurons are not the only players. Indeed, the glial cell astrocyte is known to be morphologically and functionally altered in different types of epilepsy. Although it is unclear whether these astrocyte dysfunctions can have a causative role in epileptogenesis, the hypothesis that astrocytes contribute to epileptiform activities recently received a considerable experimental support. Notably, currently used antiepileptic drugs (AEDs, that act mainly on neuronal ion channels, are ineffective in a large group of patients. Clarifying astrocyte functions in the epileptic brain tissue could unveil astrocytes as novel therapeutic targets. In this review we present first a short overview on the role of astrocytes in the epileptic brain starting from the historical observations on their fundamental modulation of brain homeostasis, such as the control of water content, ionic equilibrium and neurotransmitters concentrations. We then focus our review on most recent studies that hint at a distinct contribution of these cells in the generation of focal epileptiform activities.

  3. NADPH Oxidase-Related Pathophysiology in Experimental Models of Stroke

    Directory of Open Access Journals (Sweden)

    Hiroshi Yao

    2017-10-01

    Full Text Available Several experimental studies have indicated that nicotinamide adenine dinucleotide phosphate (NADPH oxidases (Nox exert detrimental effects on ischemic brain tissue; Nox-knockout mice generally exhibit resistance to damage due to experimental stroke following middle cerebral artery occlusion (MCAO. Furthermore, our previous MCAO study indicated that infarct size and blood-brain barrier breakdown are enhanced in mice with pericyte-specific overexpression of Nox4, relative to levels observed in controls. However, it remains unclear whether Nox affects the stroke outcome directly by increasing oxidative stress at the site of ischemia, or indirectly by modifying physiological variables such as blood pressure or cerebral blood flow (CBF. Because of technical problems in the measurement of physiological variables and CBF, it is often difficult to address this issue in mouse models due to their small body size; in our previous study, we examined the effects of Nox activity on focal ischemic injury in a novel congenic rat strain: stroke-prone spontaneously hypertensive rats with loss-of-function in Nox. In this review, we summarize the current literature regarding the role of Nox in focal ischemic injury and discuss critical issues that should be considered when investigating Nox-related pathophysiology in animal models of stroke.

  4. A review and experimental study on the application of classifiers and evolutionary algorithms in EEG-based brain-machine interface systems.

    Science.gov (United States)

    Tahernezhad-Javazm, Farajollah; Azimirad, Vahid; Shoaran, Maryam

    2018-04-01

    Considering the importance and the near-future development of noninvasive brain-machine interface (BMI) systems, this paper presents a comprehensive theoretical-experimental survey on the classification and evolutionary methods for BMI-based systems in which EEG signals are used. The paper is divided into two main parts. In the first part, a wide range of different types of the base and combinatorial classifiers including boosting and bagging classifiers and evolutionary algorithms are reviewed and investigated. In the second part, these classifiers and evolutionary algorithms are assessed and compared based on two types of relatively widely used BMI systems, sensory motor rhythm-BMI and event-related potentials-BMI. Moreover, in the second part, some of the improved evolutionary algorithms as well as bi-objective algorithms are experimentally assessed and compared. In this study two databases are used, and cross-validation accuracy (CVA) and stability to data volume (SDV) are considered as the evaluation criteria for the classifiers. According to the experimental results on both databases, regarding the base classifiers, linear discriminant analysis and support vector machines with respect to CVA evaluation metric, and naive Bayes with respect to SDV demonstrated the best performances. Among the combinatorial classifiers, four classifiers, Bagg-DT (bagging decision tree), LogitBoost, and GentleBoost with respect to CVA, and Bagging-LR (bagging logistic regression) and AdaBoost (adaptive boosting) with respect to SDV had the best performances. Finally, regarding the evolutionary algorithms, single-objective invasive weed optimization (IWO) and bi-objective nondominated sorting IWO algorithms demonstrated the best performances. We present a general survey on the base and the combinatorial classification methods for EEG signals (sensory motor rhythm and event-related potentials) as well as their optimization methods through the evolutionary algorithms. In addition

  5. Beneficial effects of minocycline and botulinum toxin-induced constraint physical therapy following experimental traumatic brain injury.

    Science.gov (United States)

    Lam, Tina I; Bingham, Deborah; Chang, Ting Ju; Lee, Chih Cheng; Shi, Jian; Wang, Dongmin; Massa, Stephen; Swanson, Raymond A; Liu, Jialing

    2013-01-01

    Effective recovery from functional impairments caused by traumatic brain injury (TBI) requires appropriate rehabilitation therapy. Multiple pathways are involved in secondary injury and recovery suggesting a role for multimodal approaches. Here, we examined the efficacy of the anti-inflammatory agent minocycline and botulinum toxin (botox)-induced limb constraint with structured physical therapy, delivered alone or in combination, after a severe TBI produced by a controlled cortical impact in rats. Minocycline was administered at 25 mg/kg daily for 2 weeks beginning 1 day after TBI or sham surgery. For constraint/physical therapy, botox-type A was injected into the nonaffected forearm muscle 1 day after injury and 2 weeks of physical therapy commenced at 5 days after injury. Functional evaluations were conducted 8 weeks after injury. Minocycline, either as a monotherapy or as combination treatment with botox/physical therapy significantly reduced impairments of spatial learning and memory in the water maze test, whereas botox/physical therapy reduced forelimb motor asymmetry and improved manual dexterity in the cylinder and vermicelli handling tests, A synergistic effect between the 2 treatments was observed when rats performed tasks requiring dexterity. Inflammation was attenuated in the peri-contusion cortex and hippocampus in all TBI groups receiving mono or combination therapies, though there was no significant difference in lesion size among groups. These data provide a rationale for incorporating anti-inflammatory treatment during rehabilitation therapy.

  6. Intranasal Brain Delivery of Cationic Nanoemulsion-Encapsulated TNFα siRNA in Prevention of Experimental Neuroinflammation

    Science.gov (United States)

    Yadav, Sunita; Gandham, Srujan K.; Panicucci, Riccardo; Amiji, Mansoor M.

    2016-01-01

    Neuroinflammation is a hallmark of acute and chronic neurodegenerative disorders. Activated microglia and secreted factors such as tumor necrosis factor-alpha (TNFα) are key mediators of neuroinflammation and may contribute to neuronal dysfunction. The main aim of this study was to evaluate the therapeutic efficacy of intranasal cationic nanoemulsions encapsulating an anti-TNFα siRNA, for potential anti-inflammatory therapy, tested in an LPS induced model of neuroinflammation. The strategy of developing a cationic nanoemulsion system for silencing the TNFα gene was to efficiently provide neuroprotection against inflammation. TNFα siRNA nanoemulsions were prepared and characterized for particle size, surface charge, morphology, and stability and encapsulation efficiency. Qualitative and quantitative intracellular uptake studies by confocal imaging and flow cytometry, respectively, showed higher uptake compared to Lipofectamine® transfected siRNA. Nanoemulsions showed significantly lower (pnanoemulsions almost 5 fold higher uptake was observed in the rat brain compared to non-encapsulated siRNA. More importantly, intranasal delivery of TNFα siRNA nanoemulsions in vivo markedly reduced the unregulated levels of TNFα in an LPS-induced model of neuroinflammation where TNFα functions as a signaling molecule, which aggravates inflammation. These results indicate that intranasal delivery of cationic nanoemulsions encapsulating TNFα siRNA offered an efficient means of gene knockdown and this approach has significant potential in prevention of neuroinflammation. PMID:26767514

  7. Transcranial current stimulation focality using disc and ring electrode configurations: FEM analysis

    Science.gov (United States)

    Datta, Abhishek; Elwassif, Maged; Battaglia, Fortunato; Bikson, Marom

    2008-06-01

    We calculated the electric fields induced in the brain during transcranial current stimulation (TCS) using a finite-element concentric spheres human head model. A range of disc electrode configurations were simulated: (1) distant-bipolar; (2) adjacent-bipolar; (3) tripolar; and three ring designs, (4) belt, (5) concentric ring, and (6) double concentric ring. We compared the focality of each configuration targeting cortical structures oriented normal to the surface ('surface-radial' and 'cross-section radial'), cortical structures oriented along the brain surface ('surface-tangential' and 'cross-section tangential') and non-oriented cortical surface structures ('surface-magnitude' and 'cross-section magnitude'). For surface-radial fields, we further considered the 'polarity' of modulation (e.g. superficial cortical neuron soma hyper/depolarizing). The distant-bipolar configuration, which is comparable with commonly used TCS protocols, resulted in diffuse (un-focal) modulation with bi-directional radial modulation under each electrode and tangential modulation between electrodes. Increasing the proximity of the two electrodes (adjacent-bipolar electrode configuration) increased focality, at the cost of more surface current. At similar electrode distances, the tripolar-electrodes configuration produced comparable peak focality, but reduced radial bi-directionality. The concentric-ring configuration resulted in the highest spatial focality and uni-directional radial modulation, at the expense of increased total surface current. Changing ring dimensions, or use of two concentric rings, allow titration of this balance. The concentric-ring design may thus provide an optimized configuration for targeted modulation of superficial cortical neurons.

  8. [Liver ultrasound: focal lesions and diffuse diseases].

    Science.gov (United States)

    Segura Grau, A; Valero López, I; Díaz Rodríguez, N; Segura Cabral, J M

    2016-01-01

    Liver ultrasound is frequently used as a first-line technique for the detection and characterization of the most common liver lesions, especially those incidentally found focal liver lesions, and for monitoring of chronic liver diseases. Ultrasound is not only used in the Bmode, but also with Doppler and, more recently, contrast-enhanced ultrasound. It is mainly used in the diagnosis of diffuse liver diseases, such as steatosis or cirrhosis. This article presents a practical approach for diagnosis workup, in which the different characteristics of the main focal liver lesions and diffuse liver diseases are reviewed. Copyright © 2014 Sociedad Española de Médicos de Atención Primaria (SEMERGEN). Publicado por Elsevier España, S.L.U. All rights reserved.

  9. Membership Functions for Fuzzy Focal Elements

    Directory of Open Access Journals (Sweden)

    Porębski Sebastian

    2016-09-01

    Full Text Available The paper presents a study on data-driven diagnostic rules, which are easy to interpret by human experts. To this end, the Dempster-Shafer theory extended for fuzzy focal elements is used. Premises of the rules (fuzzy focal elements are provided by membership functions which shapes are changing according to input symptoms. The main aim of the present study is to evaluate common membership function shapes and to introduce a rule elimination algorithm. Proposed methods are first illustrated with the popular Iris data set. Next experiments with five medical benchmark databases are performed. Results of the experiments show that various membership function shapes provide different inference efficiency but the extracted rule sets are close to each other. Thus indications for determining rules with possible heuristic interpretation can be formulated.

  10. Teal Amber Visible Focal Plane Technology

    Science.gov (United States)

    Johnson, Charles R.; Burczewski, Ron

    1981-12-01

    Deep-space surveillance missions have imposed severe demands on existing technology and simulated the search for new, advanced technology developments to provide higher performance. Defense Advanced Research Projects Agency (DARPA) sponsored Teal Amber as a visible charge-coupled device (CCD) and associated focal plane signal processing technology development and demonstration program. This paper describes this large-scale, staring-array-sensor concept. The current state of art in the resulting visibled CCD imagers is specified, along with the focal plane signal processor implementation in low power-weight-volume large-scale integrated (LSI) circuitry. Performance requirements and analytic predictions are compared to demonstration system results from an electro-optical test site in White Sands, New Mexico.

  11. Focal region fields of distorted reflectors

    Science.gov (United States)

    Buris, N. E.; Kauffman, J. F.

    1988-01-01

    The problem of the focal region fields scattered by an arbitrary surface reflector under uniform plane wave illumination is solved. The physical optics (PO) approximation is used to calculate the current induced on the reflector. The surface of the reflector is described by a number of triangular domain-wise 5th degree bivariate polynomials. A 2-dimensional Gaussian quadrature is employed to numerically evaluate the integral expressions of the scattered fields. No Freshnel or Fraunhofer zone approximations are made. The relation of the focal fields problem to surface compensation techniques and other applications are mentioned. Several examples of distorted parabolic reflectors are presented. The computer code developed is included, together with instructions on its usage.

  12. Focal Adhesion Induction at the Tip of a Functionalized Nanoelectrode

    OpenAIRE

    Fuentes, Daniela E.; Bae, Chilman; Butler, Peter J.

    2011-01-01

    Cells dynamically interact with their physical micro-environment through the assembly of nascent focal contacts and focal adhesions. The dynamics and mechanics of these contact points are controlled by transmembrane integrins and an array of intracellular adaptor proteins. In order to study the mechanics and dynamics of focal adhesion assembly, we have developed a technique for the timed induction of a nascent focal adhesion. Bovine aortic endothelial cells were approached at the apical surfa...

  13. Chest pain in focal musculoskeletal disorders

    DEFF Research Database (Denmark)

    Stochkendahl, Mette Jensen; Christensen, Henrik Wulff

    2010-01-01

    The musculoskeletal system is a recognized source of chest pain. However, despite the apparently benign origin, patients with musculoskeletal chest pain remain under-diagnosed, untreated, and potentially continuously disabled in terms of anxiety, depression, and activities of daily living. Several...... overlapping conditions and syndromes of focal disorders, including Tietze syndrome, costochondritis, chest wall syndrome, muscle tenderness, slipping rib, cervical angina, and segmental dysfunction of the cervical and thoracic spine, have been reported to cause pain. For most of these syndromes, evidence...

  14. The expanded spectrum of focal choroidal excavation.

    Science.gov (United States)

    Margolis, Ron; Mukkamala, Sri Krishna; Jampol, Lee M; Spaide, Richard F; Ober, Michael D; Sorenson, John A; Gentile, Ronald C; Miller, Joel A; Sherman, Jerome; Freund, K Bailey

    2011-10-01

    To describe the clinical and imaging findings in patients with focal choroidal excavation. Retrospective observational case series. The medical records of 12 patients (13 eyes) with focal choroidal excavation were reviewed. Clinical histories and imaging findings (including color photography, fundus autofluorescence imaging, fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and enhanced depth imaging spectral-domain optical coherence tomography) were analyzed. The mean age of the patients was 45 years (range, 22-62 years). Four patients were Asian. Mean visual acuity was 20/31 (range, 20/20 to 20/100). Mean refractive error was -3.54 diopters (D) (range, 6.00 to -8.00 D). One patient had bilateral involvement. All patients manifested varying degrees of foveal pigmentary changes that were usually hypoautofluorescent on fundus autofluorescence images. Fluorescein angiographic findings varied with degree of retinal pigment epithelial alterations. Indocyanine green angiography revealed relative hypofluorescence. In 7 eyes, spectral-domain optical coherence tomography revealed outer retinal layers conforming to retinal pigment epithelial alterations within the excavation. In the other 6 eyes, spectral-domain optical coherence tomography revealed a separation between the outer retina and the retinal pigment epithelium within the excavation. In 7 eyes studied with enhanced depth imaging spectral-domain optical coherence tomography, there was no evidence of scleral ectasia. Mean choroidal thickness of the uninvolved choroid was thicker than normal at 319 μm (range, 244-439 μm). All lesions remained stable except for in 1 eye, which had findings of central serous chorioretinopathy and secondary type 2 (subretinal) neovascularization. Focal choroidal excavation is a newly described idiopathic entity in eyes having 1 or more focal areas of choroidal excavation. In some patients, there may be an association with central

  15. Epilepsy, Acquired Aphasia with Focal Cortical Dysplasia

    Directory of Open Access Journals (Sweden)

    Girija A.S

    1999-01-01

    Full Text Available A six year old boy having complex partial seizures with secondary generalization of four months duration developing isolated expressive dysphasia, later progressing to global aphasia is being reported. His awake EEG showed a left temporal spike wave discharge and sleep EEG showed continuous spike and ware discharges. MR imaging demonstrated focal cortical dysplasia in the left frontal and opercular region, a combination that has not been reported earlier.

  16. Focal dermal hypoplasia in a male

    Science.gov (United States)

    George, Leni; Agrawal, Nisha; Hogan, Peter

    2011-01-01

    Focal dermal hypoplasia (FDH) is a rare mesoectodermal dysplasia syndrome characterized by cutaneous, skeletal, dental, ocular and soft-tissue defects. An X-linked dominant mode of inheritance with lethality in male subjects has been proposed. Only around 30 cases of FDH have been reported in male subjects. Live born affected males are mosaic for mutations in PORCN gene . We present the mosaic pattern of FDH in a young boy. PMID:25386262

  17. Focal adhesions, stress fibers and mechanical tension

    Energy Technology Data Exchange (ETDEWEB)

    Burridge, Keith, E-mail: Keith_Burridge@med.unc.edu [Department of Cell Biology and Physiology, and Lineberger Comprehensive Cancer Center, 12-016 Lineberger, CB#7295, University of North Carolina, Chapel Hill, NC (United States); Guilluy, Christophe, E-mail: christophe.guilluy@univ-nantes.fr [Inserm UMR-S1087, CNRS UMR-C6291, L' institut du Thorax, and Université de Nantes, Nantes (France)

    2016-04-10

    Stress fibers and focal adhesions are complex protein arrays that produce, transmit and sense mechanical tension. Evidence accumulated over many years led to the conclusion that mechanical tension generated within stress fibers contributes to the assembly of both stress fibers themselves and their associated focal adhesions. However, several lines of evidence have recently been presented against this model. Here we discuss the evidence for and against the role of mechanical tension in driving the assembly of these structures. We also consider how their assembly is influenced by the rigidity of the substratum to which cells are adhering. Finally, we discuss the recently identified connections between stress fibers and the nucleus, and the roles that these may play, both in cell migration and regulating nuclear function. - Highlights: • The different types of stress fiber and focal adhesion are described. • We discuss the controversy about tension and assembly of these structures. • We describe the different models used to investigate assembly of these structures. • The influence of substratum rigidity is discussed. • Stress fiber connections to the nucleus are reviewed.

  18. Multispectral linear array (MLA) focal plane mechanical and thermal design

    Science.gov (United States)

    Mitchell, A. S.; Kaminski, E. F.

    1982-01-01

    The mechanical and thermal design of an integrated focal plane subsystem of a Multispectral Linear Array (MLA) instrument is discussed in terms of focal-plane alignment, thermoelastic performance, and thermal requirements. The modular construction and thermal control of the focal plane array are discussed.

  19. Facilitated assessment of tissue loss following traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Anders eHånell

    2012-03-01

    Full Text Available All experimental models of traumatic brain injury (TBI result in a progressive loss of brain tissue. The extent of tissue loss reflects the injury severity and can be measured to evaluate the potential neuroprotective effect of experimental treatments. Quantitation of tissue volumes is commonly performed using evenly spaced brain sections stained using routine histochemical methods and digitally captured. The brain tissue areas are then measured and the corresponding volumes are calculated using the distance between the sections. Measurements of areas are usually performed using a general purpose image analysis software and the results are then transferred to another program for volume calculations. To facilitate the measurement of brain tissue loss we developed novel algorithms which automatically separate the areas of brain tissue from the surrounding image background and identify the ventricles. We implemented these new algorithms by creating a new computer program (SectionToVolume which also has functions for image organization, image adjustments and volume calculations. We analyzed brain sections from mice subjected to severe focal TBI using both SectionToVolume and ImageJ, a commonly used image analysis program. The volume measurements made by the two programs were highly correlated and analysis using SectionToVolume required considerably less time. The inter-rater reliability was high. Given the extensive use of brain tissue loss measurements in TBI research, SectionToVolume will likely be a useful tool for TBI research. We therefore provide both the source code and the program as attachments to this article.

  20. Antioxidant treatment ameliorates experimental diabetes-induced depressive-like behaviour and reduces oxidative stress in brain and pancreas.

    Science.gov (United States)

    Réus, Gislaine Z; Dos Santos, Maria Augusta B; Abelaira, Helena M; Titus, Stephanie E; Carlessi, Anelise S; Matias, Beatriz I; Bruchchen, Livia; Florentino, Drielly; Vieira, Andriele; Petronilho, Fabricia; Ceretta, Luciane B; Zugno, Alexandra I; Quevedo, João

    2016-03-01

    Studies have shown a relationship between diabetes mellitus (DM) and the development of major depressive disorder. Alterations in oxidative stress are associated with the pathophysiology of both diabetes mellitus and major depressive disorder. This study aimed to evaluate the effects of antioxidants N-acetylcysteine and deferoxamine on behaviour and oxidative stress parameters in diabetic rats. To this aim, after induction of diabetes by a single dose of alloxan, Wistar rats were treated with N-acetylcysteine or deferoxamine for 14 days, and then depressive-like behaviour was evaluated. Oxidative stress parameters were assessed in the prefrontal cortex, hippocampus, amygdala, nucleus accumbens and pancreas. Diabetic rats displayed depressive-like behaviour, and treatment with N-acetylcysteine reversed this alteration. Carbonyl protein levels were increased in the prefrontal cortex, hippocampus and pancreas of diabetic rats, and both N-acetylcysteine and deferoxamine reversed these alterations. Lipid damage was increased in the prefrontal cortex, hippocampus, amygdala and pancreas; however, treatment with N-acetylcysteine or deferoxamine reversed lipid damage only in the hippocampus and pancreas. Superoxide dismutase activity was decreased in the amygdala, nucleus accumbens and pancreas of diabetic rats. In diabetic rats, there was a decrease in catalase enzyme activity in the prefrontal cortex, amygdala, nucleus accumbens and pancreas, but an increase in the hippocampus. Treatment with antioxidants did not have an effect on the activity of antioxidant enzymes. In conclusion, animal model of diabetes produced depressive-like behaviour and oxidative stress in the brain and periphery. Treatment with antioxidants could be a viable alternative to treat behavioural and biochemical alterations induced by diabetes. Copyright © 2015 John Wiley & Sons, Ltd.

  1. An improved schlieren method for measurement and automatic reconstruction of the far-field focal spot.

    Directory of Open Access Journals (Sweden)

    Zhengzhou Wang

    Full Text Available The schlieren method of measuring far-field focal spots offers many advantages at the Shenguang III laser facility such as low cost and automatic laser-path collimation. However, current methods of far-field focal spot measurement often suffer from low precision and efficiency when the final focal spot is merged manually, thereby reducing the accuracy of reconstruction. In this paper, we introduce an improved schlieren method to construct the high dynamic-range image of far-field focal spots and improve the reconstruction accuracy and efficiency. First, a detection method based on weak light beam sampling and magnification imaging was designed; images of the main and side lobes of the focused laser irradiance in the far field were obtained using two scientific CCD cameras. Second, using a self-correlation template matching algorithm, a circle the same size as the schlieren ball was dug from the main lobe cutting image and used to change the relative region of the main lobe cutting image within a 100×100 pixel region. The position that had the largest correlation coefficient between the side lobe cutting image and the main lobe cutting image when a circle was dug was identified as the best matching point. Finally, the least squares method was used to fit the center of the side lobe schlieren small ball, and the error was less than 1 pixel. The experimental results show that this method enables the accurate, high-dynamic-range measurement of a far-field focal spot and automatic image reconstruction. Because the best matching point is obtained through image processing rather than traditional reconstruction methods based on manual splicing, this method is less sensitive to the efficiency of focal-spot reconstruction and thus offers better experimental precision.

  2. Down-regulated Na(+)/K(+)-ATPase activity in ischemic penumbra after focal cerebral ischemia/reperfusion in rats.

    Science.gov (United States)

    Huang, Hao; Chen, Yang-Mei; Zhu, Fei; Tang, Shi-Ting; Xiao, Ji-Dong; Li, Lv-Li; Lin, Xin-Jing

    2015-01-01

    This study was aimed to examine whether the Na(+)/K(+) adenosine triphosphatase (Na(+)/K(+)-ATPase) activity in ischemic penumbra is associated with the pathogenesis of ischemia/reperfusion-induced brain injury. An experimental model of cerebral ischemia/reperfusion was made by transient middle cerebral artery occlusion (tMCAO) in rats and the changes of Na(+)/K(+)-ATPase activity in the ischemic penumbra was examined by Enzyme Assay Kit. Extensive infarction was observed in the frontal and parietal cortical and subcortical areas at 6 h, 24 h, 48 h, 3 d and 7 d after tMCAO. Enzyme Assay analyses revealed the activity of Na(+)/K(+)-ATPase was decreased in the ischemic penumbra of model rats after focal cerebral ischemia/reperfusion compared with sham-operated rats, and reduced to its minimum at 48 h, while the infarct volume was enlarged gradually. In addition, accompanied by increased brain water content, apoptosis-related bcl-2 and Bax proteins, apoptotic index and neurologic deficits Longa scores, but fluctuated the ratio of bcl-2/Bax. Correlation analysis showed that the infarct volume, apoptotic index, neurologic deficits Longa scores and brain water content were negatively related with Na(+)/K(+)-ATPase activity, while the ratio of bcl-2/Bax was positively related with Na(+)/K(+)-ATPase activity. Our results suggest that down-regulated Na(+)/K(+)-ATPase activity in ischemic penumbra might be involved in the pathogenesis of cerebral ischemia/reperfusion injury presumably through the imbalance ratio of bcl-2/Bax and neuronal apoptosis, and identify novel target for neuroprotective therapeutic intervention in cerebral ischemic disease.

  3. Treatment with tanshinone IIA suppresses disruption of the blood-brain barrier and reduces expression of adhesion molecules and chemokines in experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Yang, Xue; Yan, Jun; Feng, Juan

    2016-01-15

    Tanshinone IIA (TSIIA), one of the major bioactive components of the traditional Chinese herb Salvia miltiorrhiza, has been reported to have both anti-inflammatory and immunoregulatory effects. The effect of treatment with TSIIA in multiple sclerosis, an autoimmune inflammatory neurodegenerative disease, however, remains poorly understood. In the present study, experimental autoimmune encephalomyelitis (EAE), a classical experimental model of MS, was used to investigate the therapeutic effect of TSIIA. TSIIA attenuated motor dysfunction and improved inflammation and demyelination associated with EAE in a dose-dependent manner. TSIIA also significantly reduced the levels of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adapter molecule-1 (Iba-1), and protected the integrity of the blood-brain barrier (BBB) by increasing the expression of critical endothelial tight junction (TJ) proteins. TSIIA also inhibited the expression of some adhesion molecules and chemokines, which are considered to be critical for adhesion of immune cells and migration across the BBB. TSIIA was thus shown to be effective in the treatment of EAE through preventing the infiltration of immune cells into the CNS, strengthening the integrity of the BBB and decreasing the numbers of adhesion molecules and chemokines. Copyright © 2015 Elsevier B.V. All rights reserved.

  4. Myeloid differentiation factor 88 is up-regulated in epileptic brain and contributes to experimental seizures in rats.

    Science.gov (United States)

    Wang, Na; Han, Xiong; Liu, Haipeng; Zhao, Ting; Li, Jie; Feng, Yan; Mi, Xiujuan; Zhang, Yanke; Chen, Yanan; Wang, Xuefeng

    2017-09-01

    Accumulating evidence supports that activation of inflammatory pathways is a crucial factor contributing to the pathogenesis of seizures. In particular, the activation of interleukin-1 beta (IL-1β) system exerts proconvulsant effects in a large variety of seizure models. Myeloid differentiation factor 88 (MyD88) is a critical adaptor protein in the signaling cascade elicited by IL-1β. The present study aimed to investigate the expression pattern of MyD88 in rat models of seizures and in patients with refractory temporal lobe epilepsy (TLE), and to study the role of MyD88 in epileptic seizures. Our results revealed that MyD88 was up-regulated in the hippocampus of rats in the lithium-pilocarpine model of acute seizures. Importantly, MyD88 overexpression was also significantly present in the brain from chronic epileptic rats and the temporal neocortex specimens from drug-resistant TLE patients. In the acute seizure model, both the behavioral and electrographic seizure activities were record and analyzed in rats for 90min, starting immediately after pilocarpine injection. ST2825, a synthetic MyD88 inhibitor, was administered intracerebroventricularly (2.5-5.0-10μg in 2μl) 20min before pilocarpine injection. We found that ST2825 at doses of 5μg and 10μg significantly inhibited the pilocarpine-induced behavioral and electrographic seizures. Moreover, 10μg ST2825 prevented the proconvulsant actions of IL-1β. As previous evidence suggested that IL-1β proconvulsant effects was mediated by enhancing the phosphorylation level of the NR2B subunit of N-methyl-d-aspartate (NMDA) receptor, we then probed whether this molecular was involved in the effect of the pharmacological inhibition. Our results revealed that 10μg ST2825 markedly reversed the increased Tyr(1472)-phosphorylation of the NR2B subunit of NMDA receptor observed in the proconvulsant conditions of IL-1β and in seizures induced by pilocarpine alone. These findings indicate that altered expression of MyD88

  5. EFFECT OF ELECTRICAL MUSCLE STIMULATION WITH SENSIROMOTOR TRAINING IN FOCAL HAND DYSTONIA - A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Shefali Gambhir

    2015-02-01

    Full Text Available Background: Focal hand Dystonia is shown by involuntary muscle contractions in the arm or hand while writing with a disordered neuroplastic changes in the brain. Symptoms can include lack of co-ordination, cramping and tremor and tend to be specific for each individual. So, the present study evaluates the effect of an integrated approach that is employed to improve functional independence in a patient suffering from focal hand dystonia. Case Description: The benefits of sensorimotor task specific training along with electrical muscle stimulation in the rehabilitation of focal hand dystonia is reported in this study. The treatment protocol is planned according to the problem list of the patient and an intervention of 20 days (1 hour per day, 5 days per week for 4 weeks is given to the patient. Outcome Variables: Prognosis is observed in Burke-Fahn-Marsden scale, global dystonia scale, Jedynak’s protocol and unified dystonia rating scale before & after the intervention. A Depression anxiety stress scale is also used to assess the psychological status of the patient. Conclusion: Considerable improvement is seen in writing and fine motor skills after the rehabilitation. It is observed that the electrical muscle stimulation in conjunction with sensiromostor task specific training induces excitability in the muscles and improve the clinical function in patient with focal hand dystonia.

  6. In vitro modeling of experimental succinic semialdehyde dehydrogenase deficiency (SSADHD using brain-derived neural stem cells.

    Directory of Open Access Journals (Sweden)

    Kara R Vogel

    Full Text Available We explored the utility of neural stem cells (NSCs as an in vitro model for evaluating preclinical therapeutics in succinic semialdehyde dehydrogenase-deficient (SSADHD mice. NSCs were obtained from aldh5a1+/+ and aldh5a1-/- mice (aldh5a1 = aldehyde dehydrogenase 5a1 = SSADH. Multiple parameters were evaluated including: (1 production of GHB (γ-hydroxybutyrate, the biochemical hallmark of SSADHD; (2 rescue from cell death with the dual mTOR (mechanistic target of rapamycin inhibitor, XL-765, an agent previously shown to rescue aldh5a1-/- mice from premature lethality; (3 mitochondrial number, total reactive oxygen species, and mitochondrial superoxide production, all previously documented as abnormal in aldh5a1-/- mice; (4 total ATP levels and ATP consumption; and (5 selected gene expression profiles associated with epilepsy, a prominent feature in both experimental and human SSADHD. Patterns of dysfunction were observed in all of these parameters and mirrored earlier findings in aldh5a1-/- mice. Patterns of dysregulated gene expression between hypothalamus and NSCs centered on ion channels, GABAergic receptors, and inflammation, suggesting novel pathomechanisms as well as a developmental ontogeny for gene expression potentially associated with the murine epileptic phenotype. The NSC model of SSADHD will be valuable in providing a first-tier screen for centrally-acting therapeutics and prioritizing therapeutic concepts of preclinical animal studies applicable to SSADHD.

  7. Bicuculline methiodide in the blood-brain barrier-epileptogen model of epilepsy

    Energy Technology Data Exchange (ETDEWEB)

    Remler, M.P.; Marcussen, W.H.

    Focal epilepsy can be produced by a blood-brain barrier (BBB)-excluded systemic convulsant (penicillin, folic acid, etc.) in the presence of a focal BBB lesion. Bicuculline methiodide, a gamma-aminobutyric acid blocking epileptogen, crosses the normal BBB of rats poorly and produces no consistent abnormality behaviorally or on EEG at 36 mg/kg. When the BBB is opened in 0.25 ml of cortex by 6,000 rad of alpha particles, by a pin trauma lesion, or by a heat lesion, the rats are normal clinically and on EEG. When these lesioned rats are challenged with bicuculline methiodide, 36 mg/kg, an intense, highly localized epileptiform discharge results that begins approximately 20 min after injection and lasts 30-90 min. The plausibility and experimental utility of the BBB-epileptogen model of epilepsy are enhanced by these observations.

  8. Thick lens chromatic effective focal length variation versus bending

    Science.gov (United States)

    Sparrold, Scott

    2017-11-01

    Longitudinal chromatic aberration (LCA) can limit the optical performance in refractive optical systems. Understanding a singlet's chromatic change of effective focal leads to insights and methods to control LCA. Long established, first order theory, shows the chromatic change in focal length for a zero thickness lens is proportional to it's focal length divided by the lens V number or inverse dispersion. This work presents the derivation of an equation for a thick singlet's chromatic change in effective focal length as a function of center thickness, t, dispersion, V, index of refraction, n, and the Coddington shape factor, K. A plot of bending versus chromatic focal length variation is presented. Lens thickness does not influence chromatic variation of effective focal length for a convex plano or plano convex lens. A lens's center thickness'influence on chromatic focal length variation is more pronounced for lower indices of refraction.

  9. High intensity focused ultrasound (HIFU) focal spot localization using harmonic motion imaging (HMI).

    Science.gov (United States)

    Han, Yang; Hou, Gary Yi; Wang, Shutao; Konofagou, Elisa

    2015-08-07

    Several ultrasound-based imaging modalities have been proposed for image guidance and monitoring of high-intensity focused ultrasound (HIFU) treatment. However, accurate localization and characterization of the effective region of treatment (focal spot) remain important obstacles in the clinical implementation of HIFU ablation. Harmonic motion imaging for focused ultrasound (HMIFU) is a HIFU monitoring technique that utilizes radiation-force-induced localized oscillatory displacement. HMIFU has been shown to correctly identify the formation and extent of HIFU thermal ablation lesions. However a significant problem remains in identifying the location of the HIFU focus, which is necessary for treatment planning. In this study, the induced displacement was employed to localize the HIFU focal spot inside the tissue prior to treatment. Feasibility was shown with two separate systems. The 1D HMIFU system consisted of a HIFU transducer emitting an amplitude-modulated HIFU beam for mechanical excitation and a confocal single-element, pulse-echo transducer for simultaneous RF acquisition. The 2D HIFU system consists of a HIFU phased array, and a co-axial imaging phased array for simultaneous imaging. Initial feasibility was first performed on tissue-mimicking gelatin phantoms and the focal zone was defined as the region corresponding to the -3dB full width at half maximum of the HMI displacement. Using the same parameters, in vitro experiments were performed in canine liver specimens to compare the defined focal zone with the lesion. In vitro measurements showed good agreement between the HMI predicted focal zone and the induced HIFU lesion location. HMIFU was experimentally shown to be capable of predicting and tracking the focal region in both phantoms and in vitro tissues. The accuracy of focal spot localization was evaluated by comparing with the lesion location in post-ablative tissues, with a R(2) = 0.821 at p HIFU focal spot without inducing thermal changes during

  10. High intensity focused ultrasound (HIFU) focal spot localization using harmonic motion imaging (HMI)

    Science.gov (United States)

    Han, Yang; Hou, Gary Yi; Wang, Shutao; Konofagou, Elisa

    2015-08-01

    Several ultrasound-based imaging modalities have been proposed for image guidance and monitoring of high-intensity focused ultrasound (HIFU) treatment. However, accurate localization and characterization of the effective region of treatment (focal spot) remain important obstacles in the clinical implementation of HIFU ablation. Harmonic motion imaging for focused ultrasound (HMIFU) is a HIFU monitoring technique that utilizes radiation-force-induced localized oscillatory displacement. HMIFU has been shown to correctly identify the formation and extent of HIFU thermal ablation lesions. However a significant problem remains in identifying the location of the HIFU focus, which is necessary for treatment planning. In this study, the induced displacement was employed to localize the HIFU focal spot inside the tissue prior to treatment. Feasibility was shown with two separate systems. The 1D HMIFU system consisted of a HIFU transducer emitting an amplitude-modulated HIFU beam for mechanical excitation and a confocal single-element, pulse-echo transducer for simultaneous RF acquisition. The 2D HIFU system consists of a HIFU phased array, and a co-axial imaging phased array for simultaneous imaging. Initial feasibility was first performed on tissue-mimicking gelatin phantoms and the focal zone was defined as the region corresponding to the  -3dB full width at half maximum of the HMI displacement. Using the same parameters, in vitro experiments were performed in canine liver specimens to compare the defined focal zone with the lesion. In vitro measurements showed good agreement between the HMI predicted focal zone and the induced HIFU lesion location. HMIFU was experimentally shown to be capable of predicting and tracking the focal region in both phantoms and in vitro tissues. The accuracy of focal spot localization was evaluated by comparing with the lesion location in post-ablative tissues, with a R2 = 0.821 at p  technique to localize the HIFU focal spot without

  11. Spasmodic dysphonia may respond to bilateral thalamic deep brain ...

    African Journals Online (AJOL)

    Background Spasmodic dysphonia is a primary focal dystonia manifested by loss of control of the vocal muscles during speech secondary to laryngeal muscle spasms. The pathophysiology is not well understood. Deep brain stimulation surgery (DBS) for other focal dystonias has been well reported. Methods We report the ...

  12. Treatment with a recombinant human IgM that recognizes PSA-NCAM preserves brain pathology in MOG-induced experimental autoimmune encephalomyelitis.

    Science.gov (United States)

    Lemus, Hernan Nicolas; Warrington, Arthur E; Denic, Aleksandar; Wootla, Bharath; Rodriguez, Moses

    2017-01-01

    A single peripheral dose of CNS-binding IgMs promote remyelination and preserve axons in a number of animal models of neurologic disease. A myelin-binding recombinant human IgM (rHIgM22) is presently in a safety trial in MS patients following an acute MS exacerbation. rHIgM22 (directed against oligodendrocytes) or rHIgM12 (directed against neurons) were administered to mice with MOG-induced experimental autoimmune encephalomyelitis (EAE) with study endpoints: clinical deficits and brain and spinal cord pathology. IgMs were administered at a therapeutic dose of 100 μ g intra peritoneal at the time of immunization (day -1, 0, +$1), disease onset (15 days) or peak of the disease (28 days). Disease course was not worsened by either human IgM regardless of the time of treatment. Of note, the human IgM that recognizes a carbohydrate epitope on gangliosides and NCAM, rHIgM12, reduced brain pathology when given at time of immunization or at onset of disease, but did not reduce clinical deficits or spinal cord disease burden. Hence, treatment with rHIgM12 resulted in marked reduction in meningeal inflammation. Data consistent with the hypothesis that in the EAE model this molecule has an immune-modulatory effect. Treatment with an anti-CD4 blocking IgG prevented both clinical course and CNS pathology. This pre-clinical study further supports the safety of therapeutic CNS-binding human IgMs in the presence of autoimmunity and clearly differentiates them from IgGs directed against MOG or aquaporin-4 that worsen neurologic disease.

  13. Amyloid-β peptides and tau protein as biomarkers in cerebrospinal and interstitial fluid following traumatic brain injury: A review of experimental and clinical studies

    Directory of Open Access Journals (Sweden)

    Parmenion P. Tsitsopoulos

    2013-06-01

    Full Text Available Traumatic brain injury (TBI survivors frequently suffer from life-long deficits in cognitive functions and a reduced quality of life. Axonal injury, observed in most severe TBI patients, results in accumulation of amyloid precursor protein (APP. Post-injury enzymatic cleavage of APP can generate amyloid-β (Aβ peptides, a hallmark finding in Alzheimer’s disease (AD. At autopsy, brains of AD and a subset of TBI victims display some similarities including accumulation of Aβ peptides and neurofibrillary tangles of hyperphosphorylated tau proteins. Most epidemiological evidence suggests a link between TBI and AD, implying that TBI has neurodegenerative sequelae. Aβ peptides and tau may be used as biomarkers in interstitial fluid (ISF using cerebral microdialysis and/or cerebrospinal fluid (CSF following clinical TBI. In the present review, the available clinical and experimental literature on Aβ peptides and tau as potential biomarkers following TBI is comprehensively analyzed. Elevated CSF and ISF tau protein levels have been observed following severe TBI and suggested to correlate with clinical outcome. Although Aβ peptides are produced by normal neuronal metabolism, high levels of long and/or fibrillary Aβ peptides may be neurotoxic. Increased CSF and/or ISF Aβ levels post-injury may be related to neuronal activity and/or the presence of axonal injury. The heterogeneity of animal models, clinical cohorts, analytical techniques and the complexity of TBI in available studies make the clinical value of tau and Aβ as biomarkers uncertain at present. Additionally, the link between early post-injury changes in tau and Aβ peptides and the future risk of developing AD remains unclear. Future studies using e.g. rapid biomarker sampling combined with enhanced analytical techniques and/or novel pharmacological tools could provide additional information on the importance of Aβ peptides and tau protein in both the acute pathophysiology and long

  14. Development and testing of an innovative two-arm focal-plane thermal strap (TAFTS)

    Science.gov (United States)

    Urquiza, E.; Vasquez, C.; Rodriguez, J.; Van Gorp, B.

    2012-04-01

    Temperature control of optical focal planes comes with the intrinsic challenge of creating a pathway that is both extremely flexible mechanically and highly conductive thermally. The task is further complicated because science-caliber optical focal planes are extremely delicate, yet time, cost, and their unique nature means that their mechanical resiliency is rarely tested and documented. The mechanical engineer tasked with the thermo-mechanical design must then create a highly conductive thermal link that minimizes the tensile and shear stresses transmitted to the focal plane without design parameters on an acceptable stiffness and without data on the stiffness of previously implemented thermal links. This paper describes the development and testing of the thermal link developed for the Portable Remote Imaging Spectrometer (PRISM) instrument. It will provide experimentally determined mechanical stiffness plots in the three axes of interest. Analytical and experimental thermal conductance results for the two-arm focal-plane thermal strap (TAFTS), from cryogenic to room temperatures, are also presented. The paper also briefly describes some elements of the fabrication process followed in developing a novel design solution, which provides high conductance and symmetrical mechanical loading, while providing enhanced flexibility in all three dimensions.

  15. Ultrasonographic features of focal xanthogranulomatous pyelonephritis

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Jong Chul [Chungnam National University Hospital, Daejeon (Korea, Republic of)

    2003-09-15

    To analyze ultrasonographic (US) features of focal xanthogranulomatous pyelonephritis (XGP). US features of 15 patients with pathologically proven focal XGP were retrospectively analyzed by two radiologists who reached a consensus, in terms of the location, margin, size, and echo texture of the mass-like lesion, and presence or absence of associated calculi, lymphadenopathy, or local extension. These US findings were compared with CT findings. The patients were checked for the clinical symptom and sign through the review of hospital records. Thirteen of 15 patients were adults and 2 were children, and 10 were males. Their age ranged from 6 to 57 (mean, 39) years at presentation. Eight of 15 cases (53%) were in right kidney, and on US scan 12 cases (80%) were well circumscribed. The size of the mass ranged from 2.5 to 5.8 (mean, 3.8) cm. Of 15 masses, 13 (87%) were solid and two were cystic. Thirteen solid masses were composed of 10 masses (77%) with inner hypo- or anechoic foci and the other three masses without inner hypo- or anechoic foci, and the preoperative diagnosis was either renal cell carcinoma (n=11) or Wilms' tumor (n=2). The preoperative diagnosis in two cystic lesions (13%) was renal abscess. Renal calculi were found in one case, but lymphadenopathy or local extension was not depicted. Clinical symptoms and signs of flank pain, fever, leukocytosis, or anemia were found in 11 of 15 patients. Focal XGP revealed US features of solid or cystic masses confined within the renal outline mimicking renal tumor or abscess. US features, however, in association with clinical findings and other imaging findings (such as CT or MR imaging) may help the differential diagnosis of this lesion.

  16. Characterization of DECam focal plane detectors

    Energy Technology Data Exchange (ETDEWEB)

    Diehl, H.Thomas; Angstadt, Robert; Campa, Julia; Cease, Herman; Derylo, Greg; Emes, John H.; Estrada, Juan; Kibik, Donna; Flaugher, Brenna L.; Holland, Steve E.; Jonas, Michelle; /Fermilab /Madrid, CIEMAT /LBL, Berkeley /Argonne /Pennsylvania U.

    2008-06-01

    DECam is a 520 Mpix, 3 square-deg FOV imager being built for the Blanco 4m Telescope at CTIO. This facility instrument will be used for the 'Dark Energy Survey' of the southern galactic cap. DECam has chosen 250 ?m thick CCDs, developed at LBNL, with good QE in the near IR for the focal plane. In this work we present the characterization of these detectors done by the DES team, and compare it to the DECam technical requirements. The results demonstrate that the detectors satisfy the needs for instrument.

  17. Strong reducing of the laser focal volume

    CSIR Research Space (South Africa)

    Godin, T

    2011-08-01

    Full Text Available high power within the focal volume, is much more ?general? and could then be applied to different applications such as 3-D laser prototyping, linear and non-linear fluorescence microscopy, nano-structuration of materials, optical tweezers, optical... laser beams? allowing to improve significantly the spatial resolution of a certain number of laser applications such as non-linear microscopy, optical trapping and tweezing, 3-D prototyping? Let us consider a collimated symmetrical Laguerre-Gauss 0pTEM...

  18. Focal inflammatory diseases of the liver

    Energy Technology Data Exchange (ETDEWEB)

    Oto, Aytekin; Akhan, Okan; Oezmen, Mustafa

    1999-10-01

    Inflammatory lesions constitute an important subgroup of focal liver lesions. They may mimic primary or metastatic neoplastic lesions and their differentiation from neoplasia is clinically very important since management of the patient significantly changes. Radiologists should have an important role in both the diagnosis and therapy of these lesions by performing percutaneous aspirations and drainages. In this review we discussed the radiological findings of pyogenic abscesses, amebic abscesses, candidiasis, tuberculosis, hydatic cysts, fascioliasis, ascariasis, schistosomiasis, and sarcoidosis with a special emphasis on US, CT and MR characteristics.

  19. FOCAL EPITHELIAL HYPERPLASIA: HECK’S DISEASE

    Directory of Open Access Journals (Sweden)

    Brzeziński Piotr

    2010-10-01

    Full Text Available Heck's disease (focal epithelial hyperplasia (FEH is clinically characterized by multiple circumscribed, soft elevated nodules of the oral mucosa. Papules and plaques are usually the color of normal mucosa, but may be pale or, rarely, white. Disease may persist for years, producing a significant reduction in quality of life. Lessions may be located in the area of mucous membranes of the lips, cheeks and tongue. It is believed that the two virus types are responsible for the FEH, are: HPV 13 and HPV 32. Different therapeutic procedures have been reported: surgical excision, laser ablation, cryotherapy, electrocauterization, interferon, retinoic acid, 5% immiquimod.

  20. Benign focal hepatic lesions; Benigne fokale Leberlaesionen

    Energy Technology Data Exchange (ETDEWEB)

    Baroud, S.; Bastati, N.; Prosch, H.; Ba-Ssalamah, A. [AKH, Medizinische Universitaet Wien, Universitaetsklinik fuer Radiodiagnostik, Wien (Austria); Schima, W. [Krankenhaus Goettlicher Heiland, Wien, Abteilung fuer Radiologie und Bildgebende Diagnostik, Wien (Austria)

    2011-08-15

    A profound knowledge of the various benign focal hepatic lesions and selection of the most suitable radiological examination modality is essential for achieving an accurate characterization of a hepatic lesion and in turn will determine the further patient management. This will avoid unnecessary agitation to both patient and the referring clinician and limits time-consuming, costly and risky biopsies to an absolute minimum. The following article will discuss the typical and atypical appearances of the most frequent and clinically relevant benign focal hepatic lesions with ultrasound, computed tomography and magnetic resonance imaging. (orig.) [German] Eine genaue Kenntnis des breiten Spektrums benigner fokaler Leberlaesionen und der geeigneten radiologischen Untersuchungsmethode ist essenziell, um eine sichere Diagnose bzgl. der Dignitaet und damit das weitere Vorgehen bestimmen zu koennen. Damit wird eine unnoetige Verunsicherung des Patienten und des behandelnden Arztes vermieden, und invasive, eventuell mit Komplikationen assoziierte Biopsien sowie zeit- und kostenintensive Verlaufskontrollen koennen reduziert werden. Der folgende Artikel erlaeutert die haeufigsten und klinisch wichtigsten benignen fokalen Leberlaesionen und deren typisches und atypisches Erscheinen in den 3 haeufig verwendeten bildgebenden Verfahren Sonographie, Computertomographie und Magnetresonanztomographie. (orig.)

  1. Focal cortical dysplasia and epilepsy surgery.

    Science.gov (United States)

    Lee, Sang Kun; Kim, Dong-Wook

    2013-12-01

    Focal cortical dysplasia (FCD) is the most commonly encountered developmental malformation that causes refractory epilepsy. With advances in neuroimaging techniques, in particular MRI, recent studies have revealed a higher prevalence of FCD than previously estimated and have improved the preoperative identification and classification of these abnormalities. However, MRI frequently does not show any abnormalities in patients with pathologically proven FCD. In this situation, functional neuroimaing such as FDG-PET and ictal SPECT can be helpful. FCD is thought to be intrinsically epileptogenic, because the dysplastic tissues contain aberrant neural networks that are highly susceptible to abnormal excitation. The response to the medical treatment of epilepsy has been documented as consistently poor. Therefore, surgical resection has been an important alternative treatment for patients with intractable epilepsy related to FCD. Incomplete resection of FCD has been consistently known to be a poor prognostic factor. However, the complete removal of FCD is often difficult because the demarcation of the lesion is frequently poor, and dysplastic tissues tend to be more extensive than is apparent on MRI. Evidence indicates that even patients with MRI abnormalities who have resective epilepsy surgery for FCD have worse surgical outcomes than those of patients who have surgery for other focal lesional epilepsy syndromes. Careful planning of evelauation using intracranial electrodes is necessary for successful epilepsy surgery.

  2. PI3K-AKT pathway polymerase chain reaction (PCR) array analysis of epilepsy induced by type II focal cortical dysplasia.

    Science.gov (United States)

    Lin, Y X; Lin, K; Liu, X X; Kang, D Z; Ye, Z X; Wang, X F; Zheng, S F; Yu, L H; Lin, Z Y

    2015-08-21

    The aims of this study were to observe the differential expression of PI3K-AKT pathway-related genes in seizure-inducing brain lesions in type II focal cortical dysplasia, and to explore the relationship between gene expression and histological changes in dysplastic foci and their epileptogenic mechanism. Typical lesions in brain tissue from three patients with epilepsy induced by type II focal cortical dysplasia were selected for analysis, along with normal brain tissue from two control group individuals. Following quantitative expression analysis using the RT2 Profiler(TM) PI3K-AKT PCR Array, differential expression of the pathway related genes was detected in the focal brain tissue lesions, and gene function queries were performed. Compared with the control group, thirteen related genes appeared to exhibit marked differences in expression in epileptic lesions from patients with type II focal cortical dysplasia; those genes were found to be involved in regulation of cell size, morphology, adhesion, migration, and apoptosis, and in immunity, inflammation, and many other domains. The differential expression of multiple genes in the PI3K-AKT signaling pathway in type II focal cortical dysplasia may be an important molecular mechanism underlying histological changes and recurrent seizures.

  3. In silico modeling on ADME properties of natural products: Classification models for blood-brain barrier permeability, its application to traditional Chinese medicine and in vitro experimental validation.

    Science.gov (United States)

    Zhang, Xiuqing; Liu, Ting; Fan, Xiaohui; Ai, Ni

    2017-08-01

    In silico modeling of blood-brain barrier (BBB) permeability plays an important role in early discovery of central nervous system (CNS) drugs due to its high-throughput and cost-effectiveness. Natural products (NP) have demonstrated considerable therapeutic efficacy against several CNS diseases. However, BBB permeation property of NP is scarcely evaluated both experimentally and computationally. It is well accepted that significant difference in chemical spaces exists between NP and synthetic drugs, which calls into doubt on suitability of available synthetic chemical based BBB permeability models for the evaluation of NP. Herein poor discriminative performance on BBB permeability of NP are first confirmed using internal constructed and previously published drug-derived computational models, which warrants the need for NP-oriented modeling. Then a quantitative structure-property relationship (QSPR) study on a NP dataset was carried out using four different machine learning methods including support vector machine, random forest, Naïve Bayes and probabilistic neural network with 67 selected features. The final consensus model was obtained with approximate 90% overall accuracy for the cross-validation study, which is further taken to predict passive BBB permeability of a large dataset consisting of over 10,000 compounds from traditional Chinese medicine (TCM). For 32 selected TCM molecules, their predicted BBB permeability were evaluated by in vitro parallel artificial membrane permeability assay and overall accuracy for in vitro experimental validation is around 81%. Interestingly, our in silico model successfully predicted different BBB permeation potentials of parent molecules and their known in vivo metabolites. Finally, we found that the lipophilicity, the number of hydrogen bonds and molecular polarity were important molecular determinants for BBB permeability of NP. Our results suggest that the consensus model proposed in current work is a reliable tool for

  4. Focal fatty infiltra- tion and focal fatty sparing of the liver

    African Journals Online (AJOL)

    Enrique

    Hounsfield units (HU) while the nor- mal parenchyma had a mean density measurement of 40 HU (Fig. 1a). The contrast-enhanced study demonstrat- ed decreased perfusion in those regions of low density (Fig. 1b). A diagnosis of focal fatty infiltration of the liver was made. The patient was subsequently found to have type 2.

  5. Natural course and pathogenesis of transient focal neurologic symptoms during pregnancy.

    Science.gov (United States)

    Liberman, Anatoly; Karussis, Dimitrios; Ben-Hur, Tamir; Abramsky, Oded; Leker, Ronen R

    2008-02-01

    To determine the pathogenesis and course of transient focal neurologic symptoms in pregnant women and to identify prognostic variables that will enable targeted workup. Case-control series. Tertiary care university hospital. Pregnant patients with acute transient focal neurologic symptoms. Women with histories of migraine, recurrent thromboembolism, or cerebrovascular disease were excluded. Diffusion-weighted imaging (DWI), perfusion-weighted imaging, fluid-attenuated inversion recovery (FLAIR) imaging, gradient-recalled echo imaging, and magnetic resonance venography (MRV) and angiography to determine the presence of brain ischemia and venous thrombosis. Patients underwent echocardiography, duplex ultrasonography, and a battery of hypercoagulability tests and were followed up a mean of 12 months after the event. Twenty-eight controls and 14 patients were enrolled from 23 773 pregnancies. Mean age was 31.2 (range, 24-41) years and mean gestational age at symptom onset was 28 (range, 17-44) weeks. No controls reported transient focal neurologic symptoms, migraine aura, or headache. Presenting symptoms included dysphasia (6 patients) and hemisensory (5) and hemimotor (7) syndrome. In 4 patients, these symptoms were preceded by scintillating scotoma; in 9 patients, focal symptoms were followed by a first-ever, throbbing, migraine-like headache. Only 1 patient had evidence of frank infarction on magnetic resonance imaging (MRI); 2 patients had single, small, hyperintense bright foci on FLAIR imaging without accompanying lesions on DWI, and 11 patients had normal MRI and MRV results. Echocardiography, carotid duplex ultrasonography, and hypercoagulability results were negative in all patients. None of the patients had ischemic events and 4 (29%) developed migraines with aura headaches during follow-up. Focal neurologic symptoms in healthy pregnant women are frequently preceded by aural visual phenomena and can usually be attributed to a first-ever migraine attack

  6. Functional mastery of percussive technology in nut-cracking and stone-flaking actions: experimental comparison and implications for the evolution of the human brain

    Science.gov (United States)

    Bril, Blandine; Smaers, Jeroen; Steele, James; Rein, Robert; Nonaka, Tetsushi; Dietrich, Gilles; Biryukova, Elena; Hirata, Satoshi; Roux, Valentine

    2012-01-01

    Various authors have suggested behavioural similarities between tool use in early hominins and chimpanzee nut cracking, where nut cracking might be interpreted as a precursor of more complex stone flaking. In this paper, we bring together and review two separate strands of research on chimpanzee and human tool use and cognitive abilities. Firstly, and in the greatest detail, we review our recent experimental work on behavioural organization and skill acquisition in nut-cracking and stone-knapping tasks, highlighting similarities and differences between the two tasks that may be informative for the interpretation of stone tools in the early archaeological record. Secondly, and more briefly, we outline a model of the comparative neuropsychology of primate tool use and discuss recent descriptive anatomical and statistical analyses of anthropoid primate brain evolution, focusing on cortico-cerebellar systems. By juxtaposing these two strands of research, we are able to identify unsolved problems that can usefully be addressed by future research in each of these two research areas. PMID:22106427

  7. Cooperative mechanosensitivity and allostery of focal adhesion clusters.

    Science.gov (United States)

    Foo, Darryl C W; Terentjev, Eugene

    2017-10-23

    We analyse a role of cooperative interaction between neighbouring adhesion-mechanosensor complexes by constructing an Ising-like Hamiltonian describing the free energy of cell adhesion on a substrate as a lattice of 3-state mechanosensing sites involving focal adhesion kinase (FAK). We use Monte Carlo stochastic algorithm to find equilibrium configurations of these mechanosensors in two representative geometries: on a 1D ring representing the rim of a cell on flat surface, and a 2D bounded surface representing the whole area of cell contact with flat surface. The level of FAK activation depend on the pulling force applied to the individual FAK-integrin via actin-myosin contractile networks, and the details of the coupling between individual sensors in a cluster. Strong coupling is shown to make the FAK sensors experience a sharp on-off behaviour in their activation, while at low coupling the activation/autoinhibition transition occurs over a broad range of pulling force. We find that the activation/autoinhibition transition of FAK in the 2D system with strong coupling occurs with a hysteresis, the width of which depends on the rate of change of force. The effect of introducing a regulating protein (such as Src) in limited quantity to control FAK activation is explored, and visualizations of clustering in both topologies are presented. In particular the results on the bounded 2D surface indicate that clustering of active FAK occurs preferentially at the boundary, in agreement with experimental observations of focal adhesions in cells. © 2017 IOP Publishing Ltd.

  8. Accurate acoustic power measurement for low-intensity focused ultrasound using focal axial vibration velocity

    Science.gov (United States)

    Tao, Chenyang; Guo, Gepu; Ma, Qingyu; Tu, Juan; Zhang, Dong; Hu, Jimin

    2017-07-01

    Low-intensity focused ultrasound is a form of therapy that can have reversible acoustothermal effects on biological tissue, depending on the exposure parameters. The acoustic power (AP) should be chosen with caution for the sake of safety. To recover the energy of counteracted radial vibrations at the focal point, an accurate AP measurement method using the focal axial vibration velocity (FAVV) is proposed in explicit formulae and is demonstrated experimentally using a laser vibrometer. The experimental APs for two transducers agree well with theoretical calculations and numerical simulations, showing that AP is proportional to the square of the FAVV, with a fixed power gain determined by the physical parameters of the transducers. The favorable results suggest that the FAVV can be used as a valuable parameter for non-contact AP measurement, providing a new strategy for accurate power control for low-intensity focused ultrasound in biomedical engineering.

  9. Surgical manipulation compromises leukocyte mobilisation responses and inflammation after experimental cerebral ischaemia in mice

    Directory of Open Access Journals (Sweden)

    Adam eDenes

    2014-01-01

    Full Text Available Acute brain injury results in peripheral inflammatory changes, although the impact of these processes on neuronal death and neuroinflammation is currently unclear. To facilitate the translation of experimental studies to clinical benefit, it is vital to characterize the mechanisms by which acute brain injury induces peripheral inflammatory changes, and how these are affected by surgical manipulation in experimental models. Here we show that in mice, even mild surgical manipulation of extracranial tissues induced marked granulocyte mobilisation (300% and systemic induction of cytokines. However, intracranial changes induced by craniotomy, or subsequent induction of focal cerebral ischaemia were required to induce egress of CXCR2-positive granulocytes from the bone marrow. CXCR2 blockade resulted in reduced mobilisation of granulocytes from the bone marrow, caused an unexpected increase in circulating granulocytes, but failed to effect brain injury induced by cerebral ischaemia. We also demonstrate that isoflurane anaesthesia interferes with circulating leukocyte responses, which could contribute to the reported vascular and neuroprotective effects of isoflurane. In addition, no immunosuppression develops in the bone marrow after experimental stroke. Thus, experimental models of cerebral ischaemia are compromised by surgery and anaesthesia in proportion to the severity of surgical stress and overall tissue injury. Understanding the inherent confounding effects of surgical manipulation and development of new models of cerebral ischaemia with minimal surgical intervention could facilitate better understanding of interactions between inflammation and brain injury.

  10. Multiple focal nodular hyperplasias induced by oxaliplatin-based chemotherapy

    OpenAIRE

    Donadon, M.; Di Tommaso, L; Roncalli, M; Torzilli, G.

    2013-01-01

    Focal nodular hyperplasia (FNH) is a benign condition that affects normal liver with low prevalence. Recently, the extensive use of oxaliplatin to treat patients with colorectal cancer has been reported to be associated with the development of different liver injuries, as well as focal liver lesions. The present work describes two patients with multiple bilateral focal liver lesions misdiagnosed as colorectal liver metastases, and treated with liver resection. The first patient had up to 15 s...

  11. Physical Activity Performance of Focal Middle School Students

    Science.gov (United States)

    Erfle, Stephen E.; Gelbaugh, Corey M.

    2013-01-01

    Histograms of push-ups and curl-ups from a sample of more than 9,000 students show periodic spikes at five and 10 unit intervals. This article argues that these spikes are related to focal points, a game theoretic concept popularized by Nobel Laureate Thomas Schelling. Being focal on one test makes one more likely to be focal on the other. Focal…

  12. Focal cemento-osseous dysplasia of mandible.

    Science.gov (United States)

    Cankaya, Abdülkadir Burak; Erdem, Mehmet Ali; Olgac, Vakur; Firat, Deniz Refia

    2012-09-03

    Fibro-osseous lesions are disturbances in bone metabolism in which normal bone is replaced by a connective tissue matrix that then gradually develops into cemento-osseous tissue. Typically, the lesion is asymptomatic and is detected on routine radiographic examination. Radiologically, this lesion has three stages of maturation: pure radiolucent, radiopaque/mixed radiolucent, and radiopaque appearance. During these stages the lesion can be misdiagnosed. In this case report a 69-year- old patient with a a complaint of painless swelling of the left mandibular molar and premolar area is presented along with a review of the differential diagnoses considered in order to reach a final diagnosis of focal cemento-osseous dysplasia.

  13. Focal epilepsy in the Belgian shepherd

    DEFF Research Database (Denmark)

    Berendt, Mette; Gulløv, Christina Hedal; Fredholm, Merete

    2009-01-01

    OBJECTIVES: To establish the mode of inheritance and describe the clinical features of epilepsy in the Belgian shepherd, taking the outset in an extended Danish dog family (199 individuals) of Groenendael and Tervueren with accumulated epilepsy. METHODS: Epilepsy positive individuals (living...... and deceased) were ascertained through a telephone interview using a standardised questionnaire regarding seizure history and phenomenology. Living dogs were invited to a detailed clinical evaluation. Litters more than five years of age, or where epilepsy was present in all offspring before the age of five......, were included in the calculations of inheritance. results: Out of 199 family members, 66 dogs suffered from epilepsy. The prevalence of epilepsy in the family was 33%. Fifty-five dogs experienced focal seizures with or without secondary generalisation, while four dogs experienced primary generalised...

  14. Smart trigger logic for focal plane arrays

    Energy Technology Data Exchange (ETDEWEB)

    Levy, James E; Campbell, David V; Holmes, Michael L; Lovejoy, Robert; Wojciechowski, Kenneth; Kay, Randolph R; Cavanaugh, William S; Gurrieri, Thomas M

    2014-03-25

    An electronic device includes a memory configured to receive data representing light intensity values from pixels in a focal plane array and a processor that analyzes the received data to determine which light values correspond to triggered pixels, where the triggered pixels are those pixels that meet a predefined set of criteria, and determines, for each triggered pixel, a set of neighbor pixels for which light intensity values are to be stored. The electronic device also includes a buffer that temporarily stores light intensity values for at least one previously processed row of pixels, so that when a triggered pixel is identified in a current row, light intensity values for the neighbor pixels in the previously processed row and for the triggered pixel are persistently stored, as well as a data transmitter that transmits the persistently stored light intensity values for the triggered and neighbor pixels to a data receiver.

  15. Idiopathic focal segmental glomerulosclerosis and HLA antigens

    Directory of Open Access Journals (Sweden)

    M. Gerbase-DeLima

    1998-03-01

    Full Text Available The objective of the present study was to investigate a possible association between HLA class II antigens and idiopathic focal segmental glomerulosclerosis (FSGS. HLA-A, -B, -DR and -DQ antigens were determined in 19 Brazilian patients (16 white subjects and three subjects of Japanese origin with biopsy-proven FSGS. Comparison of the HLA antigen frequencies between white patients and white local controls showed a significant increase in HLA-DR4 frequency among FSGS patients (37.7 vs 17.2%, P<0.05. In addition, the three patients of Japanese extraction, not included in the statistical analysis, also presented HLA-DR4. In conclusion, our data confirm the association of FSGS with HLA-DR4 previously reported by others, thus providing further evidence for a role of genes of the HLA complex in the susceptibility to this disease

  16. Focal adhesion kinase signaling in unexpected places.

    Science.gov (United States)

    Kleinschmidt, Elizabeth G; Schlaepfer, David D

    2017-04-01

    Focal adhesion kinase (FAK) is a cytoplasmic protein-tyrosine kinase first identified at extracellular matrix and integrin receptor cell adhesion sites and is a key regulator of cell movement. FAK is activated by a variety of stimuli. Herein, we discuss advances in conformational-associated FAK activation and dimerization mechanisms. Additionally, new roles have emerged for FAK signaling at cell adhesions, adherens junctions, endosomes, and the nucleus. In light of these new findings, we review how FAK activation at these sites is connected to the regulation of integrin recycling-activation, vascular permeability, cell survival, and transcriptional regulation, respectively. Studies uncovering FAK signaling connections in unexpected places within cells have yielded important new regulatory insights in cell biology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Focal choroidal excavation complicated by choroidal neovascularization.

    Science.gov (United States)

    Xu, Haifeng; Zeng, Fanxing; Shi, Depeng; Sun, Xiaolei; Chen, Xiuli; Bai, Yao

    2014-01-01

    To evaluate the clinical findings of focal choroidal excavation (FCE) complicated by choroidal neovascularization (CNV). Retrospective, observational case series. Twelve patients (15 eyes) with FCE and CNV. The medical records of the patients were reviewed. Clinical findings including age, sex, refraction, color photography, fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (OCT) were analyzed. Fundus fluorescein angiography, ICGA, and OCT findings. The 12 patients included 6 women and 6 men. The mean age was 46.8±13.4 years (range, 26-64 years). One half of the patients were emmetropic, and the others were myopic (-0.5 to -3.0 diopters). All subjects were Chinese. Before CNV development, normal appearance or nonspecific pigment disturbance could be seen around the choroidal excavation. Corresponding to the excavation, window defects were observed by FFA, whereas hypofluorescence was found on ICGA images. Choroidal neovascularization in all eyes was classic as revealed by FFA. The OCT images showed that all eyes had a single choroidal excavation. In 7 of the 15 eyes, the choroidal excavation was located subfoveally, and in the other 8 eyes, it was eccentric. All CNV lesions grew from the bottom or slope of the excavation. Three patients had bilateral involvement. Choroidal neovascularization occurred in both conforming and nonconforming type FCEs, regardless of whether the excavation was shallow or deep, subfoveal or eccentric. All CNV lesions responded well to intravitreal injection of anti-vascular endothelial growth factor (VEGF) agents. After a single injection, CNV regressed in 13 of 15 eyes. Two eyes received an additional injection. Nonconforming FCE changed to the conforming type after successful treatment of CNV. Focal choroidal excavation is not always stable. Choroidal neovascularization commonly can be seen in patients with FCE and responds well to intravitreal anti-VEGF agents

  18. Focal choroidal excavation: Clinical findings and complications.

    Science.gov (United States)

    Castro Navarro, V; Montero Hernández, J; Navarro Palop, C; Palomares Fort, P; Cervera Taulet, E

    2016-01-01

    To describe the clinical findings and its complications in 2 patients with focal choroidal excavation (FCE). A retrospective case-series including 4 eyes of 2 patients with FCE that underwent a comprehensive ophthalmological examination including slit-lamp examination, colour fundus photography, spectral-domain optical coherence tomography (SD-OCT), fluorescein angiography (FA), and indocyanine green angiography. In the 2 patients, both the anterior and posterior segment evaluations were mostly normal despite the of presence yellowish spots in the macular area of the right eye of patient 1, and of a small yellowish elevated lesion with serous macular detachment in the macular area of the left eye in patient 2. At diagnosis, SD-OCT revealed a conforming FCE in patient 1, and in patient 2, an FCE with perilesional subretinal fluid and a neuroepithelium detachment, suspicious of FCE complicated with central serous retinopathy (CSCR). At one year of follow-up, patient 1 developed choroidal neovascularisation (CNV) over the focal choroidal excavation. FA and indocyanine green angiography examinations revealed areas with hypofluorescence in earlier frames, and a diffuse leakage in late frames. After ranibizumab injections, the SD-OCT of patient 1 revealed no active exudation, while patient 2 showed partial resolution of subretinal fluid. FCE is a newly described entity of unclear aetiology. It is characterised by a choroidal excavation in eyes, with absence of posterior staphyloma, scleral ectasia, trauma, or retinal disease. Although most lesions remain stable, there could be an association with CRSC or CNV. Copyright © 2015 Sociedad Española de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.

  19. Focal Choroidal Excavation in Retinal Dystrophies.

    Science.gov (United States)

    Braimah, Imoro Zeba; Rapole, Shruthi; Dumpala, Sunila; Chhablani, Jay

    2016-08-17

    To investigate the presence of focal choroidal excavation (FCE) in patients with retinitis pigmentosa (RP), Stargardt's disease (STGD), and Best disease in the Indian population. This retrospective consecutive case series included 309 eyes of 157 patients with RP (183 eyes), STGD (93 eyes), and Best disease (33 eyes) with good-quality, enhanced-depth spectral domain optical coherence tomography scans. Comprehensive ophthalmic examination data were collected. Characteristics of FCE, including location of FCE, type (conforming and non-conforming), maximal width, and depth, were noted. FCE was found in 2 out of 33 (6%) eyes with Best disease and no FCE was found in eyes with RP or STGD. The location of the FCE was extrafoveal in both cases. The first case had non-conforming FCE while the second case had the conforming type and the FCE occurred in association with choroidal neovascularization in the second case. The first case maintained good visual acuity of 20/20 over the entire period of follow-up (14 months), while the second case had a visual acuity of 20/200 at the last follow-up (three years) due to scarred choroidal neovascular membranes. The FCE showed no change in both eyes over the entire duration of follow-up. Focal choroidal excavation was found in 6% of eyes with Best disease, which remained stable throughout follow up. Eyes with RP and STGD did not have any FCE. Further studies are required to determine the role of vitelliform material in FCE development in Best disease.

  20. CT findings of focal organizing pneumonia

    Energy Technology Data Exchange (ETDEWEB)

    Park, Jun Gyun; Yoon, Sang Wook; Nam, Ji Eun; Choe, Kyu Ok; Kim, Hyoung Jung; Lee, Du Yon; Kim, Sang Jin [Yonsei Univ. College of Medicine, Seoul (Korea, Republic of); Ryu, Young Hoon [Gil General Hospital, Seoul (Korea, Republic of); Ryu, Suk Jong [Inje Univ. College of Medicine, Pusan (Korea, Republic of)

    2000-12-01

    Focal organizing pneumonia (FOP) is a benign condition which is often difficult to differentiate from bronchogenic carcinoma, and many patients with FOP undergo invasive procedures. We tried to determine which CT features might help provide a confident diagnosis of FOP. We retrospectively reviewed the medical records, chest radiographs and CT scans of 13 patients with histopathologically proven FOP. Initial chest radiographs in all 13 suggested bronchogenic carcinoma. The CT scans were reviewed by three radiologists, and final decisions were reached by consensus. They were analyzed in terms of the size, shape, contour and localization of the lesion, interior characteristics of the nodule, changes in surrounding structures, and changes in any of these findings, as revealed by follow-up chest CT scanning. FOP lesions were oval or triangular in shape and between 1.8 and 6.5cm in their largest diameter. All had irregular margins and all but one were peripherally located. Eight (61.5%) were in contact with the pleura and five (38.5%) were located along the peripheral bronchovascular bundle, with pleural indentation; in eight (61.5%), post-contrast CT scanning revealed inhomogeneous enhancement, and four (30.8%) had pleural tags. In five (38.5%), there was coarse spiculation; for six (46.2%), air bronchograms were available, and in four (30.8%), satellite nodules were present. Spotty calcification and lymph node enlargement were each evident in one case only. Follow-up CT scanning, available in four cases, showed that the mass decreased in size in three and disappeared completely in one. Although there were no consistent CT features for differentiating focal organizing pneumonia from lung cancer, the possibility of the former should be considered when a peripherally-located oval or triangular-shaped mass is in broad contact with the pleura or is located along the bronchovascular bundle, and satellite nodules are also present.

  1. Focal cryotherapy: step by step technique description

    Directory of Open Access Journals (Sweden)

    Cristina Redondo

    Full Text Available ABSTRACT Introduction and objective: Focal cryotherapy emerged as an efficient option to treat favorable and localized prostate cancer (PCa. The purpose of this video is to describe the procedure step by step. Materials and methods: We present the case of a 68 year-old man with localized PCa in the anterior aspect of the prostate. Results: The procedure is performed under general anesthesia, with the patient in lithotomy position. Briefly, the equipment utilized includes the cryotherapy console coupled with an ultrasound system, argon and helium gas bottles, cryoprobes, temperature probes and an urethral warming catheter. The procedure starts with a real-time trans-rectal prostate ultrasound, which is used to outline the prostate, the urethra and the rectal wall. The cryoprobes are pretested and placed in to the prostate through the perineum, following a grid template, along with the temperature sensors under ultrasound guidance. A cystoscopy confirms the right positioning of the needles and the urethral warming catheter is installed. Thereafter, the freeze sequence with argon gas is started, achieving extremely low temperatures (-40°C to induce tumor cell lysis. Sequentially, the thawing cycle is performed using helium gas. This process is repeated one time. Results among several series showed a biochemical disease-free survival between 71-93% at 9-70 month- follow-up, incontinence rates between 0-3.6% and erectile dysfunction between 0-42% (1–5. Conclusions: Focal cryotherapy is a feasible procedure to treat anterior PCa that may offer minimal morbidity, allowing good cancer control and better functional outcomes when compared to whole-gland treatment.

  2. Focal cryotherapy: step by step technique description.

    Science.gov (United States)

    Redondo, Cristina; Srougi, Victor; da Costa, José Batista; Baghdad, Mohammed; Velilla, Guillermo; Nunes-Silva, Igor; Bergerat, Sebastien; Garcia-Barreras, Silvia; Rozet, François; Ingels, Alexandre; Galiano, Marc; Sanchez-Salas, Rafael; Barret, Eric; Cathelineau, Xavier

    2017-01-01

    Focal cryotherapy emerged as an efficient option to treat favorable and localized prostate cancer (PCa). The purpose of this video is to describe the procedure step by step. We present the case of a 68 year-old man with localized PCa in the anterior aspect of the prostate. The procedure is performed under general anesthesia, with the patient in lithotomy position. Briefly, the equipament utilized includes the cryotherapy console coupled with an ultrasound system, argon and helium gas bottles, cryoprobes, temperature probes and an urethral warming catheter. The procedure starts with a real-time trans-rectal prostate ultrasound, which is used to outline the prostate, the urethra and the rectal wall. The cryoprobes are pretested and placed in to the prostate through the perineum, following a grid template, along with the temperature sensors under ultrasound guidance. A cystoscopy confirms the right positioning of the needles and the urethral warming catheter is installed. Thereafter, the freeze sequence with argon gas is started, achieving extremely low temperatures (-40ºC) to induce tumor cell lysis. Sequentially, the thawing cycle is performed using helium gas. This process is repeated one time. Results among several series showed a biochemical disease-free survival between 71-93% at 9-70 month- follow-up, incontinence rates between 0-3.6% and erectile dysfunction between 0-42% (1-5). Focal cryotherapy is a feasible procedure to treat anterior PCa that may offer minimal morbidity, allowing good cancer control and better functional outcomes when compared to whole-gland treatment. Copyright® by the International Brazilian Journal of Urology.

  3. Brain Basics

    Medline Plus

    Full Text Available ... About Us Home > Health & Education > Educational Resources Brain Basics Introduction The Growing Brain The Working Brain Brain ... called the hypothalamic-pituitary-adrenal (HPA) axis. Brain Basics in Real Life Brain Basics in Real Life— ...

  4. Effects of Dopamine Infusion on Cerebral Blood Flow, Brain Cell Membrane Function and Energy Metabolism in Experimental Escherichia coli Meningitis in the Newborn Piglet

    National Research Council Canada - National Science Library

    Park, Won Soon; Chang, Yun Sil; Shim, Jae Won; Kim, Mi Jung; Ko, Sun Young; Kim, Sung Shin; Hwang, Jong Hee; Choi, Chang Won; Lee, Munhyang

    2003-01-01

    .... The decreased cerebral cortical cell membrane Na+, K+ -ATPase activity and increased lipid peroxidation products, indicative of meningitis-induced brain damage, were significantly attenuated by dopamine infusion...

  5. LXW7 ameliorates focal cerebral ischemia injury and attenuates inflammatory responses in activated microglia in rats

    Energy Technology Data Exchange (ETDEWEB)

    Fang, T.; Zhou, D.; Lu, L.; Tong, X.; Wu, J.; Yi, L. [Department of Neurology, Shenzhen Hospital, Peking University, Shenzhen (China)

    2016-08-01

    Inflammation plays a pivotal role in ischemic stroke, when activated microglia release excessive pro-inflammatory mediators. The inhibition of integrin αvβ3 improves outcomes in rat focal cerebral ischemia models. However, the mechanisms by which microglia are neuroprotective remain unclear. This study evaluated whether post-ischemic treatment with another integrin αvβ3 inhibitor, the cyclic arginine-glycine-aspartic acid (RGD) peptide-cGRGDdvc (LXW7), alleviates cerebral ischemic injury. The anti-inflammatory effect of LXW7 in activated microglia within rat focal cerebral ischemia models was examined. A total of 108 Sprague-Dawley rats (250–280 g) were subjected to middle cerebral artery occlusion (MCAO). After 2 h, the rats were given an intravenous injection of LXW7 (100 μg/kg) or phosphate-buffered saline (PBS). Neurological scores, infarct volumes, brain water content (BWC) and histology alterations were determined. The expressions of pro-inflammatory cytokines [tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β)], and Iba1-positive activated microglia, within peri-ischemic brain tissue, were assessed with ELISA, western blot and immunofluorescence staining. Infarct volumes and BWC were significantly lower in LXW7-treated rats compared to those in the MCAO + PBS (control) group. The LXW7 treatment lowered the expression of pro-inflammatory cytokines. There was a reduction of Iba1-positive activated microglia, and the TNF-α and IL-1β expressions were attenuated. However, there was no difference in the Zea Longa scores between the ischemia and LXW7 groups. The results suggest that LXW7 protected against focal cerebral ischemia and attenuated inflammation in activated microglia. LXW7 may be neuroprotective during acute MCAO-induced brain damage and microglia-related neurodegenerative diseases.

  6. Sighting optics including an optical element having a first focal length and a second focal length and methods for sighting

    Science.gov (United States)

    Crandall, David Lynn

    2011-08-16

    Sighting optics include a front sight and a rear sight positioned in a spaced-apart relation. The rear sight includes an optical element having a first focal length and a second focal length. The first focal length is selected so that it is about equal to a distance separating the optical element and the front sight and the second focal length is selected so that it is about equal to a target distance. The optical element thus brings into simultaneous focus for a user images of the front sight and the target.

  7. Depletion of regulatory T cells in a mouse experimental glioma model through anti-CD25 treatment results in the infiltration of non-immunosuppressive myeloid cells in the brain.

    Science.gov (United States)

    Maes, Wim; Verschuere, Tina; Van Hoylandt, Anaïs; Boon, Louis; Van Gool, Stefaan

    2013-01-01

    The recruitment and activation of regulatory T cells (Tregs) in the micro-environment of malignant brain tumors has detrimental effects on antitumoral immune responses. Hence, local elimination of Tregs within the tumor micro-environment represents a highly valuable tool from both a fundamental and clinical perspective. In the syngeneic experimental GL261 murine glioma model, Tregs were prophylactically eliminated through treatment with PC61, an anti-CD25 mAb. This resulted in specific elimination of CD4+CD25hiFoxp3+ Treg within brain-infiltrating lymphocytes and complete protection against subsequent orthotopic GL261 tumor challenge. Interestingly, PC61-treated mice also showed a pronounced infiltration of CD11b+ myeloid cells in the brain. Phenotypically, these cells could not be considered as Gr-1+ myeloid-derived suppressor cells (MDSC) but were identified as F4/80+ macrophages and granulocytes.

  8. Depletion of Regulatory T Cells in a Mouse Experimental Glioma Model through Anti-CD25 Treatment Results in the Infiltration of Non-Immunosuppressive Myeloid Cells in the Brain

    Directory of Open Access Journals (Sweden)

    Wim Maes

    2013-01-01

    Full Text Available The recruitment and activation of regulatory T cells (Tregs in the micro-environment of malignant brain tumors has detrimental effects on antitumoral immune responses. Hence, local elimination of Tregs within the tumor micro-environment represents a highly valuable tool from both a fundamental and clinical perspective. In the syngeneic experimental GL261 murine glioma model, Tregs were prophylactically eliminated through treatment with PC61, an anti-CD25 mAb. This resulted in specific elimination of CD4+CD25hiFoxp3+ Treg within brain-infiltrating lymphocytes and complete protection against subsequent orthotopic GL261 tumor challenge. Interestingly, PC61-treated mice also showed a pronounced infiltration of CD11b+ myeloid cells in the brain. Phenotypically, these cells could not be considered as Gr-1+ myeloid-derived suppressor cells (MDSC but were identified as F4/80+ macrophages and granulocytes.

  9. The brain-derived neurotrophic factor, nerve growth factor, neurotrophin-3, and induced nitric oxide synthase expressions after low-level laser therapy in an axonotmesis experimental model.

    Science.gov (United States)

    Gomes, Lessandra Esper Abdala; Dalmarco, Eduardo Monguilhott; André, Edison Sanfelice

    2012-11-01

    A robust body of evidence has shown that low-level laser therapy (LLLT) improves peripheral nerve regeneration. However, the biochemical background triggered in this process is not yet fully understood. The purpose of this study was to evaluate the mRNA expression of neurotrophic factors (brain-derived neurotrophic factor [BDNF], nerve growth factor [NGF], and neurotrophin-3, [NT-3]) and also an inflammatory marker (induced nitric oxide synthase [iNOS]) in an axonotmesis experimental model after low-level laser therapy. Thirty-six adult male Wistar rats (250-350 g) were subjected to right sciatic nerve crush injury, and 24 h later, the animals in the three different experimental groups (n=18) were irradiated on a daily basis with helium-neon laser (collimated HeNe laser, continuous emission, wavelength: 632.8 nm, power density: 0.5 mW/cm(2), irradiation time: 20 sec, energy density: 10 J/cm(2)) during 7, 14, and 21 consecutive days, respectively. The control group (n=18) underwent the same procedures, but with the equipment turned off. At the end of the experiments, animals were killed with an overdose of anesthesia to remove samples from the sciatic nerve lesion epicenter to determine the mRNA expression of BDNF, NGF, NT-3 and iNOS enzyme. Comparisons between groups showed that HeNe laser increased the mRNA expression of both BDNF and NGF factors after 14 days of LLLT, with peak expression at the 21st day. Increase in NT-3 mRNA expression was not observed. In addition, HeNe laser produced iNOS expression reduction, which played an important role in the inflammatory process. The reported data could have a relevant practical value because LLLT is a noninvasive procedure, and have revealed significant increase in neurotrophic factor expressions and inflammatory process reduction, opening the possibility of using LLLT as an important aid to nerve regeneration process.

  10. Probenecid protects against transient focal cerebral ischemic injury by inhibiting HMGB1 release and attenuating AQP4 expression in mice.

    Science.gov (United States)

    Xiong, Xiao-Xing; Gu, Li-Juan; Shen, Jian; Kang, Xian-Hui; Zheng, Yue-Ying; Yue, Si-Biao; Zhu, Sheng-Mei

    2014-01-01

    Stroke results in inflammation, brain edema, and neuronal death. However, effective neuroprotectants are not available. Recent studies have shown that high mobility group box-1 (HMGB1), a proinflammatory cytokine, contributes to ischemic brain injury. Aquaporin 4 (AQP4), a water channel protein, is considered to play a pivotal role in ischemia-induced brain edema. More recently, studies have shown that pannexin 1 channels are involved in cerebral ischemic injury and the cellular inflammatory response. Here, we examined whether the pannexin 1 channel inhibitor probenecid could reduce focal ischemic brain injury by inhibiting cerebral inflammation and edema. Transient focal ischemia was induced in C57BL/6J mice by middle cerebral artery occlusion (MCAO) for 1 h. Infarct volume, neurological score and cerebral water content were evaluated 48 h after MCAO. Immunostaining, western blot analysis and ELISA were used to assess the effects of probenecid on the cellular inflammatory response, HMGB1 release and AQP4 expression. Administration of probenecid reduced infarct size, decreased cerebral water content, inhibited neuronal death, and reduced inflammation in the brain 48 h after stroke. In addition, HMGB1 release from neurons was significantly diminished and serum HMGB1 levels were substantially reduced following probenecid treatment. Moreover, AQP4 protein expression was downregulated in the cortical penumbra following post-stroke treatment with probenecid. These results suggest that probenecid, a powerful pannexin 1 channel inhibitor, protects against ischemic brain injury by inhibiting cerebral inflammation and edema.

  11. What is a seizure network? Long-range network consequences of focal seizures.

    Science.gov (United States)

    Blumenfeld, Hal

    2014-01-01

    What defines the spatial and temporal boundaries of seizure activity in brain networks? To fully answer this question a precise and quantitative definition of seizures is needed, which unfortunately remains elusive. Nevertheless, it is possible to ask under conditions where clearly divergent patterns of activity occur in large-scale brain networks whether certain activity patterns are part of the seizure while others are not. Here we examine brain network activity during focal limbic seizures, including diverse regions such as the hippocampus, subcortical arousal systems and fronto-parietal association cortex. Based on work from patients and from animal models we describe a characteristic pattern of intense increases in neuronal firing, cerebral blood flow, cerebral blood volume, blood oxygen level dependent functional magnetic resonance imaging (BOLD fMRI) signals and cerebral metabolic rate of oxygen consumption in the hippocampus during focal limbic seizures. Similar increases are seen in certain closely linked subcortical structures such as the lateral septal nuclei and anterior hypothalamus, which contain inhibitory neurons. In marked contrast, decreases in all of these parameters are seen in the subcortical arousal systems of the upper brainstem and intralaminar thalamus, as well as in the fronto-parietal association cortex. We propose that the seizure proper can be defined as regions showing intense increases, while those areas showing opposite changes are inhibited by the seizure network and constitute long-range network consequences beyond the seizure itself. Importantly, the fronto-parietal cortex shows sleep-like slow wave activity and depressed metabolism under these conditions, associated with impaired consciousness. Understanding which