Molecular dialogues between the ischemic brain and the peripheral immune system: Dualistic roles in injury and repair

Science.gov (United States)

An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A.; Leak, Rehana K.; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

2014-01-01

Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialogue between the brain and peripheral immune system show promise as potential novel treatments for stroke. PMID:24374228

Expert medical testimony for your injured patients.

Science.gov (United States)

Lang, Gerald J

2013-10-01

Many injured patients sustain some type of loss. If someone else is responsible for the injury, the injured patient can pursue compensation for this loss. In the course of treating an injured patient, you may be asked to participate in the legal process to resolve such claims. The basic components of a personal injury claim are reviewed. An overview of the legal process will help clarify your role in the legal process. Enhanced understanding will allow you to provide important medical testimony for your injured patient.

Molecular dialogs between the ischemic brain and the peripheral immune system: dualistic roles in injury and repair.

Science.gov (United States)

An, Chengrui; Shi, Yejie; Li, Peiying; Hu, Xiaoming; Gan, Yu; Stetler, Ruth A; Leak, Rehana K; Gao, Yanqin; Sun, Bao-Liang; Zheng, Ping; Chen, Jun

2014-04-01

Immune and inflammatory responses actively modulate the pathophysiological processes of acute brain injuries such as stroke. Soon after the onset of stroke, signals such as brain-derived antigens, danger-associated molecular patterns (DAMPs), cytokines, and chemokines are released from the injured brain into the systemic circulation. The injured brain also communicates with peripheral organs through the parasympathetic and sympathetic branches of the autonomic nervous system. Many of these diverse signals not only activate resident immune cells in the brain, but also trigger robust immune responses in the periphery. Peripheral immune cells then migrate toward the site of injury and release additional cytokines, chemokines, and other molecules, causing further disruptive or protective effects in the ischemic brain. Bidirectional communication between the injured brain and the peripheral immune system is now known to regulate the progression of stroke pathology as well as tissue repair. In the end, this exquisitely coordinated crosstalk helps determine the fate of animals after stroke. This article reviews the literature on ischemic brain-derived signals through which peripheral immune responses are triggered, and the potential impact of these peripheral responses on brain injury and repair. Pharmacological strategies and cell-based therapies that target the dialog between the brain and peripheral immune system show promise as potential novel treatments for stroke. Published by Elsevier Ltd.

Neural stem cells in the ischemic and injured brain: endogenous and transplanted.

Science.gov (United States)

Dong, Jing; Liu, Baohua; Song, Lei; Lu, Lei; Xu, Haitao; Gu, Yue

2012-12-01

Neural stem cells functions as the pool of new neurons in adult brain, and plays important roles in normal brain function. Additionally, this pool reacts to brain ischemia, hemorrhage, trauma and many kinds of diseases, serving as endogenous repair mechanisms. The present manuscript discussed the responses of adult neurogenesis to brain ischemia and other insults, then the potential of neural stem cell transplantation therapy to treat such brain injury conditions.

Microdialysate concentration changes do not provide sufficient information to evaluate metabolic effects of lactate supplementation in brain-injured patients

DEFF Research Database (Denmark)

Dienel, G. A.; Rothman, D. L.; Nordström, Carl-Henrik

2016-01-01

Cerebral microdialysis is a widely used clinical tool for monitoring extracellular concentrations of selected metabolites after brain injury and to guide neurocritical care. Extracellular glucose levels and lactate/pyruvate ratios have high diagnostic value because they can detect hypoglycemia an....... In such cases, lactate will not be metabolizable and lactate flooding may be harmful. More rigorous approaches are required to evaluate metabolic and physiological effects of administration of hypertonic sodium lactate to brain-injured patients.......Cerebral microdialysis is a widely used clinical tool for monitoring extracellular concentrations of selected metabolites after brain injury and to guide neurocritical care. Extracellular glucose levels and lactate/pyruvate ratios have high diagnostic value because they can detect hypoglycemia...... and deficits in oxidative metabolism, respectively. In addition, patterns of metabolite concentrations can distinguish between ischemia and mitochondrial dysfunction, and are helpful to choose and evaluate therapy. Increased intracranial pressure can be life-threatening after brain injury, and hypertonic...

Recovery of injured Broca's portion of arcuate fasciculus in the dominant hemisphere in a patient with traumatic brain injury

OpenAIRE

Jang, Sung Ho; Ha, Ji Wan; Kim, Hyun Young; Seo, You Sung

2017-01-01

Abstract Rationale: Recovery of injured AF in patients with traumatic brain injury (TBI) has not been reported. In this study, we report on a patient with TBI who recovered from an injury to Broca's portion of AF in the dominant hemisphere, diagnosed by diffusion tensor tractography (DTT). Patient concerns: A 28-year-old right-handed male patient suffered head trauma resulting from sliding while riding a motorcycle. Diagnoses: He was diagnosed with a traumatic contusional hemorrhage in the le...

Recovery of injured Broca's portion of arcuate fasciculus in the dominant hemisphere in a patient with traumatic brain injury.

Science.gov (United States)

Jang, Sung Ho; Ha, Ji Wan; Kim, Hyun Young; Seo, You Sung

2017-12-01

Recovery of injured AF in patients with traumatic brain injury (TBI) has not been reported. In this study, we report on a patient with TBI who recovered from an injury to Broca's portion of AF in the dominant hemisphere, diagnosed by diffusion tensor tractography (DTT). A 28-year-old right-handed male patient suffered head trauma resulting from sliding while riding a motorcycle. He was diagnosed with a traumatic contusional hemorrhage in the left frontal lobe, subarachnoid hemorrhage, and subdural hemorrhage in the left fronto-temporal lobe. He underwent craniectomy on the left fronto-temporal area, and hematoma removal for the subdural hemorrhage in the neurosurgery department of a university hospital. Two weeks after the injury, he was transferred to the rehabilitation department of another university hospital. He showed severe aphasia and brain MRI showed leukomalactic lesion in the left frontal lobe. The result WAB for the patient showed severe aphasia, with an aphasia quotient of 45.3 percentile. However, his aphasia improved rapidly by 9 months with an aphasia quotient at the 100.0 percentile. 2-week DTT detected discontinuity in the subcortical white matter at the branch to Broca's area of left AF. By contrast, on 9-month DTT, the discontinued portion of left AF was elongated to the left Broca's area. Recovery of injured Broca's portion of AF in the dominant hemisphere along with excellent improvement of aphasia was demonstrated in a patient with TBI. This study has important implications in brain rehabilitation because the mechanism of recovery from aphasia following TBI has not been elucidated. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Low-doses of cisplatin injure hippocampal synapses: a mechanism for 'chemo' brain?

Science.gov (United States)

Andres, Adrienne L; Gong, Xing; Di, Kaijun; Bota, Daniela A

2014-05-01

Chemotherapy-related cognitive deficits are a major neurological problem, but the underlying mechanisms are unclear. The death of neural stem/precursor cell (NSC) by cisplatin has been reported as a potential cause, but this requires high doses of chemotherapeutic agents. Cisplatin is frequently used in modern oncology, and it achieves high concentrations in the patient's brain. Here we report that exposure to low concentrations of cisplatin (0.1μM) causes the loss of dendritic spines and synapses within 30min. Longer exposures injured dendritic branches and reduced dendritic complexity. At this low concentration, cisplatin did not affect NSC viability nor provoke apoptosis. However, higher cisplatin levels (1μM) led to the rapid loss of synapses and dendritic disintegration, and neuronal-but not NSC-apoptosis. In-vivo treatment with cisplatin at clinically relevant doses also caused a reduction of dendritic branches and decreased spine density in CA1 and CA3 hippocampal neurons. An acute increase in cell death was measured in the CA1 and CA3 neurons, as well as in the NSC population located in the subgranular zone of the dentate gyrus in the cisplatin treated animals. The density of dendritic spines is related to the degree of neuronal connectivity and function, and pathological changes in spine number or structure have significant consequences for brain function. Therefore, this synapse and dendritic damage might contribute to the cognitive impairment observed after cisplatin treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

Effective protection of rabbits' explosive brain injury through blocking ...

African Journals Online (AJOL)

Background: The gap junction plays an important role in spreading of apoptotic and necrotic signals from injured and stressed cells to the neighboring viable cells. The present study was performed to investigate the important role of gap junction communication on rabbits' explosive brain injury. Methods: Explosion of paper ...

The potential of neural transplantation for brain repair and regeneration following traumatic brain injury

Institute of Scientific and Technical Information of China (English)

Dong Sun

2016-01-01

Traumatic brain injury is a major health problem worldwide. Currently, there is no effective treatment to improve neural structural repair and functional recovery of patients in the clinic. Cell transplantation is a potential strategy to repair and regenerate the injured brain. This review article summarized recent de-velopment in cell transplantation studies for post-traumatic brain injury brain repair with varying types of cell sources. It also discussed the potential of neural transplantation to repair/promote recovery of the injured brain following traumatic brain injury.

Electroacupuncture ameliorates post-stroke learning and memory through minimizing ultrastructural brain damage and inhibiting the expression of MMP-2 and MMP-9 in cerebral ischemia-reperfusion injured rats.

Science.gov (United States)

Lin, Ruhui; Yu, Kunqiang; Li, Xiaojie; Tao, Jing; Lin, Yukun; Zhao, Congkuai; Li, Chunyan; Chen, Li-Dian

2016-07-01

The aim of the present study was to investigate the potential neuroprotective effects of electroacupuncture (EA) in the treatment of cerebral ischemia/reperfusion (I/R) injury, and to elucidate the association between this neuroprotective effect and brain ultrastructure and expression of matrix metalloproteinase (MMP)‑2 and 9. Rats underwent focal cerebral I/R injury by arterial ligation and received in vivo therapeutic EA at the Baihui (DU20) and Shenting (DU24) acupoints. The therapeutic efficacy was then evaluated following the surgery. The results of the current study demonstrated that EA treatment significantly ameliorated neurological deficits and reduced cerebral infarct volume compared with I/R injured rats. Furthermore, EA improved the learning and memory ability of rats following I/R injury, inhibited blood brain barrier breakdown and reduced neuronal damage in the ischemic penumbra. Furthermore, EA attenuated ultrastructural changes in the brain tissue following ischemia and inhibited MMP‑2/MMP‑9 expression in cerebral I/R injured rats. The results suggest that EA ameliorates anatomical deterioration, and learning and memory deficits in rats with cerebral I/R injury.

Coagulopathy: Its Pathophysiology and Treatment in the Injured Patient

Science.gov (United States)

2007-03-30

death. In fact, in their series, 77% of brain-injured patients who died had a coagulopathy at the time of hospital admission.8 Similarly, Faringer et...coagulation process. Arch Surg 1996;131:923–927. 9. Faringer PD, Mullins RJ, Johnson RL, Trunkey DD. Blood component supplementation during massive

[Development of an integrative cognitive rehabilitation program for brain injured patients in the post-acute stage].

Science.gov (United States)

Oh, Hyun Soo; Kim, Young Ran; Seo, Wha Sook; Seo, Yeon Ok

2005-04-01

This study was conducted to develop a comprehensive cognitive rehabilitation program that can be easily applied to brain injured patients by family members or nurses in community or hospital settings. A Systemic literature review design was used. Thirty-three related studies were reviewed. Based on the results of the literature review, the training tasks for attention were designated to enhancing 4 hierarchical areas, i.e., focused, selective, alternating, and divided attention. On the other hand, the memory rehabilitation tasks mainly consisted of mnemonic skills, such as the association method which helps patients memorize given information by linking together common attributes, the visual imagery method, and self-instruction method. The problem solving rehabilitation program included a task of games or plays which stimulated the patients' curiosity and interest. The training tasks for problem solving were to encourage the process of deriving reasonable solutions for a problematic situation resembling real problems that the patients were faced with in their everyday life. It is expected that the cognitive rehabilitation program developed from this study could help patients having difficulty in their every day life, due to a reduced cognitive ability resulting from brain injury, to effectively adapt to every day life.

Structural and metabolic changes in the traumatically injured rat brain. High-resolution in vivo proton magnetic resonance spectroscopy at 7 T

International Nuclear Information System (INIS)

Li, Jing; Zhao, Can; Rao, Jia-Sheng; Yang, Fei-Xiang; Yang, Zhao-Yang; Wang, Zhan-Jing; Lei, Jian-Feng; Li, Xiao-Guang

2017-01-01

The understanding of microstructural and metabolic changes in the post-traumatic brain injury is the key to brain damage suppression and repair in clinics. Ten female Wistar rats were traumatically injured in the brain CA1 region and above the cortex. Next, diffusion tensor magnetic resonance imaging (DTI) and proton magnetic resonance spectroscopy ( 1 H MRS) were used to analyze the microstructural and metabolic changes in the brain within the following 2 weeks. Anisotropy fraction (FA) and axial diffusivity (AD) of the corpus callosum (CC) began to decrease significantly at day 1, whereas radial diffusivity (RD) significantly increased immediately after injury, reflecting the loss of white matter integrity. Compared with day 3, RD decreased significantly at day 7, implicating the angioedema reduction. In the hippocampus, FA significantly increased at day 7; the choline-containing compounds (Cho) and myo-inositol (MI) remarkably increased at day 7 compared with those at day 3, indicating the proliferation of astrocytes and radial glial cells after day 7. No significant differences between DTI and 1 H MRS parameters were observed between day 1 and day 3. Day 1-3 after traumatic brain injury (TBI) may serve as a relatively appropriate time window for treatment planning and the following nerve repair. (orig.)

Structural and metabolic changes in the traumatically injured rat brain. High-resolution in vivo proton magnetic resonance spectroscopy at 7 T

Energy Technology Data Exchange (ETDEWEB)

Li, Jing; Zhao, Can; Rao, Jia-Sheng [Beihang University, Beijing Key Laboratory for Biomaterials and Neural Regeneration, School of Biological Science and Medical Engineering, Beijing (China); Yang, Fei-Xiang; Yang, Zhao-Yang [Capital Medical University, Department of Neurobiology, School of Basic Medical Sciences, Beijing (China); Wang, Zhan-Jing; Lei, Jian-Feng [Capital Medical University, Medical Experiment and Test Center, Beijing (China); Li, Xiao-Guang [Beihang University, Beijing Key Laboratory for Biomaterials and Neural Regeneration, School of Biological Science and Medical Engineering, Beijing (China); Capital Medical University, Department of Neurobiology, School of Basic Medical Sciences, Beijing (China)

2017-12-15

The understanding of microstructural and metabolic changes in the post-traumatic brain injury is the key to brain damage suppression and repair in clinics. Ten female Wistar rats were traumatically injured in the brain CA1 region and above the cortex. Next, diffusion tensor magnetic resonance imaging (DTI) and proton magnetic resonance spectroscopy ({sup 1}H MRS) were used to analyze the microstructural and metabolic changes in the brain within the following 2 weeks. Anisotropy fraction (FA) and axial diffusivity (AD) of the corpus callosum (CC) began to decrease significantly at day 1, whereas radial diffusivity (RD) significantly increased immediately after injury, reflecting the loss of white matter integrity. Compared with day 3, RD decreased significantly at day 7, implicating the angioedema reduction. In the hippocampus, FA significantly increased at day 7; the choline-containing compounds (Cho) and myo-inositol (MI) remarkably increased at day 7 compared with those at day 3, indicating the proliferation of astrocytes and radial glial cells after day 7. No significant differences between DTI and {sup 1}H MRS parameters were observed between day 1 and day 3. Day 1-3 after traumatic brain injury (TBI) may serve as a relatively appropriate time window for treatment planning and the following nerve repair. (orig.)

Recovery of an injured fornix in a stroke patient.

Science.gov (United States)

Yeo, Sang Seok; Jang, Sung Ho

2013-11-01

Knowledge about recovery of an injured fornix following brain injury is limited. We describe here a patient who showed recovery of an injured fornix following stroke. A 57-year-old female patient underwent coiling for a ruptured anterior communicating cerebral artery aneurysm, and conservative management for subarachnoid and intraventricular haemorrhage. The patient showed severe cognitive impairment 6 weeks after onset. However, her cognition showed continuous improvement with time; based on the Mini-Mental State Examination and the Memory Assessment Scale, her cognition was within the normal range 7 months after onset. Findings from diffusion tensor tractography at 6 weeks and 7 months showed discontinuations in both columns of the fornix. The proximal portion of both crus also showed discontinuation on diffusion tensor tractography at 6 weeks and 7 months; however, on 7-month diffusion tensor tractography, the end of the fornical body was shown to be connected to the splenium of the corpus callosum and then branched to the right medial temporal lobe and right thalamus. The unusual neural connection between the injured fornix and the thalamus appears to be a recovery phenomenon, which allows the injured fornix and the medial temporal lobe to obtain cholinergic innervation from cholinergic nuclei in the brainstem rather than from cholinergic nuclei in the basal forebrain.

Traumatic brain injury and post-acute decline: what role does environmental enrichment play? A scoping review

Directory of Open Access Journals (Sweden)

Diana eFrasca

2013-04-01

Full Text Available Objectives. While a number of studies provide evidence of neural and cognitive decline in traumatic brain injury (TBI survivors during the post-acute stages of injury, there is a dearth of research on the possible mechanisms underlying this decline. The purposes of this paper, therefore, are to (1 examine evidence that environmental enrichment (EE can influence long-term outcome following TBI, and (2 examine the nature of post-acute environments, whether they vary in degree of EE, and what impact these variations have on outcomes.Methods. We conducted a scoping review to identify studies on EE in animals and humans, and post-discharge experiences that relate to barriers to recovery.Results. Ninety-six articles that met inclusion criteria demonstrated the benefits of EE on brain and behaviour in healthy and brain-injured animals and humans. Nineteen papers on post-discharge experiences provided evidence that variables such as insurance coverage, financial and social support, home therapy, and transition from hospital to home, also play a vital role in regaining independence. Conclusion. There is evidence to suggest that lack of EE, whether from lack of resources or limited ability to engage in such environments, may play a role in post-recovery cognitive and neural decline. Maximizing EE in the post-acute stages of TBI may improve long-term outcomes for the individual, their family and society.

The stem cell secretome and its role in brain repair.

Science.gov (United States)

Drago, Denise; Cossetti, Chiara; Iraci, Nunzio; Gaude, Edoardo; Musco, Giovanna; Bachi, Angela; Pluchino, Stefano

2013-12-01

Compelling evidence exists that non-haematopoietic stem cells, including mesenchymal (MSCs) and neural/progenitor stem cells (NPCs), exert a substantial beneficial and therapeutic effect after transplantation in experimental central nervous system (CNS) disease models through the secretion of immune modulatory or neurotrophic paracrine factors. This paracrine hypothesis has inspired an alternative outlook on the use of stem cells in regenerative neurology. In this paradigm, significant repair of the injured brain may be achieved by injecting the biologics secreted by stem cells (secretome), rather than implanting stem cells themselves for direct cell replacement. The stem cell secretome (SCS) includes cytokines, chemokines and growth factors, and has gained increasing attention in recent years because of its multiple implications for the repair, restoration or regeneration of injured tissues. Thanks to recent improvements in SCS profiling and manipulation, investigators are now inspired to harness the SCS as a novel alternative therapeutic option that might ensure more efficient outcomes than current stem cell-based therapies for CNS repair. This review discusses the most recent identification of MSC- and NPC-secreted factors, including those that are trafficked within extracellular membrane vesicles (EVs), and reflects on their potential effects on brain repair. It also examines some of the most convincing advances in molecular profiling that have enabled mapping of the SCS. Copyright © 2013 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

Recovery of an injured cingulum concurrent with improvement of short-term memory in a patient with mild traumatic brain injury.

Science.gov (United States)

Jang, Sung Ho; Kim, Seong Ho; Seo, Jeong Pyo

2018-01-01

We reported on a patient with mild traumatic brain injury (TBI) who showed recovery of an injured cingulum concurrent with improvement of short-term memory, which was demonstrated on follow-up diffusion tensor tractography (DTT). A 55-year-old male patient suffered head trauma resulting from falling from approximately 2 m while working at a construction site. The patient showed mild memory impairment (especially short-term memory impairment) at 3 months after onset: Memory Assessment Scale (global memory: 95 (37%ile), short-term memory: 75 (5%ile), verbal memory: 80 (9%ile) and visual memory: 112 (79%ile)). By contrast, at 2 years after onset, his mild memory impairment had improved to a normal state: Memory Assessment Scale (global memory: 104 (61%ile), short-term memory: 95 (37%ile), verbal memory: 101 (53%ile) and visual memory: 106 (66%ile)). On 3-month DTT, discontinuation of the right anterior cingulum was observed over the genu of the corpus callosum, while on 2-year DTT, the discontinued right anterior cingulum was elongated to the right basal forebrain. In conclusion, recovery of an injured cingulum concurrent with improvement of short-term memory was demonstrated in a patient with mild TBI.

Role of neuroinflammation in ischemic stroke

Institute of Scientific and Technical Information of China (English)

Rui Liu; Meng-Xian Pan; Jun-Chun Tang; Ya Zhang; Hua-Bao Liao; Yang Zhuang; Dan Zhao; Qi Wan

2017-01-01

Ischemic stroke causes the depletion of energy and induce excitotoxicity and neuroinflammation in the brain that results from thrombotic blockage. Neuroinflammation occurs initially depending on activated resident microglia that has the same function as the macrophage. Activated microglia participates in the neuroinflammatory process by phagocytosing the injured brain cells and producing the pro- and anti-inflammatory mediators. In this review, the authors present an overview of the role of microglia in mediating neuroinflammation in ischemic stroke.

Inhibitory Effect on Cerebral Inflammatory Response following Traumatic Brain Injury in Rats: A Potential Neuroprotective Mechanism of N-Acetylcysteine

Directory of Open Access Journals (Sweden)

Gang Chen

2008-01-01

Full Text Available Although N-acetylcysteine (NAC has been shown to be neuroprotective for traumatic brain injury (TBI, the mechanisms for this beneficial effect are still poorly understood. Cerebral inflammation plays an important role in the pathogenesis of secondary brain injury after TBI. However, it has not been investigated whether NAC modulates TBI-induced cerebral inflammatory response. In this work, we investigated the effect of NAC administration on cortical expressions of nuclear factor kappa B (NF-κB and inflammatory proteins such as interleukin-1β (IL-1β, tumor necrosis factor-α (TNF-α, interleukin-6 (IL-6, and intercellular adhesion molecule-1 (ICAM-1 after TBI. As a result, we found that NF-κB, proinflammatory cytokines, and ICAM-1 were increased in all injured animals. In animals given NAC post-TBI, NF-κB, IL-1β, TNF-α, and ICAM-1 were decreased in comparison to vehicle-treated animals. Measures of IL-6 showed no change after NAC treatment. NAC administration reduced brain edema, BBB permeability, and apoptotic index in the injured brain. The results suggest that post-TBI NAC administration may attenuate inflammatory response in the injured rat brain, and this may be one mechanism by which NAC ameliorates secondary brain damage following TBI.

Distal axotomy enhances retrograde presynaptic excitability onto injured pyramidal neurons via trans-synaptic signaling.

Science.gov (United States)

Nagendran, Tharkika; Larsen, Rylan S; Bigler, Rebecca L; Frost, Shawn B; Philpot, Benjamin D; Nudo, Randolph J; Taylor, Anne Marion

2017-09-20

Injury of CNS nerve tracts remodels circuitry through dendritic spine loss and hyper-excitability, thus influencing recovery. Due to the complexity of the CNS, a mechanistic understanding of injury-induced synaptic remodeling remains unclear. Using microfluidic chambers to separate and injure distal axons, we show that axotomy causes retrograde dendritic spine loss at directly injured pyramidal neurons followed by retrograde presynaptic hyper-excitability. These remodeling events require activity at the site of injury, axon-to-soma signaling, and transcription. Similarly, directly injured corticospinal neurons in vivo also exhibit a specific increase in spiking following axon injury. Axotomy-induced hyper-excitability of cultured neurons coincides with elimination of inhibitory inputs onto injured neurons, including those formed onto dendritic spines. Netrin-1 downregulation occurs following axon injury and exogenous netrin-1 applied after injury normalizes spine density, presynaptic excitability, and inhibitory inputs at injured neurons. Our findings show that intrinsic signaling within damaged neurons regulates synaptic remodeling and involves netrin-1 signaling.Spinal cord injury can induce synaptic reorganization and remodeling in the brain. Here the authors study how severed distal axons signal back to the cell body to induce hyperexcitability, loss of inhibition and enhanced presynaptic release through netrin-1.

Occupational wellbeing--management of injured workers with psychosocial barriers.

Science.gov (United States)

Cotton, Peter

2006-12-01

Although most injured workers return to work with minimal intervention, approximately 20% show levels of distress and disability beyond that expected for the injury. The level of morale in a workplace seems to play a major role in this. Workers who experience positive emotions leading to increased morale are more likely to be resilient following injury. It is important for general practitioners to recognise the nonclinical factors that exert a significant influence over employee wellbeing and return to work outcomes. Some management strategies are presented. General practitioners who work collaboratively with all major stakeholders, who identify and manage psychosocial barriers early, who take an active role in promoting positive expectations, and who focus on the immediate problem rather than its industrial associations will achieve better outcomes for their injured patients.

Role of the Blood-Brain Barrier in the Formation of Brain Metastases

Directory of Open Access Journals (Sweden)

István A. Krizbai

2013-01-01

Full Text Available The majority of brain metastases originate from lung cancer, breast cancer and malignant melanoma. In order to reach the brain, parenchyma metastatic cells have to transmigrate through the endothelial cell layer of brain capillaries, which forms the morphological basis of the blood-brain barrier (BBB. The BBB has a dual role in brain metastasis formation: it forms a tight barrier protecting the central nervous system from entering cancer cells, but it is also actively involved in protecting metastatic cells during extravasation and proliferation in the brain. The mechanisms of interaction of cancer cells and cerebral endothelial cells are largely uncharacterized. Here, we provide a comprehensive review on our current knowledge about the role of junctional and adhesion molecules, soluble factors, proteolytic enzymes and signaling pathways mediating the attachment of tumor cells to brain endothelial cells and the transendothelial migration of metastatic cells. Since brain metastases represent a great therapeutic challenge, it is indispensable to understand the mechanisms of the interaction of tumor cells with the BBB in order to find targets of prevention of brain metastasis formation.

Lymphocytes Contribute to the Pathophysiology of Neonatal Brain Injury

Directory of Open Access Journals (Sweden)

Arshed Nazmi

2018-03-01

Full Text Available BackgroundPeriventricular leukomalacia (PVL is the most common form of preterm brain injury affecting the cerebral white matter. This type of injury involves a multiphase process and is induced by many factors, including hypoxia–ischemia (HI and infection. Previous studies have suggested that lymphocytes play a significant role in the pathogenesis of brain injury, and the aim of this study was to determine the contribution of lymphocyte subsets to preterm brain injury.MethodsImmunohistochemistry on brain sections from neonatal mice was performed to evaluate the extent of brain injury in wild-type and T cell and B cell-deficient neonatal mice (Rag1−/− mice using a mouse model of HI-induced preterm brain injury. Flow cytometry was performed to determine the presence of different types of immune cells in mouse brains following HI. In addition, immunostaining for CD3 T cells and CD20 B cells was performed on postmortem preterm human infant brains with PVL.ResultsMature lymphocyte-deficient Rag1−/− mice showed protection from white matter loss compared to wild type mice as indicated by myelin basic protein immunostaining of mouse brains. CD3+ T cells and CD20+ B cells were observed in the postmortem preterm infant brains with PVL. Flow cytometry analysis of mouse brains after HI-induced injury showed increased frequency of CD3+ T, αβT and B cells at 7 days after HI in the ipsilateral (injured hemisphere compared to the contralateral (control, uninjured hemisphere.ConclusionLymphocytes were found in the injured brain after injury in both mice and humans, and lack of mature lymphocytes protected neonatal mice from HI-induced brain white matter injury. This finding provides insight into the pathology of perinatal brain injury and suggests new avenues for the development of therapeutic strategies.

NNZ-2566 treatment inhibits neuroinflammation and pro-inflammatory cytokine expression induced by experimental penetrating ballistic-like brain injury in rats

Directory of Open Access Journals (Sweden)

Tortella Frank C

2009-08-01

Full Text Available Abstract Background Inflammatory cytokines play a crucial role in the pathophysiology of traumatic brain injury (TBI, exerting either deleterious effects on the progression of tissue damage or beneficial roles during recovery and repair. NNZ-2566, a synthetic analogue of the neuroprotective tripeptide Glypromate®, has been shown to be neuroprotective in animal models of brain injury. The goal of this study was to determine the effects of NNZ-2566 on inflammatory cytokine expression and neuroinflammation induced by penetrating ballistic-like brain injury (PBBI in rats. Methods NNZ-2566 or vehicle (saline was administered intravenously as a bolus injection (10 mg/kg at 30 min post-injury, immediately followed by a continuous infusion of NNZ-2566 (3 mg/kg/h, or equal volume of vehicle, for various durations. Inflammatory cytokine gene expression from the brain tissue of rats exposed to PBBI was evaluated using microarray, quantitative real time PCR (QRT-PCR, and enzyme-linked immunosorbent assay (ELISA array. Histopathology of the injured brains was examined using hematoxylin and eosin (H&E and immunocytochemistry of inflammatory cytokine IL-1β. Results NNZ-2566 treatment significantly reduced injury-mediated up-regulation of IL-1β, TNF-α, E-selectin and IL-6 mRNA during the acute injury phase. ELISA cytokine array showed that NZ-2566 treatment significantly reduced levels of the pro-inflammatory cytokines IL-1β, TNF-α and IFN-γ in the injured brain, but did not affect anti-inflammatory cytokine IL-6 levels. Conclusion Collectively, these results suggest that the neuroprotective effects of NNZ-2566 may, in part, be functionally attributed to the compound's ability to modulate expression of multiple neuroinflammatory mediators in the injured brain.

Endovascular transplantation of stem cells to the injured rat CNS

Energy Technology Data Exchange (ETDEWEB)

Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan [Karolinska University Hospital, Department of Clinical Neuroscience, Karolinska Institutet, Department of Neuroradiology, Stockholm (Sweden); Le Blanc, Katarina [Karolinska University Hospital, Department of Stem Cell Research, Karolinska Institutet, Department of Clinical Immunology, Stockholm (Sweden)

2009-10-15

Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

Endovascular transplantation of stem cells to the injured rat CNS

International Nuclear Information System (INIS)

Lundberg, Johan; Soederman, Mikael; Andersson, Tommy; Holmin, Staffan; Le Blanc, Katarina

2009-01-01

Transplantation procedures using intraparenchymal injection of stem cells result in tissue injury in addition to associated surgical risks. Intravenous injection of mesenchymal stem cells gives engraftment to lesions, but the method has low efficiency and specificity. In traumatic brain injuries (TBI), there is a transient breakdown of the blood-brain barrier and an inflammatory response, which increase migration of cells from blood to parenchyma. The aim of this investigation was to analyze the effect of intra-arterial administration on cellular engraftment. Experimental TBI was produced in a rat model. Endovascular technique was used to administer human mesenchymal stem cells in the ipsilateral internal carotid artery. Evaluation of engraftment and side effects were performed by immunohistochemical analysis of the brain and several other organs. The results were compared to intravenous administration of stem cells. Intra-arterial transplantion of mesenchymal stem cells resulted in central nervous system (CNS) engraftment without thromboembolic ischemia. We observed a significantly higher number of transplanted cells in the injured hemisphere after intra-arterial compared to intravenous administration both 1 day (p<0.01) and 5 days (p<0.05) after the transplantation. Some cells were also detected in the spleen but not in the other organs analyzed. Selective intra-arterial administration of mesenchymal stem cells to the injured CNS is a minimally invasive method for transplantation. The method is significantly more efficient than the intravenous route and causes no side effects in the current model. The technique can potentially be used for repeated transplantation to the CNS after TBI and in other diseases. (orig.)

Healing or harming? Healthcare provider interactions with injured workers and insurers in workers' compensation systems.

Science.gov (United States)

Kilgour, Elizabeth; Kosny, Agnieszka; McKenzie, Donna; Collie, Alex

2015-03-01

Healthcare providers (HCPs) are influential in the injured worker's recovery process and fulfil many roles in the delivery of health services. Interactions between HCPs and insurers can also affect injured workers' engagement in rehabilitation and subsequently their recovery and return to work. Consideration of the injured workers' perceptions and experiences as consumers of medical and compensation services can provide vital information about the quality, efficacy and impact of such systems. The aim of this systematic review was to identify and synthesize published qualitative research that focused on the interactions between injured workers, HCPs and insurers in workers' compensation systems in order to identify processes or interactions which impact injured worker recovery. A search of six electronic databases for literature published between 1985 and 2012 revealed 1,006 articles. Screening for relevance identified 27 studies which were assessed for quality against set criteria. A final 13 articles of medium and high quality were retained for data extraction. Findings were synthesized using a meta-ethnographic approach. Injured workers reported that HCPs could play both healing and harming roles in their recovery. Supportive patient-centred interaction with HCPs is important for injured workers. Difficult interactions between HCPs and insurers were highlighted in themes of adversarial relations and organisational pressures. Insurer and compensation system processes exerted an influence on the therapeutic relationship. Recommendations to improve relationships included streamlining administrative demands and increasing education and communication between the parties. Injured workers with long term complex injuries experience difficulties with healthcare in the workers' compensation context. Changes in insurer administrative demands and compensation processes could increase HCP participation and job satisfaction. This in turn may improve injured worker recovery

Effect of naloxone hydrochloride on c-fos protein expression in brain and plasma beta-endorphin level in rats with diffuse brain injury and secondary brain insult

Directory of Open Access Journals (Sweden)

Jun-jie JING

2012-09-01

Full Text Available Objective　To observe the changes of c-fos protein expression in brain and beta-endorphin (β-EP level in blood plasma in rats with diffuse brain injury (DBI and secondary brain insult (SBI after intraperitoneal injection of naloxone hydrochloride, and explore the role of c-fos andβ-EP in development of SBI in rats. Methods　Seventy health male SD rats were enrolled in the present study and randomly divided into group A (intraperitoneally injected with 0.9% saline after DBI and SBI model was reproduced, group B (injected intraperitoneally with 1.0mg/kg naloxone hydrochloride after DBI and SBI model was reproduced, and group C (intraperitoneally injected with 1.0mg/kg naloxone hydrochloride after DBI and before SBI model was reproduced. The animals were sacrificed 3, 24 and 48 hours after injury, and the number of c-fos positive cells in brain and content of β-EP in blood plasma were determined by immunohistochemistry and radioimmunoassay respectively, the water content and number of injured neurons in brain tissue were measured by pathomorphological observation of the brain tissue. Results　No significant difference was observed between group B and C for all the detection parameters. In group B and C, the water content in brain tissue at 3h and 24h was found to be decreased, while the number of injured neurons at 24h and 48h increased, number of c-fos positive cells in brain at 3h, 24h and 48h decreased, and content of β-EP in blood plasma at 3h and 24h decreased when compared with group A(P < 0.05. Conclusion　Naloxone hydrochloride could decrease the c-fos expression in brain and β-EP level in blood plasma, alleviate the nerve injury, and protect neural function. The therapeutic effect of naloxone administered either after DBI and SBI or after DBI and before SBI was similar.

Role of surgery in brain metastases.

Science.gov (United States)

Laghari, Altaf Ali; Ahmed, Syed Ijlal; Shamim, Muhammad Shahzad

2017-08-01

Brain metastases remain the commonest type of brain tumour, being four times more common than primary brain tumours. Although surgical intervention may be recommended for one of various reasons in the management of these tumours, including but not limited to conformation of diagnosis, relief of mass effect, improvement of neurological status and prolongation of survival, the guidelines for management of brain metastases remain largely subjective and therefore controversial. Herein the authors have attempted to review some of the existing evidence on role of surgery in the management of brain metastases and have presented their selected guidelines for the readers.

Assistive technologies for brain-injured gamers

OpenAIRE

Colman, Jason; Gnanayutham, Paul

2013-01-01

This chapter surveys assistive technologies which make video games more accessible for people who have an acquired brain injury (ABI). As medical care improves, an increasing number of people survive ABI. Video games have been shown to provide therapeutic benefits in many medical contexts, and rehabilitation for ABI survivors has been shown to be facilitated by playing some types of video game. Therefore, technologies which improve the accessibility of games have the potential to bring a form...

A Case of Successful Simultaneous Pancreas-Kidney Transplantation Using the Injured Pancreas Graft.

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Miyagi, S; Shimizu, K; Miyazawa, K; Nakanishi, W; Hara, Y; Tokodai, K; Nakanishi, C; Satomi, S; Goto, M; Unno, M; Kamei, T

2017-12-01

Graft injuries sometimes occur and may cause complications such as the leakage of pancreatic secretions, which is often lethal. We report our experience of a case of successful simultaneous pancreas-kidney transplantation using injured pancreas graft. The recipient was a 57-year-old woman with type 1 diabetes mellitus, and the donor was a 30-year-old man with a brain injury. In the donation, the pancreas parenchyma, splenic artery, and gastroduodenal artery were injured iatrogenically. We therefore reconstructed these arteries using vessel grafts and then performed simultaneous pancreas-kidney transplantation. Five days after transplantation, we noted a high titer of amylase in the ascites; therefore, we performed an urgent laparotomy. The origin of the amylase was the injured pancreatic parenchyma, and continued washing and drainage were carried out. We reconstructed the duodenojejunostomy using the Roux-en-Y technique to separate the passage of food from the pancreas graft to prevent injury to other organs due to exposure to pancreatic secretions. Thereafter, we inserted a decompression tube into the anastomosis thorough the blind end of the jejunum. Finally, we inserted 3 drainage tubes for lavage. Following this procedure, the patient recovered gradually and no longer required hemodialysis and insulin therapy. She was discharged from our hospital 56 days after transplantation. The restoration of the injured graft was possible by management of pancreatic secretions and use of the donor's vessel grafts. Shortage of donors is a problem throughout the world; thus, it is important to use injured grafts for transplantation if possible. Copyright © 2017 Elsevier Inc. All rights reserved.

Increased CD147 (EMMPRIN) expression in the rat brain following traumatic brain injury.

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Wei, Ming; Li, Hong; Shang, Yanguo; Zhou, Ziwei; Zhang, Jianning

2014-10-17

The extracellular matrix metalloproteinase inducer (EMMPRIN), or CD147, has been known to play a key regulatory role in vascular permeability and leukocyte activation by inducing the expression of matrix metalloproteinases (MMPs). The effects of traumatic brain injury on the expression of EMMPRIN remain poorly understood. In this study, we investigated changes in EMMPRIN expression in a rat model of fluid percussion injury (FPI) and examined the potential association between EMMPRIN and MMP-9 expression. Adult male rats were subjected to FPI. EMMPRIN expression was markedly up-regulated in the brain tissue surrounding the injured region 6-48 h after TBI, as measured by immunoblot and immunohistochemistry. EMMPRIN expression was localized to inflammatory cells. The increase in EMMPRIN expression was temporally correlated with an increase in MMP-9 levels. These data demonstrate, for the first time, changes in CD147 and MMP-9 expression following TBI. These data also suggest that CD147 and MMP-9 may play a role in vascular injuries after TBI. Copyright © 2014 Elsevier B.V. All rights reserved.

Effect of Tiaoxin Recipe (调心方) on Spatial Memory and Energy Metabolism of Oxidation Injured Alzheimer's Disease Rats

Institute of Scientific and Technical Information of China (English)

邱宏; 金国琴; 赵伟康; 张学礼

2003-01-01

Objective: To observe the effect of Tiaoxin Recipe (TXR) on the spatial memory, brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease (AD) rats, and to explore the mechanism of TXR in treating AD. Methods: Eighty-eight SD rats were randomly divided into five groups (normal group, operative group, "AD" model group,TXR group and Aricept group). An oxygen free radical generation system (dihydroxy fumaric acid-trichloroferric-adenosine diphosphate, DHF-FeCl3-ADP) was used to create oxidation injured rat models mimic to AD; spatial learning and memory impairment (Morris water maze method), the activity of Succinate-oxidase, NADH-oxidase, CytC-oxidase (Clark oxygen electrode method) and the expression of cytochrome oxidase (CO)ⅡmRNA (in situ hybridization method) were observed. Results: Compared with the normal group, the spatial memory, activity of CytC-oxidase and COⅡmRNA expression of oxidation injured "AD" rats were obviously decreased; TXR, however, could improve these functions in "AD" rat models obviously. Conclusion: The mechanism of the action of TXR in treating AD was partly related to its effect on anti-oxidation which could improve brain mitochondrial energy metabolism.

Brain disorders and the biological role of music.

Science.gov (United States)

Clark, Camilla N; Downey, Laura E; Warren, Jason D

2015-03-01

Despite its evident universality and high social value, the ultimate biological role of music and its connection to brain disorders remain poorly understood. Recent findings from basic neuroscience have shed fresh light on these old problems. New insights provided by clinical neuroscience concerning the effects of brain disorders promise to be particularly valuable in uncovering the underlying cognitive and neural architecture of music and for assessing candidate accounts of the biological role of music. Here we advance a new model of the biological role of music in human evolution and the link to brain disorders, drawing on diverse lines of evidence derived from comparative ethology, cognitive neuropsychology and neuroimaging studies in the normal and the disordered brain. We propose that music evolved from the call signals of our hominid ancestors as a means mentally to rehearse and predict potentially costly, affectively laden social routines in surrogate, coded, low-cost form: essentially, a mechanism for transforming emotional mental states efficiently and adaptively into social signals. This biological role of music has its legacy today in the disordered processing of music and mental states that characterizes certain developmental and acquired clinical syndromes of brain network disintegration. © The Author (2014). Published by Oxford University Press.

Oxygen--a limiting factor for brain recovery.

Science.gov (United States)

Hadanny, Amir; Efrati, Shai

2015-09-01

Effective brain metabolism is highly dependent on a narrow therapeutic window of oxygen. In major insults to the brain (e.g., intracerebral hemorrhage), a slight decrease in oxygen supply, as occurs in a hypobaric environment at high altitude, has devastating effects on the injured brain tissue. Conversely, increasing brain oxygenation, by the use of hyperbaric oxygen therapy, can improve brain metabolism and its dependent regenerative processes.

Oxygen - a limiting factor for brain recovery

OpenAIRE

Hadanny, Amir; Efrati, Shai

2015-01-01

Effective brain metabolism is highly dependent on a narrow therapeutic window of oxygen. In major insults to the brain (e.g., intracerebral hemorrhage), a slight decrease in oxygen supply, as occurs in a hypobaric environment at high altitude, has devastating effects on the injured brain tissue. Conversely, increasing brain oxygenation, by the use of hyperbaric oxygen therapy, can improve brain metabolism and its dependent regenerative processes.

HYSTOMORPHOLOGIC CHANGES IN INJURED MENISCI IN CHILDREN

Directory of Open Access Journals (Sweden)

V. B. Bogatov

2010-01-01

Full Text Available The purpose of the work was studying histological changes in the injured menisci in children. The histological evaluation of injured menisci received during arthroscopy was performed. The prescription of injury varied from several days till 3 years. It was shown that injured fragment of the meniscus is viable up to 3 months since trauma. It was also obvious that active migration of the meniscus cells occur in the injured fragment and microvessels are seen in 50% of the meniscus tissues.

Injured athletes' perceptions about social support.

Science.gov (United States)

Clement, Damien; Shannon, Vanessa R

2011-11-01

According to the buffering hypothesis, social support moderates the harmful effects of stress and, in turn, indirectly affects injured athletes' health and well-being. Previous research suggests that perceptions of social support influence athletes' psychological reactions, as well as their rehabilitation adherence, but additional research in this area is warranted. To examine injured athletes' perceptions regarding satisfaction, availability, and contribution for each of the 8 types of social support. Descriptive. Mid-Atlantic Division II and III institutions. 49 injured athletes. Social support was assessed using a modified version of the Social Support Survey. Injured athletes were significantly more satisfied with social support provided by athletic trainers (ATCs) than that provided by coaches and teammates. In addition, injured athletes reported that social support provided by ATCs contributed significantly more to their overall well-being. Athletes reported several significant differences regarding satisfaction and contribution to well-being among the 8 different types of social support. Injury, an unavoidable part of sport, is often accompanied by negative psychological reactions. This reaction may have a negative influence on an athlete's experience of injury and rehabilitation. Findings suggest that perceptions of social support provided by ATCs have the greatest influence on injured athletes' rehabilitation and well-being.

[Description of the severely injured in the DRG system: is treatment of the severely injured still affordable?].

Science.gov (United States)

Mahlke, L; Lefering, R; Siebert, H; Windolf, J; Roeder, N; Franz, D

2013-11-01

Due to the heterogeneity of severely injured patients (multiple trauma) it is difficult to assign them to homogeneic diagnosis-related groups (DRG). In recent years this has led to a systematic underfunding in the German reimbursement system (G-DRG) for cases of multiply injured patients. This project aimed to improve the reimbursement by modifying the case allocation algorithms of multiply injured patients within the G-DRG system. A retrospective analysis of standardized G-DRG data according to §21 of the Hospital Reimbursement Act (§ 21 KHEntgG) including case-related cost data from 3,362 critically injured patients from 2007 and 2008 from 10 university hospitals and 7 large municipal hospitals was carried out. For 1,241 cases complementary detailed information was available from the trauma registry of the German Trauma Society to monitor the case allocation of multiply injured patients within the G-DRG system. Analysis of coding and grouping, performance of case allocation and the homogeneity of costs in the G-DRG versions 2008-2012 was carried out. The results showed systematic underfunding of trauma patients in the G-DRG version 2008 but adequate cost covering in the majority of cases with the G-DRG versions 2011 and 2012. Cost coverage was foundfor multiply injured patients from the clinical viewpoint who were identified as multiple trauma by the G-DRG system. Some of the overfunded trauma patients had high intensive care costs. Also there was underfunding for multiple injured patients not identified as such in the G-DRG system. Specific modifications of the G-DRG allocation structures could increase the appropriateness of reimbursement of multiply injured patients. Data-based analysis is an essential prerequisite for a constructive development of the G-DRG system and a necessary tool for the active participation of medical specialist societies.

Centralized rehabilitation after servere traumatic brain injury

DEFF Research Database (Denmark)

Engberg, Aase Worså; Liebach, Annette; Nordenbo, Annette Mosbæk

2006-01-01

OBJECTIVES: To present results from the first 3 years of centralized subacute rehabilitation after very severe traumatic brain injury (TBI), and to compare results of centralized versus decentralized rehabilitation. MATERIAL AND METHODS: Prospectively, the most severely injured group of adults from...... post-trauma was 0.29, and at 1 year 0.055 per 100,000 population. By comparison of 39 patients from the centralized unit injured in 2000-2003 with 21 patients injured in 1982, 1987 or 1992 and with similar PTA- and age distributions and male/female ratio, Glasgow Outcome Scale score at discharge...

The role of chemotherapy in brain metastases

International Nuclear Information System (INIS)

Ohori, Hisatsugu; Takahashi, Shin; Ishioka, Chikashi

2007-01-01

Brain metastases are the most common intracranial tumors and their incidence is increasing. Untreated brain metastases have a very poor prognosis with a median survival of 1-2 months. Despite the use of surgery and radiotherapy including whole-brain radiation and stereotactic radiosurgery to locally control brain metastases, survival times for those patients has not improved. Although chemotherapy plays a limited role in the treatment of brain metastases, metastases from lung or breast cancer are often well-controlled by chemotherapy. Accumulating evidence suggest that brain metastases are equally sensitive to chemotherapy as are metastases elsewhere in the body in particular chemotherapy-naive cases. Finally, since nearly a half of patients with brain metastases die from progression of systemic disease, control of systemic disease as well as intracranial disease are both important. (author)

The role of resilience in the recovery of the burn-injured patient: an integrative review

Directory of Open Access Journals (Sweden)

Kornhaber R

2016-05-01

Full Text Available R Kornhaber,1 H Bridgman,2 L McLean,3–6 J Vandervord7 1School of Health Sciences, Faculty of Health, University of Tasmania, Hobart, TAS, 2Centre for Rural Health, School of Health Sciences, Faculty of Health, University of Tasmania, Hobart, TAS, 3Brain and Mind Centre, 4Westmead Psychotherapy Program, Discipline of Psychiatry, Sydney Medical School, University of Sydney, Sydney, NSW, 5Sydney West and Greater Southern Psychiatry Training Network, Cumberland Hospital, Western Sydney Local Health District, Sydney, NSW, 6Consultation-Liaison Psychiatry, Royal North Shore Hospital, Sydney, NSW, 7Severe Burns Injury Unit, Royal North Shore Hospital, St Leonards, NSW, Australia Abstract: Severe burn injuries are catastrophic life events resulting in significant physical and psychological effects. With long periods of hospitalization and rehabilitation, burn survivors encounter many issues, including an altered body image and loss of function and independence that subsequently influence quality of life and the family unit. Consequently, resilience has been identified as a fundamental concept that facilitates the adaptability required to navigate the lengthy and complex recovery process. However, over time, the notion of resilience has shifted from a static, innate trait to a fluid and multidimensional concept. Here, we review the evidence surrounding the role of resilience in the recovery of burn injury. This integrative review was based on a systematic search of five electronic databases. Of the 89 articles identified, ten primary research papers met the inclusion criteria. Three key themes were identified encompassing relational strengths, positive coping, and the resistance to trauma symptoms that are fundamental constructs associated with developing and sustaining resilience that resonate with the broader literature on burn recovery. However, limited evidence is currently available within the burns context. While resilience appears to be a vital

Facial Expression Recognition for Traumatic Brain Injured Patients

DEFF Research Database (Denmark)

Ilyas, Chaudhary Muhammad Aqdus; Nasrollahi, Kamal; Moeslund, Thomas B.

2018-01-01

In this paper, we investigate the issues associated with facial expression recognition of Traumatic Brain Insured (TBI) patients in a realistic scenario. These patients have restricted or limited muscle movements with reduced facial expressions along with non-cooperative behavior, impaired reason...

Can PRP effectively treat injured tendons?

Science.gov (United States)

Wang, James H-C

2014-01-01

PRP is widely used to treat tendon and other tissue injuries in orthopaedics and sports medicine; however, the efficacy of PRP treatment on injured tendons is highly controversial. In this commentary, I reason that there are many PRP- and patient-related factors that influence the outcomes of PRP treatment on injured tendons. Therefore, more basic science studies are needed to understand the mechanism of PRP on injured tendons. Finally, I suggest that better understanding of the PRP action mechanism will lead to better use of PRP for the effective treatment of tendon injuries in clinics.

Optimization of the standards clinico-neurology and beam diagnostics of an easy brain injury

International Nuclear Information System (INIS)

Vakulenko, I.P.; Semisalov, S.Ya.; Sajko, D.Yu.

2003-01-01

16825 cases of a brain injury (BI) at the persons are investigated is more senior than 14 years. Axial computer topography (ACT) at concussion of a head brain was made 1/3 injureds. The careful analysis clinico-neuralgic symptoms allows to optimize purpose the ACT at easy BI, that not only improves quality of diagnostics, but in the certain degree normalizes beam loading on the injureds

Role of Non-neuronal Cells in Tauopathies After Brain Injury

Science.gov (United States)

2017-09-01

AWARD NUMBER: W81XWH-15-1-0422 TITLE: Role of Nonneuronal Cells in Tauopathies After Brain Injury PRINCIPAL INVESTIGATOR: Sally A. Frautschy...AND SUBTITLE 5a. CONTRACT NUMBER Role of Non-neuronal Cells in Tauopathies After Brain Injury 5b. GRANT NUMBER W81XWH-15-1-0422 5c. PROGRAM...traumatic brain injury (TBI), specific inflammatory factors (complement proteins) elevated during long asymptomatic prodromal period are responsible

A starring role for microglia in brain sex differences.

Science.gov (United States)

Lenz, Kathryn M; McCarthy, Margaret M

2015-06-01

Microglia, the resident innate immune cells in the brain, have long been understood to be crucial to maintenance in the nervous system, by clearing debris, monitoring for infiltration of infectious agents, and mediating the brain's inflammatory and repair response to traumatic injury, stroke, or neurodegeneration. A wave of new research has shown that microglia are also active players in many basic processes in the healthy brain, including cell proliferation, synaptic connectivity, and physiology. Microglia, both in their capacity as phagocytic cells and via secretion of many neuroactive molecules, including cytokines and growth factors, play a central role in early brain development, including sexual differentiation of the brain. In this review, we present the vast roles microglia play in normal brain development and how perturbations in the normal neuroimmune environment during development may contribute to the etiology of brain-based disorders. There are notable differences between microglia and neuroimmune signaling in the male and female brain throughout the life span, and these differences may contribute to the vast differences in the incidence of neuropsychiatric and neurological disorders between males and females. © The Author(s) 2014.

Neuroimaging of the Injured Pediatric Brain: Methods and New Lessons.

Science.gov (United States)

Dennis, Emily L; Babikian, Talin; Giza, Christopher C; Thompson, Paul M; Asarnow, Robert F

2018-02-01

Traumatic brain injury (TBI) is a significant public health problem in the United States, especially for children and adolescents. Current epidemiological data estimate over 600,000 patients younger than 20 years are treated for TBI in emergency rooms annually. While many patients experience a full recovery, for others there can be long-lasting cognitive, neurological, psychological, and behavioral disruptions. TBI in youth can disrupt ongoing brain development and create added family stress during a formative period. The neuroimaging methods used to assess brain injury improve each year, providing researchers a more detailed characterization of the injury and recovery process. In this review, we cover current imaging methods used to quantify brain disruption post-injury, including structural magnetic resonance imaging (MRI), diffusion MRI, functional MRI, resting state fMRI, and magnetic resonance spectroscopy (MRS), with brief coverage of other methods, including electroencephalography (EEG), single-photon emission computed tomography (SPECT), and positron emission tomography (PET). We include studies focusing on pediatric moderate-severe TBI from 2 months post-injury and beyond. While the morbidity of pediatric TBI is considerable, continuing advances in imaging methods have the potential to identify new treatment targets that can lead to significant improvements in outcome.

Marrow stromal cells administrated intracisternally to rats after traumatic brain injury migrate into the brain and improve neurological function

Institute of Scientific and Technical Information of China (English)

胡德志; 周良辅; 朱剑虹

2004-01-01

@@ Marrow stromal cells(MSCs) have been reported to transplant into injured brain via intravenous or intraarterial or direct intracerebral administration.1-3 In the present study, we observed that MSCs migrated into the brain, survived and diffeneriated into neural cells after they were injected into the cisterna magna of rats, and that the behavior of the rats after traumatic brain injury (TBI) was improved.

Sugar for the brain: the role of glucose in physiological and pathological brain function.

Science.gov (United States)

Mergenthaler, Philipp; Lindauer, Ute; Dienel, Gerald A; Meisel, Andreas

2013-10-01

The mammalian brain depends upon glucose as its main source of energy, and tight regulation of glucose metabolism is critical for brain physiology. Consistent with its critical role for physiological brain function, disruption of normal glucose metabolism as well as its interdependence with cell death pathways forms the pathophysiological basis for many brain disorders. Here, we review recent advances in understanding how glucose metabolism sustains basic brain physiology. We synthesize these findings to form a comprehensive picture of the cooperation required between different systems and cell types, and the specific breakdowns in this cooperation that lead to disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

The indispensable roles of microglia and astrocytes during brain development

NARCIS (Netherlands)

Reemst, Kitty; Noctor, Stephen C.; Lucassen, Paul J.; Hol, Elly M.

2016-01-01

Glia are essential for brain functioning during development and in the adult brain. Here, we discuss the various roles of both microglia and astrocytes, and their interactions during brain development. Although both cells are fundamentally different in origin and function, they often affect the same

The Indispensable Roles of Microglia and Astrocytes during Brain Development

NARCIS (Netherlands)

Reemst, K.; Noctor, S.C.; Lucassen, P.J.; Hol, E.M.

2016-01-01

Glia are essential for brain functioning during development and in the adult brain. Here, we discuss the various roles of both microglia and astrocytes, and their interactions during brain development. Although both cells are fundamentally different in origin and function, they often affect the same

Astrocyte oxidative metabolism and metabolite trafficking after fluid percussion brain injury in adult rats.

Science.gov (United States)

Bartnik-Olson, Brenda L; Oyoyo, Udochukwu; Hovda, David A; Sutton, Richard L

2010-12-01

Despite various lines of evidence pointing to the compartmentation of metabolism within the brain, few studies have reported the effect of a traumatic brain injury (TBI) on neuronal and astrocyte compartments and/or metabolic trafficking between these cells. In this study we used ex vivo ¹³C NMR spectroscopy following an infusion of [1-¹³C] glucose and [1,2-¹³C₂] acetate to study oxidative metabolism in neurons and astrocytes of sham-operated and fluid percussion brain injured (FPI) rats at 1, 5, and 14 days post-surgery. FPI resulted in a decrease in the ¹³C glucose enrichment of glutamate in neurons in the injured hemisphere at day 1. In contrast, enrichment of glutamine in astrocytes from acetate was not significantly decreased at day 1. At day 5 the ¹³C enrichment of glutamate and glutamine from glucose in the injured hemisphere of FPI rats did not differ from sham levels, but glutamine derived from acetate metabolism in astrocytes was significantly increased. The ¹³C glucose enrichment of the C3 position of glutamate (C3) in neurons was significantly decreased ipsilateral to FPI at day 14, whereas the enrichment of glutamine in astrocytes had returned to sham levels at this time point. These findings indicate that the oxidative metabolism of glucose is reduced to a greater extent in neurons compared to astrocytes following a FPI. The increased utilization of acetate to synthesize glutamine, and the acetate enrichment of glutamate via the glutamate-glutamine cycle, suggests an integral protective role for astrocytes in maintaining metabolic function following TBI-induced impairments in glucose metabolism.

The nature and impact of stigma towards injured workers.

Science.gov (United States)

Kirsh, Bonnie; Slack, Tesha; King, Carole Anne

2012-06-01

Many injured workers experience high levels of stigma and discrimination, which compound their physical injuries and cause social and psychological harm. Despite a growing awareness of the prevalence of such stigma, there is little research that focuses on the sources, nature and consequences of stigma with respect to the lives of injured workers. The purpose of this paper is to advance knowledge related to stigma towards injured workers, specifically to explain the nature and processes of stigma and their influence on injured workers' lives. Using a constructivist grounded theory approach, data from focus groups (n = 28 participants) and individual interviews (n = 18) were analyzed to discern how stigma is exhibited and perpetuated, and its impact on the lives of injured workers. The study culminated in a preliminary theoretical framework that delineates the key components of the manifestations and impacts of stigma that includes stereotypes, unethical practices and maltreatment negatively affecting work, relationships and the mental health of injured workers. The development of sound conceptualizations in this area can advance our understanding of stigma processes and provide a framework for anti-stigma efforts. The findings have implications for public education, workplace interventions and services for injured workers.

Increased Brain Perfusion Persists over the First Month of Life in Term Asphyxiated Newborns Treated with Hypothermia: Does it Reflect Activated Angiogenesis?

Science.gov (United States)

Shaikh, Henna; Lechpammer, Mirna; Jensen, Frances E; Warfield, Simon K; Hansen, Anne H; Kosaras, Bela; Shevell, Michael; Wintermark, Pia

2015-06-01

Many asphyxiated newborns still develop brain injury despite hypothermia therapy. The development of brain injury in these newborns has been related partly to brain perfusion abnormalities. The purposes of this study were to assess brain hyperperfusion over the first month of life in term asphyxiated newborns and to search for some histopathological clues indicating whether this hyperperfusion may be related to activated angiogenesis following asphyxia. In this prospective cohort study, regional cerebral blood flow was measured in term asphyxiated newborns treated with hypothermia around day 10 of life and around 1 month of life using magnetic resonance imaging (MRI) and arterial spin labeling. A total of 32 MRI scans were obtained from 24 term newborns. Asphyxiated newborns treated with hypothermia displayed an increased cerebral blood flow in the injured brain areas around day 10 of life and up to 1 month of life. In addition, we looked at the histopathological clues in a human asphyxiated newborn and in a rat model of neonatal encephalopathy. Vascular endothelial growth factor (VEGF) was expressed in the injured brain of an asphyxiated newborn treated with hypothermia in the first days of life and of rat pups 24-48 h after the hypoxic-ischemic event, and the endothelial cell count increased in the injured cortex of the pups 7 and 11 days after hypoxia-ischemia. Our data showed that the hyperperfusion measured by imaging persisted in the injured areas up to 1 month of life and that angiogenesis was activated in the injured brain of asphyxiated newborns.

[Roles of Aquaporins in Brain Disorders].

Science.gov (United States)

Yasui, Masato

2015-06-01

Aquaporin (AQP) is a water channel protein that is expressed in the cell membranes. AQPs are related to several kinds of human diseases such as cataract. In the mammalian central nervous system (CNS), AQP4 is specifically expressed in the astrocyte membranes lining the perivascular and periventricular structures. AQP4 plays a role in the development of brain edema associated with certain brain disorders. Neuromyelitis optica (NMO) is a demyelinating disorder, and patients with NMO develop autoimmune antibodies against AQP4 in their serum. Therefore, AQP4 is involved in NMO pathogenesis. A new concept referred to as "glymphatic pathway" has been recently proposed to explain the lymphatic system in the CNS. Dysfunction of the "glymphatic pathway" may cause several neurodegenerative diseases and mood disorders. Importantly, AQP4 may play a role in the "glymphatic pathway". Further investigation of AQP4 in CNS disorders is necessary, and a new drug against AQP4 is expected.

Behavior Management for Children and Adolescents with Acquired Brain Injury

Science.gov (United States)

Slifer, Keith J.; Amari, Adrianna

2009-01-01

Behavioral problems such as disinhibition, irritability, restlessness, distractibility, and aggression are common after acquired brain injury (ABI). The persistence and severity of these problems impair the brain-injured individual's reintegration into family, school, and community life. Since the early 1980s, behavior analysis and therapy have…

Evaluation of socioeconomic factors in injured children at Mousavi and Valiasr hospitals of Zanjan

Directory of Open Access Journals (Sweden)

Maryam Hasaniha

2016-03-01

Full Text Available Background and Objective: Injury is one of the causes of morbidity and mortality that deprives the injured individuals of a normal life but also imposes high emotional and financial costs for the patients and their family. This study was done in order to determine the socioeconomic factors in injured children at Mousavi and Valiasr hospitals of Zanjan.Materials and Methods: In this cross-sectional study 650 injured children under 15 who referred to Mousavi and Valiasr hospitals of zanjan were randomly selected. Using a questionnaire, information on demographic and socioeconomic factors including sex, age, and type of injury, parents' age, occupation and salary were gathered. Data was analyzed using measure of central tendency, frequency tables and Chi-Square Test.Results: From 650 injured children, %61.5 were boys and %38.5 were girls. The mean (SD age of these children was 7.8 (4.3. Three hundred eighty five of the children (%59.2 were urban and 265 (%40.8 were rural. Most of injured children had a father who was worker or a mother who was housewife. The level of education of parents was low in most cases. Furthermore, the frequency of injuries in children had a significant association with family income and socioeconomic factors.Conclusion: The results of this study indicate that carrying out prevention programs for students and parents, especially families of low socioeconomic status has a major role in reducing injury risk factors from the children's living environment.  

Sex-related differences in effects of progesterone following neonatal hypoxic brain injury.

Science.gov (United States)

Peterson, Bethany L; Won, Soonmi; Geddes, Rastafa I; Sayeed, Iqbal; Stein, Donald G

2015-06-01

There is no satisfactory therapeutic intervention for neonatal hypoxic-ischemic (HI) encephalopathy. Progesterone is known to be effective in treating traumatic brain injury in adult animals but its effects in neonatal brains have not been reported. Brain injuries were induced by a unilateral common carotid artery ligation plus hypoxia exposure. Progesterone was administered immediately after hypoxia and daily for 5 days at 8 mg/kg, followed by a tapered dose for two days. At six weeks post-injury, lesion size and inflammatory factors were evaluated. Progesterone-treated, HI-injured male animals, but not females, showed significant long-term tissue protection compared to vehicle, suggesting an important sex difference in neuroprotection. Progesterone-treated, HI-injured male rats had fewer activated microglia in the cortex and hippocampus compared to controls. The rats were tested for neurological reflexes, motor asymmetry, and cognitive performance at multiple time points. The injured animals exhibited few detectable motor deficits, suggesting a high level of age- and injury-related neuroplasticity. There were substantial sex differences on several behavioral tests, indicating that immature males and females should be analyzed separately. Progesterone-treated animals showed modest beneficial effects in both sexes compared to vehicle-treated injured animals. Sham animals given progesterone did not behave differently from vehicle-treated sham animals on any measures. Copyright © 2015 Elsevier B.V. All rights reserved.

Polymorphonuclear neutrophil in brain parenchyma after experimental intracerebral hemorrhage.

Science.gov (United States)

Zhao, Xiurong; Sun, Guanghua; Zhang, Han; Ting, Shun-Ming; Song, Shen; Gonzales, Nicole; Aronowski, Jaroslaw

2014-10-01

Polymorphonuclear neutrophils (PMNs) infiltration into brain parenchyma after cerebrovascular accidents is viewed as a key component of secondary brain injury. Interestingly, a recent study of ischemic stroke suggests that after ischemic stroke, PMNs do not enter brain parenchyma and as such may cause no harm to the brain. Thus, the present study was designed to determine PMNs' behavior after intracerebral hemorrhage (ICH). Using the autologous blood injection model of ICH in rats and immunohistochemistry for PMNs and vascular components, we evaluated the temporal and spatial PMNs distribution in the ICH-affected brain. We found that, similar to ischemia, there is a robust increase in presence of PMNs in the ICH-injured tissue that lasts for at least 1 to 2 weeks. However, in contrast to what was suggested for ischemia, besides PMNs that stay in association with the vasculature, after ICH, we found abundance of intraparenchymal PMNs (with no obvious association with vessels) in the ICH core and hematoma border, especially between 1 and 7 days after the ictus. Interestingly, the increased presence of intraparenchymal PMNs after ICH coincided with the massive loss of microvascular integrity, suggesting vascular disruption as a potential cause of PMNs presence in the brain parenchyma. Our study indicates that in contrast to ischemic stroke, after ICH, PMNs target not only vascular compartment but also brain parenchyma in the affected brain. As such, it is possible that the pathogenic role and therapeutic implications of targeting PMNs after ICH could be different from these after ischemic stroke. Our work suggests the needs for more studies addressing the role of PMNs in ICH.

Sialic acid accelerates the electrophoretic velocity of injured dorsal root ganglion neurons

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Chen-xu Li

2015-01-01

Full Text Available Peripheral nerve injury has been shown to result in ectopic spontaneous discharges on soma and injured sites of sensory neurons, thereby inducing neuropathic pain. With the increase of membrane proteins on soma and injured site neurons, the negatively charged sialic acids bind to the external domains of membrane proteins, resulting in an increase of this charge. We therefore speculate that the electrophoretic velocity of injured neurons may be faster than non-injured neurons. The present study established rat models of neuropathic pain via chronic constriction injury. Results of the cell electrophoresis test revealed that the electrophoretic velocity of injured neuronal cells was faster than that of non-injured (control cells. We then treated cells with divalent cations of Ca 2+ and organic compounds with positive charges, polylysine to counteract the negatively charged sialic acids, or neuraminidase to specifically remove sialic acids from the membrane surface of injured neurons. All three treatments significantly reduced the electrophoretic velocity of injured neuronal cells. These findings suggest that enhanced sialic acids on injured neurons may accelerate the electrophoretic velocity of injured neurons.

The Role of Brain-Reactive Autoantibodies in Brain Pathology and Cognitive Impairment

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Simone Mader

2017-09-01

Full Text Available Antibodies to different brain proteins have been recently found to be associated with an increasing number of different autoimmune diseases. They need to penetrate the blood–brain barrier (BBB in order to bind antigens within the central nervous system (CNS. They can target either neuronal or non-neuronal antigen and result in damage either by themselves or in synergy with other inflammatory mediators. Antibodies can lead to acute brain pathology, which may be reversible; alternatively, they may trigger irreversible damage that persists even though the antibodies are no longer present. In this review, we will describe two different autoimmune conditions and the role of their antibodies in causing brain pathology. In systemic lupus erythematosus (SLE, patients can have double stranded DNA antibodies that cross react with the neuronal N-methyl-d-aspartate receptor (NMDAR, which have been recently linked to neurocognitive dysfunction. In neuromyelitis optica (NMO, antibodies to astrocytic aquaporin-4 (AQP4 are diagnostic of disease. There is emerging evidence that pathogenic T cells also play an important role for the disease pathogenesis in NMO since they infiltrate in the CNS. In order to enable appropriate and less invasive treatment for antibody-mediated diseases, we need to understand the mechanisms of antibody-mediated pathology, the acute and chronic effects of antibody exposure, if the antibodies are produced intrathecally or systemically, their target antigen, and what triggers their production. Emerging data also show that in utero exposure to some brain-reactive antibodies, such as those found in SLE, can cause neurodevelopmental impairment since they can penetrate the embryonic BBB. If the antibody exposure occurs at a critical time of development, this can result in irreversible damage of the offspring that persists throughout adulthood.

Opioid Abuse After Traumatic Brain Injury: Evaluation Using Rodet Models

Science.gov (United States)

2014-07-01

pressing behavior was less likely to occur in brain-injured subjects following both exposure to oxycodone-associated cues as well as priming with a...pain medications. There is significant overlap in anatomical brain regions involved in reward pathways associated with addiction and the brain regions...commonly damaged in TBI which suggests that TBI could alter the reward circuitry, thereby increasing the likelihood of opioid abuse and addiction

Family and home in cognitive rehabilitation after brain injury

DEFF Research Database (Denmark)

Wulf-Andersen, Camilla; Mogensen, Jesper

2017-01-01

Acquired brain injury (ABI) severely affects both the injured patient and her/his family. This fact alone calls for a therapeutic approach addressing not only the individual victim of ABI but also her/his family. Additionally, the optimal outcome of posttraumatic cognitive rehabilitation may...... be best obtained by supplementing the institution-based cognitive training with home-based training. Moving cognitive training and other therapeutic interventions into the home environment does, however, constitute an additional challenge to the family structure and psychological wellbeing of all family...... members. We presently argue in favour of an increased utilization of family-based intervention programs for the families of brain injured patients – in general and especially in case of utilization of home-based rehabilitative training....

The multiple roles of Fatty Acid Handling Proteins in brain

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Valentine SF Moullé

2012-09-01

Full Text Available Lipids are essential components of a living organism as energy source but also as constituent of the membrane lipid bilayer. In addition fatty acid (FA derivatives interact with many signaling pathways. FAs have amphipathic properties and therefore require being associated to protein for both transport and intracellular trafficking. Here we will focus on several fatty acid handling proteins, among which the fatty acid translocase/CD36 (FAT/CD36, members of fatty acid transport proteins (FATPs, and lipid chaperones fatty acid-binding proteins (FABPs. A decade of extensive studies has helped decipher the mechanism of action of these proteins in peripheral tissue with high lipid metabolism. However, considerably less information is available regarding their role in the brain, despite the high lipid content of this tissue. This review will primarily focus on the recent studies that have highlighted the crucial role of lipid handling proteins in brain FA transport, neuronal differentiation and development, cognitive processes and brain diseases. Finally a special focus will be made on the recent studies that have revealed the role of FAT/CD36 in brain lipid sensing and nervous control of energy balance.

Centralized rehabilitation after servere traumatic brain injury

DEFF Research Database (Denmark)

Engberg, Aase Worså; Liebach, Annette; Nordenbo, Annette Mosbæk

2006-01-01

OBJECTIVES: To present results from the first 3 years of centralized subacute rehabilitation after very severe traumatic brain injury (TBI), and to compare results of centralized versus decentralized rehabilitation. MATERIAL AND METHODS: Prospectively, the most severely injured group of adults fr...

Respiratory mechanics in brain injury: A review

OpenAIRE

Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

2016-01-01

Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case ...

Nursing care of the thermally injured patient.

Science.gov (United States)

Elfving, U

1980-01-01

Team work is required in the treatment of the thermally injured patient--nursing staff being part of the team. The nurses are with the patient for 24 hours a day and they have to understand the objectives of all other members of the team involved in the treatment as well as thoroughly mastering their own work. For the nursing staff the care of the thermally injured patient is a challenge. The work demands strong motivation and interest--it includes at times painful treatment, isolation and also constant alertness. It is important that the nursing staff is given continuous training so that they are able to give the required care efficiently and to keep up active interest. Practical work is the best way of getting aquainted with the complex forms of treatment of the thermally injured patient. It also lessens the fear of a badly burned patient. Nursing care of the thermally injured patient consists of good basic care, local attention and active observation. The basic care consists of basic hygiene, diet, observation of the patient's psychological condition, giving emotional support, encouraging initiative physiotherapy and postural treatment.

Evaluation of the thin agar layer method for the recovery of pressure-injured and heat-injured Listeria monocytogenes.

Science.gov (United States)

Lavieri, Nicolas A; Sebranek, Joseph G; Cordray, Joseph C; Dickson, James S; Jung, Stephanie; Manu, David K; Mendonça, Aubrey F; Brehm-Stecher, Byron F; Stock, Joseph; Stalder, Kenneth J

2014-05-01

A sublethally injured bacterial cell has been defined as a cell that survives a stress such as heating, freezing, acid treatment, or other antimicrobial intervention but can repair the cellular damage exerted by the stressor and later regain its original ability to grow. Consequently, sublethally injured cells are not likely to be included in conventional enumeration procedures, which could result in unrealistically low counts unless efforts are made to encourage recovery of the injured cells before enumeration. The objective of this study was to evaluate the use of the thin agar layer (TAL) method for the recovery of pressure-injured and heat-injured Listeria monocytogenes in a tryptic soy broth with 0.6% yeast extract system. Pressure injury consisted of treatment of a culture of mixed L. monocytogenes strains with high hydrostatic pressure at 400 or 600 MPa for 1 s, 2 min, 4 min, or 6 min at a process temperature of 12±2 °C. Heat injury consisted of treatment of a culture of mixed L. monocytogenes strains at 60±1 °C for 3, 6, or 9 min. Growth media were tryptic soy agar (TSA) with 0.6% yeast extract, modified Oxford medium (MOX), and TAL, which consisted of a 7-ml layer of TSA overlaid onto solidified MOX. Counts of viable L. monocytogenes on TAL were higher than those on MOX in the heat-injury experiment but not in the pressure-injury experiment. Therefore, the effectiveness of the TAL method may be specific to the type of injury applied to the microorganism and should be investigated in a variety of cellular injury scenarios.

Role of physical and mental training in brain network configuration

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Philip P. Foster

2015-06-01

Full Text Available Continuous remodeling of proteins of excitatory neurons is fine-tuning the scaling and strength of excitatory synapses up or down via regulation of intra-cellular metabolic and regulatory networks of the genome-transcriptome-proteome interface. Alzheimer's disease is a model of energy cost-driven small-world network disorder as the network global efficiency is impaired by the deposition of an informed agent, the amyloid-β, selectively targeting high-degree nodes. In schizophrenia, the interconnectivity and density of rich-club networks are significantly reduced. Training-induced homeostatic synaptogenesis-enhancement produces a reconfiguration of brain networks into greater small-worldness. Creation of synaptic connections in a macro-network, and, at the intra-cellular scale, micro-networks regulate the physiological mechanisms for the preferential attachment of synapses. The strongest molecular relationship of exercise and functional connectivity was identified for brain-derived neurotrophic factor (BDNF. The allele variant, rs7294919, also shows a powerful relationship with the hippocampal volume. How the brain achieves this unique quest of reconfiguration remains a puzzle. What are the underlying mechanisms of synaptogenesis promoting communications brain ↔ muscle and brain ↔ brain in such trainings? What is the respective role of independent mental, physical or combined-mental-physical trainings? Physical practice seems to be playing an instrumental role in the cognitive enhancement (brain ↔ muscle com.. However, mental training, meditation or virtual reality (films, games require only minimal motor activity and cardio-respiratory stimulation. Therefore, other potential paths (brain ↔ brain com. molding brain networks are nonetheless essential. Patients with motor neuron disease/injury (e.g. amyotrophic lateral sclerosis, traumatism also achieve successful cognitive enhancement albeit they may only elicit mental practice

Cobalt-55 positron emission tomography in traumatic brain injury : A pilot study

NARCIS (Netherlands)

Jansen, HML; vanderNaalt, J; vanZomeren, AH; Paans, AMJ; VeenmavanderDuin, L; Hew, JM; Pruim, J; Minderhoud, JM; Korf, J

Traumatic brain injury is usually assessed with the Glasgow coma scale (GCS), CT, or MRI. After such injury, the injured brain tissue is characterised by calcium mediated neuronal damage and inflammation. Positron emission tomography with the isotope cobalt-55 (Go-PET) as a calcium tracer enables

Brain aromatase: roles in reproduction and neuroprotection.

Science.gov (United States)

Roselli, Charles F

2007-01-01

It is well established that aromatization constitutes an essential part of testosterone's signaling pathway in brain and that estrogen metabolites, often together with testosterone, organize and activate masculine neural circuits. This paper summarizes the current understanding regarding the distribution, regulation and function of brain aromatase in mammals. Data from our laboratory are presented that highlight the important function of aromatase in the regulation of androgen feedback sensitivity in non-human primates and the possible role that aromatase plays in determining the brain structure and sexual partner preferences of rams. In addition, new data is presented indicating that the capacity for aromatization in cortical astrocytes is associated with cell survival and may be important for neuroprotection. It is anticipated that a better appreciation of the physiological and pathophysiological functions of aromatase will lead to important clinical insights.

Spreading depolarisations and outcome after traumatic brain injury

DEFF Research Database (Denmark)

Hartings, Jed A; Bullock, M Ross; Okonkwo, David O

2011-01-01

Pathological waves of spreading mass neuronal depolarisation arise repeatedly in injured, but potentially salvageable, grey matter in 50-60% of patients after traumatic brain injury (TBI). We aimed to ascertain whether spreading depolarisations are independently associated with unfavourable...

The iconic memory skills of brain injury survivors and non-brain injured controls after visual scanning training.

Science.gov (United States)

McClure, J T; Browning, R T; Vantrease, C M; Bittle, S T

1994-01-01

Previous research suggests that traumatic brain injury (TBI) results in impairment of iconic memory abilities.We would like to acknowledge the contribution of Jeffrey D. Vantrease, who wrote the software program for the Iconic Memory procedure and measurement. This raises serious implications for brain injury rehabilitation. Most cognitive rehabilitation programs do not include iconic memory training. Instead it is common for cognitive rehabilitation programs to focus on attention and concentration skills, memory skills, and visual scanning skills.This study compared the iconic memory skills of brain-injury survivors and control subjects who all reached criterion levels of visual scanning skills. This involved previous training for the brain-injury survivors using popular visual scanning programs that allowed them to visually scan with response time and accuracy within normal limits. Control subjects required only minimal training to reach normal limits criteria. This comparison allows for the dissociation of visual scanning skills and iconic memory skills.The results are discussed in terms of their implications for cognitive rehabilitation and the relationship between visual scanning training and iconic memory skills.

Diagnostic radiology on multiple injured patients: interdisciplinary management

International Nuclear Information System (INIS)

Linsenmaier, U.; Pfeifer, K.J.; Kanz, K.G.; Mutschler, W.

2001-01-01

The presence of a radiologist within the admitting area of an emergency department and his capability as a member of the trauma team have a major impact on the role of diagnostic radiology in trauma care. The knowledge of clinical decision criteria, algorithms, and standards of patient care are essential for the acceptance within a trauma team. We present an interdisciplinary management concept of diagnostic radiology for trauma patients, which comprises basic diagnosis, organ diagnosis, radiological ABC, and algorithms of early clinical care. It is the result of a prospective study comprising over 2000 documented multiple injured patients. The radiologist on a trauma team should support trauma surgery and anesthesia in diagnostic and clinical work-up. The radiological ABC provides a structured approach for diagnostic imaging in all steps of the early clinical care of the multiple injured patient. Radiological ABC requires a reevaluation in cases of equivocal findings or difficulties in the clinical course. Direct communication of radiological findings with the trauma team enables quick clinical decisions. In addition, the radiologist can priority-oriented influence the therapy by using interventional procedures. The clinical radiologist is an active member of the interdisciplinary trauma team, not only providing diagnostic imaging but also participating in clinical decisions. (orig.) [de

Valsartan attenuates intimal hyperplasia in balloon-injured rat aortic arteries through modulating the angiotensin-converting enzyme 2-angiotensin-(1-7)-Mas receptor axis.

Science.gov (United States)

Li, Yonghong; Cai, Shanglang; Wang, Qixin; Zhou, Jingwei; Hou, Bo; Yu, Haichu; Ge, Zhiming; Guan, Renyan; Liu, Xu

2016-05-15

The role of the Mas receptor in the activity of valsartan against intimal hyperplasia is unclear. Herein, we investigated the role of the angiotensin-converting enzyme 2 (ACE2)-angiotensin-(1-7)-Mas receptor axis on the activity of valsartan against intimal hyperplasiain balloon-injured rat aortic arteries. Wistar rats were randomized equally into the sham control group, injured group, and injured plus valsartan (20 mg/kg/d)-treated group. Valsartan significantly attenuated the vascular smooth muscle cell proliferation and intimal and medial thickening on days 14 and 28 after injury. The angiotensin-(1-7) levels as well as ACE2 and Mas receptor mRNA/protein expression were significantly decreased in the injured rats, compared to the uninjured rats; meanwhile, the angiotensin II level as well as the ACE and AT1 receptor mRNA/protein expression were increased (all P valsartan significantly increased the angiotensin-(1-7) levels as well as ACE2 and Mas receptor mRNA/protein expression but decreased the angiotensin II level, ACE and AT1 receptor mRNA/protein expression, as well as the p-ERK protein expression, compared to the injured group (all P valsartan attenuates neointimal hyperplasiain balloon-injured rat aortic arteries through activation of the ACE2-angiotensin-(1-7)-Mas axis as well as inhibition of the ACE-angiotensin II-AT1 and p-ERK pathways. Copyright © 2016 Elsevier Inc. All rights reserved.

Neuroprotective effects of collagen matrix in rats after traumatic brain injury.

Science.gov (United States)

Shin, Samuel S; Grandhi, Ramesh; Henchir, Jeremy; Yan, Hong Q; Badylak, Stephen F; Dixon, C Edward

2015-01-01

In previous studies, collagen based matrices have been implanted into the site of lesion in different models of brain injury. We hypothesized that semisynthetic collagen matrix can have neuroprotective function in the setting of traumatic brain injury. Rats were subjected to sham injury or controlled cortical impact. They either received extracellular matrix graft (DuraGen) over the injury site or did not receive any graft and underwent beam balance/beam walking test at post injury days 1-5 and Morris water maze at post injury days 14-18. Animals were sacrificed at day 18 for tissue analysis. Collagen matrix implantation in injured rats did not affect motor function (beam balance test: p = 0.627, beam walking test: p = 0.921). However, injured group with collagen matrix had significantly better spatial memory acquisition (p < 0.05). There was a significant reduction in lesion volume, as well as neuronal loss in CA1 (p < 0.001) and CA3 (p < 0.05) regions of the hippocampus in injured group with collagen matrix (p < 0.05). Collagen matrix reduces contusional lesion volume, neuronal loss, and cognitive deficit after traumatic brain injury. Further studies are needed to demonstrate the mechanisms of neuroprotection by collagen matrix.

Developmental origins of brain disorders: roles for dopamine

Directory of Open Access Journals (Sweden)

Kelli M Money

2013-12-01

Full Text Available Neurotransmitters and neuromodulators, such as dopamine, participate in a wide range of behavioral and cognitive functions in the adult brain, including movement, cognition, and reward. Dopamine-mediated signaling plays a fundamental neurodevelopmental role in forebrain differentiation and circuit formation. These developmental effects, such as modulation of neuronal migration and dendritic growth, occur before synaptogenesis and demonstrate novel roles for dopaminergic signaling beyond neuromodulation at the synapse. Pharmacologic and genetic disruptions demonstrate that these effects are brain region- and receptor subtype-specific. For example, the striatum and frontal cortex exhibit abnormal neuronal structure and function following prenatal disruption of dopamine receptor signaling. Alterations in these processes are implicated in the pathophysiology of neuropsychiatric disorders, and emerging studies of neurodevelopmental disruptions may shed light on the pathophysiology of abnormal neuronal circuitry in neuropsychiatric disorders.

Differentiation of different mixed Listeria strains and also acid-injured, heat-injured, and repaired cells of Listeria monocytogenes using fourier transform infrared spectroscopy.

Science.gov (United States)

Nyarko, Esmond; Donnelly, Catherine

2015-03-01

Fourier transform infrared (FT-IR) spectroscopy was used to differentiate mixed strains of Listeria monocytogenes and mixed strains of L. monocytogenes and Listeria innocua. FT-IR spectroscopy was also applied to investigate the hypothesis that heat-injured and acid-injured cells would return to their original physiological integrity following repair. Thin smears of cells on infrared slides were prepared from cultures for mixed strains of L. monocytogenes, mixed strains of L. monocytogenes and L. innocua, and each individual strain. Heat-injured and acid-injured cells were prepared by exposing harvested cells of L. monocytogenes strain R2-764 to a temperature of 56 ± 0.2°C for 10 min or lactic acid at pH 3 for 60 min, respectively. Cellular repair involved incubating aliquots of acid-injured and heat-injured cells separately in Trypticase soy broth supplemented with 0.6% yeast extract for 22 to 24 h; bacterial thin smears on infrared slides were prepared for each treatment. Spectral collection was done using 250 scans at a resolution of 4 cm(-1) in the mid-infrared wavelength region. Application of multivariate discriminant analysis to the wavelength region from 1,800 to 900 cm(-1) separated the individual L. monocytogenes strains. Mixed strains of L. monocytogenes and L. monocytogenes cocultured with L. innocua were successfully differentiated from the individual strains when the discriminant analysis was applied. Different mixed strains of L. monocytogenes were also successfully separated when the discriminant analysis was applied. A data set for injury and repair analysis resulted in the separation of acid-injured, heat-injured, and intact cells; repaired cells clustered closer to intact cells when the discriminant analysis (1,800 to 600 cm(-1)) was applied. FT-IR spectroscopy can be used for the rapid source tracking of L. monocytogenes strains because it can differentiate between different mixed strains and individual strains of the pathogen.

Oxidative burst of circulating neutrophils following traumatic brain injury in human.

Directory of Open Access Journals (Sweden)

Yiliu Liao

Full Text Available Besides secondary injury at the lesional site, Traumatic brain injury (TBI can cause a systemic inflammatory response, which may cause damage to initially unaffected organs and potentially further exacerbate the original injury. Here we investigated plasma levels of important inflammatory mediators, oxidative activity of circulating leukocytes, particularly focusing on neutrophils, from TBI subjects and control subjects with general trauma from 6 hours to 2 weeks following injury, comparing with values from uninjured subjects. We observed increased plasma level of inflammatory cytokines/molecules TNF-α, IL-6 and CRP, dramatically increased circulating leukocyte counts and elevated expression of TNF-α and iNOS in circulating leukocytes from TBI patients, which suggests a systemic inflammatory response following TBI. Our data further showed increased free radical production in leukocyte homogenates and elevated expression of key oxidative enzymes iNOS, COX-2 and NADPH oxidase (gp91(phox in circulating leukocytes, indicating an intense induction of oxidative burst following TBI, which is significantly greater than that in control subjects with general trauma. Furthermore, flow cytometry assay proved neutrophils as the largest population in circulation after TBI and showed significantly up-regulated oxidative activity and suppressed phagocytosis rate for circulating neutrophils following brain trauma. It suggests that the highly activated neutrophils might play an important role in the secondary damage, even outside the injured brain. Taken together, the potent systemic inflammatory response induced by TBI, especially the intensively increase oxidative activity of circulating leukocytes, mainly neutrophils, may lead to a systemic damage, dysfunction/damage of bystander tissues/organs and even further exacerbate secondary local damage. Controlling these pathophysiological processes may be a promising therapeutic strategy and will protect unaffected

Role of palliative radiotherapy in brain metastases

Directory of Open Access Journals (Sweden)

Ramesh S Bilimagga

2009-01-01

Full Text Available Background: Brain metastases are a common manifestation of systemic cancer and exceed primary brain tumors in number and are a significant cause of neurologic problems. They affect 20-40% of all cancer patients. Aggressive management of brain metastases is effective in both symptom palliation and prolonging the life. Radiotherapy has a major role to play in the management of brain metastases. AIM: The aim of the study was to know the outcome of palliative radiotherapy in symptomatic brain metastases in terms of improvement in their performance status. Materials and Methods: This is a retrospective study of 63 patients diagnosed to have brain metastases and treated with palliative whole brain radiotherapy to a dose of 30 Gy in 10 fractions over two weeks between June 1998 and June 2007. Diagnosis was done in most of the cases with computed tomography scan and in a few with magnetic resonance imaging. Improvement in presenting symptoms has been assessed in terms of improvement in their performance status by using the ECOG scale. Results: Fifty-four patients completed the planned treatment. Eight patients received concurrent Temozolamide; 88% of patients had symptom relief at one month follow-up; 39/54 patients had a follow-up of just one to three months. Hence survival could not be assessed in this study. Conclusion: External beam radiotherapy in the dose of 30 Gy over two weeks achieved good palliation in terms improvement in their performance status in 88% of patients. Addition of concurrent and adjuvant Timozolamide may improve the results.

The role of the immune system in central nervous system plasticity after acute injury.

Science.gov (United States)

Peruzzotti-Jametti, Luca; Donegá, Matteo; Giusto, Elena; Mallucci, Giulia; Marchetti, Bianca; Pluchino, Stefano

2014-12-26

Acute brain injuries cause rapid cell death that activates bidirectional crosstalk between the injured brain and the immune system. In the acute phase, the damaged CNS activates resident and circulating immune cells via the local and systemic release of soluble mediators. This early immune activation is necessary to confine the injured tissue and foster the clearance of cellular debris, thus bringing the inflammatory reaction to a close. In the chronic phase, a sustained immune activation has been described in many CNS disorders, and the degree of this prolonged response has variable effects on spontaneous brain regenerative processes. The challenge for treating acute CNS damage is to understand how to optimally engage and modify these immune responses, thus providing new strategies that will compensate for tissue lost to injury. Herein we have reviewed the available information regarding the role and function of the innate and adaptive immune responses in influencing CNS plasticity during the acute and chronic phases of after injury. We have examined how CNS damage evolves along the activation of main cellular and molecular pathways that are associated with intrinsic repair, neuronal functional plasticity and facilitation of tissue reorganization. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Decompressive craniectomy following brain injury: factors important ...

African Journals Online (AJOL)

2010-01-07

Jan 7, 2010 ... Background: Decompressive craniectomy (DC) is often performed as an empirical lifesaving measure to protect the injured brain from the damaging effects of propagating oedema and intracranial hypertension. However, there are no clearly defined indications or specified guidelines for patient selection for ...

Use of a special airbed for transporting injured persons

Energy Technology Data Exchange (ETDEWEB)

Hacker, R

1981-04-01

A description is given of a special airbed for the purpose of transporting injured persons, especially those with injuries to the spinal column. This special airbed moulds itself to the shape of the injured party. (In German)

The Neurological Wake-up Test—A Role in Neurocritical Care Monitoring of Traumatic Brain Injury Patients?

Directory of Open Access Journals (Sweden)

Niklas Marklund

2017-10-01

Full Text Available The most fundamental clinical monitoring tool in traumatic brain injury (TBI patients is the repeated clinical examination. In the severe TBI patient treated by continuous sedation in a neurocritical care (NCC unit, sedation interruption is required to enable a clinical evaluation (named the neurological wake-up test; NWT assessing the level of consciousness, pupillary diameter and reactivity to light, and presence of focal neurological deficits. There is a basic conflict regarding the NWT in the NCC setting; can the clinical information obtained by the NWT justify the risk of inducing a stress response in a severe TBI patient? Furthermore, in the presence of advanced multimodal monitoring and neuroimaging, is the NWT necessary to identify important clinical alterations? In studies of severe TBI patients, the NWT was consistently shown to induce a stress reaction including brief increases in intracranial pressure (ICP and changes in cerebral perfusion pressure (CPP. However, it has not been established whether these short-lived ICP and CPP changes are detrimental to the injured brain. Daily interruption of sedation is associated with a reduced ventilator time, shorter hospital stay and reduced mortality in many studies of general intensive care unit patients, although such clinical benefits have not been firmly established in TBI. To date, there is no consensus on the use of the NWT among NCC units and systematic studies are scarce. Thus, additional studies evaluating the role of the NWT in clinical decision-making are needed. Multimodal NCC monitoring may be an adjunct in assessing in which TBI patients the NWT can be safely performed. At present, the NWT remains the golden standard for clinical monitoring and detection of neurological changes in NCC and could be considered in TBI patients with stable baseline ICP and CPP readings. The focus of the present review is an overview of the existing literature on the role of the NWT as a clinical

Brain Vulnerability to Repeated Blast Overpressure and Polytrauma

Science.gov (United States)

2010-05-28

devoid of any obvious cell loss or injury when assessed using either Nissl or Fluoro Jade stains , they consistently showed widespread fiber degeneration...injured brain after thionine (l) or silver (r) staining . experimental parameters (e.g. driver volume, tube position, Mylar membrane thickness, and type...5. Thionine- (top) and silver- (bottom) stained brain sections following exposure to 126 kPa airblast at the mouth of the tube. From Long et al

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 ...... of biomolecules required for brain repair, thereby stimulating brain plasticity. Pharmacological targeting of the sigma-1 receptor provides new opportunities for stroke treatment beyond the therapeutic window of neuroprotection....

[Decision making and executive function in severe traumatic brain injured patients: validation of a decision-making task and correlated features].

Science.gov (United States)

Wiederkehr, S; Barat, M; Dehail, P; de Sèze, M; Lozes-Boudillon, S; Giroire, J-M

2005-02-01

At the chronic stage, severe traumatic brain injured (TBI) patients experience difficulty in making decisions. Several studies have demonstrated the involvement of the prefrontal cortex, in particular the orbitofrontal region, in decision-making. The aim of the present study was to validate a decision-making task in this population and to ascertain whether the components of their dysexecutive syndrome may affect their decision-making and lead to difficulties for social rehabilitation. Fifteen TBI patients and 15 controlled subjects matched for age, sex and years of education were assessed by a battery of executive tests (GREFEX) and by the gambling task (GT). The TBI subjects performed significantly worse than the controlled group in five out of six GREFEX tests. The TBI choices are significantly more disadvantageous than the choices of the control group when considering the three last blocks of 20 cards of the GT. The GT total score correlated significantly with execution time of the Stroop interference condition and the Trail Making Task B, as well as with the two measures (correct sequence span and number of crossed boxes) of the double condition of Baddeley's task. We postulate that executive functioning (supervisory attentional system) influence performance in the gambling task through mechanisms of inhibitory control, divided attention and working memory. Thus, this task seems to be determined by multiple factors; the process of decision-making may depend on frontal integrity.

Role of bromocriptine in multi-spectral manifestations of traumatic brain injury

OpenAIRE

Munakomi, Sunil; Bhattarai, Binod; Mohan Kumar, Bijoy

2017-01-01

Purpose: Despite the prevalence and cost of traumatic brain injury related disabilities, there is paucity in the literature on modern approaches to pharmacotherapy. Medications may promote recovery by enhancing some neurological functions without impacting others. Herein we discussed the role of bromocriptine in neurorehabilitation for patients with traumatic brain injury. Methods: A cohort comprising of 36 selective nonsurgical cases of traumatic brain injury in minimally conscious state ...

Postmortem magnetic resonance images of the injured brain: effective evidence in the courtroom.

Science.gov (United States)

Harris, L S

1991-09-01

Magnetic resonance images (MRI) of the whole, formalin-fixed brain produce details of pathologic changes deep within brain substance not apparent on external examination. Photographs of these radiographic images present pathologic features in a black-and-white, 2-dimensional format which has proven particularly effective in court before judge and jury. This pathologist has noted acceptance of such photographs in explaining to jurors the details of his testimony in selected cases where brain trauma resulted in a wrongful death. Penetrating missile wounds and blunt impact injuries are particularly well documented by this method.

Environmental Enrichment, Performance, and Brain Injury in Male and Female Rats

National Research Council Canada - National Science Library

Elliott, Brenda M

2004-01-01

...) and physical enrichment (PE) on the cognitive performance of neurologically intact and brain-injured rats and to determine if there are gender differences in these effects. Measures of basic (i.e...

Metallothioneins are multipurpose neuroprotectants during brain pathology

DEFF Research Database (Denmark)

Penkowa, Milena

2006-01-01

Metallothioneins (MTs) constitute a family of cysteine-rich metalloproteins involved in cytoprotection during pathology. In mammals there are four isoforms (MT-I - IV), of which MT-I and -II (MT-I + II) are the best characterized MT proteins in the brain. Accumulating studies have demonstrated MT......-I overexpression demonstrated the importance of MT-I + II for coping with brain pathology. In addition, exogenous MT-I or MT-II injected intraperitoneally is able to promote similar effects as those of endogenous MT-I + II, which indicates that MT-I + II have both extra- and intracellular actions. In injured brain...

The Potential of Stem Cells in Treatment of Traumatic Brain Injury.

Science.gov (United States)

Weston, Nicole M; Sun, Dong

2018-01-25

Traumatic brain injury (TBI) is a global public health concern, with limited treatment options available. Despite improving survival rate after TBI, treatment is lacking for brain functional recovery and structural repair in clinic. Recent studies have suggested that the mature brain harbors neural stem cells which have regenerative capacity following brain insults. Much progress has been made in preclinical TBI model studies in understanding the behaviors, functions, and regulatory mechanisms of neural stem cells in the injured brain. Different strategies targeting these cell population have been assessed in TBI models. In parallel, cell transplantation strategy using a wide range of stem cells has been explored for TBI treatment in pre-clinical studies and some in clinical trials. This review summarized strategies which have been explored to enhance endogenous neural stem cell-mediated regeneration and recent development in cell transplantation studies for post-TBI brain repair. Thus far, neural regeneration through neural stem cells either by modulating endogenous neural stem cells or by stem cell transplantation has attracted much attention. It is highly speculated that targeting neural stem cells could be a potential strategy to repair and regenerate the injured brain. Neuroprotection and neuroregeneration are major aspects for TBI therapeutic development. With technique advancement, it is hoped that stem cell-based therapy targeting neuroregeneration will be able to translate to clinic in not so far future.

The Role of Glucose Transporters in Brain Disease: Diabetes and Alzheimer’s Disease

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Shah, Kaushik; DeSilva, Shanal; Abbruscato, Thomas

2012-01-01

The occurrence of altered brain glucose metabolism has long been suggested in both diabetes and Alzheimer’s diseases. However, the preceding mechanism to altered glucose metabolism has not been well understood. Glucose enters the brain via glucose transporters primarily present at the blood-brain barrier. Any changes in glucose transporter function and expression dramatically affects brain glucose homeostasis and function. In the brains of both diabetic and Alzheimer’s disease patients, changes in glucose transporter function and expression have been observed, but a possible link between the altered glucose transporter function and disease progress is missing. Future recognition of the role of new glucose transporter isoforms in the brain may provide a better understanding of brain glucose metabolism in normal and disease states. Elucidation of clinical pathological mechanisms related to glucose transport and metabolism may provide common links to the etiology of these two diseases. Considering these facts, in this review we provide a current understanding of the vital roles of a variety of glucose transporters in the normal, diabetic and Alzheimer’s disease brain. PMID:23202918

Role of physical and mental training in brain network configuration.

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Foster, Philip P

2015-01-01

It is hypothesized that the topology of brain networks is constructed by connecting nodes which may be continuously remodeled by appropriate training. Efficiency of physical and/or mental training on the brain relies on the flexibility of networks' architecture molded by local remodeling of proteins and synapses of excitatory neurons producing transformations in network topology. Continuous remodeling of proteins of excitatory neurons is fine-tuning the scaling and strength of excitatory synapses up or down via regulation of intra-cellular metabolic and regulatory networks of the genome-transcriptome-proteome interface. Alzheimer's disease is a model of "energy cost-driven small-world network disorder" with dysfunction of high-energy cost wiring as the network global efficiency is impaired by the deposition of an informed agent, the amyloid-β, selectively targeting high-degree nodes. In schizophrenia, the interconnectivity and density of rich-club networks are significantly reduced. Training-induced homeostatic synaptogenesis-enhancement, presumably via reconfiguration of brain networks into greater small-worldness, appears essential in learning, memory, and executive functions. A macroscopic cartography of creation-removal of synaptic connections in a macro-network, and at the intra-cellular scale, micro-networks regulate the physiological mechanisms for the preferential attachment of synapses. The strongest molecular relationship of exercise and functional connectivity was identified for brain-derived neurotrophic factor (BDNF). The allele variant, rs7294919, also shows a powerful relationship with the hippocampal volume. How the brain achieves this unique quest of reconfiguration remains a puzzle. What are the underlying mechanisms of synaptogenesis promoting communications brain ↔ muscle and brain ↔ brain in such trainings? What is the respective role of independent mental, physical, or combined-mental-physical trainings? Physical practice seems to be

Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury

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Zhou, Hai-xiao; Liu, Zhi-gang; Liu, Xiao-jiao; Chen, Qian-xue

2016-01-01

Transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen (HBO) treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized fluid (2.5–3.0 atm impact force). The injured rats were then administered UC-MSC transplantation via the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function significantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and significantly promotes recovery of neurological functions. PMID:26981097

Umbilical cord-derived mesenchymal stem cell transplantation combined with hyperbaric oxygen treatment for repair of traumatic brain injury

Directory of Open Access Journals (Sweden)

Hai-xiao Zhou

2016-01-01

Full Text Available Transplantation of umbilical cord-derived mesenchymal stem cells (UC-MSCs for repair of traumatic brain injury has been used in the clinic. Hyperbaric oxygen (HBO treatment has long been widely used as an adjunctive therapy for treating traumatic brain injury. UC-MSC transplantation combined with HBO treatment is expected to yield better therapeutic effects on traumatic brain injury. In this study, we established rat models of severe traumatic brain injury by pressurized fluid (2.5-3.0 atm impact force. The injured rats were then administered UC-MSC transplantation via the tail vein in combination with HBO treatment. Compared with monotherapy, aquaporin 4 expression decreased in the injured rat brain, but growth-associated protein-43 expression, calaxon-like structures, and CM-Dil-positive cell number increased. Following combination therapy, however, rat cognitive and neurological function significantly improved. UC-MSC transplantation combined with HBO therapyfor repair of traumatic brain injury shows better therapeutic effects than monotherapy and significantly promotes recovery of neurological functions.

What Is the Relationship of Fear Avoidance to Physical Function and Pain Intensity in Injured Athletes?

NARCIS (Netherlands)

Fischerauer, Stefan F.; Talaei-Khoei, Mojtaba; Bexkens, Rens; Ring, David C.; Oh, Luke S.; Vranceanu, Ana-Maria

2018-01-01

Fear avoidance can play a prominent role in maladaptive responses to an injury. In injured athletes, such pain-related fear or fear avoidance behavior may have a substantial influence on the recovery process. Specifically, it may explain why some are able to reach their preinjury abilities, whereas

Maladaptation of cerebral perfusion in the spinal cord injured individuals

Energy Technology Data Exchange (ETDEWEB)

Cho, Ihn Ho; Chun, Kyung A.; Lee, Hyoung Woo; Ahn, Sang Ho; Hayashida, Kohei [National Cardiovascular Center, Osaka (Korea, Republic of)

2001-07-01

The aim of this study was to evaluate the tilt-induced alteration of cerebral perfusion of spinal cord injured individuals. Supine and upright sitting brain SPECT was performed using a 1-day protocol with {sup 99m}Tc-ethylcysteinate dimer (ECD) in 11 SCI individuals (mean age, 32.6 y), with lesions between C3 and T4, ad 5 AB individuals (mean age, 31.4 y). The patients rested on a wheelchair in the supine position. Then, they sat up and, at the same time 555MBq of ECD was injected. The upright SPECT was done. Finally, 740MBq of ECD was injected and supine SPECT was performed again. The SPECT data were acquired with dual head gamma camera (E-cam, Siemens). For semiquantitative analysis, 14 ROIs were drawn on the brain. In the SCI individuals, the radiotracer uptake in the frontal, temporal and parietal areas were significantly decreased in the upright SPECT. No postural changes was evident in the occipital lobe, basal ganglia and thalamus in the SCI individuals. In the AB individuals, there were no such changes on the upright SPECT. Postural cerebral hypoperfusion in the frontal, temporal and parietal areas in the SCI individuals might relate to maladaptation of the vascular response during the upright position.

Determining the quality of life in persons with acquired brain injury

OpenAIRE

Balanč, Mateja

2017-01-01

Identifying and assessing the quality of life of persons with acquired brain injury is an important element of rehabilitation, and enables assistance and support to both the injured and their families. By identifying and assessing quality of life, we can better understand the impact of injuries on the individual and his/her life. Different levels of injuries can severely affect cognitive, physical, emotional-behavioral and social life not only of a injured person but also of members of his f...

Prospective Study on Noninvasive Assessment of Intracranial Pressure in Traumatic Brain-Injured Patients: Comparison of Four Methods.

Science.gov (United States)

Cardim, Danilo; Robba, Chiara; Donnelly, Joseph; Bohdanowicz, Michal; Schmidt, Bernhard; Damian, Maxwell; Varsos, Georgios V; Liu, Xiuyun; Cabeleira, Manuel; Frigieri, Gustavo; Cabella, Brenno; Smielewski, Peter; Mascarenhas, Sergio; Czosnyka, Marek

2016-04-15

Elevation of intracranial pressure (ICP) may occur in many diseases, and therefore the ability to measure it noninvasively would be useful. Flow velocity signals from transcranial Doppler (TCD) have been used to estimate ICP; however, the relative accuracy of these methods is unclear. This study aimed to compare four previously described TCD-based methods with directly measured ICP in a prospective cohort of traumatic brain-injured patients. Noninvasive ICP (nICP) was obtained using the following methods: 1) a mathematical "black-box" model based on interaction between TCD and arterial blood pressure (nICP_BB); 2) based on diastolic flow velocity (nICP_FVd); 3) based on critical closing pressure (nICP_CrCP); and 4) based on TCD-derived pulsatility index (nICP_PI). In time domain, for recordings including spontaneous changes in ICP greater than 7 mm Hg, nICP_PI showed the best correlation with measured ICP (R = 0.61). Considering every TCD recording as an independent event, nICP_BB generally showed to be the best estimator of measured ICP (R = 0.39; p area under the curve [AUC] = 0.66; p AUC (0.70; p AUC = 0.64; p > 0.05). nICP_PI was not related to measured ICP using any of the above statistical indicators. We also introduced a new estimator (nICP_Av) based on the average of three methods (nICP_BB, nICP_FVd, and nICP_CrCP), which overall presented improved statistical indicators (R = 0.47; p AUC = 0.73; p < 0.05). nICP_PI appeared to reflect changes in ICP in time most accurately. nICP_BB was the best estimator for ICP "as a number." nICP_Av demonstrated to improve the accuracy of measured ICP estimation.

Role of sound stimulation in reprogramming brain connectivity.

Science.gov (United States)

Chaudhury, Sraboni; Nag, Tapas C; Jain, Suman; Wadhwa, Shashi

2013-09-01

Sensory stimulation has a critical role to play in the development of an individual. Environmental factors tend to modify the inputs received by the sensory pathway. The developing brain is most vulnerable to these alterations and interacts with the environment to modify its neural circuitry. In addition to other sensory stimuli, auditory stimulation can also act as external stimuli to provide enrichment during the perinatal period. There is evidence that suggests that enriched environment in the form of auditory stimulation can play a substantial role in modulating plasticity during the prenatal period. This review focuses on the emerging role of prenatal auditory stimulation in the development of higher brain functions such as learning and memory in birds and mammals. The molecular mechanisms of various changes in the hippocampus following sound stimulation to effect neurogenesis, learning and memory are described. Sound stimulation can also modify neural connectivity in the early postnatal life to enhance higher cognitive function or even repair the secondary damages in various neurological and psychiatric disorders. Thus, it becomes imperative to examine in detail the possible ameliorating effects of prenatal sound stimulation in existing animal models of various psychiatric disorders, such as autism.

Dendrimer Brain Uptake and Targeted Therapy for Brain Injury in a Large Animal Model of Hypothermic Circulatory Arrest

Science.gov (United States)

2015-01-01

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer–drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems. PMID:24499315

Dendrimer brain uptake and targeted therapy for brain injury in a large animal model of hypothermic circulatory arrest.

Science.gov (United States)

Mishra, Manoj K; Beaty, Claude A; Lesniak, Wojciech G; Kambhampati, Siva P; Zhang, Fan; Wilson, Mary A; Blue, Mary E; Troncoso, Juan C; Kannan, Sujatha; Johnston, Michael V; Baumgartner, William A; Kannan, Rangaramanujam M

2014-03-25

Treatment of brain injury following circulatory arrest is a challenging health issue with no viable therapeutic options. Based on studies in a clinically relevant large animal (canine) model of hypothermic circulatory arrest (HCA)-induced brain injury, neuroinflammation and excitotoxicity have been identified as key players in mediating the brain injury after HCA. Therapy with large doses of valproic acid (VPA) showed some neuroprotection but was associated with adverse side effects. For the first time in a large animal model, we explored whether systemically administered polyamidoamine (PAMAM) dendrimers could be effective in reaching target cells in the brain and deliver therapeutics. We showed that, upon systemic administration, hydroxyl-terminated PAMAM dendrimers are taken up in the brain of injured animals and selectively localize in the injured neurons and microglia in the brain. The biodistribution in other major organs was similar to that seen in small animal models. We studied systemic dendrimer-drug combination therapy with two clinically approved drugs, N-acetyl cysteine (NAC) (attenuating neuroinflammation) and valproic acid (attenuating excitotoxicity), building on positive outcomes in a rabbit model of perinatal brain injury. We prepared and characterized dendrimer-NAC (D-NAC) and dendrimer-VPA (D-VPA) conjugates in multigram quantities. A glutathione-sensitive linker to enable for fast intracellular release. In preliminary efficacy studies, combination therapy with D-NAC and D-VPA showed promise in this large animal model, producing 24 h neurological deficit score improvements comparable to high dose combination therapy with VPA and NAC, or free VPA, but at one-tenth the dose, while significantly reducing the adverse side effects. Since adverse side effects of drugs are exaggerated in HCA, the reduced side effects with dendrimer conjugates and suggestions of neuroprotection offer promise for these nanoscale drug delivery systems.

Role of brain orexin in the pathophysiology of functional gastrointestinal disorders.

Science.gov (United States)

Okumura, Toshikatsu; Nozu, Tsukasa

2011-04-01

Orexins are neuropeptides that are localized in neurons within the lateral hypothalamic area and regulate feeding behavior. The lateral hypothalamic area plays an important role in not only feeding but the central regulation of other functions including gut physiology. Accumulating evidence have shown that orexins acts in the brain to regulate a wide variety of body functions including gastrointestinal functions. The purpose of this review is to summarize relevant findings on brain orexins and a digestive system, and discuss the pathophysiological roles of the peptides with special reference to functional gastrointestinal disorders. Exogenously administered orexin or endogenously released orexin in the brain potently stimulates gastric acid secretion in pylorus-ligated conscious rats. The vagal cholinergic pathway is involved in the orexin-induced stimulation of acid secretion, suggesting that orexin-containing neurons in lateral hypothalamic area activates neurons in the dorsal motor nucleus in medulla oblongata, followed by increasing vagal outflow, thereby stimulating gastric acid secretion. In addition, brain orexin stimulates gastric motility, pancreatic secretion and induce gastroprotective action. On the other hand, brain orexin is involved in a number of physiological functions other than gut physiology, such as control of sleep/awake cycle and anti-depressive action in addition to increase in appetite. From these evidence, we would like to make a hypothesis that decreased orexin signaling in the brain may play a role in the pathophysiology in a part of patients with functional gastrointestinal disorders who are frequently accompanied with appetite loss, sleep disturbance, depressive state and the inhibition of gut function. © 2011 Journal of Gastroenterology and Hepatology Foundation and Blackwell Publishing Asia Pty Ltd.

The role and dynamics of β-catenin in precondition induced neuroprotection after traumatic brain injury.

Directory of Open Access Journals (Sweden)

Gali Umschweif

Full Text Available Preconditioning via heat acclimation (34°C 30 d results in neuroprotection from traumatic brain injury due to constitutive as well as dynamic changes triggered by the trauma. Among these changes is Akt phosphorylation, which decreases apoptosis and induces HIF1α. In the present study we investigated the Akt downstream GSK3β/β-catenin pathway and focused on post injury alternations of β catenin and its impact on the cellular response in preconditioned heat acclimated mice. We found that the reduction in motor disability is accompanied with attenuation of depressive like behavior in heat acclimated mice that correlates with the GSK3β phosphorylation state. Concomitantly, a robust β catenin phosphorylation is not followed by its degradation, or by reduced nuclear accumulation. Enhanced tyrosine phosphorylation of β catenin in the injured area weakens the β catenin-N cadherin complex. Membrane β catenin is transiently reduced in heat acclimated mice and its recovery 7 days post TBI is accompanied by induction of the synaptic marker synaptophysin. We suggest a set of cellular events following traumatic brain injury in heat acclimated mice that causes β catenin to participate in cell-cell adhesion alternations rather than in Wnt signaling. These events may contribute to synaptogenesis and the improved motor and cognitive abilities seen heat acclimated mice after traumatic brain injury.

Diffusion-weighted MR and apparent diffusion coefficient in the evaluation of severe brain injury

International Nuclear Information System (INIS)

Nakahara, M.; Ericson, K.; Bellander, B.M.

2001-01-01

Purpose: To study apparent diffusion coefficient (ADC) maps in severely brain-injured patients. Material and Methods: Four deeply comatose patients with severe brain injury were investigated with single-shot, diffusion-weighted, spin-echo echo planar imaging. The tetrahedral diffusion gradient configuration and four iterations of a set of b-values (one time of 0 mm2/s, and four times of 1000 mm2/s) were used to create isotropic ADC maps with high signal-to-noise ratio. ADC values of gray and white matter were compared among patients and 4 reference subjects. Results: one patient was diagnosed as clinically brain dead after the MR examination. The patient's ADC values of gray and white matter were significantly lower than those of 3 other brain-injured patients. In addition the ADC value of white matter was significantly lower than that of gray matter. Conclusion: The patient with fatal outcome shortly after MR examination differed significantly from other patients with severe brain injury but non-fatal outcome, with regard to ADC values in gray and white matter. This might indicate a prognostic value of ADC maps in the evaluation of traumatic brain injury

Organisation and functional role of the brain angiotensin system

Directory of Open Access Journals (Sweden)

Catherine Llorens-Cortes

2002-03-01

Full Text Available The discovery that all components of the renin-angiotensin system (RAS are present in the brain led investigators to postulate the existence of a local brain RAS. Supporting this, angiotensin immunoreactive neurones have been visualised in the brain. Two major pathways were described: a forebrain pathway which connects circumventricular organs to the median preoptic nucleus, paraventricular and supraoptic nuclei, and a second pathway connecting the hypothalamus to the medulla oblongata. Blood-brain-barrier deficient circumventricular organs are rich in angiotensin II (Ang II receptors. By activating these receptors, circulating Ang II may act on central cardiovascular centres via angiotensinergic neurones, providing a link between peripheral and central Ang II systems. Among the effector peptides of the brain RAS, Ang II and angiotensin III (Ang III have the same affinity for type 1 and type 2 Ang II receptors. When injected into the brain, both peptides increase blood pressure (BP, water intake and pituitary hormone release and may modify learning and memory. Since Ang II is converted in vivo to Ang III, the nature of the true effector is unknown. This review summarises new insights into the predominant role of brain Ang III in the control of BP and underlines the fact that brain aminopeptidase A, the enzyme forming central Ang III, could constitute a putative central therapeutic target for the treatment of hypertension.

Present status of severe head injured patients with an admission glasgow coma scale score of 3 based on the Japan neurotrauma data bank

International Nuclear Information System (INIS)

Uzura, Masahiko

2011-01-01

Severe head injured patients presenting with Glasgow Coma Scale (GCS) score of 3 have been hesitated to treat aggressively. We analyzed present status of patients with GCS score of 3 from the Project 2004 in the Japan Neurotrauma Data Bank. Among 1,101 cases registered, 805 cases with GCS score of 8 or less on admission. Of those, 215 cases with GCS score of 3 were classified the survival group (51 cases) and the dead group (164 cases) and compared each group. These results showed that the characteristics associated with favorable outcome including absence of cardiopulmonary arrest, no abnormality of pupil findings, stable condition of respiration and circulation, serum glucose level (less than 184 mg/dl), absence of initial CT findings including skull base fracture, pneumocephalus and subarachnoid hemorrhage, no serious extracranial injures including Injury Severity Scale score of less than 25, critic al care including intracranial pressure monitoring and temperature management. We suggest that it is important to treat brain and systemic problems aggressively in severe head injured patients with GCS score of 3. (author)

Neural stem cells in the immature, but not the mature, subventricular zone respond robustly to traumatic brain injury.

Science.gov (United States)

Goodus, Matthew T; Guzman, Alanna M; Calderon, Frances; Jiang, Yuhui; Levison, Steven W

2015-01-01

Pediatric traumatic brain injury is a significant problem that affects many children each year. Progress is being made in developing neuroprotective strategies to combat these injuries. However, investigators are a long way from therapies to fully preserve injured neurons and glia. To restore neurological function, regenerative strategies will be required. Given the importance of stem cells in repairing damaged tissues and the known persistence of neural precursors in the subventricular zone (SVZ), we evaluated regenerative responses of the SVZ to a focal brain lesion. As tissues repair more slowly with aging, injury responses of male Sprague Dawley rats at 6, 11, 17, and 60 days of age and C57Bl/6 mice at 14 days of age were compared. In the injured immature animals, cell proliferation in the dorsolateral SVZ more than doubled by 48 h. By contrast, the proliferative response was almost undetectable in the adult brain. Three approaches were used to assess the relative numbers of bona fide neural stem cells, as follows: the neurosphere assay (on rats injured at postnatal day 11, P11), flow cytometry using a novel 4-marker panel (on mice injured at P14) and staining for stem/progenitor cell markers in the niche (on rats injured at P17). Precursors from the injured immature SVZ formed almost twice as many spheres as precursors from uninjured age-matched brains. Furthermore, spheres formed from the injured brain were larger, indicating that the neural precursors that formed these spheres divided more rapidly. Flow cytometry revealed a 2-fold increase in the percentage of stem cells, a 4-fold increase in multipotential progenitor-3 cells and a 2.5-fold increase in glial-restricted progenitor-2/multipotential-3 cells. Analogously, there was a 2-fold increase in the mitotic index of nestin+/Mash1- immunoreactive cells within the immediately subependymal region. As the early postnatal SVZ is predominantly generating glial cells, an expansion of precursors might not

Various irrigation fluids affect postoperative brain edema and cellular damage during experimental neurosurgery in rats.

Science.gov (United States)

Doi, Kazuhisa; Kawano, Takeshi; Morioka, Yujiro; Fujita, Yasutaka; Nishimura, Masuhiro

2006-12-01

This study was conducted to investigate how various irrigation fluids used during neurosurgical procedures affect the degree of postoperative brain edema and cellular damage during experimental neurosurgery in rats. The cerebral cortex was exposed and incised crosswise with a surgical knife under irrigation with an artificial CSF, lactated Ringer's solution, or normal saline. Four hours after injury, irrigation was stopped and brain tissue samples were obtained from injured and uninjured sites. Specific gravity, cerebrovascular permeability, and TTC staining of the samples were evaluated. Incision and irrigation of the brain were not performed on the control group. At the injured site, specific gravities of the samples in the normal saline group and the lactated Ringer's solution group were significantly lower than the specific gravity in the artificial CSF group. The EB concentration was significantly higher in the lactated Ringer's solution group and relatively high in the normal saline group as compared with the artificial CSF group. TTC staining did not differ significantly between the artificial CSF group and the control group. It was significantly lower in the lactated Ringer's solution group and the normal saline group than in the control group and the artificial CSF group. As compared with normal saline and lactated Ringer's solution, artificial CSF reduced postoperative brain edema, cerebrovascular permeability, and cellular damage in sites injured by experimental neurosurgery in rats.

The imaging diagnosis of diffuse brain swelling due to severe brain trauma

International Nuclear Information System (INIS)

Shen Jianqiang; Hu Jiawang

2008-01-01

Objective: To discuss the clinical and pathological characteristics and the imaging types of the diffuse brain swelling due to severe brain trauma. Methods: The clinical data and CT and MR images on 48 cases with diffuse brain swelling due to severe brain trauma were analyzed. Results: Among these 48 cases of the diffuse brain swelling due to severe brain trauma, 33 cases were complicated with brain contusions (including 12 cases brain diffuse axonal injury, 1 case infarct of the right basal ganglion), 31 cases were complicated with hematoma (epidural, subdural or intracerebral), 27 cases were complicated with skull base fracture, and 10 cases were complicated with subarachnoid hematoma. The CT and MR imaging of the diffuse brain swelling included as followed: (1) Symmetrically diffuse brain swelling in both cerebral hemispheres with cerebral ventricles decreased or disappeared, without median line shift. (2)Diffuse brain swelling in one side cerebral hemisphere with cerebral ventricles decreased or disappeared at same side, and median line shift to other side. (3) Subarachnoid hematoma or little subcortex intracerebral hematoma were complicated. (4) The CT value of the cerebral could be equal, lower or higher comparing with normal. Conclusion: The pathological reason of diffuse brain swelling was the brain vessel expanding resulting from hypothalamus and brainstem injured in severe brain trauma. There were four CT and MR imaging findings in diffuse brain swelling. The diffuse brain swelling without hematoma may be caused by ischemical reperfusion injury. (authors)

Self-awareness of prospective memory failure in adults with traumatic brain injury.

Science.gov (United States)

Roche, Nadine L; Fleming, Jennifer M; Shum, David H K

2002-11-01

The frequency of prospective memory failure in individuals with severe traumatic brain injury (TBI) was investigated by comparison with a non-brain-injured control group. Self-awareness of prospective memory function was also assessed by comparing self-ratings with ratings by significant others. Study participants included 33 individuals with severe TBI and 29 non-brain-injured persons. Each participant nominated a close friend or relative who completed the informant's version of the questionnaire. Participants and their significant others both rated the participants' frequency of prospective memory lapses using the Comprehensive Assessment of Prospective Memory (CAPM). An independent groups design was adopted to compare the TBI and control groups. No significant difference was found between the TBI and control participants' self-ratings of frequency of prospective memory failure, but ratings by significant others were significantly different. The TBI group demonstrated less self-awareness (i.e. underestimated the frequency of prospective memory failure compared to significant others) than the control group.

Effects of radiochemical impurities on measurements of transfer constants for [14C]sucrose permeation of normal and injured blood-brain barrier of rats.

Science.gov (United States)

Preston, E; Foster, D O; Mills, P A

1998-01-01

Radiolabeled sucrose is often used to assess blood-brain barrier (BBB) injury in the rat, but published transfer constants (K[i]s) for sucrose permeation of the intact BBB (control K[i]s) are highly discrepant. A potential problem with the commonly used tracer, [14C(U)]sucrose, is radiolytic generation, preuse, of radiocontaminants that might readily penetrate the BBB. How such contaminants might affect measurements of sucrose K(i)s was examined for both the intact and the ischemically injured BBB. Three stocks of [14C(U)]sucrose were studied: newly purchased ("new"), 4-year-old, and 7-year-old. A high purity (99.9%) "new" and a 2-year-old stock of [3H(fructose-1)]sucrose were also tested. Pentobarbital-anesthetized male Sprague-Dawley rats were injected i.v. with each tracer separately (six to eight rats) and K(i)s in five brain regions were measured by the multiple-time graphical method. The "new" 14C-, "new" 3H-, and 2-year-old 3H-sucrose yielded comparable K(i)s , ranging from 1.2 +/- 0.1 to 2.4 +/- 0.3 nl x g(-1) x s(-1) (mean +/- SE) across the regions. The two old stocks of 14C-sucrose yielded significantly higher regional K(i)s : 5.1-6.3 (4-year-old) and 8.4-9.7 (7-year-old). Thin-layer chromatography of the three 14C-tracers revealed that each contained radioimpurities (ca. 2% in both the "new" and 4-year-old, and 9% in the 7-year-old), but that the old stocks contained larger amounts of relatively mobile (more lipophilic) impurities, which can be suspected as the main cause of the elevated K(i)s obtained. Additional rats were subjected to 10 min of cerebral ischemia, which effects a delayed BBB injury, and 6 h later the "new" 3H- and the 4-year-old 14C-sucrose were injected together. The K(i)s for both tracers were elevated by like, absolute amounts (deltaK[i]s), but by very different percentages, over their disparate baseline values in uninjured rats (for striatum and hippocampus, the most injured regions, deltaK(i)s were 3.9 to 4.4 nl x g[-1] x s[-1

Non invasive brain stimulation to enhance post-stroke recovery

OpenAIRE

Nathalie Kubis; Nathalie Kubis

2016-01-01

Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first days, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical exci...

Non-Invasive Brain Stimulation to Enhance Post-Stroke Recovery

OpenAIRE

Kubis, Nathalie

2016-01-01

Brain plasticity after stroke remains poorly understood. Patients may improve spontaneously within the first 3 months and then more slowly in the coming year. The first day, decreased edema and reperfusion of the ischemic penumbra may possibly account for these phenomena, but the improvement during the next weeks suggests plasticity phenomena and cortical reorganization of the brain ischemic areas and of more remote areas. Indeed, the injured ischemic motor cortex has a reduced cortical excit...

Spray method for recovery of heat-injured Salmonella Typhimurium and Listeria monocytogenes.

Science.gov (United States)

Back, Kyeong-Hwan; Kim, Sang-Oh; Park, Ki-Hwan; Chung, Myung-Sub; Kang, Dong-Hyun

2012-10-01

Selective agar is inadequate for supporting recovery of injured cells. During risk assessment of certain foods, both injured and noninjured cells must be enumerated. In this study, a new method (agar spray method) for recovering sublethally heat-injured microorganisms was developed and used for recovery of heat-injured Salmonella Typhimurium and Listeria monocytogenes. Molten selective agar was applied as an overlay to presolidified nonselective tryptic soy agar (TSA) by spray application. Heat-injured cells (55°C for 10 min in 0.1% peptone water or 55°C for 15 min in sterilized skim milk) were inoculated directly onto solidified TSA. After a 2-h incubation period for cell repair, selective agar was applied to the TSA surface with a sprayer, and the plates were incubated. The recovery rate for heat-injured Salmonella Typhimurium and L. monocytogenes with the spray method was compared with the corresponding rates associated with TSA alone, selective media alone, and the conventional overlay method (selective agar poured on top of resuscitated cells grown on TSA and incubated for 2 h). No significant differences (P > 0.05) were found in pathogen recovery obtained with TSA, the overlay method, and the spray method. However, a lower recovery rate (P recovery and detection of injured cells.

Neuroprotective Role of Nerve Growth Factor in Hypoxic-Ischemic Brain Injury

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Antonio Chiaretti

2013-06-01

Full Text Available Hypoxic-ischemic brain injuries (HIBI in childhood are frequently associated with poor clinical and neurological outcome. Unfortunately, there is currently no effective therapy to restore neuronal loss and to determine substantial clinical improvement. Several neurotrophins, such as Nerve Growth Factor (NGF, Brain-Derived Neurotrophic Factor (BDNF, and Glial Derived Neurotrophic Factor (GDNF, play a key role in the development, differentiation, and survival of the neurons of the peripheral and central nervous system. Experimental animal studies demonstrated their neuroprotective role in HIBI, while only a few studies examined the neuroprotective mechanisms in patients with severe HIBI. We report two cases of children with HIBI and prolonged comatose state who showed a significant improvement after intraventricular NGF administration characterized by amelioration of electroencephalogram (EEG and cerebral perfusion at single-photon emission computed tomography (SPECT. The improvement in motor and cognitive functions of these children could be related to the neuroprotective role exerted by NGF in residual viable cholinergic neurons, leading to the restoration of neuronal networks in the damaged brain.

Pattern of brain computed tomography findings of adult patients with ...

African Journals Online (AJOL)

two adult head injured patients referred to the Radiology department for brain CT over a 3-year period was done. The patients were scanned using Toshiba Aquilion 64 slice spiral CT scan machine, data was collected using a proforma and ...

Comparison of postural stability between injured and uninjured ballet dancers.

Science.gov (United States)

Lin, Cheng-Feng; Lee, I-Jung; Liao, Jung-Hsien; Wu, Hong-Wen; Su, Fong-Chin

2011-06-01

Ballet movements require a limited base of support; thus, ballet dancers require a high level of postural control. However, postural stability in ballet dancers is still unclear and needs to be understood. To evaluate ballet dancers' postural stability in performing single-leg standing, the en pointe task, and the first and fifth positions and to determine differences in task performance among healthy nondancers, healthy dancers, and dancers with ankle sprains. Controlled laboratory study. Injured dancers, uninjured dancers, and nondancers were recruited for this study (N = 33 age-matched participants; n= 11 per group). The tasks tested were single-leg standing with eyes open and closed, first position, fifth position, and en pointe. Center of pressure parameters were calculated from the ground-reaction force collected with 1 force plate. Analysis of variance was used to assess the differences of center of pressure parameters among 3 groups in single-leg standing; independent t test was used to examine the differences of center of pressure parameters between injured and uninjured dancers. During single-leg standing, injured dancers had significantly greater maximum displacement in the medial-lateral direction and total trajectory of center of pressure, compared with the uninjured dancers and nondancers. During the first and fifth positions, the injured dancers demonstrated significantly greater standard deviation of center of pressure position in the medial-lateral and anterior-posterior directions, compared with the uninjured dancers. During en pointe, the injured dancers had significantly greater maximum displacement in the medial-lateral direction and the anterior-posterior direction, compared with the uninjured dancers. The injured and uninjured dancers demonstrated differences in postural stability in the medial-lateral direction during single-leg standing and the ballet postures. Although the injured dancers received ballet training, their postural stability

Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism.

Science.gov (United States)

Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

2016-03-11

Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism.

Bexarotene reduces blood-brain barrier permeability in cerebral ischemia-reperfusion injured rats.

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Lu Xu

Full Text Available Matrix metalloproteinase-9 (MMP-9 over-expression disrupts the blood-brain barrier (BBB in the ischemic brain. The retinoid X receptor agonist bexarotene suppresses MMP-9 expression in endothelial cells and displays neuroprotective effects. Therefore, we hypothesized that bexarotene may have a beneficial effect on I/R-induced BBB dysfunction.A total of 180 rats were randomized into three groups (n = 60 each: (i a sham-operation group, (ii a cerebral ischemia-reperfusion (I/R group, and (iii an I/R+bexarotene group. Brain water content was measured by the dry wet weight method. BBB permeability was analyzed by Evans Blue staining and the magnetic resonance imaging contrast agent Omniscan. MMP-9 mRNA expression, protein expression, and activity were assessed by reverse transcription polymerase chain reaction, Western blotting, and gelatin zymography, respectively. Apolipoprotein E (apoE, claudin-5, and occludin expression were analyzed by Western blotting.After 24 h, 48 h, and 72 h post-I/R, several effects were observed with bexarotene administration: (i brain water content and BBB permeability were significantly reduced; (ii MMP-9 mRNA and protein expression as well as activity were significantly decreased; (iii claudin-5 and occludin expression were significantly increased; and (iv apoE expression was significantly increased.Bexarotene decreases BBB permeability in rats with cerebral I/R injury. This effect may be due in part to bexarotene's upregulation of apoE expression, which has been previously shown to reduce BBB permeability through suppressing MMP-9-mediated degradation of the tight junction proteins claudin-5 and occludin. This work offers insight to aid future development of therapeutic agents for cerebral I/R injury in human patients.

Pathways for insulin access to the brain: the role of the microvascular endothelial cell

OpenAIRE

Meijer, Rick I.; Gray, Sarah M.; Aylor, Kevin W.; Barrett, Eugene J.

2016-01-01

New understanding of the directional flow of subarachnoid cerebrospinal fluid (CSF) through the Virchow-Robin space (VRS) to brain parenchyma, coupled with the demonstration here of rapid, insulin receptor-dependent trapping of plasma insulin by the brain microvasculature, underscores the direct role of insulin's blood-brain barrier transit to insulin delivery to the brain.

Inhibition of 2-arachydonoylgycerol degradation attenuates orofacial neuropathic pain in trigeminal nerve-injured mice.

Science.gov (United States)

Kamimura, Rantaro; Hossain, Mohammad Z; Unno, Shumpei; Ando, Hiroshi; Masuda, Yuji; Takahashi, Kojiro; Otake, Masanori; Saito, Isao; Kitagawa, Junichi

2018-03-24

Current therapeutics are not effective for orofacial neuropathic pain, and better options are needed. The present study used inferior orbital nerve (ION)-injured mice to investigate the effect of inhibiting monoacylglycerol lipase (MAGL), an enzyme that degrades the major endocannabinoid 2-arachydonoylgycerol (2-AG) in orofacial neuropathic pain. The head-withdrawal threshold to mechanical stimulation of the whisker pad was reduced on days 3, 5, and 7 after ION injury. Injection of JZL184, a selective inhibitor of MAGL, on day 7 after ION injury attenuated the reduction in head-withdrawal threshold at 2 h after administration. Moreover, the numbers of MAGL-immunoreactive neurons in the trigeminal subnucleus caudalis (Vc) and upper cervical spinal cord (C1-C2) were significantly greater in ION-injured mice than in sham-operated mice but were reduced after administration of JZL184. The increase in MAGL immunoreactivity suggests that increased 2-AG production is followed by rapid enzymatic degradation of 2-AG. JZL184 inhibited this degradation and thus increased 2-AG concentration in the brain, particularly in the Vc and C1-C2 regions, thus attenuating pain. Our findings suggest that inhibition of 2-AG degradation by MAGL inhibitors is a promising therapeutic option for treatment of orofacial neuropathic pain.

Role of adhesion molecules and inflammation in Venezuelan equine encephalitis virus infected mouse brain

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Honnold Shelley P

2011-04-01

Full Text Available Abstract Background Neuroinvasion of Venezuelan equine encephalitis virus (VEEV and subsequent initiation of inflammation in the brain plays a crucial role in the outcome of VEEV infection in mice. Adhesion molecules expressed on microvascular endothelial cells in the brain have been implicated in the modulation of the blood brain barrier (BBB and inflammation in brain but their role in VEEV pathogenesis is not very well understood. In this study, we evaluated the expression of extracellular matrix and adhesion molecules genes in the brain of VEEV infected mice. Findings Several cell to cell adhesion molecules and extracellular matrix protein genes such as ICAM-1, VCAM-1, CD44, Cadherins, integrins, MMPs and Timp1 were differentially regulated post-VEEV infection. ICAM-1 knock-out (IKO mice infected with VEEV had markedly reduced inflammation in the brain and demonstrated a delay in the onset of clinical symptoms of disease. A differential regulation of inflammatory genes was observed in the IKO mice brain compared to their WT counterparts. Conclusions These results improve our present understanding of VEEV induced inflammation in mouse brain.

Detection of spreading depolarization with intraparenchymal electrodes in the injured human brain

DEFF Research Database (Denmark)

Jeffcote, Toby; Hinzman, Jason M; Jewell, Sharon L

2014-01-01

be detected using intra-cortical electrodes, opening the way for electrode insertion via burr hole. METHODS: Animal work was carried out on adult Sprague-Dawley rats in a laboratory setting to investigate the feasibility of recording depolarization events. Subsequently, 8 human patients requiring craniotomy...... for craniotomy. The method provides a new investigative tool for the evaluation of the contribution of these events to secondary brain injury in human patients.......BACKGROUND: Spreading depolarization events following ischemic and traumatic brain injury are associated with poor patient outcome. Currently, monitoring these events is limited to patients in whom subdural electrodes can be placed at open craniotomy. This study examined whether these events can...

Metabolic crisis in severely head-injured patients: is ischemia just the tip of the iceberg?

Science.gov (United States)

Carre, Emilie; Ogier, Michael; Boret, Henry; Montcriol, Ambroise; Bourdon, Lionel; Jean-Jacques, Risso

2013-10-11

Ischemia and metabolic crisis are frequent post-traumatic secondary brain insults that negatively influence outcome. Clinicians commonly mix up these two types of insults, mainly because high lactate/pyruvate ratio (LPR) is the common marker for both ischemia and metabolic crisis. However, LPR elevations during ischemia and metabolic crisis reflect two different energetic imbalances: ischemia (Type 1 LPR elevations with low oxygenation) is characterized by a drastic deprivation of energetic substrates, whereas metabolic crisis (Type 2 LPR elevations with normal or high oxygenation) is associated with profound mitochondrial dysfunction but normal supply of energetic substrates. The discrimination between ischemia and metabolic crisis is crucial because conventional recommendations against ischemia may be detrimental for patients with metabolic crisis. Multimodal monitoring, including microdialysis and brain tissue oxygen monitoring, allows such discrimination, but these techniques are not easily accessible to all head-injured patients. Thus, a new "gold standard" and adapted medical education are required to optimize the management of patients with metabolic crisis.

Metabolic crisis in severely head-injured patients: is ischemia just the tip of the iceberg?

Directory of Open Access Journals (Sweden)

Emilie eCarre

2013-10-01

Full Text Available Ischemia and metabolic crisis are frequent post-traumatic secondary brain insults that negatively influence outcome. Clinicians commonly mix up these two types of insults, mainly because high lactate/pyruvate ratio (LPR is the common marker for both ischemia and metabolic crisis. However, LPR elevations during ischemia and metabolic crisis reflect two different energetic imbalances: ischemia (Type 1 LPR elevations with low oxygenation is characterized by a drastic deprivation of energetic substrates, whereas metabolic crisis (Type 2 LPR elevations with normal or high oxygenation is associated with profound mitochondrial dysfunction but normal supply of energetic substrates. The discrimination between ischemia and metabolic crisis is crucial because conventional recommendations against ischemia may be detrimental for patients with metabolic crisis. Multimodal monitoring, including microdialysis and brain tissue oxygen monitoring, allows such discrimination, but these techniques are not easily accessible to all head-injured patients. Thus, a new gold standard and adapted medical education are required to optimize the management of patients with metabolic crisis.

A role for sex and a common HFE gene variant in brain iron uptake.

Science.gov (United States)

Duck, Kari A; Neely, Elizabeth B; Simpson, Ian A; Connor, James R

2018-03-01

HFE (high iron) is an essential protein for regulating iron transport into cells. Mutations of the HFE gene result in loss of this regulation causing accumulation of iron within the cell. The mutated protein has been found increasingly in numerous neurodegenerative disorders in which increased levels of iron in the brain are reported. Additionally, evidence that these mutations are associated with elevated brain iron challenges the paradigm that the brain is protected by the blood-brain barrier. While much has been studied regarding the role of HFE in cellular iron uptake, it has remained unclear what role the protein plays in the transport of iron into the brain. We investigated regulation of iron transport into the brain using a mouse model with a mutation in the HFE gene. We demonstrated that the rate of radiolabeled iron ( 59 Fe) uptake was similar between the two genotypes despite higher brain iron concentrations in the mutant. However, there were significant differences in iron uptake between males and females regardless of genotype. These data indicate that brain iron status is consistently maintained and tightly regulated at the level of the blood-brain barrier.

Rebuilding the injured brain: use of MRS in clinical regenerative medicine

Science.gov (United States)

Zare, Alina; Weiss, Michael; Gader, Paul

2011-03-01

Hypoxic-Ischemic Encephalopathy (HIE) is the brain manifestation of systemic asphyxia that occurs in 20 out of 1000 births. HIE triggers an immediate neuronal and glial injury leading to necrosis secondary to cellular edema and lysis. Because of this destructive neuronal injury, up to 25% of neonates exhibit severe permanent neuropsychological handicaps in the form of cerebral palsy, with or without associated mental retardation, learning disabilities, or epilepsy. Due to the devastating consequences of HIE, much research has focused on interrupting the cascade of events triggered by HIE. To date, none of these therapies, with the exception of hypothermia, have been successful in the clinical environment. Even in the case of hypothermia, only neonates with mild to moderate HIE respond to therapy. Stem cell therapy offers an attractive potential treatment for HIE. The ability to replace necrotic cells with functional cells could limit the degree of long-term neurological deficits. The neonatal brain offers a unique milieu for stem cell therapy due to its overall plasticity and the continued division of cells in the sub-ventricular zones. New powerful imaging tools allow researchers to track stem cells in vivo post-transplant, as shown in Figure 1. However, neuroimaging still leaves numerous questions unresolved: How can we identify stem cells without using tracking agents, what cells types are destroyed in the brain post injury? What is the final phenotypic fate of transplanted cells? Are the transplanted cells still viable? Do the transplanted cells spare endogenous neuronal tissue? We hypothesize that magnetic resonance spectroscopy (MRS), a broadly used clinical technique that can be performed at the time of a standard MRI scan, can provide answers to these questions when coupled with advanced computational approaches. MRS is widely available clinically, and is a relative measure of different metabolites within the sampled area. These measures are presented as a

Exercise and plasticize the brain

DEFF Research Database (Denmark)

Mala, Hana; Wilms, Inge

Neuroscientific studies continue to shed light on brain’s plasticity and its innate mechanisms to recover. The recovery process includes re-wiring of the existing circuitry, establishment of new connections, and recruitment of peri-lesional and homologous areas in the opposite hemisphere....... The plasticity of the brain can be stimulated and enhanced through training, which serves as a fundamental element of neurorehabilitative strategies. For instance, intensive cognitive and physical training promote the activation of processes that may help the brain to adapt to new conditions and needs. However...... neurorehabilitation is to understand and define how to stimulate the injured brain to elicit the desired adaptation. Research focuses on uncovering specific elements relevant for training planning and execution in order to create an environment that stimulates and maximizes the exploitation of the brain’s plastic...

“Nobody's ever asked me what it's like”: The role of family networks in the transitions of injured soldiers engaging with higher education.

OpenAIRE

Lambert-Heggs, Wendy

2016-01-01

An increasing number of injured service personnel returning from active combat duty will not be redeployed and many of them face discharge from military service. A number of these men and women have sustained life-threatening injuries which may, if the individual survives, result in reduced physical and mental health functioning. This research is focused on the transitions and processes that injured personnel go through when contemplating a new career through engagement with a higher educatio...

Residual cognitive disability after completion of inpatient rehabilitation among injured children.

Science.gov (United States)

Zonfrillo, Mark R; Durbin, Dennis R; Winston, Flaura K; Zhang, Xuemei; Stineman, Margaret G

2014-01-01

To determine the prevalence and nature of residual cognitive disability after inpatient rehabilitation for children aged 7-18 years with traumatic injuries. This retrospective cohort study included children aged 7-18 years in the Uniform Data System for Medical Rehabilitation who underwent inpatient rehabilitation for traumatic injuries in 523 facilities from 2002-2011. Traumatic injuries were identified by standardized Medicare Inpatient Rehabilitation Facility-Patient Assessment Instrument codes. Cognitive outcomes were measured by the Functional Independence Measure instrument. A validated, categorical staging system derived from responses to the items in the cognitive domain of the functional independence measure was used and consisted of clinically relevant levels of cognitive achievement from stage 1 (total cognitive disability) to stage 7 (completely independent cognitive function). There were 13,798 injured children who completed inpatient rehabilitation during the 10-year period. On admission to inpatient rehabilitation, patients with traumatic brain injury (TBI) had more cognitive disability (median stage 2) than those with spinal cord injury or other injuries (median stage 5). Cognitive functioning improved for all patients, but children with TBI still tended to have significant residual cognitive disability (median stage on discharge, 4). Injured children gained cognitive functionality throughout inpatient rehabilitation. Those with TBI had more severe cognitive disability on admission and more residual disability on discharge. This is important not only for patient and family expectation setting but also for resource and service planning, as discharge from inpatient rehabilitation is a critical milestone for reintegration into society for children with serious injury. Copyright © 2014 Mosby, Inc. All rights reserved.

Health and Occupational Outcomes Among Injured, Nonstandard Shift Workers.

Science.gov (United States)

Wong, Imelda S; Smith, Peter M; Mustard, Cameron A; Gignac, Monique A M

2015-11-01

This study compares health and occupational outcomes following a work-related injury for nonstandard and day-shift workers. National Population Health Survey data were used to explore outcomes 2 years post-work injury. Retrospective-matched cohort analyses examined main effects and interactions of shift schedule and work injury with changes in health, shift schedule, and labor force status. Models were adjusted for respondent characteristics, baseline health status, and occupational strength requirements. Injured nonstandard shift workers reported lower health utility index scores, compared with uninjured and injured daytime workers and uninjured nonstandard-shift workers. No significant interactions between shift and injury were found with schedule change and leaving the labor force. Injured nonstandard-shift workers are as likely to remain employed as other groups, but may be vulnerable in terms of diminished health.

EXPERIMENTAL WORK AND RESEARCH Effect of Tiaoxin Recipe（调心方）on Spatial Memory and Energy Metabolism of Oxidation Injured Alzheimers Disease Rats

Institute of Scientific and Technical Information of China (English)

QIUHong; ZHAOWei－kang; 等

2003-01-01

Objective:To observe the effect of Tiaoxin Recipe(TXR) on the spatial memory,brain mitochondrial energy metabolism of oxidation injured Alzheimer's disease(AD) rats,and to explore the mechanism of TXR in treating AD.Methods:Eighty-eight SD rats were randomly divided into five groups (normal group,operative group,“AD”model group,TXR group and Aricept group).An oxygen free rad-ical generation system (dihydroxy fumaric acid-trichloroferric-adenosine diphosphate,DHF-FeCl3-ADP)was used to create oxidation injured rat models mimic to AD; spatial learning and memeory impairment (Morris water maze method),the activity of Succinate-oxidase,NADH-oxidase,CytC-oxidase(Clark ox-ygen electrode method)and the expression of cytochrome oxidase(CO)ⅡmRNA(in situ hybridization method)were observed.Results:Compared with the normal group,the spatial memory,activity of CytC-oxidase and COⅡmRNA expression of oxidation injured“AD”rats were obviously decreased;TXR,how-ever,could improve these functions in “AD”rat models obviously.Conclusion:The mechanism of the ac-tion of TXR in treating AD was partly related to its effect on anti-oxidation which could improve brain mi-tochondrial energy metabolism.

THE ROLE OF MULTIDRUG RESISTANCE ASSOCIATED PROTEIN (MRP) IN THE BLOOD-BRAIN BARRIER AND OPIOID ANALGESIA

Science.gov (United States)

Su, Wendy; Pasternak, Gavril W.

2013-01-01

The blood brain barrier protects the brain from circulating compounds and drugs. The ATP-binding cassette (ABC) transporter P-glycoprotein (Pgp) is involved with the barrier, both preventing the influx of agent from the blood into the brain and facilitating the efflux of compounds from the brain into the blood, raising the possibility of a similar role for other transporters. Multidrug resistance associated protein (MRP), a 190 kDa protein similar to Pgp is also ABC transport that has been implicated in the blood brain barrier. The current study explores its role in opioid action. Immunohistochemically, it is localized in the choroid plexus in ratsand can be selectively downregulated by antisense treatment at both the level of mRNA, as shown by RT-PCR, and protein, as demonstrated immunohistochemically. Behaviorally, downregulation of MRP significantly enhances the analgesic potency of systemic morphine in MRP knockout mice and in antisense-treated rats by lowering the blood brain barrier. Following intracerebroventricular administration, a number of compounds, including some opioids, are rapidly secreted from the brain into the blood where they contribute to the overall analgesic effects by activating peripheral systems. MRP plays a role in this efflux. Downregulating MRP expression leads to a corresponding decrease in the transport and a diminished analgesic response from opioids administered intracerebroventricularly. Thus, the transporter protein MRP plays a role in maintaining the blood-brain barrier and modulates the activity of opioids. PMID:23508590

Family and home in cognitive rehabilitation after brain injury: The importance of family oriented interventions.

Science.gov (United States)

Wulf-Andersen, Camilla; Mogensen, Jesper

2017-01-01

Acquired brain injury (ABI) severely affects both the injured patient and her/his family. This fact alone calls for a therapeutic approach addressing not only the individual victim of ABI but also her/his family. Additionally, the optimal outcome of posttraumatic cognitive rehabilitation may be best obtained by supplementing the institution-based cognitive training with home-based training. Moving cognitive training and other therapeutic interventions into the home environment does, however, constitute an additional challenge to the family structure and psychological wellbeing of all family members. We presently argue in favour of an increased utilization of family-based intervention programs for the families of brain injured patients - in general and especially in case of utilization of home-based rehabilitative training.

Lactate storm marks cerebral metabolism following brain trauma.

Science.gov (United States)

Lama, Sanju; Auer, Roland N; Tyson, Randy; Gallagher, Clare N; Tomanek, Boguslaw; Sutherland, Garnette R

2014-07-18

Brain metabolism is thought to be maintained by neuronal-glial metabolic coupling. Glia take up glutamate from the synaptic cleft for conversion into glutamine, triggering glial glycolysis and lactate production. This lactate is shuttled into neurons and further metabolized. The origin and role of lactate in severe traumatic brain injury (TBI) remains controversial. Using a modified weight drop model of severe TBI and magnetic resonance (MR) spectroscopy with infusion of (13)C-labeled glucose, lactate, and acetate, the present study investigated the possibility that neuronal-glial metabolism is uncoupled following severe TBI. Histopathology of the model showed severe brain injury with subarachnoid and hemorrhage together with glial cell activation and positive staining for Tau at 90 min post-trauma. High resolution MR spectroscopy of brain metabolites revealed significant labeling of lactate at C-3 and C-2 irrespective of the infused substrates. Increased (13)C-labeled lactate in all study groups in the absence of ischemia implied activated astrocytic glycolysis and production of lactate with failure of neuronal uptake (i.e. a loss of glial sensing for glutamate). The early increase in extracellular lactate in severe TBI with the injured neurons rendered unable to pick it up probably contributes to a rapid progression toward irreversible injury and pan-necrosis. Hence, a method to detect and scavenge the excess extracellular lactate on site or early following severe TBI may be a potential primary therapeutic measure. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

Alcohol and drugs in seriously injured drivers in 6 European countries

DEFF Research Database (Denmark)

Legrand, Sara-Ann; Isalberti, Cristina; Linden, Trudy Van der

2012-01-01

Objective: To determine the presence of alcohol and drugs in drivers severely injured in traffic crashes in 6 European countries. Methods: Data were collected from 2492 seriously injured drivers of cars and vans in Belgium, Denmark, Finland, Italy, Lithuania and The Netherlands, between 2007...

Psychosocial care for seriously injured children and their families: a qualitative study among emergency department nurses and physicians.

Science.gov (United States)

Alisic, Eva; Conroy, Rowena; Magyar, Joanne; Babl, Franz E; O'Donnell, Meaghan L

2014-09-01

Approximately one in five children who sustain a serious injury develops persistent stress symptoms. Emergency Department nurses and physicians have a pivotal role in psychosocial care for seriously injured children. However, little is known about staff's views on this role. Our aim was to investigate Emergency Department staff's views on psychosocial care for seriously injured children. We conducted semi-structured interviews with 20 nurses and physicians working in an Australian Paediatric Emergency Department. We used purposive sampling to obtain a variety of views. The interviews were transcribed verbatim and major themes were derived in line with the summative analysis method. We also mapped participants' strategies for child and family support on the eight principles of Psychological First Aid (PFA). Five overarching themes emerged: (1) staff find psychosocial issues important but focus on physical care; (2) staff are aware of individual differences but have contrasting views on vulnerability; (3) parents have a central role; (4) staff use a variety of psychosocial strategies to support children, based on instinct and experience but not training; and (5) staff have individually different wishes regarding staff- and self-care. Staff elaborated most on strategies related to the PFA elements 'contact and engagement', 'stabilization', 'connection with social supports' and least on 'informing about coping'. The strong notion of individual differences in views suggests a need for training in psychosocial care for injured children and their families. In addition, further research on paediatric traumatic stress and psychosocial care in the ED will help to overcome the current paucity of the literature. Finally, a system of peer support may accommodate wishes regarding staff care. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brain injury impairs working memory and prefrontal circuit function

Directory of Open Access Journals (Sweden)

Colin James Smith

2015-11-01

Full Text Available More than 2.5 million Americans suffer a traumatic brain injury (TBI each year. Even mild to moderate traumatic brain injury causes long-lasting neurological effects. Despite its prevalence, no therapy currently exists to treat the underlying cause of cognitive impairment suffered by TBI patients. Following lateral fluid percussion injury (LFPI, the most widely used experimental model of TBI, we investigated alterations in working memory and excitatory/inhibitory synaptic balance in the prefrontal cortex. LFPI impaired working memory as assessed with a T-maze behavioral task. Field excitatory postsynaptic potentials recorded in the prefrontal cortex were reduced in slices derived from brain-injured mice. Spontaneous and miniature excitatory postsynaptic currents onto layer 2/3 neurons were more frequent in slices derived from LFPI mice while inhibitory currents onto layer 2/3 neurons were smaller after LFPI. Additionally, an increase in action potential threshold and concomitant decrease in firing rate was observed in layer 2/3 neurons in slices from injured animals. Conversely, no differences in excitatory or inhibitory synaptic transmission onto layer 5 neurons were observed; however, layer 5 neurons demonstrated a decrease in input resistance and action potential duration after LFPI. These results demonstrate synaptic and intrinsic alterations in prefrontal circuitry that may underlie working memory impairment caused by TBI.

Estrone is neuroprotective in rats after traumatic brain injury.

Science.gov (United States)

Gatson, Joshua W; Liu, Ming-Mei; Abdelfattah, Kareem; Wigginton, Jane G; Smith, Scott; Wolf, Steven; Simpkins, James W; Minei, Joseph P

2012-08-10

In various animal and human studies, early administration of 17β-estradiol, a strong antioxidant, anti-inflammatory, and anti-apoptotic agent, significantly decreases the severity of injury in the brain associated with cell death. Estrone, the predominant estrogen in postmenopausal women, has been shown to be a promising neuroprotective agent. The overall goal of this project was to determine if estrone mitigates secondary injury following traumatic brain injury (TBI) in rats. Male rats were given either placebo (corn oil) or estrone (0.5 mg/kg) at 30 min after severe TBI. Using a controlled cortical impact device in rats that underwent a craniotomy, the right parietal cortex was injured using the impactor tip. Non-injured control and sham animals were also included. At 72 h following injury, the animals were perfused intracardially with 0.9% saline followed by 10% phosphate-buffered formalin. The whole brain was removed, sliced, and stained for TUNEL-positive cells. Estrone decreased cortical lesion volume (pcerebral cortical levels of TUNEL-positive staining (pprotective pathways such as the ERK1/2 and BDNF pathways, decreases ischemic secondary injury, and decreases apoptotic-mediated cell death. These results suggest that estrone may afford protection to those suffering from TBI.

Electrical stimulation promotes regeneration of injured oculomotor nerves in dogs

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Lei Du

2016-01-01

Full Text Available Functional recovery after oculomotor nerve injury is very poor. Electrical stimulation has been shown to promote regeneration of injured nerves. We hypothesized that electrical stimulation would improve the functional recovery of injured oculomotor nerves. Oculomotor nerve injury models were created by crushing the right oculomotor nerves of adult dogs. Stimulating electrodes were positioned in both proximal and distal locations of the lesion, and non-continuous rectangular, biphasic current pulses (0.7 V, 5 Hz were administered 1 hour daily for 2 consecutive weeks. Analysis of the results showed that electrophysiological and morphological recovery of the injured oculomotor nerve was enhanced, indicating that electrical stimulation improved neural regeneration. Thus, this therapy has the potential to promote the recovery of oculomotor nerve dysfunction.

Alcohol and drugs in seriously injured drivers in six European countries

DEFF Research Database (Denmark)

Legrand, Sara‐Ann; Isalberti, Cristina; Linden, Trudy Van

2013-01-01

The objective of this study was to determine the presence of alcohol and drugs in drivers severely injured in traffic crashes in six European countries. Data were collected from 2492 seriously injured drivers of cars and vans in Belgium, Denmark, Finland, Italy, Lithuania, and the Netherlands...

Long-term observations on calcium accumulation in postischemic gerbil brain

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Araki, T.; Kato, H.; Inoue, T.; Kogure, K. (Department of Neurology, Institute of Brain Diseases, Tohoku University School of Medicine, Sendai (Japan))

1991-01-01

We studied delayed postischemic calcium accumulation and neuronal damage in the gerbil brain, using {sup 45}Ca autoradiography as a marker for detection of injured tissue and light microscopy. Transient cerebral ischemia was induced for 15 min. Sham-operated gerbils showed no abnormal calcium accumulation and neuronal damage throughout the brain. At 2 and 7 days following 15 min of ischemia, marked calcium accumulation and mild to severe neuronal damage were found in the selectively vulnerable areas such as neocortex, striatum, hippocampus and thalamus, and brainstem such as medial geniculate body, substantia nigra and inferior colliculus. After 1-2 months of recirculation, the calcium accumulation was not recognized in the brainstem. But, the accumulation was still detectable in the striatum, the hippocampus and the thalamus. Morphological study showed that marked proliferation of glia cells was rapid in the inferior colliculus and was relatively slow in the striatum and the hippocampus, although these structures were severely damaged after ischemia. The result suggests that the speed of restoration of injured tissue and the mechanisms for the damage after cerebral ischemia may be different between the selectively vulnerable areas and the brainstem. Furthermore, they suggest that {sup 45}Ca autoradiographic technique may provide a useful approach for diagnosis of the restoration of injured tissue at chronic stage following cerebral ischemia. (author).

Changes in event-related potential functional networks predict traumatic brain injury in piglets.

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Atlan, Lorre S; Lan, Ingrid S; Smith, Colin; Margulies, Susan S

2018-06-01

Traumatic brain injury is a leading cause of cognitive and behavioral deficits in children in the US each year. None of the current diagnostic tools, such as quantitative cognitive and balance tests, have been validated to identify mild traumatic brain injury in infants, adults and animals. In this preliminary study, we report a novel, quantitative tool that has the potential to quickly and reliably diagnose traumatic brain injury and which can track the state of the brain during recovery across multiple ages and species. Using 32 scalp electrodes, we recorded involuntary auditory event-related potentials from 22 awake four-week-old piglets one day before and one, four, and seven days after two different injury types (diffuse and focal) or sham. From these recordings, we generated event-related potential functional networks and assessed whether the patterns of the observed changes in these networks could distinguish brain-injured piglets from non-injured. Piglet brains exhibited significant changes after injury, as evaluated by five network metrics. The injury prediction algorithm developed from our analysis of the changes in the event-related potentials functional networks ultimately produced a tool with 82% predictive accuracy. This novel approach is the first application of auditory event-related potential functional networks to the prediction of traumatic brain injury. The resulting tool is a robust, objective and predictive method that offers promise for detecting mild traumatic brain injury, in particular because collecting event-related potentials data is noninvasive and inexpensive. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

Evaluation of electrical aversion therapy for inappropriate sexual behaviour after traumatic brain injury: a single case experimental design study

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ter Mors, Bert Jan; van Heugten, Caroline M; van Harten, Peter N

2012-01-01

Inappropriate sexual behaviour after acquired brain injury is a severe complication. Evidence for effective treatment is not available. Electrical aversion therapy (EAT) is a behavioural therapeutic option used in persons with intellectual disabilities, which might be suitable for brain-injured individuals for whom other therapies are not effective. The effect of EAT in brain injury has not been investigated previously. A single case experimental design was used. In an ABBA (baseline-treatment-treatment-withdrawal) design the frequency of the target behaviour (ie, inappropriate sexual behaviour) in a 40-year-old man was measured daily. A total of 551 measurements were recorded. A significant reduction of the target behaviour was seen after the first treatment phase (baseline 12.18 (2.59) vs 3.15 (3.19) mean target behaviours daily); this reduction remained stable over time. We conclude that EAT was effective in this patient with inappropriate sexual behaviour due to severe brain injury. EAT can therefore be considered in therapy resistant inappropriate sexual behaviour in brain-injured patients. PMID:22922913

Predicting brain mechanics during closed head impact : numerical and constitutive aspects

NARCIS (Netherlands)

Brands, D.W.A.

2002-01-01

Annually, motor vehicle crashes world wide cause over a million fatalities and over a hundred million injuries. Of all body parts, the head is identified as the body region most frequently involved in life-threatening injury. To understand how the brain gets injured during an accident, the

The role of mitochondrial ROS in the aging brain.

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Stefanatos, Rhoda; Sanz, Alberto

2018-03-01

The brain is the most complex human organ, consuming more energy than any other tissue in proportion to its size. It relies heavily on mitochondria to produce energy and is made up of mitotic and postmitotic cells that need to closely coordinate their metabolism to maintain essential bodily functions. During aging, damaged mitochondria that produce less ATP and more reactive oxygen species (ROS) accumulate. The current consensus is that ROS cause oxidative stress, damaging mitochondria and resulting in an energetic crisis that triggers neurodegenerative diseases and accelerates aging. However, in model organisms, increasing mitochondrial ROS (mtROS) in the brain extends lifespan, suggesting that ROS may participate in signaling that protects the brain. Here, we summarize the mechanisms by which mtROS are produced at the molecular level, how different brain cells and regions produce different amounts of mtROS, and how mtROS levels change during aging. Finally, we critically discuss the possible roles of ROS in aging as signaling molecules and damaging agents, addressing whether age-associated increases in mtROS are a cause or a consequence of aging. © 2017 Federation of European Biochemical Societies.

Naftidrofuryl affects neurite regeneration by injured adult auditory neurons.

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Lefebvre, P P; Staecker, H; Moonen, G; van de Water, T R

1993-07-01

Afferent auditory neurons are essential for the transmission of auditory information from Corti's organ to the central auditory pathway. Auditory neurons are very sensitive to acute insult and have a limited ability to regenerate injured neuronal processes. Therefore, these neurons appear to be a limiting factor in restoration of hearing function following an injury to the peripheral auditory receptor. In a previous study nerve growth factor (NGF) was shown to stimulate neurite repair but not survival of injured auditory neurons. In this study, we have demonstrated a neuritogenesis promoting effect of naftidrofuryl in an vitro model for injury to adult auditory neurons, i.e. dissociated cell cultures of adult rat spiral ganglia. Conversely, naftidrofuryl did not have any demonstrable survival promoting effect on these in vitro preparations of injured auditory neurons. The potential uses of this drug as a therapeutic agent in acute diseases of the inner ear are discussed in the light of these observations.

Drowning stars: reassessing the role of astrocytes in brain edema.

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Thrane, Alexander S; Rangroo Thrane, Vinita; Nedergaard, Maiken

2014-11-01

Edema formation frequently complicates brain infarction, tumors, and trauma. Despite the significant mortality of this condition, current treatment options are often ineffective or incompletely understood. Recent studies have revealed the existence of a brain-wide paravascular pathway for cerebrospinal (CSF) and interstitial fluid (ISF) exchange. The current review critically examines the contribution of this 'glymphatic' system to the main types of brain edema. We propose that in cytotoxic edema, energy depletion enhances glymphatic CSF influx, whilst suppressing ISF efflux. We also argue that paravascular inflammation or 'paravasculitis' plays a critical role in vasogenic edema. Finally, recent advances in diagnostic imaging of glymphatic function may hold the key to defining the edema profile of individual patients, and thus enable more targeted therapy. Copyright © 2014 Elsevier Ltd. All rights reserved.

Brain Energy and Oxygen Metabolism: Emerging Role in Normal Function and Disease

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Michelle E. Watts

2018-06-01

Full Text Available Dynamic metabolic changes occurring in neurons are critically important in directing brain plasticity and cognitive function. In other tissue types, disruptions to metabolism and the resultant changes in cellular oxidative state, such as increased reactive oxygen species (ROS or induction of hypoxia, are associated with cellular stress. In the brain however, where drastic metabolic shifts occur to support physiological processes, subsequent changes to cellular oxidative state and induction of transcriptional sensors of oxidative stress likely play a significant role in regulating physiological neuronal function. Understanding the role of metabolism and metabolically-regulated genes in neuronal function will be critical in elucidating how cognitive functions are disrupted in pathological conditions where neuronal metabolism is affected. Here, we discuss known mechanisms regulating neuronal metabolism as well as the role of hypoxia and oxidative stress during normal and disrupted neuronal function. We also summarize recent studies implicating a role for metabolism in regulating neuronal plasticity as an emerging neuroscience paradigm.

The role of insulin receptor signaling in the brain.

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Plum, Leona; Schubert, Markus; Brüning, Jens C

2005-03-01

The insulin receptor (IR) is expressed in various regions of the developing and adult brain, and its functions have become the focus of recent research. Insulin enters the central nervous system (CNS) through the blood-brain barrier by receptor-mediated transport to regulate food intake, sympathetic activity and peripheral insulin action through the inhibition of hepatic gluconeogenesis and reproductive endocrinology. On a molecular level, some of the effects of insulin converge with those of the leptin signaling machinery at the point of activation of phosphatidylinositol 3-kinase (PI3K), resulting in the regulation of ATP-dependent potassium channels. Furthermore, insulin inhibits neuronal apoptosis via activation of protein kinase B in vitro, and it regulates phosphorylation of tau, metabolism of the amyloid precursor protein and clearance of beta-amyloid from the brain in vivo. These findings indicate that neuronal IR signaling has a direct role in the link between energy homeostasis, reproduction and the development of neurodegenerative diseases.

Reorganization of Functional Brain Maps After Exercise Training: Importance of Cerebellar-Thalamic-Cortical Pathway

OpenAIRE

Holschneider, DP; Yang, J; Guo, Y; Maarek, J-M I

2007-01-01

Exercise training (ET) causes functional and morphologic changes in normal and injured brain. While studies have examined effects of short-term (same day) training on functional brain activation, less work has evaluated effects of long-term training, in particular treadmill running. An improved understanding is relevant as changes in neural reorganization typically require days to weeks, and treadmill training is a component of many neurorehabilitation programs.

The role of p97 in iron metabolism in human brain glioma cells

International Nuclear Information System (INIS)

Xia Chunlin; Chen Guiwen; Qian Zhongming

2000-01-01

Objective: To investigate the role of p97 (melanotransferrin) in iron uptake in human brain glioma cells . Methods: Human brain glioma cell lines, GBM and BT325 were incubated in the medium containing 59 Fe-Citrate. The cells were treated with phosphatidylinositol-phospholipase C (PI-PLC) and pronase. The iron uptake of the cells was expressed as relative iron uptake level according to the cpm measured by the gamma scintillation counter. Results: 59 Fe uptake of the cells was significantly declined with the certain concentration of PI-PCL. 59 Fe uptake of the cells treated with pronase tended to coincide with that of the cells treated without pronase in the increasing concentration of PI-PLC. Conclusion: p97 expresses a high level and plays an important role in iron uptake in human brain glioma cells

Low-frequency pulsed electromagnetic field pretreated bone marrow-derived mesenchymal stem cells promote the regeneration of crush-injured rat mental nerve.

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Seo, NaRi; Lee, Sung-Ho; Ju, Kyung Won; Woo, JaeMan; Kim, BongJu; Kim, SoungMin; Jahng, Jeong Won; Lee, Jong-Ho

2018-01-01

Bone marrow-derived mesenchymal stem cells (BMSCs) have been shown to promote the regeneration of injured peripheral nerves. Pulsed electromagnetic field (PEMF) reportedly promotes the proliferation and neuronal differentiation of BMSCs. Low-frequency PEMF can induce the neuronal differentiation of BMSCs in the absence of nerve growth factors. This study was designed to investigate the effects of low-frequency PEMF pretreatment on the proliferation and function of BMSCs and the effects of low-frequency PEMF pre-treated BMSCs on the regeneration of injured peripheral nerve using in vitro and in vivo experiments. In in vitro experiments, quantitative DNA analysis was performed to determine the proliferation of BMSCs, and reverse transcription-polymerase chain reaction was performed to detect S100 (Schwann cell marker), glial fibrillary acidic protein (astrocyte marker), and brain-derived neurotrophic factor and nerve growth factor (neurotrophic factors) mRNA expression. In the in vivo experiments, rat models of crush-injured mental nerve established using clamp method were randomly injected with low-frequency PEMF pretreated BMSCs, unpretreated BMSCs or PBS at the injury site (1 × 10 6 cells). DiI-labeled BMSCs injected at the injury site were counted under the fluorescence microscope to determine cell survival. One or two weeks after cell injection, functional recovery of the injured nerve was assessed using the sensory test with von Frey filaments. Two weeks after cell injection, axonal regeneration was evaluated using histomorphometric analysis and retrograde labeling of trigeminal ganglion neurons. In vitro experiment results revealed that low-frequency PEMF pretreated BMSCs proliferated faster and had greater mRNA expression of growth factors than unpretreated BMSCs. In vivo experiment results revealed that compared with injection of unpretreated BMSCs, injection of low-frequency PEMF pretreated BMSCs led to higher myelinated axon count and axon density and

Nonmechanical Roles of Dystrophin and Associated Proteins in Exercise, Neuromuscular Junctions, and Brains

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Bailey Nichols

2015-07-01

Full Text Available Dystrophin-glycoprotein complex (DGC is an important structural unit in skeletal muscle that connects the cytoskeleton (f-actin of a muscle fiber to the extracellular matrix (ECM. Several muscular dystrophies, such as Duchenne muscular dystrophy, Becker muscular dystrophy, congenital muscular dystrophies (dystroglycanopathies, and limb-girdle muscular dystrophies (sarcoglycanopathies, are caused by mutations in the different DGC components. Although many early studies indicated DGC plays a crucial mechanical role in maintaining the structural integrity of skeletal muscle, recent studies identified novel roles of DGC. Beyond a mechanical role, these DGC members play important signaling roles and act as a scaffold for various signaling pathways. For example, neuronal nitric oxide synthase (nNOS, which is localized at the muscle membrane by DGC members (dystrophin and syntrophins, plays an important role in the regulation of the blood flow during exercise. DGC also plays important roles at the neuromuscular junction (NMJ and in the brain. In this review, we will focus on recently identified roles of DGC particularly in exercise and the brain.

A High-Performance Application Specific Integrated Circuit for Electrical and Neurochemical Traumatic Brain Injury Monitoring.

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Pagkalos, Ilias; Rogers, Michelle L; Boutelle, Martyn G; Drakakis, Emmanuel M

2018-05-22

This paper presents the first application specific integrated chip (ASIC) for the monitoring of patients who have suffered a Traumatic Brain Injury (TBI). By monitoring the neurophysiological (ECoG) and neurochemical (glucose, lactate and potassium) signals of the injured human brain tissue, it is possible to detect spreading depolarisations, which have been shown to be associated with poor TBI patient outcome. This paper describes the testing of a new 7.5 mm 2 ASIC fabricated in the commercially available AMS 0.35 μm CMOS technology. The ASIC has been designed to meet the demands of processing the injured brain tissue's ECoG signals, recorded by means of depth or brain surface electrodes, and neurochemical signals, recorded using microdialysis coupled to microfluidics-based electrochemical biosensors. The potentiostats use switchedcapacitor charge integration to record currents with 100 fA resolution, and allow automatic gain changing to track the falling sensitivity of a biosensor. This work supports the idea of a "behind the ear" wireless microplatform modality, which could enable the monitoring of currently non-monitored mobile TBI patients for the onset of secondary brain injury. ©2018 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA.

Relationship between changes of N-methyl-D-aspartate receptor activity and brain edema after brain injury in rats

Institute of Scientific and Technical Information of China (English)

无

2001-01-01

Objective:　To investigate the relationship between the changes of N-methyl-D-aspartate (NMDA) receptor activity and brain edema after injury in rats. 　　Methods:　The brain injury models were made by using a free-falling body. The treatment model was induced by means of injecting AP5 into lateral ventricle before brain injury; water contents in brain cortex were measured with dry-wet method; and NMDA receptor activity was detected with a radio ligand binding assay. 　　Results:　The water contents began to increase at 30 minutes and reached the peak at 6 hours after brain injury. The maximal binding (Bmax) of NMDA receptor increased significantly at 15 minutes and reached the peak at 30 minutes, then decreased gradually and had the lowest value 6 hours after brain injury. Followed the treatment with AP5, NMDA receptor activity in the injured brain showed a normal value; and the water contents were lower than that of AP5-free injury group 24 hours after brain injury. 　　Conclusions:　It suggests that excessive activation of NMDA receptor may be one of the most important factors to induce the secondary cerebral impairments, and AP5 may protect the brain from edema after brain injury.

Understanding the Role of Neuroscience in Brain Based Products: A Guide for Educators and Consumers

Science.gov (United States)

Sylvan, Lesley J.; Christodoulou, Joanna A.

2010-01-01

The term "brain" based is often used to describe learning theories, principles, and products. Although there have been calls urging educators to be cautious in interpreting and using such material, consumers may find it challenging to understand the role of the brain and to discriminate among brain based products to determine which would be…

Neuroanatomical substrates of action perception and understanding: an anatomic likelihood estimation meta-analysis of lesion-symptom mapping studies in brain injured patients.

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Cosimo eUrgesi

2014-05-01

Full Text Available Several neurophysiologic and neuroimaging studies suggested that motor and perceptual systems are tightly linked along a continuum rather than providing segregated mechanisms supporting different functions. Using correlational approaches, these studies demonstrated that action observation activates not only visual but also motor brain regions. On the other hand, brain stimulation and brain lesion evidence allows tackling the critical question of whether our action representations are necessary to perceive and understand others’ actions. In particular, recent neuropsychological studies have shown that patients with temporal, parietal and frontal lesions exhibit a number of possible deficits in the visual perception and the understanding of others’ actions. The specific anatomical substrates of such neuropsychological deficits however are still a matter of debate. Here we review the existing literature on this issue and perform an anatomic likelihood estimation meta-analysis of studies using lesion-symptom mapping methods on the causal relation between brain lesions and non-linguistic action perception and understanding deficits. The meta-analysis encompassed data from 361 patients tested in 11 studies and identified regions in the inferior frontal cortex, the inferior parietal cortex and the middle/superior temporal cortex, whose damage is consistently associated with poor performance in action perception and understanding tasks across studies. Interestingly, these areas correspond to the three nodes of the action observation network that are strongly activated in response to visual action perception in neuroimaging research and that have been targeted in previous brain stimulation studies. Thus, brain lesion mapping research provides converging causal evidence that premotor, parietal and temporal regions play a crucial role in action recognition and understanding.

Role of the Prostaglandin E2 EP1 Receptor in Traumatic Brain Injury

Science.gov (United States)

Glushakov, Alexander V.; Fazal, Jawad A.; Narumiya, Shuh; Doré, Sylvain

2014-01-01

Brain injuries promote upregulation of so-called proinflammatory prostaglandins, notably prostaglandin E2 (PGE2), leading to overactivation of a class of its cognate G-protein-coupled receptors, including EP1, which is considered a promising target for treatment of ischemic stroke. However, the role of the EP1 receptor is complex and depends on the type of brain injury. This study is focused on the investigation of the role of the EP1 receptor in a controlled cortical impact (CCI) model, a preclinical model of traumatic brain injury (TBI). The therapeutic effects of post-treatments with a widely studied EP1 receptor antagonist, SC-51089, were examined in wildtype and EP1 receptor knockout C57BL/6 mice. Neurological deficit scores (NDS) were assessed 24 and 48 h following CCI or sham surgery, and brain immunohistochemical pathology was assessed 48 h after surgery. In wildtype mice, CCI resulted in an obvious cortical lesion and localized hippocampal edema with an associated significant increase in NDS compared to sham-operated animals. Post-treatments with the selective EP1 receptor antagonist SC-51089 or genetic knockout of EP1 receptor had no significant effects on cortical lesions and hippocampal swelling or on the NDS 24 and 48 h after CCI. Immunohistochemistry studies revealed CCI-induced gliosis and microglial activation in selected ipsilateral brain regions that were not affected by SC-51089 or in the EP1 receptor-deleted mice. This study provides further clarification on the respective contribution of the EP1 receptor in TBI and suggests that, under this experimental paradigm, the EP1 receptor would have limited effects in modulating acute neurological and anatomical pathologies following contusive brain trauma. Findings from this protocol, in combination with previous studies demonstrating differential roles of EP1 receptor in ischemic, neurotoxic, and hemorrhagic conditions, provide scientific background and further clarification of potential therapeutic

A prospective study on time to recovery in 254 injured novice runners.

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Rasmus Oestergaard Nielsen

Full Text Available Describe the diagnoses and the time to recovery of running-related injuries in novice runners.Prospective cohort study on injured runners.This paper is a secondary data analysis of a 933-person cohort study (DANO-RUN aimed at characterizing risk factors for injury in novice runners. Among those sustaining running-related injuries, the types of injuries and time to recovery is described in the present paper. All injured runners were diagnosed after a thorough clinical examination and then followed prospectively during their recovery. If they recovered completely from injury, time to recovery of each injury was registered.A total of 254 runners were injured. The proportion of runners diagnosed with medial tibial stress syndrome was 15%, 10% for patellofemoral pain, 9% for medial meniscal injury, 7% for Achilles tendinopathy and 5% for plantar fasciitis. Among the 220 runners (87% recovering from their injury, the median time to recovery was 71 days (minimum  = 9 days, maximum  = 617 days.Medial tibial stress syndrome was the most common injury followed by patellofemoral pain, medial meniscal injury and Achilles tendinopathy. Half of the injured runners were unable to run 2×500 meters without pain after 10 weeks. Almost 5% of the injured runners received surgical treatment.

Safety knowledge and risk behaviour of injured and uninjured young skiers and snowboarders.

Science.gov (United States)

Macnab, A J; Cadman, R E; Greenlaw, J V

1998-09-01

Earlier studies of ski injury indicated that youths were at increased risk of injury, that males were most likely to injure the head or face, and that females were most likely to injure the knee. To obtain information about safety knowledge and risk behaviour that might contribute to injury among young skiers and snow-boarders. Survey of knowledge and behaviour in injured and noninjured cohorts. Blackcomb Mountain, Whistler, British Columbia. A total of 863 noninjured and 118 injured skiers and snowboarders aged five to 17 years using Blackcomb during 1993/94. Skier Knowledge Inventory Questionnaire. The injured cohort had less knowledge of the Skiers Responsibility Code. In both groups, almost half had had no lessons, 31% had had bindings adjusted by nonprofessionals and chair lift safety bars were used one ride in four by children age 13 to 17 years. The injuried cohort wore helmets slightly less often. Both groups regularly skied through the trees (60% to 70%), and one-thirds had skied on closed runs. Excessive speed was identified as the major cause of injury. Skiers did not recognize jumping as contributing to injury. Lack of knowledge of safety rules was more prevalent among the injured cohort. Skiing without due care - including skiing through tress, skiing on closed runs, skiing with excessive speed and jumping, particularly by snowboarders - were identified as potential causes of injury.

β1 integrin signaling promotes neuronal migration along vascular scaffolds in the post-stroke brain

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Teppei Fujioka

2017-02-01

Full Text Available Cerebral ischemic stroke is a main cause of chronic disability. However, there is currently no effective treatment to promote recovery from stroke-induced neurological symptoms. Recent studies suggest that after stroke, immature neurons, referred to as neuroblasts, generated in a neurogenic niche, the ventricular-subventricular zone, migrate toward the injured area, where they differentiate into mature neurons. Interventions that increase the number of neuroblasts distributed at and around the lesion facilitate neuronal repair in rodent models for ischemic stroke, suggesting that promoting neuroblast migration in the post-stroke brain could improve efficient neuronal regeneration. To move toward the lesion, neuroblasts form chain-like aggregates and migrate along blood vessels, which are thought to increase their migration efficiency. However, the molecular mechanisms regulating these migration processes are largely unknown. Here we studied the role of β1-class integrins, transmembrane receptors for extracellular matrix proteins, in these migrating neuroblasts. We found that the neuroblast chain formation and blood vessel-guided migration critically depend on β1 integrin signaling. β1 integrin facilitated the adhesion of neuroblasts to laminin and the efficient translocation of their soma during migration. Moreover, artificial laminin-containing scaffolds promoted neuroblast chain formation and migration toward the injured area. These data suggest that laminin signaling via β1 integrin supports vasculature-guided neuronal migration to efficiently supply neuroblasts to injured areas. This study also highlights the importance of vascular scaffolds for cell migration in development and regeneration.

Effect of Mindfulness Based Stress Reduction (MBSR in Increasing Pain Tolerance and Improving the Mental Health of Injured Athletes

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Warhel Asim Mohammed

2018-05-01

Full Text Available Literature indicates that injured athletes face both physical and psychological distress after they have been injured. In this study, a Mindfulness Based Stress Reduction (MBSR was utilised as an intervention for use during the period of recovery with injured athletes and, to the best of our knowledge, this is the first study using MBSR as an intervention for this purpose.Objective: The aim of this research was to investigate the role of MBSR practise in reducing the perception of pain and decreasing anxiety/stress, as well as increasing pain tolerance and mindfulness. An additional aim was to increase positive mood and decrease negative mood in injured athletes.Methods: The participants comprised of twenty athletes (male = 14; female = 6; age range = 21–36 years who had severe injuries, preventing their participation in sport for more than 3 months. Prior to their injury, the participants had trained regularly with their University teams and participated in official university championships. Both groups followed their normal physiotherapy treatment, but in addition, the intervention group practised mindfulness meditation for 8 weeks (one 90-min session/week. A Cold Pressor Test (CPT was used to assess pain tolerance. In contrast, the perception of pain was measured using a Visual Analogue Scale. Other measurements used were the Mindful Attention Awareness Scale (MAAS, Depression Anxiety and Stress Scale (DASS, and Profile of Mood States (POMS.Results: Our results demonstrated an increase in pain tolerance for the intervention group and an increase in mindful awareness for injured athletes. Moreover, our findings observed a promising change in positive mood for both groups. Regarding the Stress/Anxiety scores, our findings showed a notable decrease across sessions; however, no significant changes were observed in other main and interaction effects in both groups.Conclusion: Injured athletes can benefit from using mindfulness as part of the

Plasticity and regeneration in the injured spinal cord after cell transplantation therapy.

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Nori, Satoshi; Nakamura, Masaya; Okano, Hideyuki

2017-01-01

Spinal cord injury (SCI) typically damages the long axonal tracts of the spinal cord which results in permanent disability. However, regeneration of the injured spinal cord is approaching reality according to the advances in stem cell biology. Cell transplantation therapy holds potential to lead to recovery following SCI through some positive mechanisms. Grafted cells induce plasticity and regeneration in the injured spinal cord by promoting remyelination of damaged axons, reconstruction of neural circuits by synapse formation between host neurons and graft-derived neurons, and secreting neurotrophic factors to promote axonal elongation as well as reduce retrograde axonal degeneration. In this review, we will delineate (1) the microenvironment of the injured spinal cord that influence the plasticity and regeneration capacity after SCI, (2) a number of different kinds of cell transplantation therapies for SCI that has been extensively studied by researchers, and (3) potential mechanisms of grafted cell-induced regeneration and plasticity in the injured spinal cord. © 2017 Elsevier B.V. All rights reserved.

The Role of P-Glycoprotein in Transport of Danshensu across the Blood-Brain Barrier

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Peng-Fei Yu

2011-01-01

Full Text Available Danshensu (3-(3, 4-dihydroxyphenyl lactic acid, a water-soluble active component isolated from the root of Salvia miltiorrhiza Bunge, is widely used for the treatment of cerebrovascular diseases. The present study aims to investigate the role of P-glycoprotein in transport of Danshensu across the blood-brain barrier. Sprague-Dawley rats were pretreated with verapamil at a dose of 20 mg kg−1 (verapamil group or the same volume of normal saline (control group. Ninety minutes later, the animals were administrated with Danshensu (15 mg kg−1 by intravenous injection. At 15 min, 30 min, and 60 min after Danshensu administration, the levels of Danshensu in the blood and brain were detected by high-performance liquid chromatography-electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS. The results showed that Danshensu concentrations in the brain of the rats pretreated with verapamil were significantly increased. In addition, the brain-plasma ratios of the group pretreated with verapamil were much higher than that of the control group. There was no difference in Danshensu level in plasma between the verapamil group and control group. The findings indicated that Danshensu can pass the blood-brain barrier, and P-glycoprotein plays an important role in Danshensu transportation in brain.

3-62 Protective Effects of Hydroxysaffor Yellow A on Brain Injury in Mice Irradiated by 300 MeV/u 12C6+ Ions

Institute of Scientific and Technical Information of China (English)

Gan; Lu[1; Zhang; Hong[1

2015-01-01

Radiotherapy is a common treatment modality for head and neck cancers, nasopharyngeal cancers, primary brain tumors and brain metastases. A large number of patients in the world with primary or metastatic brain tumors will require large volume or whole brain irradiation every year. However, therapeutic irradiation not only kills tumor cells, but also injures normal brain tissue, which is commonly associated with significant functional morbidity and decreased quality of life in patients treated with brain radiotherapy[1].

Psychiatric morbidity among physically injured Syrian refugees in Turkey.

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Al-Nuaimi, Saleem; Aldandashi, Samer; Easa, Abdul Kadir Saed; Saqqur, Maher

2018-01-01

To the best of our knowledge, the mental health status of physically injured Syrian refugees has not yet been investigated. The aim of this study was to examine the prevalence of psychiatric morbidity among physically injured Syrian refugees in Turkey receiving treatment at the main rehabilitation centre near the Syrian border. This is a cross sectional study. Information was collected from consenting injured Syrian refugees at Dar-el-Shefa'a Hospital in Reyhanlı (Turkey) during a one week period in December 2012 and another one week period in August 2013. A clinical psychiatric interview was conducted to determine a diagnosis according to the diagnostic criteria of the Diagnostic and Statistical Manual of Mental Disorders (DSM) IV-TR. A total of 40 refugees consented and completed a clinical psychiatric interview. All refugees in this study did not have a significant past psychiatric history. The most prevalent current diagnosis was major depressive disorder (22.5%), adjustment disorder (20%), and post-traumatic stress disorder (15%). Five (12.5%) patients had no evidence of a psychiatric disorder. The prevalence of psychiatric morbidity among injured Syrian refugees in our study was extremely high. This may help guide the treatment and management of this select population. This study had a low number of participants. The method of assessment was not standardized with a validated tool. This study may help guide the treatment and management of this select population, both in neighbouring countries and as resettled refugees in Western host countries. Copyright © 2017 Elsevier Inc. All rights reserved.

The Ror1 receptor tyrosine kinase plays a critical role in regulating satellite cell proliferation during regeneration of injured muscle.

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Kamizaki, Koki; Doi, Ryosuke; Hayashi, Makoto; Saji, Takeshi; Kanagawa, Motoi; Toda, Tatsushi; Fukada, So-Ichiro; Ho, Hsin-Yi Henry; Greenberg, Michael Eldon; Endo, Mitsuharu; Minami, Yasuhiro

2017-09-22

The Ror family receptor tyrosine kinases, Ror1 and Ror2, play important roles in regulating developmental morphogenesis and tissue- and organogenesis, but their roles in tissue regeneration in adult animals remain largely unknown. In this study, we examined the expression and function of Ror1 and Ror2 during skeletal muscle regeneration. Using an in vivo skeletal muscle injury model, we show that expression of Ror1 and Ror2 in skeletal muscles is induced transiently by the inflammatory cytokines, TNF-α and IL-1β, after injury and that inhibition of TNF-α and IL-1β by neutralizing antibodies suppresses expression of Ror1 and Ror2 in injured muscles. Importantly, expression of Ror1 , but not Ror2 , was induced primarily in Pax7-positive satellite cells (SCs) after muscle injury, and administration of neutralizing antibodies decreased the proportion of Pax7-positive proliferative SCs after muscle injury. We also found that stimulation of a mouse myogenic cell line, C2C12 cells, with TNF-α or IL-1β induced expression of Ror1 via NF-κB activation and that suppressed expression of Ror1 inhibited their proliferative responses in SCs. Intriguingly, SC-specific depletion of Ror1 decreased the number of Pax7-positive SCs after muscle injury. Collectively, these findings indicate for the first time that Ror1 has a critical role in regulating SC proliferation during skeletal muscle regeneration. We conclude that Ror1 might be a suitable target in the development of diagnostic and therapeutic approaches to manage muscular disorders. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Psychosocial Adjustment and Life Satisfaction until 5 Years after Severe Brain Damage

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Sorbo, Ann K.; Blomqvist, Maritha; Emanuelsson, Ingrid M.; Rydenhag, Bertil

2009-01-01

The objectives of this study were to describe psychosocial adjustment and outcome over time for severely brain-injured patients and to find suitable outcome measures for clinical practice during the rehabilitation process and for individual rehabilitation planning after discharge from hospital. The methods include a descriptive, prospective,…

Mitochondrial targeted neuron focused genes in hippocampus of rats with traumatic brain injury.

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Sharma, Pushpa; Su, Yan A; Barry, Erin S; Grunberg, Neil E; Lei, Zhang

2012-09-01

Mild traumatic brain injury (mTBI) represents a major health problem in civilian populations as well as among the military service members due to (1) lack of effective treatments, and (2) our incomplete understanding about the progression of secondary cell injury cascades resulting in neuronal cell death due to deficient cellular energy metabolism and damaged mitochondria. The aim of this study was to identify and delineate the mitochondrial targeted genes responsible for altered brain energy metabolism in the injured brain. Rats were either grouped into naïve controls or received lateral fluid percussion brain injury (2-2.5 atm) and followed up for 7 days. Rats were either grouped into naïve controls or received lateral fluid percussion brain injury (2-2.5 atm) and followed for 7 days. The severity of brain injury was evaluated by the neurological severity scale-revised (NSS-R) at 3 and 5 days post TBI and immunohistochemical analyses at 7 days post TBI. The expression profiles of mitochondrial-targeted genes across the hippocampus from TBI and naïe rats were also examined by oligo-DNA microarrays. NSS-R scores of TBI rats (5.4 ± 0.5) in comparison to naïe rats (3.9 ± 0.5) and H and E staining of brain sections suggested a mild brain injury. Bioinformatics and systems biology analyses showed 31 dysregulated genes, 10 affected canonical molecular pathways including a number of genes involved in mitochondrial enzymes for oxidative phosphorylation, mitogen-activated protein Kinase (MAP), peroxisome proliferator-activated protein (PPAP), apoptosis signaling, and genes responsible for long-term potentiation of Alzheimer's and Parkinson's diseases. Our results suggest that dysregulated mitochondrial-focused genes in injured brains may have a clinical utility for the development of future therapeutic strategies aimed at the treatment of TBI.

Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

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Michinaga, Shotaro; Nagase, Marina; Matsuyama, Emi; Yamanaka, Daisuke; Seno, Naoki; Fuka, Mayu; Yamamoto, Yui; Koyama, Yutaka

2014-01-01

Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs) are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice). Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV) administration of BQ788 (ETB antagonist), IRL-2500 (ETB antagonist), or FR139317 (ETA antagonist) prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

On the crucial cerebellar wound healing-related pathways and their cross-talks after traumatic brain injury in Danio rerio.

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Chia-Chou Wu

Full Text Available Upon injury, the direct damage and the subsequent secondary injury in the brain often result in chronic neurological disorders. Due to multifactorial nature of secondary injury and subsequent complex cellular responses, much of the underlying mechanisms are unclear. This study used an adult zebrafish cerebellum injury model to investigate the phenotypes and the secondary injury responses for recovery mechanisms of injured brain. Using the time course microarray analysis, a candidate protein-protein interaction (PPI network was refined as cerebellar wound healing PPI network by dynamic modeling and big data mining. Pathway enrichment and ontological analysis were incorporated into the refined network to highlight the main molecular scheme of cerebellar wound healing. Several significant pathways, including chemokine, Phosphatidylinositide 3-kinases, and axon guidance signaling pathway and their cross-talks through PI3K, PAK2, and PLXNA3 were identified to coordinate for neurogenesis and angiogenesis, which are essential for the restoration of the injured brain. Our finding provides an insight into the molecular restoration mechanisms after traumatic brain injury, and open up new opportunity to devise the treatment for traumatic brain injury in human.

From an unlicensed philosopher: reflections on brain, mind, society, culture--each other's environments with equal "ontologic standing".

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Shay, Jonathan

2010-10-01

Philosophic conclusions drawn from work with psychologically and morally injured combat veterans include that brain, mind, society, and culture "co-evolved." The four encompass the complete human phenomenon, but not all are reducible to the physical brain. None of the four are "ontologically prior" to the others, when viewed over the entire lifecycle. All four are what I call "each other's environments," with obligatory cross-boundary flows--each with each in both directions. Rigorous, but nonreductionist interdisciplinary research, in the vein of "evo-devo" in embryology, is called for in the study of the human phenomena. On the basis of these conclusions, I offer a few practical comments on clinical work with psychologically and morally injured combat veterans. © 2010 Association for Research in Nervous and Mental Disease.

The UDP-glucuronosyltransferases of the blood-brain barrier: their role in drug metabolism and detoxication

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Mohamed eOuzzine

2014-10-01

Full Text Available UDP-glucuronosyltransferases (UGTs form a multigenic family of membrane-bound enzymes expressed in various tissues, including brain. They catalyze the formation of β-Dglucuronides from structurally unrelated substances (drugs, other xenobiotics, as well as endogenous compounds by the linkage of glucuronic acid from the high energy donor, UDP-αD-glucuronic acid. In brain, UGTs actively participate to the overall protection of the tissue against the intrusion of potentially harmful lipophilic substances that are metabolized as hydrophilic glucuronides. These metabolites are generally inactive, except for important pharmacologically glucuronides such as morphine-6-glucuronide. UGTs are mainly expressed in endothelial cells and astrocytes of the blood brain barrier. They are also associated to brain interfaces devoid of blood-brain barrier, such as circumventricular organ, pineal gland, pituitary gland and neuro-olfactory tissues. Beside their key-role as a detoxication barrier, UGTs play a role in the steady-state of endogenous compounds, like steroids or dopamine that participate to the function of the brain. UGT isoforms of family 1A, 2A, 2B and 3A are expressed in brain tissues to various levels and are known to present distinct but overlapping substrate specificity. The importance of these enzyme species with regard to the formation of toxic, pharmacologically or physiologically relevant glucuronides in the brain will be discussed.

Decreased resting functional connectivity after traumatic brain injury in the rat.

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Asht Mangal Mishra

Full Text Available Traumatic brain injury (TBI contributes to about 10% of acquired epilepsy. Even though the mechanisms of post-traumatic epileptogenesis are poorly known, a disruption of neuronal networks predisposing to altered neuronal synchrony remains a viable candidate mechanism. We tested a hypothesis that resting state BOLD-fMRI functional connectivity can reveal network abnormalities in brain regions that are connected to the lesioned cortex, and that these changes associate with functional impairment, particularly epileptogenesis. TBI was induced using lateral fluid-percussion injury in seven adult male Sprague-Dawley rats followed by functional imaging at 9.4T 4 months later. As controls we used six sham-operated animals that underwent all surgical operations but were not injured. Electroencephalogram (EEG-functional magnetic resonance imaging (fMRI was performed to measure resting functional connectivity. A week after functional imaging, rats were implanted with bipolar skull electrodes. After recovery, rats underwent pentyleneterazol (PTZ seizure-susceptibility test under EEG. For image analysis, four pairs of regions of interests were analyzed in each hemisphere: ipsilateral and contralateral frontal and parietal cortex, hippocampus, and thalamus. High-pass and low-pass filters were applied to functional imaging data. Group statistics comparing injured and sham-operated rats and correlations over time between each region were calculated. In the end, rats were perfused for histology. None of the rats had epileptiform discharges during functional imaging. PTZ-test, however revealed increased seizure susceptibility in injured rats as compared to controls. Group statistics revealed decreased connectivity between the ipsilateral and contralateral parietal cortex and between the parietal cortex and hippocampus on the side of injury as compared to sham-operated animals. Injured animals also had abnormal negative connectivity between the ipsilateral and

Brain Death in Islamic Jurisprudence

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A Nikzad

2016-07-01

Full Text Available BACKGROUND AND OBJECTIVE: In today's world, Islamic jurisprudence encounters  new issues. One of the areas where jurisprudence gets involved is the issues concerned with brain death, whether brain death in jurisprudence and Islamic law is considered the end of life. In this study, brain death was discussed from the Shiite jurisprudence perspective and also the opinions of the specialists are taken into account. METHODS: This study is designed based on library collection and review of the literature in the field of brain death. Also, Quranic verses, hadiths and fatwas (religious opinions of the scholars are used. Some of the articles which were centered around Islamic jurisprudence, particularly Shiite jurisprudence that explain and deal with brain death were given special consideration. FINDINGS: Brain death from religious and jurisprudence perspective is considered the termination of life and removing the vital organs from the body is not viewed as committing manslaughter. A person with brain death is not a normally known injured man who is still alive. The brain death patinets have no life and getting rid of the body does not constitute a case of manslaughter. Amputation of the organs of brain death patients for donation and transplantation amounts to the amputation of a dead body. If the life of a Muslim is subject to transplant of organs from the body of a brain death patient, it will be permissible. CONCLUSION: In principle, if the life of a Muslim entails transplant of organs of brain death patients, it will be permissible 

Repetitive long-term hyperbaric oxygen treatment (HBOT administered after experimental traumatic brain injury in rats induces significant remyelination and a recovery of sensorimotor function.

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Klaus Kraitsy

Full Text Available Cells in the central nervous system rely almost exclusively on aerobic metabolism. Oxygen deprivation, such as injury-associated ischemia, results in detrimental apoptotic and necrotic cell loss. There is evidence that repetitive hyperbaric oxygen therapy (HBOT improves outcomes in traumatic brain-injured patients. However, there are no experimental studies investigating the mechanism of repetitive long-term HBOT treatment-associated protective effects. We have therefore analysed the effect of long-term repetitive HBOT treatment on brain trauma-associated cerebral modulations using the lateral fluid percussion model for rats. Trauma-associated neurological impairment regressed significantly in the group of HBO-treated animals within three weeks post trauma. Evaluation of somatosensory-evoked potentials indicated a possible remyelination of neurons in the injured hemisphere following HBOT. This presumption was confirmed by a pronounced increase in myelin basic protein isoforms, PLP expression as well as an increase in myelin following three weeks of repetitive HBO treatment. Our results indicate that protective long-term HBOT effects following brain injury is mediated by a pronounced remyelination in the ipsilateral injured cortex as substantiated by the associated recovery of sensorimotor function.

Role of Intercellular Adhesion Molecule-1 in Radiation-Induced Brain Injury

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Wu, K.-L.; Tu Ba; Li Yuqing; Wong, C. Shun

2010-01-01

Purpose: To determine the role of intercellular adhesion molecule-1 (ICAM-1) in the pathogenesis of brain injury after irradiation (IR). Methods and Materials: We assessed the expression of ICAM-1 in mouse brain after cranial IR and determined the histopathologic and behavioral changes in mice that were either wildtype (+/+) or knockout (-/-) of the ICAM-1 gene after IR. Results: There was an early dose-dependent increase in ICAM-1 mRNA and protein expression after IR. Increased ICAM-1 immunoreactivity was observed in endothelia and glia of ICAM-1+/+ mice up to 8 months after IR. ICAM-1-/- mice showed no expression. ICAM-1+/+ and ICAM-1-/- mice showed similar vascular abnormalities at 2 months after 10-17 Gy, and there was evidence for demyelination and inhibition of hippocampal neurogenesis at 8 months after 10 Gy. After 10 Gy, irradiated ICAM-1+/+ and ICAM-1-/- mice showed similar behavioral changes at 2-6 months in open field, light-dark chamber, and T-maze compared with age-matched genotype controls. Conclusion: There is early and late upregulation of ICAM-1 in the vasculature and glia of mouse brain after IR. ICAM-1, however, does not have a causative role in the histopathologic injury and behavioral dysfunction after moderate single doses of cranial IR.

Sexuality and sexual dysfunction in spinal cord-injured men in Turkey.

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Akman, Ramazan Yavuz; Coşkun Çelik, Evrim; Karataş, Metin

2015-01-01

To provide a comprehensive evaluation of sexual function and dysfunction in spinal cord-injured men based on self-reports of patients. Forty-seven spinal cord-injured men who completed the spinal shock and rehabilitation period were included. Patients were asked to complete a questionnaire developed to assess social status, sexual activities, abilities, and sexuality education after injury. Neurologic levels of patients were classified according to American Spinal Cord Injury Association protocol. Erectile function was evaluated by International Index of Erectile Function-5 (IIEF-5) questionnaire. Patients were aged between 20 and 62 years (mean: 35.2). Twenty-eight patients had T10 and above, 15 between T11 and L2, and 4 cauda conus injury. While 61.7% of the patients declared sexual activity, 93.6% declared some degree of erection. Mean IIEF-5 score was 5.3 and 87.3% of the patients had moderate to severe erectile dysfunction. Continuation of sexual activity after injury is very important and has a great impact on quality of life and interpersonal relationships for spinal cord-injured men. More attention must be given to sexuality after spinal cord injury. A very high rate of sexual dysfunction in spinal cord-injured patients was found and the importance of sexual education was emphasized in this study.

Voltage-gated sodium channel expression in mouse DRG after SNI leads to re-evaluation of projections of injured fibers.

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Laedermann, Cédric J; Pertin, Marie; Suter, Marc R; Decosterd, Isabelle

2014-03-11

Dysregulation of voltage-gated sodium channels (Na(v)s) is believed to play a major role in nerve fiber hyperexcitability associated with neuropathic pain. A complete transcriptional characterization of the different isoforms of Na(v)s under normal and pathological conditions had never been performed on mice, despite their widespread use in pain research. Na(v)s mRNA levels in mouse dorsal root ganglia (DRG) were studied in the spared nerve injury (SNI) and spinal nerve ligation (SNL) models of neuropathic pain. In the SNI model, injured and non-injured neurons were intermingled in lumbar DRG, which were pooled to increase the tissue available for experiments. A strong downregulation was observed for every Na(v)s isoform expressed except for Na(v)1.2; even Na(v)1.3, known to be upregulated in rat neuropathic pain models, was lower in the SNI mouse model. This suggests differences between these two species. In the SNL model, where the cell bodies of injured and non-injured fibers are anatomically separated between different DRG, most Na(v)s were observed to be downregulated in the L5 DRG receiving axotomized fibers. Transcription was then investigated independently in the L3, L4 and L5 DRG in the SNI model, and an important downregulation of many Na(v)s isoforms was observed in the L3 DRG, suggesting the presence of numerous injured neurons there after SNI. Consequently, the proportion of axotomized neurons in the L3, L4 and L5 DRG after SNI was characterized by studying the expression of activating transcription factor 3 (ATF3). Using this marker of nerve injury confirmed that most injured fibers find their cell bodies in the L3 and L4 DRG after SNI in C57BL/6 J mice; this contrasts with their L4 and L5 DRG localization in rats. The spared sural nerve, through which pain hypersensitivity is measured in behavioral studies, mostly projects into the L4 and L5 DRG. The complex regulation of Na(v)s, together with the anatomical rostral shift of the DRG harboring injured

The Relationship between Perceived Sleep Quality, Polysomnographic Measures and Depressive Symptoms in Chemically-Injured Veterans: A Pilot Study.

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Moshkani Farahani, Davood; Tavallaie, Abbas; Vahedi, Ensieh; Rezaiemaram, Peyman; Naderi, Zohreh; Talaie, Akram

2014-07-01

Sleep complaints are common among Iranian chemically-injured veterans. The growing body of research has investigated (in) equalities between such subjective complaints and objective sleep records. Moreover, sleep complaints are associated with depressive symptoms. Depressive symptoms, also, have been frequently reported in chemically-injured veterans. Therefore, the purpose of this pilot study was to investigate the relationship between perceived sleep quality, polysomnographic measures and depressive symptoms in Iranian veterans with chemical injuries. In this pilot study, 35 Iranian veterans with chemical injuries complaining of a sleep problem were selected. Initially, participants were evaluated via all-night polysomnography, then, they completed the research questionnaires. Collected data were analyzed using Pearson correlation coefficients. Data analyses showed that there was no significant correlation between many of self-reposted variables and polysomnogaphic recordings, however, remarkable relationships were found between the Pittsburgh Sleep Quality Index and the Beck Depression Inventory scores. The findings indicated that sleep complaints of chemically-injured veterans are not equivalent to objective sleep disturbances, however, these complaints are largely associated with level of depression. This study emphasizes the important role of mood in sleep evaluation. Further, the findings suggest using a combination of both subjective and objective measures for accurate assessment of sleep quality in Iranian veterans with chemical injuries (i.e., multimethod approach).

Brain Basis of Self: Self-Organization and Lessons from Dreaming

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David eKahn

2013-07-01

Full Text Available Through dreaming a different facet of the self is created as a result of a self-organizing process in the brain. Self-organization in biological systems often happens as an answer to an environmental change for which the existing system cannot cope; self-organization creates a system that can cope in the newly changed environment. In dreaming, self-organization serves the function of organizing disparate memories into a dream since the dreamer herself is not able to control how individual memories become weaved into a dream. The self-organized dream provides, thereby, a wide repertoire of experiences; this expanded repertoire of experience results in an expansion of the self beyond that obtainable when awake. Since expression of the self is associated with activity in specific areas of the brain, the article also discusses the brain basis of the self by reviewing studies of brain injured patients, discussing brain imaging studies in normal brain functioning when focused, when daydreaming and when asleep and dreaming.

Child passengers injured in motor vehicle crashes.

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Romano, Eduardo; Kelley-Baker, Tara

2015-02-01

During 2010, 171,000 children aged 0-14 were injured in motor vehicle crashes. Despite the severity of the problem, research has been limited, and most of what we know about these children emanates from fatal crash databases. Using information from the General Estimates System, this effort examines the occurrence of non-fatal crashes among children aged 0-14 over the last decade. We found that about 1% of the non-injured children in the file had been driven by a driver who was positive for alcohol. This percentage climbed to about 2% among children who had suffered injuries. Compared with the proportion of alcohol-positive drivers at the time of the crash, the proportion of drivers who sped or failed to obey a traffic signal was significantly higher. The finding that drinking and driving with children did not decrease over time questions the adequacy of the extant child endangerment laws. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

Minocycline Transiently Reduces Microglia/Macrophage Activation but Exacerbates Cognitive Deficits Following Repetitive Traumatic Brain Injury in the Neonatal Rat

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Hanlon, Lauren A.; Huh, Jimmy W.

2016-01-01

Elevated microglial/macrophage-associated biomarkers in the cerebrospinal fluid of infant victims of abusive head trauma (AHT) suggest that these cells play a role in the pathophysiology of the injury. In a model of AHT in 11-day-old rats, 3 impacts (24 hours apart) resulted in spatial learning and memory deficits and increased brain microglial/macrophage reactivity, traumatic axonal injury, neuronal degeneration, and cortical and white-matter atrophy. The antibiotic minocycline has been effective in decreasing injury-induced microglial/macrophage activation while simultaneously attenuating cellular and functional deficits in models of neonatal hypoxic ischemia, but the potential for this compound to rescue deficits after impact-based trauma to the immature brain remains unexplored. Acute minocycline administration in this model of AHT decreased microglial/macrophage reactivity in the corpus callosum of brain-injured animals at 3 days postinjury, but this effect was lost by 7 days postinjury. Additionally, minocycline treatment had no effect on traumatic axonal injury, neurodegeneration, tissue atrophy, or spatial learning deficits. Interestingly, minocycline-treated animals demonstrated exacerbated injury-induced spatial memory deficits. These results contrast with previous findings in other models of brain injury and suggest that minocycline is ineffective in reducing microglial/macrophage activation and ameliorating injury-induced deficits following repetitive neonatal traumatic brain injury. PMID:26825312

Differences in kinematics of single leg squatting between anterior cruciate ligament-injured patients and healthy controls.

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Yamazaki, J; Muneta, T; Ju, Y J; Sekiya, I

2010-01-01

Seventy to eighty percent of all anterior cruciate ligament (ACL) injuries are due to non-contact injury mechanisms. It has been reported that the majority of injuries due to single leg landing come from valgus positioning of the lower leg. Preventing valgus positioning during single leg landing is expected to help reduce the number of ACL injuries. We found that many ACL-deficient patients cannot perform stable single leg squatting. Therefore, we performed 3D motion analysis of the single-legged half squat for ACL-injured patients to evaluate its significance as a risk factor for ACL injuries. We evaluated the relative angles between the body, thigh, and lower leg using an electromagnetic device during single leg half squatting performed by 63 ACL-injured patients (32 males, 31 females) the day before ACL reconstruction and by 26 healthy control subjects with no knee problems. The uninjured leg of ACL-injured male subjects demonstrated significantly less external knee rotation than that of the dominant leg of the male control. The uninjured leg of ACL-injured female subjects demonstrated significantly more external hip rotation and knee flexion and less hip flexion than that of the dominant leg of the female control. Comparing injured and uninjured legs, the injured leg of male subjects demonstrated significantly less external knee and hip rotation, less knee flexion, and more knee varus than that of the uninjured leg of male subjects. The injured leg of female subjects demonstrated more knee varus than that of the uninjured leg of female subjects. Regarding gender differences, female subjects demonstrated significantly more external hip rotation and knee valgus than male subjects did in both the injured and uninjured legs (P < 0.05). The current kinematic study exhibited biomechanical characteristics of female ACL-injured subjects compared with that of control groups. Kinematic correction during single leg half squat would reduce ACL reinjury in female ACL-injured

[Classification of severely injured patients in the G-DRG System 2008].

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Juhra, C; Franz, D; Roeder, N; Vordemvenne, T; Raschke, M J

2009-05-01

Since the introduction of a per-case reimbursement system in Germany (German Diagnosis-Related Groups, G-DRG), the correct reimbursement for the treatment of severely injured patients has been much debated. While the classification of a patient in a polytrauma DRG follows different rules than the usual clinical definition, leading to a high number of patients not grouped as severely injured by the system, the system was also criticized in 2005 for its shortcomings in financing the treatment of severely injured patients. The development of financial reimbursement will be discussed in this paper. 167 patients treated in 2006 and 2007 due to a severe injury at the University-Hospital Münster and grouped into a polytrauma-DRG were included in this study. For each patient, cost-equivalents were estimated. For those patients treated in 2007 (n=110), exact costs were calculated following the InEK cost-calculation method. The reimbursement was calculated using the G-DRG-Systems of 2007, 2008 and 2009. Cost-equivalents/costs and clinical parameters were correlated. A total of 167 patients treated in 2006 and 2007 for a severe injury at the Münster University Hospital and grouped into a polytrauma DRG were included in this study. Cost equivalents were estimated for each patient. For those patients treated in 2007 (n=110), exact costs were calculated following the InEK (Institute for the Hospital Remuneration System) cost calculation method. Reimbursement was calculated using the G-DRG systems of 2007, 2008 and 2009. Cost equivalents/costs and clinical parameters were correlated. With the ongoing development of the G-DRG system, reimbursement for the treatment of severely injured patient has improved, but the amount of underfinancing remains substantial. As treatment of severely injured patients must be reimbursed using the G-DRG system, this system must be further adapted to better meet the needs of severely injured patients. Parameters such as total surgery time, injury

Amelioration of cold injury-induced cortical brain edema formation by selective endothelin ETB receptor antagonists in mice.

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Shotaro Michinaga

Full Text Available Brain edema is a potentially fatal pathological condition that often occurs in stroke and head trauma. Following brain insults, endothelins (ETs are increased and promote several pathophysiological responses. This study examined the effects of ETB antagonists on brain edema formation and disruption of the blood-brain barrier in a mouse cold injury model (Five- to six-week-old male ddY mice. Cold injury increased the water content of the injured cerebrum, and promoted extravasation of both Evans blue and endogenous albumin. In the injury area, expression of prepro-ET-1 mRNA and ET-1 peptide increased. Intracerebroventricular (ICV administration of BQ788 (ETB antagonist, IRL-2500 (ETB antagonist, or FR139317 (ETA antagonist prior to cold injury significantly attenuated the increase in brain water content. Bolus administration of BQ788, IRL-2500, or FR139317 also inhibited the cold injury-induced extravasation of Evans blue and albumin. Repeated administration of BQ788 and IRL-2500 beginning at 24 h after cold injury attenuated both the increase in brain water content and extravasation of markers. In contrast, FR139317 had no effect on edema formation when administrated after cold injury. Cold injury stimulated induction of glial fibrillary acidic protein-positive reactive astrocytes in the injured cerebrum. Induction of reactive astrocytes after cold injury was attenuated by ICV administration of BQ788 or IRL-2500. These results suggest that ETB receptor antagonists may be an effective approach to ameliorate brain edema formation following brain insults.

Role of Estrogen and Other Sex Hormones in Brain Aging. Neuroprotection and DNA Repair

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Zárate, Sandra; Stevnsner, Tinna; Gredilla, Ricardo

2017-01-01

Aging is an inevitable biological process characterized by a progressive decline in physiological function and increased susceptibility to disease. The detrimental effects of aging are observed in all tissues, the brain being the most important one due to its main role in the homeostasis of the organism. As our knowledge about the underlying mechanisms of brain aging increases, potential approaches to preserve brain function rise significantly. Accumulating evidence suggests that loss of genomic maintenance may contribute to aging, especially in the central nervous system (CNS) owing to its low DNA repair capacity. Sex hormones, particularly estrogens, possess potent antioxidant properties and play important roles in maintaining normal reproductive and non-reproductive functions. They exert neuroprotective actions and their loss during aging and natural or surgical menopause is associated with mitochondrial dysfunction, neuroinflammation, synaptic decline, cognitive impairment and increased risk of age-related disorders. Moreover, loss of sex hormones has been suggested to promote an accelerated aging phenotype eventually leading to the development of brain hypometabolism, a feature often observed in menopausal women and prodromal Alzheimer’s disease (AD). Although data on the relation between sex hormones and DNA repair mechanisms in the brain is still limited, various investigations have linked sex hormone levels with different DNA repair enzymes. Here, we review estrogen anti-aging and neuroprotective mechanisms, which are currently an area of intense study, together with the effect they may have on the DNA repair capacity in the brain. PMID:29311911

Role of Estrogen and Other Sex Hormones in Brain Aging. Neuroprotection and DNA Repair

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Sandra Zárate

2017-12-01

Full Text Available Aging is an inevitable biological process characterized by a progressive decline in physiological function and increased susceptibility to disease. The detrimental effects of aging are observed in all tissues, the brain being the most important one due to its main role in the homeostasis of the organism. As our knowledge about the underlying mechanisms of brain aging increases, potential approaches to preserve brain function rise significantly. Accumulating evidence suggests that loss of genomic maintenance may contribute to aging, especially in the central nervous system (CNS owing to its low DNA repair capacity. Sex hormones, particularly estrogens, possess potent antioxidant properties and play important roles in maintaining normal reproductive and non-reproductive functions. They exert neuroprotective actions and their loss during aging and natural or surgical menopause is associated with mitochondrial dysfunction, neuroinflammation, synaptic decline, cognitive impairment and increased risk of age-related disorders. Moreover, loss of sex hormones has been suggested to promote an accelerated aging phenotype eventually leading to the development of brain hypometabolism, a feature often observed in menopausal women and prodromal Alzheimer’s disease (AD. Although data on the relation between sex hormones and DNA repair mechanisms in the brain is still limited, various investigations have linked sex hormone levels with different DNA repair enzymes. Here, we review estrogen anti-aging and neuroprotective mechanisms, which are currently an area of intense study, together with the effect they may have on the DNA repair capacity in the brain.

Traumatic Brain Injury Increases Cortical Glutamate Network Activity by Compromising GABAergic Control.

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Cantu, David; Walker, Kendall; Andresen, Lauren; Taylor-Weiner, Amaro; Hampton, David; Tesco, Giuseppina; Dulla, Chris G

2015-08-01

Traumatic brain injury (TBI) is a major risk factor for developing pharmaco-resistant epilepsy. Although disruptions in brain circuitry are associated with TBI, the precise mechanisms by which brain injury leads to epileptiform network activity is unknown. Using controlled cortical impact (CCI) as a model of TBI, we examined how cortical excitability and glutamatergic signaling was altered following injury. We optically mapped cortical glutamate signaling using FRET-based glutamate biosensors, while simultaneously recording cortical field potentials in acute brain slices 2-4 weeks following CCI. Cortical electrical stimulation evoked polyphasic, epileptiform field potentials and disrupted the input-output relationship in deep layers of CCI-injured cortex. High-speed glutamate biosensor imaging showed that glutamate signaling was significantly increased in the injured cortex. Elevated glutamate responses correlated with epileptiform activity, were highest directly adjacent to the injury, and spread via deep cortical layers. Immunoreactivity for markers of GABAergic interneurons were significantly decreased throughout CCI cortex. Lastly, spontaneous inhibitory postsynaptic current frequency decreased and spontaneous excitatory postsynaptic current increased after CCI injury. Our results suggest that specific cortical neuronal microcircuits may initiate and facilitate the spread of epileptiform activity following TBI. Increased glutamatergic signaling due to loss of GABAergic control may provide a mechanism by which TBI can give rise to post-traumatic epilepsy. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Sites of inhibition of mitochondrial electron transport in macrophage-injured neoplastic cells.

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Granger, D L; Lehninger, A L

1982-11-01

Previous work has shown that injury of neoplastic cells by cytotoxic macrophages (CM) in cell culture is accompanied by inhibition of mitochondrial respiration. We have investigated the nature of this inhibition by studying mitochondrial respiration in CM-injured leukemia L1210 cells permeabilized with digitonin. CM-induced injury affects the mitochondrial respiratory chain proper. Complex I (NADH-coenzyme Q reductase) and complex II (succinate-coenzyme Q reductase) are markedly inhibited. In addition a minor inhibition of cytochrome oxidase was found. Electron transport from alpha-glycerophosphate through the respiratory chain to oxygen is unaffected and permeabilized CM-injured L1210 cells oxidizing this substrate exhibit acceptor control. However, glycerophosphate shuttle activity was found not to occur within CM-injured or uninjured L1210 cells in culture hence, alpha-glycerophosphate is apparently unavailable for mitochondrial oxidation in the intact cell. It is concluded that the failure of respiration of intact neoplastic cells injured by CM is caused by the nearly complete inhibition of complexes I and II of the mitochondrial electron transport chain. The time courses of CM-induced electron transport inhibition and arrest of L1210 cell division are examined and the possible relationship between these phenomena is discussed.

Do workers' compensation laws protect industrial hygienists from lawsuits by injured workers?

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Stout, N C

1993-11-01

Workers' compensation laws provide injured employees with a swifter, more certain, and less litigious system of compensation than existed under the common law. Although workers' compensation is almost always an injured employee's exclusive remedy against the employer, the employee may bring a common-law tort action against a "third party" who may be liable in whole or in part for the employee's injury. This article investigates whether industrial hygienists are "third parties" and therefore subject to suit by injured employees who claim that industrial hygienists negligently caused their injuries. The author concludes that in most states, where the industrial hygienist and the injured worker are fellow employees, the industrial hygienist shares the employer's immunity from suit. As to the consultant who performs industrial hygiene services as an independent contractor, the author concludes that the employer's nondelegable duty to provide a safe workplace offers industrial hygiene consultants an argument that they share the employer's immunity from suit. Countervailing arguments, however, leave the industrial hygiene consultant vulnerable to negligence claims in many jurisdictions. There is a trend among the states to extend the employer's immunity to those who provide safety and health services to the employer.

Characterization of high hydrostatic pressure-injured Bacillus subtilis cells.

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Inaoka, Takashi; Kimura, Keitarou; Morimatsu, Kazuya; Yamamoto, Kazutaka

2017-06-01

High hydrostatic pressure (HHP) affects various cellular processes. Using a sporulation-deficient Bacillus subtilis strain, we characterized the properties of vegetative cells subjected to HHP. When stationary-phase cells were exposed to 250 MPa of HHP for 10 min at 25 °C, approximately 50% of cells were viable, although they exhibited a prolonged growth lag. The HHP-injured cells autolyzed in the presence of NaCl or KCl (at concentrations ≥100 mM). Superoxide dismutase slightly protected the viability of HHP-treated cells, whereas vegetative catalases had no effect. Thus, unlike HHP-injured Escherichia coli, oxidative stress only slightly affected vegetative B. subtilis subjected to HHP.

Effect of mannose targeting of hydroxyl PAMAM dendrimers on cellular and organ biodistribution in a neonatal brain injury model.

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Sharma, Anjali; Porterfield, Joshua E; Smith, Elizabeth; Sharma, Rishi; Kannan, Sujatha; Kannan, Rangaramanujam M

2018-06-05

Neurotherapeutics for the treatment of central nervous system (CNS) disorders must overcome challenges relating to the blood-brain barrier (BBB), brain tissue penetration, and the targeting of specific cells. Neuroinflammation mediated by activated microglia is a major hallmark of several neurological disorders, making these cells a desirable therapeutic target. Building on the promise of hydroxyl-terminated generation four polyamidoamine (PAMAM) dendrimers (D4-OH) for penetrating the injured BBB and targeting activated glia, we explored if conjugation of targeting ligands would enhance and modify brain and organ uptake. Since mannose receptors [cluster of differentiation (CD) 206] are typically over-expressed on injured microglia, we conjugated mannose to the surface of multifunctional D4-OH using highly efficient, atom-economical, and orthogonal Cu(I)-catalyzed alkyne-azide cycloaddition (CuAAC) click chemistry and evaluated the effect of mannose conjugation on the specific cell uptake of targeted and non-targeted dendrimers both in vitro and in vivo. In vitro results indicate that the conjugation of mannose as a targeting ligand significantly changes the mechanism of dendrimer internalization, giving mannosylated dendrimer a preference for mannose receptor-mediated endocytosis as opposed to non-specific fluid phase endocytosis. We further investigated the brain uptake and biodistribution of targeted and non-targeted fluorescently labeled dendrimers in a maternal intrauterine inflammation-induced cerebral palsy (CP) rabbit model using quantification methods based on fluorescence spectroscopy and confocal microscopy. We found that the conjugation of mannose modified the distribution of D4-OH throughout the body in this neonatal rabbit CP model without lowering the amount of dendrimer delivered to injured glia in the brain, even though significantly higher glial uptake was not observed in this model. Mannose conjugation to the dendrimer modifies the dendrimer

Solute transport across the articular surface of injured cartilage.

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Chin, Hooi Chuan; Moeini, Mohammad; Quinn, Thomas M

2013-07-15

Solute transport through extracellular matrix (ECM) is important to physiology and contrast agent-based clinical imaging of articular cartilage. Mechanical injury is likely to have important effects on solute transport since it involves alteration of ECM structure. Therefore it is of interest to characterize effects of mechanical injury on solute transport in cartilage. Using cartilage explants injured by an established mechanical compression protocol, effective partition coefficients and diffusivities of solutes for transport across the articular surface were measured. A range of fluorescent solutes (fluorescein isothiocyanate, 4 and 40kDa dextrans, insulin, and chondroitin sulfate) and an X-ray contrast agent (sodium iodide) were used. Mechanical injury was associated with a significant increase in effective diffusivity versus uninjured explants for all solutes studied. On the other hand, mechanical injury had no effects on effective partition coefficients for most solutes tested, except for 40kDa dextran and chondroitin sulfate where small but significant changes in effective partition coefficient were observed in injured explants. Findings highlight enhanced diffusive transport across the articular surface of injured cartilage, which may have important implications for injury and repair situations. Results also support development of non-equilibrium methods for identification of focal cartilage lesions by contrast agent-based clinical imaging. Copyright © 2013 Elsevier Inc. All rights reserved.

Understanding contextual influences of community reintegration among injured servicemembers.

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Hawkins, Brent L; McGuire, Francis A; Linder, Sandra M; Britt, Thomas W

2015-01-01

As part of a larger mixed-methods research project investigating the influence of contextual factors on community reintegration (CR), this qualitative study sought to understand the subjective experiences of injured servicemembers and their perception of how contextual factors influenced their CR. More specifically, this article addresses how the influences of contextual factors differ between injured servicemembers with different levels of CR. Using a phenomenological framework, semistructured interviews were conducted with nine injured, community-dwelling servicemembers with low, moderate, and high levels of CR (three per category). Participants provided in-depth descriptions of the contextual barriers and facilitators of CR. Thematic analysis indicated the importance of social support and personal factors (e.g., self-efficacy, personal motivation) as the primary means for being reintegrated into their homes and communities. Other themes indicated factors that had an indirect but important influence on CR, including adapted sports, recreation, and other social programs; rehabilitation programs and therapists; school, work, and volunteering; and organizations and policies in developing social supports and personal factors. Comparisons between servicemembers indicated participants with low CR described many more contextual barriers and far fewer contextual facilitators to reintegration than those with high CR. Those with moderate CR were unique in that they described many facilitators and barriers to reintegration.

Helicopter versus ground emergency medical services for the transportation of traumatically injured children.

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Stewart, Camille L; Metzger, Ryan R; Pyle, Laura; Darmofal, Joe; Scaife, Eric; Moulton, Steven L

2015-02-01

Helicopter emergency medical services (HEMS) are a common mode of transportation for pediatric trauma patients. We hypothesized that HEMS improve outcomes for traumatically injured children compared to ground emergency medical services (GEMS). We queried trauma registries of two level 1 pediatric trauma centers for children 0-17 years, treated from 2003 to 2013, transported by HEMS or GEMS, with known transport starting location and outcome. A geocoding service estimated travel distance and time. Multivariate regression analyses were performed to adjust for injury severity variables and travel distance/time. We identified 14,405 traumatically injured children; 3870 (26.9%) transported by HEMS and 10,535 (73.1%) transported by GEMS. Transport type was not significantly associated with survival, ICU length of stay, or discharge disposition. Transport by GEMS was associated with a 68.6%-53.1% decrease in hospital length of stay, depending on adjustment for distance/time. Results were similar for children with severe injuries, and with propensity score matched cohorts. Of note, 862/3850 (22.3%) of HEMS transports had an ISS<10 and hospitalization<1 day. HEMS do not independently improve outcomes for traumatically injured children, and 22.3% of children transported by HEMS are not significantly injured. These factors should be considered when requesting HEMS for transport of traumatically injured children. Copyright © 2015 Elsevier Inc. All rights reserved.

Describing and comparing the characteristics of injured bicyclists and other injured road users: a prospective cohort study

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Bamini Gopinath

2016-04-01

Full Text Available Abstract Background We aimed to establish the frequency and characteristics (e.g. socioeconomic, pre-injury, and crash-related parameters of injured bicyclists and other injured road users. Methods 748 participants aged ≥17 years who had sustained a minor or non-catastrophic injury in a land-transport crash, were interviewed after presenting to a metro hospital emergency department in New South Wales, Australia. A telephone-administered questionnaire obtained information on socio-economic, pre-injury health, and crash-related characteristics. These factors were then compared between injured bicyclists and other road users (car driver/passengers, motorcyclists/pillion and pedestrians/skateboarders. Cycling injury severity was characterized by three metrics (sustaining multiple injuries; hospital admission for ≥12 h; and sustaining a head/neck and/or facial injury. Results In this cohort of people with injuries, 238 (32 % were bicyclists. Frequency of cycling injuries were significantly different between age-groups among men (p = 0.0002, and were more common in men aged 45–59. Bicyclists were more likely to be aged 45–59, married, have university/tertiary qualifications and have a professional occupation compared to other road users (all p <0.0001. Bicyclists compared to participants involved in other types of land transport crashes were more likely to self-report excellent general health (p = 0.01, and were less likely to report a great/overwhelming perceived danger of death or 15.0 % versus 23–41 %; p <0.0001. Frequency of upper extremity and lower extremity injuries in bicyclists were 81.9 % and 60.5 %, respectively. Explanatory variables significantly associated with injury severity metrics were age, education level, paid work status and perceived danger of death/disability in the crash. Conclusions Minor cycling injuries were a relatively common cause of mild-moderate injury presentations to metro emergency

The experience of being a partner to a spinal cord injured person:

DEFF Research Database (Denmark)

Angel, Sanne; Buus, Niels

2011-01-01

tasks. Some sought to reestablish their usual functions outside the family, whereas others focused on establishing a new life together. The partners experienced much distress and appreciated the support they got, but felt that they were mainly left to manage the difficult process on their own.......This qualitative interview study focuses on the personal experiences of partners to a spinal cord injured person. Using a Ricoeurian phenomenological-hermeneutic approach, we analysed seven partners’ narratives 1 and 2 years after their partner’s injury. The study revealed how the injury...... supporting the injured partner and the demanding tasks of everyday life outside the institution. After discharge, partners struggled for the injured partner to regain a well-functioning everyday life and for reestablishing life as a couple. The partner struggled to manage the overwhelming amount of everyday...

Neural stem cells encapsulated in a functionalized self-assembling peptide hydrogel for brain tissue engineering.

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Cheng, Tzu-Yun; Chen, Ming-Hong; Chang, Wen-Han; Huang, Ming-Yuan; Wang, Tzu-Wei

2013-03-01

Brain injury is almost irreparable due to the poor regenerative capability of neural tissue. Nowadays, new therapeutic strategies have been focused on stem cell therapy and supplying an appropriate three dimensional (3D) matrix for the repair of injured brain tissue. In this study, we specifically linked laminin-derived IKVAV motif on the C-terminal to enrich self-assembling peptide RADA(16) as a functional peptide-based scaffold. Our purpose is providing a functional self-assembling peptide 3D hydrogel with encapsulated neural stem cells to enhance the reconstruction of the injured brain. The physiochemical properties reported that RADA(16)-IKVAV can self-assemble into nanofibrous morphology with bilayer β-sheet structure and become gelationed hydrogel with mechanical stiffness similar to brain tissue. The in vitro results showed that the extended IKVAV sequence can serve as a signal or guiding cue to direct the encapsulated neural stem cells (NSCs) adhesion and then towards neuronal differentiation. Animal study was conducted in a rat brain surgery model to demonstrate the damage in cerebral neocortex/neopallium loss. The results showed that the injected peptide solution immediately in situ formed the 3D hydrogel filling up the cavity and bridging the gaps. The histological analyses revealed the RADA(16)-IKVAV self-assembling peptide hydrogel not only enhanced survival of encapsulated NSCs but also reduced the formation of glial astrocytes. The peptide hydrogel with IKVAV extended motifs also showed the support of encapsulated NSCs in neuronal differentiation and the improvement in brain tissue regeneration after 6 weeks post-transplantation. Copyright © 2012 Elsevier Ltd. All rights reserved.

The recently identified P2Y-like receptor GPR17 is a sensor of brain damage and a new target for brain repair.

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Davide Lecca

Full Text Available Deciphering the mechanisms regulating the generation of new neurons and new oligodendrocytes, the myelinating cells of the central nervous system, is of paramount importance to address new strategies to replace endogenous damaged cells in the adult brain and foster repair in neurodegenerative diseases. Upon brain injury, the extracellular concentrations of nucleotides and cysteinyl-leukotrienes (cysLTs, two families of endogenous signaling molecules, are markedly increased at the site of damage, suggesting that they may act as "danger signals" to alert responses to tissue damage and start repair. Here we show that, in brain telencephalon, GPR17, a recently deorphanized receptor for both uracil nucleotides and cysLTs (e.g., UDP-glucose and LTD(4, is normally present on neurons and on a subset of parenchymal quiescent oligodendrocyte precursor cells. We also show that induction of brain injury using an established focal ischemia model in the rodent induces profound spatiotemporal-dependent changes of GPR17. In the lesioned area, we observed an early and transient up-regulation of GPR17 in neurons expressing the cellular stress marker heat shock protein 70. Magnetic Resonance Imaging in living mice showed that the in vivo pharmacological or biotechnological knock down of GPR17 markedly prevents brain infarct evolution, suggesting GPR17 as a mediator of neuronal death at this early ischemic stage. At later times after ischemia, GPR17 immuno-labeling appeared on microglia/macrophages infiltrating the lesioned area to indicate that GPR17 may also acts as a player in the remodeling of brain circuitries by microglia. At this later stage, parenchymal GPR17+ oligodendrocyte progenitors started proliferating in the peri-injured area, suggesting initiation of remyelination. To confirm a specific role for GPR17 in oligodendrocyte differentiation, the in vitro exposure of cortical pre-oligodendrocytes to the GPR17 endogenous ligands UDP-glucose and LTD(4

Stromal Derived Factor-1/CXCR4 Axis Involved in Bone Marrow Mesenchymal Stem Cells Recruitment to Injured Liver

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Kuai Xiao Ling

2016-01-01

Full Text Available The molecular mechanism of bone marrow mesenchymal stromal stem cells (BMSCs mobilization and migration to the liver was poorly understood. Stromal cell-derived factor-1 (SDF-1 participates in BMSCs homing and migration into injury organs. We try to investigate the role of SDF-1 signaling in BMSCs migration towards injured liver. The expression of CXCR4 in BMSCs at mRNA level and protein level was confirmed by RT-PCR, flow cytometry, and immunocytochemistry. The SDF-1 or liver lysates induced BMSCs migration was detected by transwell inserts. CXCR4 antagonist, AMD3100, and anti-CXCR4 antibody were used to inhibit the migration. The Sprague-Dawley rat liver injury model was established by intraperitoneal injection of thioacetamide. The concentration of SDF-1 increased as modeling time extended, which was determined by ELISA method. The Dir-labeled BMSCs were injected into the liver of the rats through portal vein. The cell migration in the liver was tracked by in vivo imaging system and the fluorescent intensity was measured. In vivo, BMSCs migrated into injured liver which was partially blocked by AMD3100 or anti-CXCR4 antibody. Taken together, the results demonstrated that the migration of BMSCs was regulated by SDF-1/CXCR4 signaling which involved in BMSCs recruitment to injured liver.

The Relationship between Perceived Sleep Quality, Polysomnographic Measures and Depressive Symptoms in Chemically-Injured Veterans: A Pilot Study.

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Davood Moshkani Farahani

2014-09-01

Full Text Available Sleep complaints are common among Iranian chemically-injured veterans. The growing body of research has investigated (in equalities between such subjective complaints and objective sleep records. Moreover, sleep complaints are associated with depressive symptoms. Depressive symptoms, also, have been frequently reported in chemically-injured veterans. Therefore, the purpose of this pilot study was to investigate the relationship between perceived sleep quality, polysomnographic measures and depressive symptoms in Iranian veterans with chemical injuries.In this pilot study, 35 Iranian veterans with chemical injuries complaining of a sleep problem were selected. Initially, participants were evaluated via all-night polysomnography, then, they completed the research questionnaires. Collected data were analyzed using Pearson correlation coefficients.Data analyses showed that there was no significant correlation between many of self-reposted variables and polysomnogaphic recordings, however, remarkable relationships were found between the Pittsburgh Sleep Quality Index and the Beck Depression Inventory scores.The findings indicated that sleep complaints of chemically-injured veterans are not equivalent to objective sleep disturbances, however, these complaints are largely associated with level of depression. This study emphasizes the important role of mood in sleep evaluation. Further, the findings suggest using a combination of both subjective and objective measures for accurate assessment of sleep quality in Iranian veterans with chemical injuries (i.e., multimethod approach.

Development of a CPM Machine for Injured Fingers.

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Fu, Yili; Zhang, Fuxiang; Ma, Xin; Meng, Qinggang

2005-01-01

Human fingers are easy to be injured. A CPM machine is a mechanism based on the rehabilitation theory of continuous passive motion (CPM). To develop a CPM machine for the clinic application in the rehabilitation of injured fingers is a significant task. Therefore, based on the theories of evidence based medicine (EBM) and CPM, we've developed a set of biomimetic mechanism after modeling the motions of fingers and analyzing its kinematics and dynamics analysis. We also design an embedded operating system based on ARM (a kind of 32-bit RISC microprocessor). The equipment can achieve the precise control of moving scope of fingers, finger's force and speed. It can serves as a rational checking method and a way of assessment for functional rehabilitation of human hands. Now, the first prototype has been finished and will start the clinical testing in Harbin Medical University shortly.

Interpersonal Relatedness and Psychological Functioning Following Traumatic Brain Injury: Implications for Marital and Family Therapists

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Bay, Esther H.; Blow, Adrian J.; Yan, Xie

2012-01-01

Recovery from a mild-to-moderate traumatic brain injury (TBI) is a challenging process for injured persons and their families. Guided by attachment theory, we investigated whether relationship conflict, social support, or sense of belonging were associated with psychological functioning. Community-dwelling persons with TBI (N = 75) and their…

Correlations Between Personality and Brain Structure: A Crucial Role of Gender.

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Nostro, Alessandra D; Müller, Veronika I; Reid, Andrew T; Eickhoff, Simon B

2017-07-01

Previous studies have shown that males and females differ in personality and gender differences have also been reported in brain structure. However, effects of gender on this "personality-brain" relationship are yet unknown. We therefore investigated if the neural correlates of personality differ between males and females. Whole brain voxel-based morphometry was used to investigate the influence of gender on associations between NEO FFI personality traits and gray matter volume (GMV) in a matched sample of 182 males and 182 females. In order to assess associations independent of and dependent on gender, personality-GMV relationships were tested across the entire sample and separately for males and females. There were no significant correlations between any personality scale and GMV in the analyses across the entire sample. In contrast, significant associations with GMV were detected for neuroticism, extraversion, and conscientiousness only in males. Interestingly, GMV in left precuneus/parieto-occipital sulcus correlated with all 3 traits. Thus, our results indicate that brain structure-personality relationships are highly dependent on gender, which might be attributable to hormonal interplays or differences in brain organization between males and females. Our results thus provide possible neural substrates of personality-behavior relationships and underline the important role of gender in these associations. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Multi-drug resistant Acinetobacter infections in critically injured Canadian forces soldiers

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Brisebois Ronald

2007-08-01

Full Text Available Abstract Background Military members, injured in Afghanistan or Iraq, have returned home with multi-drug resistant Acinetobacter baumannii infections. The source of these infections is unknown. Methods Retrospective study of all Canadian soldiers who were injured in Afghanistan and who required mechanical ventilation from January 1 2006 to September 1 2006. Patients who developed A. baumannii ventilator associated pneumonia (VAP were identified. All A. baumannii isolates were retrieved for study patients and compared with A. baumannii isolates from environmental sources from the Kandahar military hospital using pulsed-field gel electrophoresis (PFGE. Results During the study period, six Canadian Forces (CF soldiers were injured in Afghanistan, required mechanical ventilation and were repatriated to Canadian hospitals. Four of these patients developed A. baumannii VAP. A. baumannii was also isolated from one environmental source in Kandahar – a ventilator air intake filter. Patient isolates were genetically indistinguishable from each other and from the isolates cultured from the ventilator filter. These isolates were resistant to numerous classes of antimicrobials including the carbapenems. Conclusion These results suggest that the source of A. baumannii infection for these four patients was an environmental source in the military field hospital in Kandahar. A causal linkage, however, was not established with the ventilator. This study suggests that infection control efforts and further research should be focused on the military field hospital environment to prevent further multi-drug resistant A. baumannii infections in injured soldiers.

GHSR deficiency suppresses neointimal formation in injured mouse arteries

International Nuclear Information System (INIS)

Li, Jing; Zhang, Man; Wang, Mo; Wang, Zhipeng; Liu, Yahan; Zhang, Weizhen; Wang, Nanping

2016-01-01

Growth hormone secretagogue receptor (GHSR) is involved in appetite regulation and energy homeostasis. In the present study, we examined the role of GHSR in neointimal formation following vascular injury. In the mouse model of femoral artery wire injury, we found that vessel intima-to-media ratio was significantly reduced in GHSR deficiency (GHSR −/− ) mice compared with that in wild-type mice. Immunohistochemical staining showed that the smooth muscle cell (SMCs) in the neointima were significantly decreased in the injured arteries of GHSR −/− mice which was associated with decreased SMC proliferation and migration. Furthermore, immunoblotting demonstrated that, in cultured rat aortic SMCs, small interfering RNA-mediated GHSR knockdown suppressed the activation of Akt and ERK1/2 signaling pathway. These findings suggested a novel role of GHSR in neointimal formation likely via promoting the proliferation and migration of SMCs involving Akt and ERK1/2 signaling. Therefore, GHSR may be a potential therapeutic target in restenosis and vascular remodeling. - Highlights: • GHSR deficiency inhibits neointimal formation after vascular injury. • GHSR deficiency suppresses SMCs numbers in vivo. • Knockdown GHSR represses SMCs proliferation and migration in vitro. • Knockdown GHSR inhibited Akt and ERK1/2 phosphorylation in SMCs.

Effect of Posttraumatic Serum Thyroid Hormone Levels on Severity and Mortality of Patients with Severe Traumatic Brain Injury

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Forough Saki

2012-02-01

Full Text Available Traumatic brain injury (TBI is an important cause of death and disability in young adults ,and may lead to physical disabilities and long-term cognitive, behavioral psychological and social defects. There is a lack of definite result about the effect of thyroid hormones after traumatic brain injury in the severity and no data about their effect on mortality of the injury. The aim of this study is to evaluate the effect of thyroid hormones after traumatic brain injury in the severity and mortality and gain a clue in brain injury prognosis. In a longitudinal prospective study from February 2010 until February 2011, we checked serum levels of T3, T4, TSH and TBG of severely brain injured patients and compared the relationship of them with primary Glasgow Coma Scale (GCS score and mortality of patients. Statistical analysis used SPSS 11.5 software with using chi-square and Fisher exact test. Serum levels of T3 and T4 were decreased after brain trauma but not TSH and TBG. Mortality rates were higher in patients with lower T4 serum levels. The head injury was more severe in whom with low T3 and T4. Follow a severe brain injury a secondary hypothyroidism is happened due to pituitary dysfunction. Also, serum level of T3 and T4 on the first day admission affect on primary GCS score of patients which is an indicator of severity of brain injury. In addition, mortality rates of severely brain injured patients have a high correlation with the serum level of T4 in the first day admission.

Acute Chemical Incidents With Injured First Responders, 2002-2012.

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Melnikova, Natalia; Wu, Jennifer; Yang, Alice; Orr, Maureen

2018-04-01

IntroductionFirst responders, including firefighters, police officers, emergency medical services, and company emergency response team members, have dangerous jobs that can bring them in contact with hazardous chemicals among other dangers. Limited information is available on responder injuries that occur during hazardous chemical incidents. We analyzed 2002-2012 data on acute chemical incidents with injured responders from 2 Agency for Toxic Substances and Disease Registry chemical incident surveillance programs. To learn more about such injuries, we performed descriptive analysis and looked for trends. The percentage of responders among all injured people in chemical incidents has not changed over the years. Firefighters were the most frequently injured group of responders, followed by police officers. Respiratory system problems were the most often reported injury, and the respiratory irritants, ammonia, methamphetamine-related chemicals, and carbon monoxide were the chemicals more often associated with injuries. Most of the incidents with responder injuries were caused by human error or equipment failure. Firefighters wore personal protective equipment (PPE) most frequently and police officers did so rarely. Police officers' injuries were mostly associated with exposure to ammonia and methamphetamine-related chemicals. Most responders did not receive basic awareness-level hazardous material training. All responders should have at least basic awareness-level hazardous material training to recognize and avoid exposure. Research on improving firefighter PPE should continue. (Disaster Med Public Health Preparedness. 2018;12:211-221).

Replantation and revascularization vs. amputation in injured digits

NARCIS (Netherlands)

Mulders, Marjolein A. M.; Neuhaus, Valentin; Becker, Stéphanie J. E.; Lee, Sang-Gil; Ring, David C.

2013-01-01

The purpose of this study was to analyze factors associated with the decision to replant or revascularize rather than amputate an injured digit as well as factors associated with successful replantation or revascularization. We reviewed 315 complete and subtotal amputations at or proximal to the

The acutely ACL injured knee assessed by MRI

DEFF Research Database (Denmark)

Frobell, R B; Roos, H P; Roos, E M

2008-01-01

OBJECTIVES: To map by magnetic resonance imaging (MRI) and quantitative MRI (qMRI) concomitant fractures and meniscal injuries, and location and volume of traumatic bone marrow lesions (BMLs) in the acutely anterior cruciate ligament (ACL) injured knee. To relate BML location and volume to cortic...

Eye tracking detects disconjugate eye movements associated with structural traumatic brain injury and concussion.

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Samadani, Uzma; Ritlop, Robert; Reyes, Marleen; Nehrbass, Elena; Li, Meng; Lamm, Elizabeth; Schneider, Julia; Shimunov, David; Sava, Maria; Kolecki, Radek; Burris, Paige; Altomare, Lindsey; Mehmood, Talha; Smith, Theodore; Huang, Jason H; McStay, Christopher; Todd, S Rob; Qian, Meng; Kondziolka, Douglas; Wall, Stephen; Huang, Paul

2015-04-15

Disconjugate eye movements have been associated with traumatic brain injury since ancient times. Ocular motility dysfunction may be present in up to 90% of patients with concussion or blast injury. We developed an algorithm for eye tracking in which the Cartesian coordinates of the right and left pupils are tracked over 200 sec and compared to each other as a subject watches a short film clip moving inside an aperture on a computer screen. We prospectively eye tracked 64 normal healthy noninjured control subjects and compared findings to 75 trauma subjects with either a positive head computed tomography (CT) scan (n=13), negative head CT (n=39), or nonhead injury (n=23) to determine whether eye tracking would reveal the disconjugate gaze associated with both structural brain injury and concussion. Tracking metrics were then correlated to the clinical concussion measure Sport Concussion Assessment Tool 3 (SCAT3) in trauma patients. Five out of five measures of horizontal disconjugacy were increased in positive and negative head CT patients relative to noninjured control subjects. Only one of five vertical disconjugacy measures was significantly increased in brain-injured patients relative to controls. Linear regression analysis of all 75 trauma patients demonstrated that three metrics for horizontal disconjugacy negatively correlated with SCAT3 symptom severity score and positively correlated with total Standardized Assessment of Concussion score. Abnormal eye-tracking metrics improved over time toward baseline in brain-injured subjects observed in follow-up. Eye tracking may help quantify the severity of ocular motility disruption associated with concussion and structural brain injury.

Employment among Spinal Cord Injured Patients Living in Turkey: A Cross-Sectional Study

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Gunduz, Berrin; Erhan, Belgin; Bardak, Ayse Nur

2010-01-01

The aim of this study was to determine the rate of employment and to establish the factors affecting vocational status in spinal cord injured patients living in Turkey. One hundred and fifty-two traumatic spinal cord injured patients older than 18 years with injury duration of at least 1 year and living in the community were included in the study;…

Role of DHA in aging-related changes in mouse brain synaptic plasma membrane proteome.

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Sidhu, Vishaldeep K; Huang, Bill X; Desai, Abhishek; Kevala, Karl; Kim, Hee-Yong

2016-05-01

Aging has been related to diminished cognitive function, which could be a result of ineffective synaptic function. We have previously shown that synaptic plasma membrane proteins supporting synaptic integrity and neurotransmission were downregulated in docosahexaenoic acid (DHA)-deprived brains, suggesting an important role of DHA in synaptic function. In this study, we demonstrate aging-induced synaptic proteome changes and DHA-dependent mitigation of such changes using mass spectrometry-based protein quantitation combined with western blot or messenger RNA analysis. We found significant reduction of 15 synaptic plasma membrane proteins in aging brains including fodrin-α, synaptopodin, postsynaptic density protein 95, synaptic vesicle glycoprotein 2B, synaptosomal-associated protein 25, synaptosomal-associated protein-α, N-methyl-D-aspartate receptor subunit epsilon-2 precursor, AMPA2, AP2, VGluT1, munc18-1, dynamin-1, vesicle-associated membrane protein 2, rab3A, and EAAT1, most of which are involved in synaptic transmission. Notably, the first 9 proteins were further reduced when brain DHA was depleted by diet, indicating that DHA plays an important role in sustaining these synaptic proteins downregulated during aging. Reduction of 2 of these proteins was reversed by raising the brain DHA level by supplementing aged animals with an omega-3 fatty acid sufficient diet for 2 months. The recognition memory compromised in DHA-depleted animals was also improved. Our results suggest a potential role of DHA in alleviating aging-associated cognitive decline by offsetting the loss of neurotransmission-regulating synaptic proteins involved in synaptic function. Published by Elsevier Inc.

The ethical and legal aspects of palliative sedation in severely brain-injured patients: a French perspective

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Puybasset Louis

2011-02-01

Full Text Available Abstract To fulfill their crucial duty of relieving suffering in their patients, physicians may have to administer palliative sedation when they implement treatment-limitation decisions such as the withdrawal of life-supporting interventions in patients with poor prognosis chronic severe brain injury. The issue of palliative sedation deserves particular attention in adults with serious brain injuries and in neonates with severe and irreversible brain lesions, who are unable to express pain or to state their wishes. In France, treatment limitation decisions for these patients are left to the physicians. Treatment-limitation decisions are made collegially, based on the presence of irreversible brain lesions responsible for chronic severe disorders of consciousness. Before these decisions are implemented, they are communicated to the relatives. Because the presence and severity of pain cannot be assessed in these patients, palliative analgesia and/or sedation should be administered. However, palliative sedation is a complex strategy that requires safeguards to prevent a drift toward hastening death or performing covert euthanasia. In addition to the law on patients' rights at the end of life passed in France on April 22, 2005, a recent revision of Article 37 of the French code of medical ethics both acknowledges that treatment-limitation decisions and palliative sedation may be required in patients with severe brain injuries and provides legal and ethical safeguards against a shift towards euthanasia. This legislation may hold value as a model for other countries where euthanasia is illegal and for countries such as Belgium and Netherlands where euthanasia is legal but not allowed in patients incapable of asking for euthanasia but in whom a treatment limitation decision has been made.

The ethical and legal aspects of palliative sedation in severely brain-injured patients: a French perspective

Science.gov (United States)

2011-01-01

To fulfill their crucial duty of relieving suffering in their patients, physicians may have to administer palliative sedation when they implement treatment-limitation decisions such as the withdrawal of life-supporting interventions in patients with poor prognosis chronic severe brain injury. The issue of palliative sedation deserves particular attention in adults with serious brain injuries and in neonates with severe and irreversible brain lesions, who are unable to express pain or to state their wishes. In France, treatment limitation decisions for these patients are left to the physicians. Treatment-limitation decisions are made collegially, based on the presence of irreversible brain lesions responsible for chronic severe disorders of consciousness. Before these decisions are implemented, they are communicated to the relatives. Because the presence and severity of pain cannot be assessed in these patients, palliative analgesia and/or sedation should be administered. However, palliative sedation is a complex strategy that requires safeguards to prevent a drift toward hastening death or performing covert euthanasia. In addition to the law on patients' rights at the end of life passed in France on April 22, 2005, a recent revision of Article 37 of the French code of medical ethics both acknowledges that treatment-limitation decisions and palliative sedation may be required in patients with severe brain injuries and provides legal and ethical safeguards against a shift towards euthanasia. This legislation may hold value as a model for other countries where euthanasia is illegal and for countries such as Belgium and Netherlands where euthanasia is legal but not allowed in patients incapable of asking for euthanasia but in whom a treatment limitation decision has been made. PMID:21303504

The ethical and legal aspects of palliative sedation in severely brain-injured patients: a French perspective.

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Baumann, Antoine; Claudot, Frédérique; Audibert, Gérard; Mertes, Paul-Michel; Puybasset, Louis

2011-02-08

To fulfill their crucial duty of relieving suffering in their patients, physicians may have to administer palliative sedation when they implement treatment-limitation decisions such as the withdrawal of life-supporting interventions in patients with poor prognosis chronic severe brain injury. The issue of palliative sedation deserves particular attention in adults with serious brain injuries and in neonates with severe and irreversible brain lesions, who are unable to express pain or to state their wishes. In France, treatment limitation decisions for these patients are left to the physicians. Treatment-limitation decisions are made collegially, based on the presence of irreversible brain lesions responsible for chronic severe disorders of consciousness. Before these decisions are implemented, they are communicated to the relatives. Because the presence and severity of pain cannot be assessed in these patients, palliative analgesia and/or sedation should be administered. However, palliative sedation is a complex strategy that requires safeguards to prevent a drift toward hastening death or performing covert euthanasia. In addition to the law on patients' rights at the end of life passed in France on April 22, 2005, a recent revision of Article 37 of the French code of medical ethics both acknowledges that treatment-limitation decisions and palliative sedation may be required in patients with severe brain injuries and provides legal and ethical safeguards against a shift towards euthanasia. This legislation may hold value as a model for other countries where euthanasia is illegal and for countries such as Belgium and Netherlands where euthanasia is legal but not allowed in patients incapable of asking for euthanasia but in whom a treatment limitation decision has been made.

Role of scintigraphy and computer-assisted tomography in brain examination

International Nuclear Information System (INIS)

Akerman, M.; Oproiu, A.; Comoy, C.; Guiot, G.

1981-01-01

To assess the role of computer-assisted tomography (CAT) and scintigraphy in brain exploration, the authors analysed: (1) the diagnostic effectiveness of the two methods in 300 patients examined over a period of seven months; (2) the role assigned to each investigation in 169 patients operated on for intracranial lesion during the same period. The isotopic brain examination always included an initial angiographic study after the intravenous injection of a technetium compound. Study of the circulation of the cerebrospinal fluid was made with 111 In-DTPA. The detection efficiency of CAT is higher than for scintigraphy in expansive processes, whereas, conversely, in cerebrovascular accidents of ischaemic origin, isotope angiography coupled with static imaging enables one to gain more information on cerebral perfusion than CAT. Similarly, when studying the cerebrospinal fluid, scintigraphy provides a greater amount of specific data on the mechanisms governing hydrocephalus, the mode of operation of a shunt, or the site of a cerebrospinal fluid fistula. Within a neurosurgical context, CAT by and large takes precedence in brain examination, but the investigation is usually accompanied by scintigraphy or a conventional neuroradiological examination. Scintigraphy was performed on 66% of the patients, whereas for neuroradiological examination the figure was 44%. Most of the scintigraphy came after CAT so as to obtain additional diagnostic information on the vascularization, the nature and, on occasion, the exact location of the lesion revealed by CAT. In more than one case out of two, scintigraphy provides enough additional information for one to avoid neuroradiological examination, which is more 'aggressive' and more dangerous. Hence scintigraphy represents an effective complement to CAT and can compete with the conventional neuroradiological technique. (author)

Are severely injured trauma victims in Norway offered advanced pre-hospital care? National, retrospective, observational cohort.

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Wisborg, T; Ellensen, E N; Svege, I; Dehli, T

2017-08-01

Studies of severely injured patients suggest that advanced pre-hospital care and/or rapid transportation provides a survival benefit. This benefit depends on the disposition of resources to patients with the greatest need. Norway has 19 Emergency Helicopters (HEMS) staffed by anaesthesiologists on duty 24/7/365. National regulations describe indications for their use, and the use of the national emergency medical dispatch guideline is recommended. We assessed whether severely injured patients had been treated or transported by advanced resources on a national scale. A national survey was conducted collecting data for 2013 from local trauma registries at all hospitals caring for severely injured patients. Patients were analysed according to hospital level; trauma centres or acute care hospitals with trauma functions. Patients with an Injury Severity Score (ISS) > 15 were considered severely injured. Three trauma centres (75%) and 17 acute care hospitals (53%) had data for trauma patients from 2013, a total of 3535 trauma registry entries (primary admissions only), including 604 victims with an ISS > 15. Of these 604 victims, advanced resources were treating and/or transporting 51%. Sixty percent of the severely injured admitted directly to trauma centres received advanced services, while only 37% of the severely injured admitted primarily to acute care hospitals received these services. A highly developed and widely distributed HEMS system reached only half of severely injured trauma victims in Norway in 2013. © 2017 The Authors. Acta Anaesthesiologica Scandinavica published by John Wiley & Sons Ltd on behalf of Acta Anaesthesiologica Scandinavica Foundation.

Relating Education, Brain Structure, and Cognition: The Role of Cardiovascular Disease Risk Factors

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Moyra E. Mortby

2014-01-01

Full Text Available The protective effect of education on cognitive and brain health is well established. While the direct effects of individual cardiovascular disease (CVD risk factors (i.e., hypertension, smoking, diabetes, and obesity on cerebral structure have been investigated, little is understood about the possible interaction between the protective effect of education and the deleterious effects of CVD risk factors in predicting brain ageing and cognition. Using data from the PATH Through Life study (N=266, we investigated the protective effect of education on cerebral structure and function and tested a possible mediating role of CVD risk factors. Higher education was associated with larger regional grey/white matter volumes in the prefrontal cortex in men only. The association between education and cognition was mediated by brain volumes but only for grey matter and only in relation to information processing speed. CVD risk factors did not mediate the association between regional volumes and cognition. This study provides additional evidence in support for a protective effect of education on cerebral structures and cognition. However, it does not provide support for a mediating role of CVD risk factors in these associations.

Bacoside A: Role in Cigarette Smoking Induced Changes in Brain

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G. Vani

2015-01-01

Full Text Available Cigarette smoking (CS is a major health hazard that exerts diverse physiologic and biochemical effects mediated by the components present and generated during smoking. Recent experimental studies have shown predisposition to several biological consequences from both active and passive cigarette smoke exposure. In particular, passive smoking is linked to a number of adverse health effects which are equally harmful as active smoking. A pragmatic approach should be considered for designing a pharmacological intervention to combat the adverse effects of passive smoking. This review describes the results from a controlled experimental condition, testing the effect of bacoside A (BA on the causal role of passive/secondhand smoke exposure that caused pathological and neurological changes in rat brain. Chronic exposure to cigarette smoke induced significant changes in rat brain histologically and at the neurotransmitter level, lipid peroxidation states, mitochondrial functions, membrane alterations, and apoptotic damage in rat brain. Bacoside A is a neuroactive agent isolated from Bacopa monnieri. As a neuroactive agent, BA was effective in combating these changes. Future research should examine the effects of BA at molecular level and assess its functional effects on neurobiological and behavioral processes associated with passive smoke.

Influence of Tryptophan and Serotonin on Mood and Cognition with a Possible Role of the Gut-Brain Axis

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Jenkins, Trisha A.; Nguyen, Jason C. D.; Polglaze, Kate E.; Bertrand, Paul P.

2016-01-01

The serotonergic system forms a diffuse network within the central nervous system and plays a significant role in the regulation of mood and cognition. Manipulation of tryptophan levels, acutely or chronically, by depletion or supplementation, is an experimental procedure for modifying peripheral and central serotonin levels. These studies have allowed us to establish the role of serotonin in higher order brain function in both preclinical and clinical situations and have precipitated the finding that low brain serotonin levels are associated with poor memory and depressed mood. The gut-brain axis is a bi-directional system between the brain and gastrointestinal tract, linking emotional and cognitive centres of the brain with peripheral functioning of the digestive tract. An influence of gut microbiota on behaviour is becoming increasingly evident, as is the extension to tryptophan and serotonin, producing a possibility that alterations in the gut may be important in the pathophysiology of human central nervous system disorders. In this review we will discuss the effect of manipulating tryptophan on mood and cognition, and discuss a possible influence of the gut-brain axis. PMID:26805875

Radioimmunoassay of serum creatine kinase BB as index of brain damage after head injury

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Phillips, J P; Jones, H M; Hitchcock, R; Adams, N; Thompson, R J [Addenbrooke' s Hospital, Cambridge (UK)

1980-09-20

Brain-type creatine kinase isoenzyme (CK-BB) was measured by radioimmunoassay in the serum of 54 patients with head injuries. CK-BB was not detectable in 476 out of 1006 controls, the remaining 530 normal samples containing a mean of 1.5 +- SDO.75 ..mu..g/l. The mean CK-BB concentrations in patients with mild, moderate, and fatal head injuries were all significantly higher than the control value (p<0.01 in each instance). Patients with serious head injury had serum concentrations many times the normal value, in two cases within 30 minutes after impact. Fatally injured patients continued to have high serum concentrations several days after injury. In less serious cases values approached normal within two or three days. Every patient with evidence of cerebral laceration, bruising, or swelling had a serum CK-BB concentration above normal. Raised concentrations were found in 14 out of 22 patients with concussion only. Thus the serum CK-BB concentration appears to be a sensitive index of brain damage and may prove useful in the management and follow-up of head-injured patients.

Radioimmunoassay of serum creatine kinase BB as index of brain damage after head injury

International Nuclear Information System (INIS)

Phillips, J.P.; Jones, H.M.; Hitchcock, R.; Adams, N.; Thompson, R.J.

1980-01-01

Brain-type creatine kinase isoenzyme (CK-BB) was measured by radioimmunoassay in the serum of 54 patients with head injuries. CK-BB was not detectable in 476 out of 1006 controls, the remaining 530 normal samples containing a mean of 1.5 +- SDO.75 μg/l. The mean CK-BB concentrations in patients with mild, moderate, and fatal head injuries were all significantly higher than the control value (p<0.01 in each instance). Patients with serious head injury had serum concentrations many times the normal value, in two cases within 30 minutes after impact. Fatally injured patients continued to have high serum concentrations several days after injury. In less serious cases values approached normal within two or three days. Every patient with evidence of cerebral laceration, bruising, or swelling had a serum CK-BB concentration above normal. Raised concentrations were found in 14 out of 22 patients with concussion only. Thus the serum CK-BB concentration appears to be a sensitive index of brain damage and may prove useful in the management and follow-up of head-injured patients. (author)

Screening injured children for physical abuse or neglect in emergency departments: a systematic review.

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Woodman, J; Lecky, F; Hodes, D; Pitt, M; Taylor, B; Gilbert, Ruth

2010-03-01

Screening markers are used in emergency departments (EDs) to identify children who should be assessed for possible physical abuse and neglect. We conducted three systematic reviews evaluating age, repeat attendance and injury type as markers for physical abuse or neglect in injured children attending EDs. We included studies comparing markers in physically abused or neglected children and non-abused injured children attending ED or hospital. We calculated likelihood ratios (LRs) for age group, repeat attendance and injury type (head injury, bruises, fractures, burns or other). Given the low prevalence of abuse or neglect, we considered that an LR of 10 or more would be clinically useful. All studies were poor quality. Infancy increased the risk of physical abuse or neglect in severely injured or admitted children (LRs 7.7-13.0, 2 studies) but was not strongly associated in children attending the ED (LR 1.5, 95% CI: 0.9, 2.8; one study). Repeat attendance did not substantially increase the risk of abuse or neglect and may be confounded by chronic disease and socio-economic status (LRs 0.8-3.9, 3 studies). One study showed no evidence that the type of injury substantially increased the risk of physical abuse or neglect in severely injured children. There was no evidence that any of the markers (infancy, type of injury, repeated attendance) were sufficiently accurate (i.e. LR >or= 10) to screen injured children in the ED to identify those requiring paediatric assessment for possible physical abuse or neglect. Clinicians should be aware that among injured children at ED a high proportion of abused children will present without these characteristics and a high proportion of non-abused children will present with them. Information about age, injury type and repeat attendances should be interpreted in this context.

Cut your losses: self-amputation of injured limbs increases survival.

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Emberts, Zachary; Miller, Christine W; Kiehl, Daniel; St Mary, Colette M

2017-01-01

Autotomy, self-induced limb loss, is an extreme trait observed throughout the animal kingdom; lizards drop their tails, crickets release their legs, and crabs drop their claws. These repeated evolutionary origins suggest that autotomy is adaptive. Yet, we do not have a firm understanding of the selective pressures that promote and maintain this extreme trait. Although multiple adaptive hypotheses exist, research has generally focused on autotomy's adaptive value as a form of predator escape. However, autotomy could also be selected to reduce the cost of an injured limb, which we investigate here. Previously, this alternative hypothesis has been challenging to directly test because when an injury occurs on an autotomizable limb, that limb is almost always dropped (i.e., autotomy is behaviorally fixed within populations). Recently, however, we have identified a species, Narnia femorata (Insecta: Hemiptera: Coreidae), where some individuals autotomize limbs in response to injury, but some do not. This natural variation allowed us to investigate both the survival costs of retaining an injured limb and the benefits of autotomizing it. In this study, we find a positive association between autotomizing injured limbs and survival, thereby quantifying a new and likely widespread benefit of autotomy-reducing the cost of injury.

The effect of expedited rotator cuff surgery in injured workers: a case-control study.

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Razmjou, Helen; Lincoln, Sandra; Boljanovic, Dragana; Gallay, Stephen; Henry, Patrick; Richards, Robin R; Holtby, Richard

2017-07-01

Expediting rotator cuff surgery is expected to facilitate recovery and return to work in injured workers. This case-control study examined the effect of expedited rotator cuff surgery on recovery and work status in injured workers. Injured workers who had undergone an expedited rotator cuff surgery funded by parallel-pay insurance (study group) were compared with workers who had used the public health insurance (control group) while adjusting for sex, age, severity of pathology, and follow-up period. Disability was measured by the American Shoulder and Elbow Surgeons (ASES) Standardized Assessment Form score. The percentage of patients who exceeded the minimal clinically important difference of 17 points in the ASES was calculated. The study group waited less time to have surgery than the control group (P workers who underwent expedited rotator cuff surgery reported less disability and had a more successful return to work after surgery than injured workers who waited longer for specialist assessment and surgery within the public health system. Copyright © 2016 Journal of Shoulder and Elbow Surgery Board of Trustees. Published by Elsevier Inc. All rights reserved.

Clinical relevance of cortical spreading depression in neurological disorders: migraine, malignant stroke, subarachnoid and intracranial hemorrhage, and traumatic brain injury

DEFF Research Database (Denmark)

Lauritzen, Martin; Dreier, Jens Peter; Fabricius, Martin

2011-01-01

Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence....... The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD...... treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves....

A novel microglial subset plays a key role in myelinogenesis in developing brain

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Wlodarczyk, Agnieszka; Holtman, Inge; Krueger, Martin

2017-01-01

Microglia are resident macrophages of the central nervous system that contribute to homeostasis and neuroinflammation. Although known to play an important role in brain development, their exact function has not been fully described. Here we show that in contrast to healthy adult and inflammation......-activated cells, neonatal microglia show a unique myelinogenic and neurogenic phenotype. A CD11c+ microglial subset that predominates in primary myelinating areas of the developing brain expresses genes for neuronal and glial survival, migration and differentiation. These cells are the major source of insulin...

Neurosteroid Transport in the Brain: Role of ABC and SLC Transporters

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Markus Grube

2018-04-01

Full Text Available Neurosteroids, comprising pregnane, androstane, and sulfated steroids can alter neuronal excitability through interaction with ligand-gated ion channels and other receptors and have therefore a therapeutic potential in several brain disorders. They can be formed in brain cells or are synthesized by an endocrine gland and reach the brain by penetrating the blood–brain barrier (BBB. Especially sulfated steroids such as pregnenolone sulfate (PregS and dehydroepiandrosterone sulfate (DHEAS depend on transporter proteins to cross membranes. In this review, we discuss the involvement of ATP-binding cassette (ABC- and solute carrier (SLC-type membrane proteins in the transport of these compounds at the BBB and in the choroid plexus (CP, but also in the secretion from neurons and glial cells. Among the ABC transporters, especially BCRP (ABCG2 and several MRP/ABCC subfamily members (MRP1, MRP4, MRP8 are expressed in the brain and known to efflux conjugated steroids. Furthermore, several SLC transporters have been shown to mediate cellular uptake of steroid sulfates. These include members of the OATP/SLCO subfamily, namely OATP1A2 and OATP2B1, as well as OAT3 (SLC22A3, which have been reported to be expressed at the BBB, in the CP and in part in neurons. Furthermore, a role of the organic solute transporter OSTα-OSTβ (SLC51A/B in brain DHEAS/PregS homeostasis has been proposed. This transporter was reported to be localized especially in steroidogenic cells of the cerebellum and hippocampus. To date, the impact of transporters on neurosteroid homeostasis is still poorly understood. Further insights are desirable also with regard to the therapeutic potential of these compounds.

Role of infectious agents in the carcinogenesis of brain and head and neck cancers

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Alibek Kenneth

2013-02-01

Full Text Available Abstract This review concentrates on tumours that are anatomically localised in head and neck regions. Brain cancers and head and neck cancers together account for more than 873,000 cases annually worldwide, with an increasing incidence each year. With poor survival rates at late stages, brain and head and neck cancers represent serious conditions. Carcinogenesis is a multi-step process and the role of infectious agents in this progression has not been fully identified. A major problem with such research is that the role of many infectious agents may be underestimated due to the lack of or inconsistency in experimental data obtained globally. In the case of brain cancer, no infection has been accepted as directly oncogenic, although a number of viruses and parasites are associated with the malignancy. Our analysis of the literature showed the presence of human cytomegalovirus (HCMV in distinct types of brain tumour, namely glioblastoma multiforme (GBM and medulloblastoma. In particular, there are reports of viral protein in up to 100% of GBM specimens. Several epidemiological studies reported associations of brain cancer and toxoplasmosis seropositivity. In head and neck cancers, there is a distinct correlation between Epstein-Barr virus (EBV and nasopharyngeal carcinoma (NPC. Considering that almost every undifferentiated NPC is EBV-positive, virus titer levels can be measured to screen high-risk populations. In addition there is an apparent association between human papilloma virus (HPV and head and neck squamous cell carcinoma (HNSCC; specifically, 26% of HNSCCs are positive for HPV. HPV type 16 was the most common type detected in HNSCCs (90% and its dominance is even greater than that reported in cervical carcinoma. Although there are many studies showing an association of infectious agents with cancer, with various levels of involvement and either a direct or indirect causative effect, there is a scarcity of articles covering the role of

Recovery of neurological function despite immediate sleep disruption following diffuse brain injury in the mouse: clinical relevance to medically untreated concussion.

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Rowe, Rachel K; Harrison, Jordan L; O'Hara, Bruce F; Lifshitz, Jonathan

2014-04-01

We investigated the relationship between immediate disruption of posttraumatic sleep and functional outcome in the diffuse brain-injured mouse. Adult male C57BL/6 mice were subjected to moderate midline fluid percussion injury (n = 65; 1.4 atm; 6-10 min righting reflex time) or sham injury (n = 44). Cohorts received either intentional sleep disruption (minimally stressful gentle handling) or no sleep disruption for 6 h following injury. Following disruption, serum corticosterone levels (enzyme-linked immunosorbent assay) and posttraumatic sleep (noninvasive piezoelectric sleep cages) were measured. For 1-7 days postinjury, sensorimotor outcome was assessed by Rotarod and a modified Neurological Severity Score (NSS). Cognitive function was measured using Novel Object Recognition (NOR) and Morris water maze (MWM) in the first week postinjury. Neurotrauma research laboratory. Disrupting posttraumatic sleep for 6 h did not affect serum corticosterone levels or functional outcome. In the hour following the first dark onset, sleep-disrupted mice exhibited a significant increase in sleep; however, this increase was not sustained and there was no rebound of lost sleep. Regardless of sleep disruption, mice showed a time-dependent improvement in Rotarod performance, with brain-injured mice having significantly shorter latencies on day 7 compared to sham. Further, brain-injured mice, regardless of sleep disruption, had significantly higher NSS scores postinjury compared with sham. Cognitive behavioral testing showed no group differences among any treatment group measured by MWM and NOR. Short-duration disruption of posttraumatic sleep did not affect functional outcome, measured by motor and cognitive performance. These data raise uncertainty about posttraumatic sleep as a mechanism of recovery from diffuse brain injury.

Traumatic Brain Injury: Exploring the Role of Cooperative Extension in Kansas Communities

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Sellers, Debra M.; Garcia, Jane Mertz

2012-01-01

TBI"options" helps survivors of traumatic brain injury and their families identify, locate, and contact helpful organizations in their local communities to promote successful living. This article discusses the role of county agents in the program and the support offered by community partners. Results of pre- and post-surveys for both…

[Brain repair after ischemic stroke: role of neurotransmitters in post-ischemic neurogenesis].

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Sánchez-Mendoza, Eduardo; Bellver-Landete, Víctor; González, María Pilar; Merino, José Joaquín; Martínez-Murillo, Ricardo; Oset-Gasque, María Jesús

2012-11-01

Brain ischemia and reperfusion produce alterations in the microenvironment of the parenchyma, including ATP depletion, ionic homeostasis alterations, inflammation, release of multiple cytokines and abnormal release of neurotransmitters. As a consequence, the induction of proliferation and migration of neural stem cells towards the peri-infarct region occurs. The success of new neurorestorative treatments for damaged brain implies the need to know, with greater accuracy, the mechanisms in charge of regulating adult neurogenesis, both under physiological and pathological conditions. Recent evidence demonstrates that many neurotransmitters, glutamate in particular, control the subventricular zone, thus being part of the complex signalling network that influences the production of new neurons. Neurotransmitters provide a link between brain activity and subventricular zone neurogenesis. Therefore, a deeper knowledge of the role of neurotransmitters systems, such as glutamate and its transporters, in adult neurogenesis, may provide a valuable tool to be used as a neurorestorative therapy in this pathology.

El Boxeo, es el deporte con mayor frecuencia de trauma ocular Is Boxing the sports of highest ocular injure frequency

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Agustín Fernández Sánchez

2006-12-01

Full Text Available El trauma ocular lo constituye cualquier lesión causada en el ojo por factores externos que no se relacionan con enfermedades del paciente. Las causas más frecuentes encontradas, son los accidentes domésticos, laborales y la práctica deportiva. En el caso específico del boxeo, existe una polémica en la que algunos afirman que con la medicina moderna, las nuevas reglas de arbitraje y las novedosas técnicas de entrenamiento, este deporte es casi inofensivo al que lo practique. Otros afirman que los traumatismos repetitivos provocan lesiones cerebrales responsables de la decadencia neuropsicológica de un gran número de pugilistas. Se revisaron 24 trabajos internacionales y un nacional (el único publicado hasta el momento. Se refieren estudios comparativos entre varios deportes 20 (80%, entre los cuales se observa que 17 (85% son deportes donde se refieren una gran cantidad de severos traumatismos oculares (football, hockey y squash; y se mantiene el boxeo en un lugar de baja incidencia con respecto a estos y a otros deportes. A partir de los resultados hasta ahora obtenidos, concluimos que el boxeo tiene una baja incidencia en la ocurrencia de traumatismos ocularesThe ocular injure is any eye lesion caused by external factors that are not related to the patient`s disease. The most common causes are domestic, work accidents and sports practicing. In the particular case of boxing, there is a controversy in which some state that the modern medicine, the new refereeing rules and the novel training techniques, this sports is almost harmless to the individuals practicing it. Other people say that repeated traumas bring about brain injures responsible for neuropsychological decline of a great number of boxers. Twenty four international and one national (the only one so far published papers were reviewed. Comparative studies among several sports 20 (80 % are mentioned; it was observed that 17 (85 % are sports where a great deal of severe ocular

In-hospital mortality pattern of severely injured children

DEFF Research Database (Denmark)

Do, Hien Quoc; Steinmetz, Jacob; Rasmussen, Lars S

2012-01-01

the mortality pattern of severely injured children admitted to a Danish level I trauma centre. METHODS: We included trauma patients aged 15 years or less, who subsequent a trauma team activation were admitted during the 9-year period 1999-2007. Data were collected prospectively for subjects who had a length...

Evaluation of Porin Interaction with Adenine Nucleotide Translocase and Cyclophilin-D Proteins after Brain Ischemia and Reperfusion

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Mohammad Ali Atlasi

2011-01-01

Full Text Available Objective (s Porin is a mitochondrial outer membrane channel, which usually functions as the pathway for the movement of various substances in and out of the mitochondria and is considered to be a component of the permeability transition (PT pore complex that plays a role in the PT. We addressed the hypothesis that porin interacts with other mitochondrial proteins after ischemic injury.Materials and MethodsFor this purpose, we used in vivo 4-vessel occlusion model of rat brain and porin purification method by hydroxyapatite column. After SDS gel electrophoresis and silver nitrate staining, Western blotting was done for porin, adenine nucleotide translocase and cyclophilin-D proteins.Results Porin was purified from mitochondrial mixture in ischemic brain and control groups. Investigation of interaction of adenine nucleotide transposes (ANT and cyclophilin-D with porin by Western blotting showed no proteins co-purified with porin from injured tissues.Conclusion The present study implies that there may not be interaction between porin, and ANT or cyclophilin-D, and if there is any, it is not maintained during the purification procedure.

Driving difficulties of brain-injured drivers in reaction to high-crash-risk simulated road events: a question of impaired divided attention?

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Cyr, Andrée-Ann; Stinchcombe, Arne; Gagnon, Sylvain; Marshall, Shawn; Hing, Malcolm Man-Son; Finestone, Hillel

2009-05-01

This study examined the role of impaired divided attention and speed of processing in traumatic brain injury (TBI) drivers in high-crash-risk simulated road events. A total of 17 TBI drivers and 16 healthy participants were exposed to four challenging simulated roadway events to which behavioral reactions were recorded. Participants were also asked to perform a dual task during portions of the driving task, and TBI individuals were administered standard measures of divided attention and reaction time. Results indicated that the TBI group crashed significantly more than controls (p < .05) and that dual-task performance correlated significantly with crash rate (r = .58, p = .05).

Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo

International Nuclear Information System (INIS)

Guizar-Sahagun, G.; Rivera, F.; Babinski, E.; Berlanga, E.; Madrazo, M.; Franco-Bourland, R.; Grijalva, I.; Gonzalez, J.; Contreras, B.; Madrazo, I.

1994-01-01

We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. (orig.)

Magnetic resonance imaging of the normal and chronically injured adult rat spinal cord in vivo

Energy Technology Data Exchange (ETDEWEB)

Guizar-Sahagun, G [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo XXI, Inst. Mexicano del Seguro Social, Mexico City (Mexico); Rivera, F [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico); Babinski, E [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico); Berlanga, E [Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico); Madrazo, M [Dept. of Magnetic Resonance Imaging, Hospital Angeles del Pedregal, Mexico City (Mexico); Franco-Bourland, R [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Biochemistry, Inst. Nacional de la Nutricion, Mexico City (Mexico); Grijalva, I [Centro de Investigacion del Proyecto Camina, Mexico City (Mexico) Dept. of Clinical Research in Neurology and Neurosurgery, Hospital de Especialidades, Centro Medico Nacional Siglo

1994-08-01

We assessed the capacity of MRI to show and characterise the spinal cord (SC) in vivo in normal and chronically injured adult rats. In the chronically injured animals the SC was studied by MRI and histological examination. MRI was performed at 1.5 T, using gradient-echo and spin-echo (SE) sequences, the latter with and without gadolinium-DTPA (Gd-DTPA). Several positions were tried for good alignment and to diminish interference by respiratory movements. Images of the SC were obtained in sagittal, coronal, and axial planes. Normal SC was observed as a continuous intensity in both sequences, although contrast resolution was better using SE; it was not possible to differentiate the grey and white matter. Low signal was seen in the damaged area in chronically injured rats, which corresponded to cysts, trabeculae, mononuclear infiltrate, and fibroglial wall on histological examination. Gd-DTPA failed to enhance the SC in normal or chronically injured rats. It did, however, cause enhancement of the lesion after acute SC injury. (orig.)

Bidirectional brain-gut interactions and chronic pathological changes after traumatic brain injury in mice.

Science.gov (United States)

Ma, Elise L; Smith, Allen D; Desai, Neemesh; Cheung, Lumei; Hanscom, Marie; Stoica, Bogdan A; Loane, David J; Shea-Donohue, Terez; Faden, Alan I

2017-11-01

Traumatic brain injury (TBI) has complex effects on the gastrointestinal tract that are associated with TBI-related morbidity and mortality. We examined changes in mucosal barrier properties and enteric glial cell response in the gut after experimental TBI in mice, as well as effects of the enteric pathogen Citrobacter rodentium (Cr) on both gut and brain after injury. Moderate-level TBI was induced in C57BL/6mice by controlled cortical impact (CCI). Mucosal barrier function was assessed by transepithelial resistance, fluorescent-labelled dextran flux, and quantification of tight junction proteins. Enteric glial cell number and activation were measured by Sox10 expression and GFAP reactivity, respectively. Separate groups of mice were challenged with Cr infection during the chronic phase of TBI, and host immune response, barrier integrity, enteric glial cell reactivity, and progression of brain injury and inflammation were assessed. Chronic CCI induced changes in colon morphology, including increased mucosal depth and smooth muscle thickening. At day 28 post-CCI, increased paracellular permeability and decreased claudin-1 mRNA and protein expression were observed in the absence of inflammation in the colon. Colonic glial cell GFAP and Sox10 expression were significantly increased 28days after brain injury. Clearance of Cr and upregulation of Th1/Th17 cytokines in the colon were unaffected by CCI; however, colonic paracellular flux and enteric glial cell GFAP expression were significantly increased. Importantly, Cr infection in chronically-injured mice worsened the brain lesion injury and increased astrocyte- and microglial-mediated inflammation. These experimental studies demonstrate chronic and bidirectional brain-gut interactions after TBI, which may negatively impact late outcomes after brain injury. Copyright © 2017 Elsevier Inc. All rights reserved.

Experienced emotional burden in caregivers: psychometric properties of the Involvement Evaluation Questionnaire in caregivers of brain injured patients.

NARCIS (Netherlands)

Geurtsen, G.J.; Meijer, R.; Heugten, C.M. van; Martina, J.D.; Geurts, A.C.H.

2010-01-01

OBJECTIVE: To examine the psychometric properties (internal consistency, discriminant validity, and responsiveness) of the Involvement Evaluation Questionnaire for Brain Injury measuring emotional burden in caregivers of patients with chronic acquired brain injury. DESIGN: Inception cohort study.

Experienced emotional burden in caregivers: psychometric properties of the Involvement Evaluation Questionnaire in caregivers of brain injured patients

NARCIS (Netherlands)

Geurtsen, Gert J.; Meijer, Ron; van Heugten, Caroline M.; Martina, Juan D.; Geurts, Alexander C. H.

2010-01-01

To examine the psychometric properties (internal consistency, discriminant validity, and responsiveness) of the Involvement Evaluation Questionnaire for Brain Injury measuring emotional burden in caregivers of patients with chronic acquired brain injury. Inception cohort study. Caregivers of chronic

Saving the injured: Rescue behavior in the termite-hunting ant Megaponera analis.

Science.gov (United States)

Frank, Erik Thomas; Schmitt, Thomas; Hovestadt, Thomas; Mitesser, Oliver; Stiegler, Jonas; Linsenmair, Karl Eduard

2017-04-01

Predators of highly defensive prey likely develop cost-reducing adaptations. The ant Megaponera analis is a specialized termite predator, solely raiding termites of the subfamily Macrotermitinae (in this study, mostly colonies of Pseudocanthotermes sp.) at their foraging sites. The evolutionary arms race between termites and ants led to various defensive mechanisms in termites (for example, a caste specialized in fighting predators). Because M. analis incurs high injury/mortality risks when preying on termites, some risk-mitigating adaptations seem likely to have evolved. We show that a unique rescue behavior in M. analis , consisting of injured nestmates being carried back to the nest, reduces combat mortality. After a fight, injured ants are carried back by their nestmates; these ants have usually lost an extremity or have termites clinging to them and are able to recover within the nest. Injured ants that are forced experimentally to return without help, die in 32% of the cases. Behavioral experiments show that two compounds, dimethyl disulfide and dimethyl trisulfide, present in the mandibular gland reservoirs, trigger the rescue behavior. A model accounting for this rescue behavior identifies the drivers favoring its evolution and estimates that rescuing enables maintenance of a 28.7% larger colony size. Our results are the first to explore experimentally the adaptive value of this form of rescue behavior focused on injured nestmates in social insects and help us to identify evolutionary drivers responsible for this type of behavior to evolve in animals.

Possible Role of Brain-Derived Neurotrophic Factor (BDNF) in Autism Spectrum Disorder: Current Status

International Nuclear Information System (INIS)

Halepoto, D. M.; Bashir, S.; AL-Ayadhi, L.

2014-01-01

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays a vital role in the growth, development, maintenance, and function of several neuronal systems. The purpose of this review is to document the support for the involvement of this molecule in the maintenance of normal cognitive, emotional functioning, and to outline recent developments in the content of Autism spectrum disorder (ASD). Current and future treatment development can be guided by developing understanding of this molecules actions in the brain and the ways the expression of BDNF can be planned. Over the years, research findings suggested a critical role played by BDNF in the development of autism including increased serum concentrations of BDNF in children with autism and identification of different forms of BDNF in families of autistic individuals. (author)

Possible Role of Brain-Derived Neurotrophic Factor (BDNF) in Autism Spectrum Disorder: Current Status

Energy Technology Data Exchange (ETDEWEB)

Halepoto, D. M.; Bashir, S.; AL-Ayadhi, L. [King Saud Univ., Riyadh (Saudi Arabia). Dept. of Physiology

2014-04-15

Brain-derived neurotrophic factor (BDNF), a member of the neurotrophin family of survival-promoting molecules, plays a vital role in the growth, development, maintenance, and function of several neuronal systems. The purpose of this review is to document the support for the involvement of this molecule in the maintenance of normal cognitive, emotional functioning, and to outline recent developments in the content of Autism spectrum disorder (ASD). Current and future treatment development can be guided by developing understanding of this molecules actions in the brain and the ways the expression of BDNF can be planned. Over the years, research findings suggested a critical role played by BDNF in the development of autism including increased serum concentrations of BDNF in children with autism and identification of different forms of BDNF in families of autistic individuals. (author)

Combining stereotactic radiosurgery and systemic therapy for brain metastases: a potential role for temozolomide

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Hardee, Matthew E. [Department of Radiation Oncology, New York University Langone Medical Center, New York, NY (United States); Formenti, Silvia C., E-mail: silvia.formenti@nyumc.org [Department of Radiation Oncology, New York University Langone Medical Center, New York, NY (United States); Department of Medical Oncology, New York University Langone Medical Center, New York, NY (United States)

2012-08-09

Brain metastases are unfortunately very common in the natural history of many solid tumors and remain a life-threatening condition, associated with a dismal prognosis, despite many clinical trials aimed at improving outcomes. Radiation therapy options for brain metastases include whole brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS). SRS avoids the potential toxicities of WBRT and is associated with excellent local control (LC) rates. However, distant intracranial failure following SRS remains a problem, suggesting that untreated intracranial micrometastatic disease is responsible for failure of treatment. The oral alkylating agent temozolomide (TMZ), which has demonstrated efficacy in primary malignant central nervous system tumors such as glioblastoma, has been used in early phase trials in the treatment of established brain metastases. Although results of these studies in established, macroscopic metastatic disease have been modest at best, there is clinical and preclinical data to suggest that TMZ is more efficacious at treating and controlling clinically undetectable intracranial micrometastatic disease. We review the available data for the primary management of brain metastases with SRS, as well as the use of TMZ in treating established brain metastases and undetectable micrometastatic disease, and suggest the role for a clinical trial with the aims of treating macroscopically visible brain metastases with SRS combined with TMZ to address microscopic, undetectable disease.

Cortical neurogenesis in adult rats after ischemic brain injury: most new neurons fail to mature

Directory of Open Access Journals (Sweden)

Qing-quan Li

2015-01-01

Full Text Available The present study examines the hypothesis that endogenous neural progenitor cells isolated from the neocortex of ischemic brain can differentiate into neurons or glial cells and contribute to neural regeneration. We performed middle cerebral artery occlusion to establish a model of cerebral ischemia/reperfusion injury in adult rats. Immunohistochemical staining of the cortex 1, 3, 7, 14 or 28 days after injury revealed that neural progenitor cells double-positive for nestin and sox-2 appeared in the injured cortex 1 and 3 days post-injury, and were also positive for glial fibrillary acidic protein. New neurons were labeled using bromodeoxyuridine and different stages of maturity were identified using doublecortin, microtubule-associated protein 2 and neuronal nuclei antigen immunohistochemistry. Immature new neurons coexpressing doublecortin and bromodeoxyuridine were observed in the cortex at 3 and 7 days post-injury, and semi-mature and mature new neurons double-positive for microtubule-associated protein 2 and bromodeoxyuridine were found at 14 days post-injury. A few mature new neurons coexpressing neuronal nuclei antigen and bromodeoxyuridine were observed in the injured cortex 28 days post-injury. Glial fibrillary acidic protein/bromodeoxyuridine double-positive astrocytes were also found in the injured cortex. Our findings suggest that neural progenitor cells are present in the damaged cortex of adult rats with cerebral ischemic brain injury, and that they differentiate into astrocytes and immature neurons, but most neurons fail to reach the mature stage.

Effect of Mindfulness Based Stress Reduction on Quality of Life (SF-36) and Spirometry Parameters, in Chemically Pulmonary Injured Veterans.

Science.gov (United States)

Arefnasab, Zahra; Ghanei, Mostafa; Noorbala, Ahmad Ali; Alipour, Ahmad; Babamahmoodi, Farhang; Babamahmoodi, Abdolreza; Salehi, Maryam

2013-09-01

Studies have shown that Mindfulness Based Stress Reduction (MBSR) has positive effect on physical and psychological dimensions of chronic illnesses. In this study for the first time we examine the effect of this new technique on quality of life and pulmonary function in chemically pulmonary injured veterans who have chronic pulmonary problem, psychological problems and low quality of life. Forty male pulmonary injured veterans were randomly replaced in two groups with 20 participants (MBSR and control Wait List (WL)). Then MBSR group received 8-weekly sessions intervention. We evaluate quality of life (used SF-36 questionnaire) and Spirometry parameters two times; before and after intervention in two group. We used "mixed factorial analyses of variance" test for analyzing data in each dependent variables. Then if we have significant interactional effect, we used -paired- sample t-test" for comparing before and after intervention data of each group, and "Independent-Sample t-test" for comparing after intervention data of two groups. The MBSR compare to WL group improved SF-36 total score, (F (1, 38) =12.09, P=0.001), "Role limitations due to physical problems"(F(1,38)= 6.92, P=0.01), "Role limitations due to emotional problems"(F(1,38)= 7.75, P=0.008), "Social functioning"(F(1,38)= 9.89, P=0.003), "Mental health"(F(1,38)= 15.93, P=0), "Vitality"(F(1,38)= 40.03, P≤0.001), and "Pain"(F(1,38)= 27.60, P≤0.001). MBSR had no significant effect on "FEV1" (F (1, 38) = 0.03, P=0.85),"FVC" (F (1, 38) = 0.16, P=0.69) and "FEV1/FVC" (F (1, 38) = 2.21, P=0.14). MBSR can improve individual's quality of life but not lung function in chemically pulmonary injured veterans.

The role of Tc-99m HMPAO brain perfusion SPECT in the psychiatric disability evaluation of patients with chronic traumatic brain injury

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So, Young [Nuclear Medicne, Seoul National Univ., Seoul (Korea, Republic of); Lee, Kang Wook; Lee, Sun Woo; Ghi, Lek Sung; Song, Chang June [College of Medicine, Chungnam National Univ., Taejon (Korea, Republic of)

2002-08-01

We studied whether brain perfusion SPECT is useful in the psychiatric disability evaluation of patients with chronic traumatic brain injury (TBI). Sixty-nine patients (M:F=58:11, age 39 {+-} 14 years) who underwent Tc-99m HMPAO brain SPECT, brain MRI and neuropsychological (NP) tests during hospitalization in psychiatric wards for the psychiatric disability evaluation were included; the severity of injury was mild in 31, moderate in 17 and severe in 21. SPECT, MRI, NP tests were performed 6 {approx} 61 months (mean 23 months) post-injury. Diagnostic accuracy of SPECT and MRI to show hypoperfusion or abnormal signal intensity in patients with cognitive impairment represented by NP test results were compared. Forty-two patients were considered to have cognitive impairment on NP tests and 27 not. Brain SPECT showed 71% sensitivity and 85% specificity, while brain MRI showed 62% sensitivity and 93% specificity (p>0.05, McNemar test). SPECT found more cortical lesions and MRI was superior in detecting white matter lesions. sensitivity and specificity of 31 mild TBI patients were 45%, 90% for SPECT and 27%, 100% for MRI (p>0.05, McNemar test). Among 41 patients with normal brain MRI, SEPCT showed 63% sensitivity (50% for mild TBI) and 88% specificity (85% for malingerers). Brain SPECT has a supplementary role to neuropsychological tests in the psychiatric disability evaluation of chronic TBI patients by detecting more cortical lesions than MRI.

The role of Tc-99m HMPAO brain perfusion SPECT in the psychiatric disability evaluation of patients with chronic traumatic brain injury

International Nuclear Information System (INIS)

So, Young; Lee, Kang Wook; Lee, Sun Woo; Ghi, Lek Sung; Song, Chang June

2002-01-01

We studied whether brain perfusion SPECT is useful in the psychiatric disability evaluation of patients with chronic traumatic brain injury (TBI). Sixty-nine patients (M:F=58:11, age 39 ± 14 years) who underwent Tc-99m HMPAO brain SPECT, brain MRI and neuropsychological (NP) tests during hospitalization in psychiatric wards for the psychiatric disability evaluation were included; the severity of injury was mild in 31, moderate in 17 and severe in 21. SPECT, MRI, NP tests were performed 6 ∼ 61 months (mean 23 months) post-injury. Diagnostic accuracy of SPECT and MRI to show hypoperfusion or abnormal signal intensity in patients with cognitive impairment represented by NP test results were compared. Forty-two patients were considered to have cognitive impairment on NP tests and 27 not. Brain SPECT showed 71% sensitivity and 85% specificity, while brain MRI showed 62% sensitivity and 93% specificity (p>0.05, McNemar test). SPECT found more cortical lesions and MRI was superior in detecting white matter lesions. sensitivity and specificity of 31 mild TBI patients were 45%, 90% for SPECT and 27%, 100% for MRI (p>0.05, McNemar test). Among 41 patients with normal brain MRI, SEPCT showed 63% sensitivity (50% for mild TBI) and 88% specificity (85% for malingerers). Brain SPECT has a supplementary role to neuropsychological tests in the psychiatric disability evaluation of chronic TBI patients by detecting more cortical lesions than MRI

Brain Stimulation and the Role of the Right Hemisphere in Aphasia Recovery.

Science.gov (United States)

Turkeltaub, Peter E

2015-11-01

Aphasia is a common consequence of left hemisphere stroke and causes a disabling loss of language and communication ability. Current treatments for aphasia are inadequate, leaving a majority of aphasia sufferers with ongoing communication difficulties for the rest of their lives. In the past decade, two forms of noninvasive brain stimulation, repetitive transcranial magnetic stimulation and transcranial direct current stimulation, have emerged as promising new treatments for aphasia. The most common brain stimulation protocols attempt to inhibit the intact right hemisphere based on the hypothesis that maladaptive activity in the right hemisphere limits language recovery in the left. There is now sufficient evidence to demonstrate that this approach, at least for repetitive transcranial magnetic stimulation, improves specific language abilities in aphasia. However, the biological mechanisms that produce these behavioral improvements remain poorly understood. Taken in the context of the larger neurobiological literature on aphasia recovery, the role of the right hemisphere in aphasia recovery remains unclear. Additional research is needed to understand biological mechanisms of recovery, in order to optimize brain stimulation treatments for aphasia. This article summarizes the current evidence on noninvasive brain stimulation methods for aphasia and the neuroscientific considerations surrounding treatments using right hemisphere inhibition. Suggestions are provided for further investigation and for clinicians whose patients ask about brain stimulation treatments for aphasia.

[The psychopathology of the unawareness of cognitive impairments and behavioral limitations in traumatic brain-injured patients].

Science.gov (United States)

Oppenheim-Gluckman, H; Fayol, P; de Collasson, P; Dumond, J J; Azouvi, P

2003-02-01

To explore the unawareness of cognitive impairments and behavioral limitations using a psychopathological approach. Fifteen patients with chronic severe TBI. Outpatient TBI rehabilitation programs in three different centers. Case reports. The data from semi-structured interviews with the patients and their families, at least six months after the accident, were compared with data supplied by the Patient Competency Rating Scale (PCRS) and the Neurobehavioral Rating Scale-Revised (NRS-R). Nine patients demonstrated unawareness of their limitations according to the PCRS (Group I), whereas six did not (Group II). Psychic phenomena specific to patients of group I were found. Some of these were specific to brain injury, such as the lack of representation of cognitive impairments and behavioral limitations or the difficulty to integrate the brain-injury into one's psychic space. Others were not specific to brain injury such as mourning process difficulties, personality characteristics, defense mechanisms. Several psychic phenomena coexisted in the same patient. This study shows the complexity of unawareness of cognitive impairments and behavioral limitations and makes future clinical and theoretical definition indispensable.

Sirtuins and Their Roles in Brain Aging and Neurodegenerative Disorders.

Science.gov (United States)

Jęśko, Henryk; Wencel, Przemysław; Strosznajder, Robert P; Strosznajder, Joanna B

2017-03-01

Sirtuins (SIRT1-SIRT7) are unique histone deacetylases (HDACs) whose activity depends on NAD + levels and thus on the cellular metabolic status. SIRTs regulate energy metabolism and mitochondrial function. They orchestrate the stress response and damage repair. Through these functions sirtuins modulate the course of aging and affect neurodegenerative diseases. SIRTSs interact with multiple signaling proteins, transcription factors (TFs) and poly(ADP-ribose) polymerases (PARPs) another class of NAD + -dependent post-translational protein modifiers. The cross-talk between SIRTs TFs and PARPs is a highly promising research target in a number of brain pathologies. This review describes updated results on sirtuins in brain aging/neurodegeneration. It focuses on SIRT1 but also on the roles of mitochondrial SIRTs (SIRT3, 4, 5) and on SIRT6 and SIRT2 localized in the nucleus and in cytosol, respectively. The involvement of SIRTs in regulation of insulin-like growth factor signaling in the brain during aging and in Alzheimer's disease was also focused. Moreover, we analyze the mechanism(s) and potential significance of interactions between SIRTs and several TFs in the regulation of cell survival and death. A critical view is given on the application of SIRT activators/modulators in therapy of neurodegenerative diseases.

Multisensory training for postural sway control in non-injured elderly ...

African Journals Online (AJOL)

Multisensory training for postural sway control in non-injured elderly females. ... Elderly adults demonstrate increased postural sway, which may ultimately lead to falls. ... Keywords: multisensory training, postural sway control, balance ability, ...

A novel first aid stretcher for immobilization and transportation of spine injured patients.

Science.gov (United States)

Liu, Yan-Sheng; Feng, Ya-Ping; Xie, Jia-Xin; Luo, Zhuo-Jing; Shen, Cai-Hong; Niu, Fang; Zou, Jian; Tang, Shao-Feng; Hao, Jiang; Xu, Jia-Xiang; Xiao, Li-Ping; Xu, Xiao-Ming; Zhu, Hui

2012-01-01

Effective immobilization and transportation are vital to the life-saving acute medical care needed when treating critically injured people. However, the most common types of stretchers used today are wrought with problems that can lead to further medical complications, difficulty in employment and rescue, and ineffective transitions to hospital treatment. Here we report a novel first aid stretcher called the "emergency carpet", which solves these problems with a unique design for spine injured patients. Polyurethane composite material, obtained by a novel process of manually mixing isocyanate and additives, can be poured into a specially designed fabric bag and allowed to harden to form a rigid human-shaped stretcher. The effectiveness of the emergency carpet was examined in the pre-hospital management of victims with spinal fractures. Additionally, it was tested on flat ground and complex terrain as well as in the sea and air. We demonstrated that the emergency carpet can be assembled and solidified on the scene in 5 minutes, providing effective immobilization to the entire injured body. With the protection of the emergency carpet, none of the 20 patients, who were finally confirmed to have spinal column fracture or dislocation, had any neurological deterioration during transportation. Furthermore, the carpet can be handled and transported by multiple means under differing conditions, without compromising immobilization. Finally, the emergency carpet allows the critically injured patient to receive multiple examinations such as X-ray, CT, and MRI without being removed from the carpet. Our results demonstrate that the emergency carpet has ideal capabilities for immobilization, extrication, and transportation of the spine injured patients. Compared with other stretchers, it allows for better mobility, effective immobilization, remarkable conformity to the body, and various means for transportation. The emergency carpet is promising for its intrinsic advantages in

A novel first aid stretcher for immobilization and transportation of spine injured patients.

Directory of Open Access Journals (Sweden)

Yan-Sheng Liu

Full Text Available Effective immobilization and transportation are vital to the life-saving acute medical care needed when treating critically injured people. However, the most common types of stretchers used today are wrought with problems that can lead to further medical complications, difficulty in employment and rescue, and ineffective transitions to hospital treatment. Here we report a novel first aid stretcher called the "emergency carpet", which solves these problems with a unique design for spine injured patients. Polyurethane composite material, obtained by a novel process of manually mixing isocyanate and additives, can be poured into a specially designed fabric bag and allowed to harden to form a rigid human-shaped stretcher. The effectiveness of the emergency carpet was examined in the pre-hospital management of victims with spinal fractures. Additionally, it was tested on flat ground and complex terrain as well as in the sea and air. We demonstrated that the emergency carpet can be assembled and solidified on the scene in 5 minutes, providing effective immobilization to the entire injured body. With the protection of the emergency carpet, none of the 20 patients, who were finally confirmed to have spinal column fracture or dislocation, had any neurological deterioration during transportation. Furthermore, the carpet can be handled and transported by multiple means under differing conditions, without compromising immobilization. Finally, the emergency carpet allows the critically injured patient to receive multiple examinations such as X-ray, CT, and MRI without being removed from the carpet. Our results demonstrate that the emergency carpet has ideal capabilities for immobilization, extrication, and transportation of the spine injured patients. Compared with other stretchers, it allows for better mobility, effective immobilization, remarkable conformity to the body, and various means for transportation. The emergency carpet is promising for its

Effect of glycyrrhizin on traumatic brain injury in rats and its mechanism

Directory of Open Access Journals (Sweden)

Gu Xiangjin

2014-02-01

Full Text Available 【Abstract】Objective: To investigate the neuroprotective effects of glycyrrhizin (Gly as well as its effect on expression of high-mobility group box 1 (HMGB1 in rats after traumatic brain injury (TBI. Methods: Male Sprague-Dawley rats were randomly divided into three groups: sham group, TBI group, and TBI+Gly group (n=36 per group. Rat TBI model was made by using the modified Feeney’s method. In TBI+Gly group, Gly was administered intravenously at a dosage of 10 mg/kg 30 min after TBI. At 24 h after TBI, motor function and brain water content were evaluated. Meanwhile, HMGB1/HMGB1 receptors including toll-like receptor 4 (TLR4 and receptor for advanced glycation end products (RAGE/nuclear factor- κB(NF- κB signaling pathway and inflammatory cytokines in the injured brain tissues were detected using quantitative real-time polymerase chain reaction, western blot, electrophoretic mobility shift assay and enzyme-linked immunosorbent assay. Furthermore, HMGB1, RAGE and TLR4 immunohistochemistry and apoptosis were analyzed. Results: Beam walking performance impairment and brain edema were significantly reduced in TBI+Gly group compared with TBI group; meanwhile, the over-expressions of HMGB1/HMGB1 receptors (TLR4 and RAGE/NF-κB DNA-binding activity and inflammatory cytokines were inhibited. The percentages of HMGB1, RAGE and TLR4- positive cells and apoptotic cells were respectively 58.37%±5.06%, 54.15%±4.65%, 65.50%± 4.83%, 52.02%± 4.63% in TBI group and 39.99%±4.99%, 34.87%±5.02%, 43.33%±4.54%, 37.84%±5.16% in TBI+Gly group (all P<0.01 compared with TBI group. Conclusion: Gly can reduce secondary brain injury and improve outcomes in rat following TBI by down-regulation of HMGB1/HMGB1 receptors (TLR4 and RAGE/NF-κB - mediated inflammatory responses in the injured rat brain.

Fasting and Fast Food Diet Play an Opposite Role in Mice Brain Aging.

Science.gov (United States)

Castrogiovanni, Paola; Li Volti, Giovanni; Sanfilippo, Cristina; Tibullo, Daniele; Galvano, Fabio; Vecchio, Michele; Avola, Roberto; Barbagallo, Ignazio; Malaguarnera, Lucia; Castorina, Sergio; Musumeci, Giuseppe; Imbesi, Rosa; Di Rosa, Michelino

2018-01-20

Fasting may be exploited as a possible strategy for prevention and treatment of several diseases such as diabetes, obesity, and aging. On the other hand, high-fat diet (HFD) represents a risk factor for several diseases and increased mortality. The aim of the present study was to evaluate the impact of fasting on mouse brain aging transcriptome and how HFD regulates such pathways. We used the NCBI Gene Expression Omnibus (GEO) database, in order to identify suitable microarray datasets comparing mouse brain transcriptome under fasting or HFD vs aged mouse brain transcriptome. Three microarray datasets were selected for this study, GSE24504, GSE6285, and GSE8150, and the principal molecular mechanisms involved in this process were evaluated. This analysis showed that, regardless of fasting duration, mouse brain significantly expressed 21 and 30 upregulated and downregulated genes, respectively. The involved biological processes were related to cell cycle arrest, cell death inhibition, and regulation of cellular metabolism. Comparing mouse brain transcriptome under fasting and aged conditions, we found out that the number of genes in common increased with the duration of fasting (222 genes), peaking at 72 h. In addition, mouse brain transcriptome under HFD resembles for the 30% the one of the aged mice. Furthermore, several molecular processes were found to be shared between HFD and aging. In conclusion, we suggest that fasting and HFD play an opposite role in brain transcriptome of aged mice. Therefore, an intermittent diet could represent a possible clinical strategy to counteract aging, loss of memory, and neuroinflammation. Furthermore, low-fat diet leads to the inactivation of brain degenerative processes triggered by aging.

Gamma knife irradiation of injured sciatic nerve induces histological and behavioral improvement in the rat neuropathic pain model.

Directory of Open Access Journals (Sweden)

Yuki Yagasaki

Full Text Available We examined the effects of gamma knife (GK irradiation on injured nerves using a rat partial sciatic nerve ligation (PSL model. GK irradiation was performed at one week after ligation and nerve preparations were made three weeks after ligation. GK irradiation is known to induce immune responses such as glial cell activation in the central nervous system. Thus, we determined the effects of GK irradiation on macrophages using immunoblot and histochemical analyses. Expression of Iba-1 protein, a macrophage marker, was further increased in GK-treated injured nerves as compared with non-irradiated injured nerves. Immunohistochemical study of Iba-1 in GK-irradiated injured sciatic nerves demonstrated Iba-1 positive macrophage accumulation to be enhanced in areas distal to the ligation point. In the same area, myelin debris was also more efficiently removed by GK-irradiation. Myelin debris clearance by macrophages is thought to contribute to a permissive environment for axon growth. In the immunoblot study, GK irradiation significantly increased expressions of βIII-tubulin protein and myelin protein zero, which are markers of axon regeneration and re-myelination, respectively. Toluidine blue staining revealed the re-myelinated fiber diameter to be larger at proximal sites and that the re-myelinated fiber number was increased at distal sites in GK-irradiated injured nerves as compared with non-irradiated injured nerves. These results suggest that GK irradiation of injured nerves facilitates regeneration and re-myelination. In a behavior study, early alleviation of allodynia was observed with GK irradiation in PSL rats. When GK-induced alleviation of allodynia was initially detected, the expression of glial cell line-derived neurotrophic factor (GDNF, a potent analgesic factor, was significantly increased by GK irradiation. These results suggested that GK irradiation alleviates allodynia via increased GDNF. This study provides novel evidence that GK

How to Train an Injured Brain? A Pilot Feasibility Study of Home-Based Computerized Cognitive Training.

Science.gov (United States)

Verhelst, Helena; Vander Linden, Catharine; Vingerhoets, Guy; Caeyenberghs, Karen

2017-02-01

Computerized cognitive training programs have previously shown to be effective in improving cognitive abilities in patients suffering from traumatic brain injury (TBI). These studies often focused on a single cognitive function or required expensive hardware, making it difficult to be used in a home-based environment. This pilot feasibility study aimed to evaluate the feasibility of a newly developed, home-based, computerized cognitive training program for adolescents who suffered from TBI. Additionally, feasibility of study design, procedures, and measurements were examined. Case series, longitudinal, pilot, feasibility intervention study with one baseline and two follow-up assessments. Nine feasibility outcome measures and criteria for success were defined, including accessibility, training motivation/user experience, technical smoothness, training compliance, participation willingness, participation rates, loss to follow-up, assessment timescale, and assessment procedures. Five adolescent patients (four boys, mean age = 16 years 7 months, standard deviation = 9 months) with moderate to severe TBI in the chronic stage were recruited and received 8 weeks of cognitive training with BrainGames. Effect sizes (Cohen's d) were calculated to determine possible training-related effects. The new cognitive training intervention, BrainGames, and study design and procedures proved to be feasible; all nine feasibility outcome criteria were met during this pilot feasibility study. Estimates of effect sizes showed small to very large effects on cognitive measures and questionnaires, which were retained after 6 months. Our pilot study shows that a longitudinal intervention study comprising our novel, computerized cognitive training program and two follow-up assessments is feasible in adolescents suffering from TBI in the chronic stage. Future studies with larger sample sizes will evaluate training-related effects on cognitive functions and underlying brain structures.

Reduction of superoxide dismutase activity correlates with visualization of edema by T2-weighted MR imaging in focal ischemic rat brain

International Nuclear Information System (INIS)

Imaizumi, Shigeki; Chang, LeeHong; Cohen, Yoram; Chan, P.H.; Weinstein, P.R.; James, T.L.; Yoshimoto, Takashi.

1994-01-01

This study investigated the correlation between in vivo serial T 2 -weighted magnetic resonance (MR) imaging and changes in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and water, sodium ion (Na + ), and potassium ion (K + ) contents measured in vitro using rat brain following right middle cerebral artery occlusion in conjunction with bilateral common carotid artery (CCA) occlusion. One hour later the left CCA was released. Serial MR images showed edema developed from the outer cortex towards the center. The T 2 signal intensity of the injured right cortex increased with time compared to that of the contralateral cortex. Increased Na + and water and decreased K + contents occurred in the injured cortex, indicating that serial T 2 -weighted MR imaging reflects the changes in water content and Na + and K + concentrations determined by biochemical techniques. GSH-Px activity was little changed. Total SOD in the injured cortex decreased 1 hour after ischemia and remained low throughout the experiment. In contrast, SOD activity in the noninfarcted left cortex also decreased after 1 hour but returned to normal after 2 hours of ischemia. Our results suggest that oxygen free radicals are important in developing ischemic brain edema and cerebral infarction. (author)

Slow elimination of injured liver DNA bases of γ-irradiated old mice

International Nuclear Information System (INIS)

Gaziev, A.I.; Malakhov, L.V.; Fomenko, L.A.

1982-01-01

The paper presents a study of the elimination of injured bases from the liver DNA of old and young mice after their exposure to γ rays. The presented data show that if DNA from the liver of irradiated mice is treated with incision enzymes, its priming activity is increased. In the case of enzymatic treatment of DNA isolated 5 h after irradiation we find a great difference between the priming activity of the liver DNA of old and young mice. The reason for this difference is that the liver DNA of 20-month old mice 5 h after irradiation still has many unrepaired injured bases. These data indicated that the rate of incision of γ-injured DNA bases in the liver of old mice is lower than in the liver of young mice. In the liver of mice of different age the rate of restitution of DNA, single-strand breaks induced by γ rays in doses up to 100 Gy is the same. At the same time, the level of induced reparative synthesis of DNA in cells of an old organism is lower than in cells of a young organism. The obtained data suggest that reduction of the rate of elimination of modified bases from the cell DNA of 20-month old mice is due to reduction of the activity of the DNA repair enzymes or to restrictions in the chromatin in the access of these enzymes to the injured regions of DNA in the cells of old animals

Long-term functional health status of severely injured patients

NARCIS (Netherlands)

Holtslag, H. R.; Post, M. W.; Lindeman, E.; Van der Werken, Chr.

Background: Studies of the consequences of major trauma have traditionally focused on mortality rates. The aims of this study were, firstly, to investigate the long-term functional health status in a large, unselected group of severely injured patients and to compare this with normative data, and

Targeting the ecology within: The role of the gut-brain axis and human microbiota in drug addiction.

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Skosnik, Patrick D; Cortes-Briones, Jose A

2016-08-01

Despite major advances in our understanding of the brain using traditional neuroscience, reliable and efficacious treatments for drug addiction have remained elusive. Hence, the time has come to utilize novel approaches, particularly those drawing upon contemporary advances in fields outside of established neuroscience and psychiatry. Put another way, the time has come for a paradigm shift in the addiction sciences. Apropos, a revolution in the area of human health is underway, which is occurring at the nexus between enteric microbiology and neuroscience. It has become increasingly clear that the human microbiota (the vast ecology of bacteria residing within the human organism), plays an important role in health and disease. This is not surprising, as it has been estimated that bacteria living in the human body (approximately 1kg of mass, roughly equivalent to that of the human brain) outnumber human cells 10 to 1. While advances in the understanding of the role of microbiota in other areas of human health have yielded intriguing results (e.g., Clostridium difficile, irritable bowel syndrome, autism, etc.), to date, no systematic programs of research have examined the role of microbiota in drug addiction. The current hypothesis, therefore, is that gut dysbiosis plays a key role in addictive disorders. In the context of this hypothesis, this paper provides a rationale for future research to target the "gut-brain axis" in addiction. A brief background of the gut-brain axis is provided, along with a series of hypothesis-driven ideas outlining potential treatments for addiction via manipulations of the "ecology within." Copyright © 2016 Elsevier Ltd. All rights reserved.

Role of miRNA-9 in Brain Development

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Balachandar Radhakrishnan

2016-01-01

Full Text Available MicroRNAs (miRNAs are a class of small regulatory RNAs involved in gene regulation. The regulation is effected by either translational inhibition or transcriptional silencing. In vertebrates, the importance of miRNA in development was discovered from mice and zebrafish dicer knockouts. The miRNA-9 (miR-9 is one of the most highly expressed miRNAs in the early and adult vertebrate brain. It has diverse functions within the developing vertebrate brain. In this article, the role of miR-9 in the developing forebrain (telencephalon and diencephalon, midbrain, hindbrain, and spinal cord of vertebrate species is highlighted. In the forebrain, miR-9 is necessary for the proper development of dorsoventral telencephalon by targeting marker genes expressed in the telencephalon. It regulates proliferation in telencephalon by regulating Foxg1, Pax6, Gsh2 , and Meis2 genes. The feedback loop regulation between miR-9 and Nr2e1/Tlx helps in neuronal migration and differentiation. Targeting Foxp1 and Foxp2 , and Map1b by miR-9 regulates the radial migration of neurons and axonal development. In the organizers, miR-9 is inversely regulated by hairy1 and Fgf8 to maintain zona limitans interthalamica and midbrain-hindbrain boundary (MHB. It maintains the MHB by inhibiting Fgf signaling genes and is involved in the neurogenesis of the midbrain-hindbrain by regulating Her genes. In the hindbrain, miR-9 modulates progenitor proliferation and differentiation by regulating Her genes and Elav3. In the spinal cord, miR-9 modulates the regulation of Foxp1 and Onecut1 for motor neuron development. In the forebrain, midbrain, and hindbrain, miR-9 is necessary for proper neuronal progenitor maintenance, neurogenesis, and differentiation. In vertebrate brain development, miR-9 is involved in regulating several region-specific genes in a spatiotemporal pattern.

Regional pressure and temperature variations across the injured human brain: comparisons between paired intraparenchymal and ventricular measurements.

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Childs, Charmaine; Shen, Liang

2015-06-23

Intraparenchymal, multimodality sensors are commonly used in the management of patients with severe traumatic brain injury (TBI). The 'gold standard', based on accuracy, reliability and cost for intracranial pressure (ICP) monitoring is within the cerebral ventricle (external strain gauge). There are no standards yet for intracerebral temperature monitoring and little is known of temperature differences between brain tissue and ventricle. The aim of the study therefore was to determine pressure and temperature differences at intraparenchymal and ventricular sites during five days of continuous neuromonitoring. Patients with severe TBI requiring emergency surgery. patients who required ICP monitoring were eligible for recruitment. Two intracerebral probe types were used: a) intraventricular, dual parameter sensor (measuring pressure, temperature) with inbuilt catheter for CSF drainage: b) multiparameter intraparenchymal sensor measuring pressure, temperature and oxygen partial pressure. All sensors were inserted during surgery and under aseptic conditions. Seventeen patients, 12 undergoing neurosurgery (decompressive craniectomy n = 8, craniotomy n = 4) aged 21-78 years were studied. Agreement of measures for 9540 brain tissue-ventricular temperature 'pairs' and 10,291 brain tissue-ventricular pressure 'pairs' were determined using mixed model to compare mean temperature and pressure for longitudinal data. There was no significant overall difference for mean temperature (p = 0.92) or mean pressure readings (p = 0.379) between tissue and ventricular sites. With 95.8 % of paired temperature readings within 2SD (-0.4 to 0.4 °C) differences in temperature between brain tissue and ventricle were clinically insignificant. For pressure, 93.5 % of readings pairs fell within the 2SD range (-9.4756 to 7.8112 mmHg). However, for individual patients, agreement for mean tissue-ventricular pressure differences was poor on occasions. There is good overall agreement between paired

Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons

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Jung Ho-Joong

2009-05-01

Full Text Available Abstract Ligaments and tendons are soft connective tissues which serve essential roles for biomechanical function of the musculoskeletal system by stabilizing and guiding the motion of diarthrodial joints. Nevertheless, these tissues are frequently injured due to repetition and overuse as well as quick cutting motions that involve acceleration and deceleration. These injuries often upset this balance between mobility and stability of the joint which causes damage to other soft tissues manifested as pain and other morbidity, such as osteoarthritis. The healing of ligament and tendon injuries varies from tissue to tissue. Tendinopathies are ubiquitous and can take up to 12 months for the pain to subside before one could return to normal activity. A ruptured medial collateral ligament (MCL can generally heal spontaneously; however, its remodeling process takes years and its biomechanical properties remain inferior when compared to the normal MCL. It is also known that a midsubstance anterior cruciate ligament (ACL tear has limited healing capability, and reconstruction by soft tissue grafts has been regularly performed to regain knee function. However, long term follow-up studies have revealed that 20–25% of patients experience unsatisfactory results. Thus, a better understanding of the function of ligaments and tendons, together with knowledge on their healing potential, may help investigators to develop novel strategies to accelerate and improve the healing process of ligaments and tendons. With thousands of new papers published in the last ten years that involve biomechanics of ligaments and tendons, there is an increasing appreciation of this subject area. Such attention has positively impacted clinical practice. On the other hand, biomechanical data are complex in nature, and there is a danger of misinterpreting them. Thus, in these review, we will provide the readers with a brief overview of ligaments and tendons and refer them to

Role of biomechanics in the understanding of normal, injured, and healing ligaments and tendons

Science.gov (United States)

Jung, Ho-Joong; Fisher, Matthew B; Woo, Savio L-Y

2009-01-01

Ligaments and tendons are soft connective tissues which serve essential roles for biomechanical function of the musculoskeletal system by stabilizing and guiding the motion of diarthrodial joints. Nevertheless, these tissues are frequently injured due to repetition and overuse as well as quick cutting motions that involve acceleration and deceleration. These injuries often upset this balance between mobility and stability of the joint which causes damage to other soft tissues manifested as pain and other morbidity, such as osteoarthritis. The healing of ligament and tendon injuries varies from tissue to tissue. Tendinopathies are ubiquitous and can take up to 12 months for the pain to subside before one could return to normal activity. A ruptured medial collateral ligament (MCL) can generally heal spontaneously; however, its remodeling process takes years and its biomechanical properties remain inferior when compared to the normal MCL. It is also known that a midsubstance anterior cruciate ligament (ACL) tear has limited healing capability, and reconstruction by soft tissue grafts has been regularly performed to regain knee function. However, long term follow-up studies have revealed that 20–25% of patients experience unsatisfactory results. Thus, a better understanding of the function of ligaments and tendons, together with knowledge on their healing potential, may help investigators to develop novel strategies to accelerate and improve the healing process of ligaments and tendons. With thousands of new papers published in the last ten years that involve biomechanics of ligaments and tendons, there is an increasing appreciation of this subject area. Such attention has positively impacted clinical practice. On the other hand, biomechanical data are complex in nature, and there is a danger of misinterpreting them. Thus, in these review, we will provide the readers with a brief overview of ligaments and tendons and refer them to appropriate methodologies used to

Possible role of Toxoplasma gondii in brain cancer through modulation of host microRNAs

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Thirugnanam Sivasakthivel

2013-02-01

Full Text Available Abstract Background The obligate intracellular protozoan parasite Toxoplasma gondii infects humans and other warm-blooded animals and establishes a chronic infection in the central nervous system after invasion. Studies showing a positive correlation between anti-Toxoplasma antibodies and incidences of brain cancer have led to the notion that Toxoplasma infections increase the risk of brain cancer. However, molecular events involved in Toxoplasma induced brain cancers are not well understood. Presentation of the hypothesis Toxoplasma gains control of host cell functions including proliferation and apoptosis by channelizing parasite proteins into the cell cytoplasm and some of the proteins are targeted to the host nucleus. Recent studies have shown that Toxoplasma is capable of manipulating host micro RNAs (miRNAs, which play a central role in post-transcriptional regulation of gene expression. Therefore, we hypothesize that Toxoplasma promotes brain carcinogenesis by altering the host miRNAome using parasitic proteins and/or miRNAs. Testing the hypothesis The miRNA expression profiles of brain cancer specimens obtained from patients infected with Toxoplasma could be analyzed and compared with that of normal tissues as well as brain cancer tissues from Toxoplasma uninfected individuals to identify dysregulated miRNAs in Toxoplasma-driven brain cancer cells. Identified miRNAs will be further confirmed by studying cancer related miRNA profiles of the different types of brain cells before and after Toxoplasma infection using cell lines and experimental animals. Expected outcome The miRNAs specifically associated with brain cancers that are caused by Toxoplasma infection will be identified. Implications of the hypothesis Toxoplasma infection may promote initiation and progression of cancer by modifying the miRNAome in brain cells. If this hypothesis is true, the outcome of this research would lead to the development of novel biomarkers and

Quantitative Study of Vibrational Symmetry of Injured Vocal Folds via Digital Kymography in Excised Canine Larynges

Science.gov (United States)

Krausert, Christopher R.; Ying, Di; Zhang, Yu; Jiang, Jack J.

2011-01-01

Purpose: Digital kymography and vocal fold curve fitting are blended with detailed symmetry analysis of kymograms to provide a comprehensive characterization of the vibratory properties of injured vocal folds. Method: Vocal fold vibration of 12 excised canine larynges was recorded under uninjured, unilaterally injured, and bilaterally injured…

Traumatic brain injury and obesity induce persistent central insulin resistance.

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Karelina, Kate; Sarac, Benjamin; Freeman, Lindsey M; Gaier, Kristopher R; Weil, Zachary M

2016-04-01

Traumatic brain injury (TBI)-induced impairments in cerebral energy metabolism impede tissue repair and contribute to delayed functional recovery. Moreover, the transient alteration in brain glucose utilization corresponds to a period of increased vulnerability to the negative effects of a subsequent TBI. In order to better understand the factors contributing to TBI-induced central metabolic dysfunction, we examined the effect of single and repeated TBIs on brain insulin signalling. Here we show that TBI induced acute brain insulin resistance, which resolved within 7 days following a single injury but persisted until 28 days following repeated injuries. Obesity, which causes brain insulin resistance and neuroinflammation, exacerbated the consequences of TBI. Obese mice that underwent a TBI exhibited a prolonged reduction of Akt (also known as protein kinase B) signalling, exacerbated neuroinflammation (microglial activation), learning and memory deficits, and anxiety-like behaviours. Taken together, the transient changes in brain insulin sensitivity following TBI suggest a reduced capacity of the injured brain to respond to the neuroprotective and anti-inflammatory actions of insulin and Akt signalling, and thus may be a contributing factor for the damaging neuroinflammation and long-lasting deficits that occur following TBI. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

The role of brain barriers in fluid movement in the CNS: is there a 'glymphatic' system?

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Abbott, N Joan; Pizzo, Michelle E; Preston, Jane E; Janigro, Damir; Thorne, Robert G

2018-03-01

Brain fluids are rigidly regulated to provide stable environments for neuronal function, e.g., low K + , Ca 2+ , and protein to optimise signalling and minimise neurotoxicity. At the same time, neuronal and astroglial waste must be promptly removed. The interstitial fluid (ISF) of the brain tissue and the cerebrospinal fluid (CSF) bathing the CNS are integral to this homeostasis and the idea of a glia-lymph or 'glymphatic' system for waste clearance from brain has developed over the last 5 years. This links bulk (convective) flow of CSF into brain along the outside of penetrating arteries, glia-mediated convective transport of fluid and solutes through the brain extracellular space (ECS) involving the aquaporin-4 (AQP4) water channel, and finally delivery of fluid to venules for clearance along peri-venous spaces. However, recent evidence favours important amendments to the 'glymphatic' hypothesis, particularly concerning the role of glia and transfer of solutes within the ECS. This review discusses studies which question the role of AQP4 in ISF flow and the lack of evidence for its ability to transport solutes; summarizes attributes of brain ECS that strongly favour the diffusion of small and large molecules without ISF flow; discusses work on hydraulic conductivity and the nature of the extracellular matrix which may impede fluid movement; and reconsiders the roles of the perivascular space (PVS) in CSF-ISF exchange and drainage. We also consider the extent to which CSF-ISF exchange is possible and desirable, the impact of neuropathology on fluid drainage, and why using CSF as a proxy measure of brain components or drug delivery is problematic. We propose that new work and key historical studies both support the concept of a perivascular fluid system, whereby CSF enters the brain via PVS convective flow or dispersion along larger caliber arteries/arterioles, diffusion predominantly regulates CSF/ISF exchange at the level of the neurovascular unit associated with

Associations between damage location and five main body region injuries of MAIS 3-6 injured occupants.

Science.gov (United States)

Tang, Youming; Cao, Libo; Kan, Steven

2014-05-08

To examine the damage location distribution of five main body region injuries of maximum abbreviated injury score (MAIS) 3-6 injured occupants for nearside struck vehicle in front-to-side impact crashes. MAIS 3-6 injured occupants information was extracted from the US-National Automotive Sampling System/Crashworthiness Data System in the year 2007; it included the head/face/neck, chest, pelvis, upper extremity and lower extremity. Struck vehicle collision damage was classified in a three-dimensional system according to the J224 Collision Deformation Classification of SAE Surface Vehicle Standard. Nearside occupants seated directly adjacent to the struck side of the vehicle with MAIS 3-6 injured, in light truck vehicles-passenger cars (LTV-PC) side impact crashes. Distribution of MAIS 3-6 injured occupants by body regions and specific location of damage (lateral direction, horizontal direction and vertical direction) were examined. Injury risk ratio was also assessed. The lateral crush zone contributed to MAIS 3-6 injured occupants (n=705) and 50th centile injury risks when extended into zone 3. When the crush extended to zone 4, the injury risk ratio of MAIS 3-6 injured occupants approached 81%. The horizontal crush zones contributing to the highest injury risk ratio of MAIS 3-6 occupants were zones 'D' and 'Y', and the injury risk ratios were 25.4% and 36.9%, respectively. In contrast, the lowest injury risk ratio was 5.67% caused by zone 'B'. The vertical crush zone which contributed to the highest injury risk ratio of MAIS 3-6 occupants was zone 'E', whose injury risk ratio was 58%. In contrast, the lowest injury risk ratio was 0.14% caused by zone 'G+M'. The highest injury risk ratio of MAIS 3-6 injured occupants caused by crush intrusion between 40 and 60 cm in LTV-PC nearside impact collisions and the damage region of the struck vehicle was in the zones 'E' and 'Y'.

The Role of Oxidative Stress in Severity of Obstructive Pulmonary Complications in Sputum of Sulfur Mustard-Injured Patients

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Javad Heydari

2017-09-01

Full Text Available Background: Sulfur mustard (SM is a strong bifunctional alkylating agent that causes delayed complications in organs such as lung. Oxidative stress plays a pivotal role in the pathogenesis and progression of many pulmonary diseases. The aim of this study was to investigate the oxidative stress in sputum of SM exposed patients with mild, moderate and severe pulmonary dysfunction and assessing their relationship with pulmonary function. Methods: In this cross–sectional study, oxidative stress biomarkers in sputum were examined on 26 patients with SM-induced bronchiolitis obliterans (9 mild, 14 moderate and 3 severe and 12 matched healthy controls referred to Baqiyatallah Hospital, Tehran between October 2015 and April 2016. Results: Sputum superoxide dismutase, catalase and glutathione S-transferase activities and malondialdehyde level in moderate and severe groups were significantly higher than in the control group (P=0.002, P=0.004, P=0.014 and P=0.009, respectively. Glutathione (GSH level in moderate (22.29%, P=0.025 and severe (45.07%, P=0.004 groups were significantly lower than the control. A decreased in GSH level in severe (41.7% groups was observed as compared with the mild group. Pearson analysis revealed strong correlations between disease severity and oxidative stress biomarkers in sputum of patients with moderate and severe injuries. Conclusions: Oxidative stress is involved in the pathogenesis of patients with moderate and severe pulmonary dysfunction following SM exposure. The presence of enhanced oxidative stress relates to the decline lung function and the progression of the disease. Sputum induction in SM-injured patients can be used to the assessment of the antioxidant status of bronchial secretions.

The Extreme Male Brain Theory and Gender Role Behaviour in Persons with an Autism Spectrum Condition

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Stauder, J. E. A.; Cornet, L. J. M.; Ponds, R. W. H. M.

2011-01-01

According to the Extreme Male Brain theory persons with autism possess masculinised cognitive traits. In this study masculinisation of gender role behaviour is evaluated in 25 persons with an autism spectrum condition (ASC) and matched controls with gender role behaviour as part of a shortened version of the Minnesota Multiphasic Personality…

Imaging of injured and atherosclerotic arteries in mice using fluorescence-labeled glycoprotein VI-Fc

Energy Technology Data Exchange (ETDEWEB)

Bigalke, Boris, E-mail: boris.bigalke@med.uni-tuebingen.de [Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universitaet Tuebingen (Germany); Division of Imaging Sciences, St Thomas' Hospital, King' s College London (United Kingdom); Pohlmeyer, Ilka; Schoenberger, Tanja [Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universitaet Tuebingen (Germany); Griessinger, Christoph M. [Labor fuer Praeklinische Bildgebung und Bildgebungstechnologie der Werner-Siemens-Stiftung, Radiologische Klinik, Eberhard-Karls-Universitaet Tuebingen (Germany); Ungerer, Martin [Corimmun GmbH, Martinsried (Germany); Botnar, Rene M. [Division of Imaging Sciences, St Thomas' Hospital, King' s College London (United Kingdom); Pichler, Bernd J. [Labor fuer Praeklinische Bildgebung und Bildgebungstechnologie der Werner-Siemens-Stiftung, Radiologische Klinik, Eberhard-Karls-Universitaet Tuebingen (Germany); Gawaz, Meinrad [Medizinische Klinik III, Kardiologie und Kreislauferkrankungen, Eberhard-Karls-Universitaet Tuebingen (Germany)

2011-08-15

Purpose: To assess endothelial injury and repair using fluorescence-labeled glycoprotein VI (GPVI)-Fc in a murine model. Materials and methods: Three 4-week-old male ApoE-deficient (ApoE{sup -/-})-mice were fed with a 1.25% cholesterol diet over 16 weeks and compared to three wild type (WT) C57BL/6J-mice in a wire-induced vascular injury model. Another group of WT mice (n = 10) were mechanically injured by carotid ligation. Fluorescence-labeled GPVI-Fc (150 {mu}g/mouse) was administered and assessed by optical imaging 24 h after injury and compared to another group (n = 3) which was injected two days after injury and sacrificed another day later. Results: After denudation, all injured carotids of WT mice showed a higher mean fluorescence signal than the corresponding intact carotids of the same animals (48.4 {+-} 18.9 vs. 10.4 {+-} 1.0; P = 0.028). Injection of unlabeled GPVI-Fc 20 h and 3 h before injecting GPVI-Fc-FITC significantly reduced the fluorescence signal in injured carotids to 14.6 {+-} 4.6, while intact carotids showed a signal of 9.2 {+-} 1.1; P = 0.046. Ligation injury resulted with an increased GPVI-Fc-binding to injured carotids compared to intact carotids (31.53 {+-} 6.18 vs. 16.48 {+-} 5.15; P = 0.039). Three days after injury and 24 h after GPVI-Fc-FITC injection, differences between intact and injured carotids have vanished (12.51 {+-} 2.76 vs. 14.76 {+-} 1.59; P = 0.519). Conclusions: A GPVI-based plaque imaging system could help to identify vascular lesions and to take a precautionary measure as necessary.

Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice.

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Sindhu K Madathil

Full Text Available Traumatic brain injury (TBI survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1, a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal overexpression of IGF-1 using the controlled cortical impact (CCI injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI.

Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice

Science.gov (United States)

Madathil, Sindhu K.; Carlson, Shaun W.; Brelsfoard, Jennifer M.; Ye, Ping; D’Ercole, A. Joseph; Saatman, Kathryn E.

2013-01-01

Traumatic brain injury (TBI) survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1), a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal) overexpression of IGF-1 using the controlled cortical impact (CCI) injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d) hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI. PMID:23826235

Comparison of lorazepam and zopiclone for insomnia in patients with stroke and brain injury: a randomized, crossover, double-blinded trial.

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Li Pi Shan, Rodney S; Ashworth, Nigel L

2004-06-01

To determine if lorazepam or zopiclone is more effective in providing a restful night of sleep and to assess the effects of these medications on cognition. A randomized, double-blinded, crossover trial was performed at a tertiary care rehabilitation inpatient unit in a teaching hospital. A total of 18 brain-injured and stroke patients, aged 20-78 yrs, were administered lorazepam, 0.5-1.0 mg, orally at bedtime as needed for 7 days and zopiclone, 3.75-7.5 mg, orally at bedtime as needed for 7 days. Total sleep time and characteristics of sleep were measured. Effects on cognition were also measured using the Folstein Mini Mental Status Exam. There was no difference in average sleep duration or in subjective measures of sleep. Cognition as assessed by the Mini Mental Status Exam revealed no difference in the zopiclone arm compared with the lorazepam arm. Zopiclone is equally effective as lorazepam in the treatment of insomnia in stroke and brain-injured patients.

Reduction of superoxide dismutase activity correlates with visualization of edema by T[sub 2]-weighted MR imaging in focal ischemic rat brain

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Imaizumi, Shigeki; Chang, LeeHong; Cohen, Yoram; Chan, P H; Weinstein, P R; James, T L [California Univ., San Francisco, CA (United States); Yoshimoto, Takashi

1994-01-01

This study investigated the correlation between in vivo serial T[sub 2]-weighted magnetic resonance (MR) imaging and changes in superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities, and water, sodium ion (Na[sup +]), and potassium ion (K[sup +]) contents measured in vitro using rat brain following right middle cerebral artery occlusion in conjunction with bilateral common carotid artery (CCA) occlusion. One hour later the left CCA was released. Serial MR images showed edema developed from the outer cortex towards the center. The T[sub 2] signal intensity of the injured right cortex increased with time compared to that of the contralateral cortex. Increased Na[sup +] and water and decreased K[sup +] contents occurred in the injured cortex, indicating that serial T[sub 2]-weighted MR imaging reflects the changes in water content and Na[sup +] and K[sup +] concentrations determined by biochemical techniques. GSH-Px activity was little changed. Total SOD in the injured cortex decreased 1 hour after ischemia and remained low throughout the experiment. In contrast, SOD activity in the noninfarcted left cortex also decreased after 1 hour but returned to normal after 2 hours of ischemia. Our results suggest that oxygen free radicals are important in developing ischemic brain edema and cerebral infarction. (author).

Short-term low-frequency electrical stimulation enhanced remyelination of injured peripheral nerves by inducing the promyelination effect of brain-derived neurotrophic factor on Schwann cell polarization.

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Wan, Lidan; Xia, Rong; Ding, Wenlong

2010-09-01

Electrical stimulation (ES) has been found to aid repair of nerve injuries and have been shown to increase and direct neurite outgrowth during stimulation. However, the effect of ES on peripheral remyelination after nerve damage has been investigated less well, and the mechanism underlying its action remains unclear. In the present study, the crush-injured sciatic nerves in rats were subjected to 1 hr of continuous ES (20 Hz, 100 microsec, 3 V). Electron microscopy and nerve morphometry were performed to investigate the extent of regenerated nerve myelination. The expression profiles of P0, Par-3, and brain-derived neurotrophic factor (BDNF) in the injuried sciatic nerves and in the dorsal root ganglion neuron/Schwann cell cocultures were examined by Western blotting. Par-3 localization in the sciatic nerves was determined by immunohistochemistry to demonstrate Schwann cell polarization during myelination. We reported that 20-Hz ES increased the number of myelinated fibers and the thickness myelin sheath at 4 and 8 weeks postinjury. P0 level in the ES-treated groups, both in vitro and in vivo, was enhanced compared with the controls. The earlier peak of Par-3 in the ES-treated groups indicated an earlier initiation of Schwann cell myelination. Additionally, ES significantly elevated BDNF expression in nerve tissues and in cocultures. ES on the site of nerve injury potentiates axonal regrowth and myelin maturation during peripheral nerve regeneration. Furthermore, the therapeutic actions of ES on myelination are mediated via enhanced BDNF signals, which drive the promyelination effect on Schwann cells at the onset of myelination.

Resting State Functional Connectivity in Mild Traumatic Brain Injury at the Acute Stage: Independent Component and Seed-Based Analyses

OpenAIRE

Iraji, Armin; Benson, Randall R.; Welch, Robert D.; O'Neil, Brian J.; Woodard, John L.; Imran Ayaz, Syed; Kulek, Andrew; Mika, Valerie; Medado, Patrick; Soltanian-Zadeh, Hamid; Liu, Tianming; Haacke, E. Mark; Kou, Zhifeng

2015-01-01

Mild traumatic brain injury (mTBI) accounts for more than 1 million emergency visits each year. Most of the injured stay in the emergency department for a few hours and are discharged home without a specific follow-up plan because of their negative clinical structural imaging. Advanced magnetic resonance imaging (MRI), particularly functional MRI (fMRI), has been reported as being sensitive to functional disturbances after brain injury. In this study, a cohort of 12 patients with mTBI were pr...

Prevalence of alcohol and other psychoactive substances in injured drivers : comparison between Belgium and The Netherlands.

NARCIS (Netherlands)

Legrand, S.-A. Houwing, S. Hagenzieker, M. & Verstraete, A.G.

2013-01-01

The study objective was to compare the prevalence of alcohol and (il)licit drugs in seriously injured drivers in Belgium (BE) and the Netherlands (NL). Injured car and van drivers admitted to the emergency departments of five hospitals in Belgium and three in the Netherlands from January 2008 to May

The role of stereotactic radiation therapy in the management of children with brain tumors.

Science.gov (United States)

Lew, C M; LaVally, B

1995-10-01

Conventional radiation therapy plays an important role in the management of intracranial tumors in children. For certain tumors radiation therapy serves as the primary mode of treatment, and for others it plays an adjuvant role with surgery and/or chemotherapy. Improvements in long-term survival rates have focused attention on the long-term sequelae of brain tumors and their treatment, and the sequelae, in turn, have become important targets for clinical investigation. Long-term side effects of particular concern in children include cranial nerve damage, memory and intellectual deficits, pituitary-hypothalamic dysfunction, demyelinization of brain tissue, and secondary malignancies. A new form of radiation therapy, stereotactic radiotherapy (SRT), merges the technologies of stereotactic surgery and conventional fractionated radiotherapy. The intent is to deliver maximum tumoricidal doses to the target while limiting the dose to normal surrounding brain tissue. The key feature of SRT is a noninvasive, relocatable immobilization system to assure accurate and reproducible positioning during planning and treatment. The headframes used for children have been modified to address their specific needs. The complexities of this process require careful preparation of patients and their families and the participation of many disciplines. Long-term follow-up will be essential to evaluate the effectiveness of this innovative treatment.

Role of 99mTc labelled GHA in post treatment evaluation of brain tumours

International Nuclear Information System (INIS)

Choudhury, P.

2003-01-01

Full text: Introduction: Biochemical investigations have a major role to play in the management of primary brain tumours. It is well known that major biochemical changes occur during cancerous transformation including changes in the energy metabolism of the cell. Changes take place in terms of utilization of glucose and other substrates, protein synthesis and expression of antigens and receptors. Changes also take place in disruption of transport mechanisms across cell membranes and other physiological boundaries like blood brain barrier. In the management of primary brain tumours positron emitting tracers have an undisputed role and the role of cationic tracers like Thallium-201, 99m-Tc MIBI and 99m-Tc tetrofosmin has been cited as an alternative to positron tracers in neuro oncology. It must be borne in mind that the cationic tracers are expensive to procure and facilities for positron emission tomography are not available in most of the developing countries. Tc-99m GHA Brain Imaging: Keeping in view the above, a cheaper alternative for PET radio tracers was evaluated. We have so far conducted more than 100 brain SPECT studies, using Tc-99m Glucoheptonic acid (GHA), in 60 patients of brain tumour, both at the time of their diagnosis, as well as after treatment during the follow-up period. Tc-99m Glucoheptonic acid (GHA) is a chemical glucose analogue. Avid concentration of the radiopharmaceutical was noted in viable tumor tissue in the SPECT images done one hour after injection of 740 MBq of 99m-Tc GHA. This was subsequently confirmed by histopathological examination in patients undergoing re-surgery for residual disease or follow up and clinical correlation in patients under remission. Avid tracer concentration was also well demonstrated in recurrent disease (proven by clinical examination, histopathology and/or magnetic resonance imaging (MRI). No significant tracer uptake was seen in areas of radiation induced necrosis. Non-specific uptake in the tumor bed was

Injured pedestrians in Cape Town - the role of alcohol

African Journals Online (AJOL)

pedestrians and attempt to define the role which alcohol plays in this ... Forensic Chemistry Laboratory, Department of National Health, Cape. Town. J. Monis .... Short term « 8 wks). 80. 40.8. 47. 39.2. 33. 43.4. Long tenn (;;. 8 wks). 54 27.6.

Quantifying anisotropy and fiber orientation in human brain histological sections

Directory of Open Access Journals (Sweden)

Matthew D Budde

2013-02-01

Full Text Available Diffusion weighted imaging (DWI has provided unparalleled insight into the microscopic structure and organization of the central nervous system. Diffusion tensor imaging (DTI and other models of the diffusion MRI signal extract microstructural properties of tissues with relevance to the normal and injured brain. Despite the prevalence of such techniques and applications, accurate and large-scale validation has proven difficult, particularly in the human brain. In this report, human brain sections obtained from a digital public brain bank were employed to quantify anisotropy and fiber orientation using structure tensor analysis. The derived maps depict the intricate complexity of white matter fibers at a resolution not attainable with current DWI experiments. Moreover, the effects of multiple fiber bundles (i.e. crossing fibers and intravoxel fiber dispersion were demonstrated. Examination of the cortex and hippocampal regions validated specific features of previous in vivo and ex vivo DTI studies of the human brain. Despite the limitation to two dimensions, the resulting images provide a unique depiction of white matter organization at resolutions currently unattainable with DWI. The method of analysis may be used to validate tissue properties derived from DTI and alternative models of the diffusion signal.

Substance use and social, health and safety-related factors among fatally injured drivers.

Science.gov (United States)

Karjalainen, Karoliina; Blencowe, Tom; Lillsunde, Pirjo

2012-03-01

The aim of this study was to examine different socio-demographic, health and safety-related factors, and psychoactive substance use among fatally injured drivers in road traffic accidents in Finland during 2006-2008. An accident information register maintained by the Traffic Safety Committee of Insurance Companies (VALT) of the Finnish Motor Insurers' Centre was used as basic data, and the basic data were complemented with further toxicological analytical information retrieved from autopsy reports from the Department of Forensic Medicine, Helsinki University. The data included all the drivers (n=556) who were driving a motor vehicle and who died in a road traffic accident in Finland during 2006-2008. Of all the 556 fatally injured drivers 43% (n=238) had psychoactive substance findings. 51% (n=121) of substance positive drivers had a finding for alcohol only, the rest had a finding for one or more illicit/medicinal drugs impairing driving ability, and possibly also alcohol. Fatally injured drivers with alcohol findings were significantly younger (mean age 34 years) than sober drivers (mean age 44 years) or drivers with findings for drugs (mean age 45 years). Socio-demographic background did not differ substantially among drunken/drugged and sober drivers, although drivers with alcohol findings had a slightly lower education and socioeconomic position. Previous substance abuse problems were highly prevalent among drivers with substance findings and mental or both mental and physical health problems were more common among drivers with drug findings. The non-use of safety equipment and driving at a high speed were more common among fatally injured drivers with substance findings. Substance abuse and mental health problems, as well as reckless driving behavior were more pronounced among fatally injured drivers with substance findings when compared to sober drivers. Thus, prevention and early intervention concerning substance abuse, mental health problems and DUI are

DO GENERAL MEDICAL PRACTITIONERS EXAMINE INJURED RUNNERS?

DEFF Research Database (Denmark)

Videbæk, Solvej; Jensen, A V; Rasmussen, S

2017-01-01

BACKGROUND: General Medical Practitioners (GMP) in Denmark perform clinical examinations of patients with musculoskeletal pain. However, the prevalence proportion of examinations caused by running-related injuries remains unknown. PURPOSE: The primary purpose of the present study was to estimate...... the prevalence proportion of consultations in general medical practice caused by running-related injuries. The secondary purpose was to estimate the prevalence proportion of injured runners, who consult their GMP, that are referred to additional examinations or treatments. STUDY DESIGN: A survey-based study...

Imaging of injured and atherosclerotic arteries in mice using fluorescence-labeled glycoprotein VI-Fc

International Nuclear Information System (INIS)

Bigalke, Boris; Pohlmeyer, Ilka; Schoenberger, Tanja; Griessinger, Christoph M.; Ungerer, Martin; Botnar, Rene M.; Pichler, Bernd J.; Gawaz, Meinrad

2011-01-01

Purpose: To assess endothelial injury and repair using fluorescence-labeled glycoprotein VI (GPVI)-Fc in a murine model. Materials and methods: Three 4-week-old male ApoE-deficient (ApoE -/- )-mice were fed with a 1.25% cholesterol diet over 16 weeks and compared to three wild type (WT) C57BL/6J-mice in a wire-induced vascular injury model. Another group of WT mice (n = 10) were mechanically injured by carotid ligation. Fluorescence-labeled GPVI-Fc (150 μg/mouse) was administered and assessed by optical imaging 24 h after injury and compared to another group (n = 3) which was injected two days after injury and sacrificed another day later. Results: After denudation, all injured carotids of WT mice showed a higher mean fluorescence signal than the corresponding intact carotids of the same animals (48.4 ± 18.9 vs. 10.4 ± 1.0; P = 0.028). Injection of unlabeled GPVI-Fc 20 h and 3 h before injecting GPVI-Fc-FITC significantly reduced the fluorescence signal in injured carotids to 14.6 ± 4.6, while intact carotids showed a signal of 9.2 ± 1.1; P = 0.046. Ligation injury resulted with an increased GPVI-Fc-binding to injured carotids compared to intact carotids (31.53 ± 6.18 vs. 16.48 ± 5.15; P = 0.039). Three days after injury and 24 h after GPVI-Fc-FITC injection, differences between intact and injured carotids have vanished (12.51 ± 2.76 vs. 14.76 ± 1.59; P = 0.519). Conclusions: A GPVI-based plaque imaging system could help to identify vascular lesions and to take a precautionary measure as necessary.

Use of brain electrical activity for the identification of hematomas in mild traumatic brain injury.

Science.gov (United States)

Hanley, Daniel F; Chabot, Robert; Mould, W Andrew; Morgan, Timothy; Naunheim, Rosanne; Sheth, Kevin N; Chiang, William; Prichep, Leslie S

2013-12-15

This study investigates the potential clinical utility in the emergency department (ED) of an index of brain electrical activity to identify intracranial hematomas. The relationship between this index and depth, size, and type of hematoma was explored. Ten minutes of brain electrical activity was recorded from a limited montage in 38 adult patients with traumatic hematomas (CT scan positive) and 38 mild head injured controls (CT scan negative) in the ED. The volume of blood and distance from recording electrodes were measured by blinded independent experts. Brain electrical activity data were submitted to a classification algorithm independently developed traumatic brain injury (TBI) index to identify the probability of a CT+traumatic event. There was no significant relationship between the TBI-Index and type of hematoma, or distance of the bleed from recording sites. A significant correlation was found between TBI-Index and blood volume. The sensitivity to hematomas was 100%, positive predictive value was 74.5%, and positive likelihood ratio was 2.92. The TBI-Index, derived from brain electrical activity, demonstrates high accuracy for identification of traumatic hematomas. Further, this was not influenced by distance of the bleed from the recording electrodes, blood volume, or type of hematoma. Distance and volume limitations noted with other methods, (such as that based on near-infrared spectroscopy) were not found, thus suggesting the TBI-Index to be a potentially important adjunct to acute assessment of head injury. Because of the life-threatening risk of undetected hematomas (false negatives), specificity was permitted to be lower, 66%, in exchange for extremely high sensitivity.

Role of the ubiquitin-proteasome system in brain ischemia: friend or foe?

Science.gov (United States)

Caldeira, Margarida V; Salazar, Ivan L; Curcio, Michele; Canzoniero, Lorella M T; Duarte, Carlos B

2014-01-01

The ubiquitin-proteasome system (UPS) is a catalytic machinery that targets numerous cellular proteins for degradation, thus being essential to control a wide range of basic cellular processes and cell survival. Degradation of intracellular proteins via the UPS is a tightly regulated process initiated by tagging a target protein with a specific ubiquitin chain. Neurons are particularly vulnerable to any change in protein composition, and therefore the UPS is a key regulator of neuronal physiology. Alterations in UPS activity may induce pathological responses, ultimately leading to neuronal cell death. Brain ischemia triggers a complex series of biochemical and molecular mechanisms, such as an inflammatory response, an exacerbated production of misfolded and oxidized proteins, due to oxidative stress, and the breakdown of cellular integrity mainly mediated by excitotoxic glutamatergic signaling. Brain ischemia also damages protein degradation pathways which, together with the overproduction of damaged proteins and consequent upregulation of ubiquitin-conjugated proteins, contribute to the accumulation of ubiquitin-containing proteinaceous deposits. Despite recent advances, the factors leading to deposition of such aggregates after cerebral ischemic injury remain poorly understood. This review discusses the current knowledge on the role of the UPS in brain function and the molecular mechanisms contributing to UPS dysfunction in brain ischemia with consequent accumulation of ubiquitin-containing proteins. Chemical inhibitors of the proteasome and small molecule inhibitors of deubiquitinating enzymes, which promote the degradation of proteins by the proteasome, were both shown to provide neuroprotection in brain ischemia, and this apparent contradiction is also discussed in this review. Copyright © 2013 Elsevier Ltd. All rights reserved.

Masculine role adherence and outcomes among men with traumatic brain injury.

Science.gov (United States)

Schopp, Laura H; Good, Glenn E; Barker, Katharine B; Mazurek, Micah O; Hathaway, Stefani L

2006-10-01

Traumatic brain injury (TBI) is a significant health problem disproportionately affecting men and is often associated with changes in masculine role functioning in life domains such as vocational functioning, sexual and inter-personal functioning and personal independence. These changes could have serious implications for men's adjustment following injury. The aim of this study was to examine the relations among traditional masculine role adherence, psychosocial adjustment and rehabilitation outcomes in men with TBI. A correlational design was chosen to examine the relations among variables. Spearman correlations and Wilcoxon Rank Sum tests were used to examine relationships between masculine role variables and outcome variables. The study included 33 men with TBI who had been discharged from inpatient rehabilitation within 5 years. Participants completed surveys on traditional masculine gender role adherence and gender role conflict and additional data, including measures of functional outcome, life satisfaction, psychosocial outcomes and earnings, were obtained through the TBI Model System longitudinal data collection system. The results revealed significant associations between masculine role adherence and satisfaction with life, follow-up earnings and FIM change from admission to discharge. In the current study, particular masculine role variables corresponded to different functional and psychological outcomes. Understanding these differences provides new directions for treatment and offers important information about aspects of traditional masculine roles that may enhance or hinder adjustment to injury.

Work Safety Climate, Musculoskeletal Discomfort, Working While Injured, and Depression Among Migrant Farmworkers in North Carolina

Science.gov (United States)

O’Hara, Heather; Grzywacz, Joseph G.; Isom, Scott; Chen, Haiying; Quandt, Sara A.

2012-01-01

Objectives. This analysis described Latino migrant farmworkers’ work safety climate and its association with musculoskeletal discomfort, working while injured or ill, and depressive symptoms. Methods. Data were from a cross-sectional survey of 300 farmworkers conducted in North Carolina in 2009. Generalized estimating equations models were used to investigate the association of work safety climate with health and safety outcomes. Results. Farmworkers perceived their work safety climate to be poor. About 40% had elevated musculoskeletal discomfort, 5.0% had worked at least 1 day while injured or ill, and 27.9% had elevated depressive symptoms. The odds of elevated musculoskeletal discomfort were 12% lower and the odds of working while injured or ill were 15% lower with each 1-unit increase in the work safety climate. Work safety climate was not associated with depressive symptoms. Conclusions. Work safety climate was important for agricultural workers. Poor work safety climate was associated with health outcomes (musculoskeletal discomfort) and safety (working while injured or ill). Interventions to improve work safety climate in agriculture are needed, with these interventions being directed to employers and workers. PMID:22401520

Traumatic brain injury and disturbed sleep and wakefulness.

Science.gov (United States)

Baumann, Christian R

2012-09-01

Traumatic brain injury is a frequent condition worldwide, and sleep-wake disturbances often complicate the course after the injuring event. Current evidence suggests that the most common sleep-wake disturbances following traumatic brain injury include excessive daytime sleepiness and posttraumatic hypersomnia, that is, increased sleep need per 24 h. The neuromolecular basis of posttraumatic sleep pressure enhancement is not entirely clear. First neuropathological and clinical studies suggest that impaired hypocretin (orexin) signalling might contribute to sleepiness, but direct or indirect traumatic injury also to other sleep-wake modulating systems in the brainstem and the mesencephalon is likely. Posttraumatic insomnia may be less common than posttraumatic sleepiness, but studies on its frequency revealed conflicting results. Furthermore, insomnia is often associated with psychiatric comorbidities, and some patients with posttraumatic disruption of their circadian rhythm may be misdiagnosed as insomnia patients. The pathophysiology of posttraumatic circadian sleep disorders remains elusive; however, there is some evidence that reduced evening melatonin production due to traumatic brain damage may cause disruption of circadian regulation of sleep and wakefulness.

Return to work for severely injured survivors of the Christchurch earthquake: influences in the first 2 years.

Science.gov (United States)

Nunnerley, Joanne; Dunn, Jennifer; McPherson, Kathryn; Hooper, Gary; Woodfield, Tim

2016-01-01

This study looked at the influences on the return to work (RTW) in the first 2 years for people severely injured in the 22 February 2011 Christchurch earthquake. We used a constructivist grounded theory approach using semi-structured interviews to collect data from 14 people injured in the earthquake. Analysis elicited three themes that appeared to influence the process of RTW following the Christchurch earthquake. Living the earthquake experience, the individual's experiences of the earthquake and how their injury framed their expectations; rebuilding normality, the desire of the participants to return to life as it was; while dealing with the secondary effects of the earthquake includes the earthquake specific effects which were both barriers and facilitators to returning to work. The consequences of the earthquake impacted on experience, process and outcome of RTW for those injured in the Christchurch Earthquake. Work and RTW appeared key tools to enhance recovery after serious injury following the earthquake. The altered physical, social and economic environment must be considered when working on the return to work (RTW) of individuals with earthquake injuries. Providing tangible emotional and social support so injured earthquake survivors feel safe in their workplace may facilitate RTW. Engaging early with employers may assist the RTW of injured earthquake survivors.

Role of the Brain's Reward Circuitry in Depression: Transcriptional Mechanisms.

Science.gov (United States)

Nestler, Eric J

2015-01-01

Increasing evidence supports an important role for the brain's reward circuitry in controlling mood under normal conditions and contributing importantly to the pathophysiology and symptomatology of a range of mood disorders, such as depression. Here we focus on the nucleus accumbens (NAc), a critical component of the brain's reward circuitry, in depression and other stress-related disorders. The prominence of anhedonia, reduced motivation, and decreased energy level in most individuals with depression supports the involvement of the NAc in these conditions. We concentrate on several transcription factors (CREB, ΔFosB, SRF, NFκB, and β-catenin), which are altered in the NAc in rodent depression models--and in some cases in the NAc of depressed humans, and which produce robust depression- or antidepressant-like effects when manipulated in the NAc in animal models. These studies of the NAc have established novel approaches toward modeling key symptoms of depression in animals and could enable the development of antidepressant medications with fundamentally new mechanisms of action. © 2015 Elsevier Inc. All rights reserved.

Alexithymia, impulsiveness, and psychopathology in nonsuicidal self-injured adolescents

Directory of Open Access Journals (Sweden)

Gatta M

2016-09-01

Full Text Available Michela Gatta,1 Francesco Dal Santo,1 Alessio Rago,1 Andrea Spoto,2 Pier Antonio Battistella1 1Childhood Adolescence Family Unit, Ulss 16 – Padua University, 2Department of General Psychology, Padua University, Padova, Italy Introduction: Nonsuicidal self-injury (NSSI is a multifaceted phenomenon and a major health issue among adolescents. A better understanding of self-injury comorbidities is crucial to improve our ability to assess, treat, and prevent NSSI.Purpose: This study aimed at analyzing some of the psychobehavioral correlates of NSSI: psychological problems, alexithymia, impulsiveness, and sociorelational aspects.Patients and methods: This was a case–control study. The clinical sample (n=33 included adolescents attending our unit for NSSI and other issues; the controls (n=79 were high-school students. Data were collected using six questionnaires: Youth Self-Report, Barratt’s Impulsiveness Scale, Toronto Alexithymia Scale, Children’s Depression Inventory, Symptom Checklist-90-R, and Child Behavior Checklist.Results: Cases scored significantly higher in all questionnaires. Habitual self-injurers scored higher on impulsiveness and alexithymia. The gesture’s repetition seems relevant to the global clinical picture: habitual self-injurers appear more likely to seek help from the sociosanitary services. We found a difference between the self-injurers’ and their parents’ awareness of the disorder.Conclusion: Habitual self-injurers show signs of having difficulty with assessing the consequences of their actions (nonplanning impulsiveness and the inability to manage their feelings. Given the significantly higher scores found for cases than for controls on all the psychopathological scales, NSSI can be seen as a cross-category psychiatric disorder, supporting the Diagnostic and Statistical Manual of Mental Disorders decision to include it as a pathological entity in its own right. Keywords: NSSI, self-cutting, psychiatric

The SAMP8 mouse for investigating memory and the role of insulin in the brain.

Science.gov (United States)

Rhea, Elizabeth M; Banks, William A

2017-08-01

SAMP8 mice exhibit changes that commonly occur with normal aging late in life, but do so at a much earlier age. These changes include impairments in learning and memory as early as 8months of age and so the SAMP8 is a useful model to investigate those age-related brain changes that may affect cognition. As brain insulin signaling and memory decline with aging, the SAMP8 model is useful for investigating these changes and interventions that might prevent the decline. This review will summarize the SAMP8 mouse model, highlight changes in brain insulin signaling and its role in memory, and discuss intranasal insulin delivery in investigating effects on insulin metabolism and memory in the SAMP8 mice. Published by Elsevier Inc.

Huperzine A alleviates neuroinflammation, oxidative stress and improves cognitive function after repetitive traumatic brain injury.

Science.gov (United States)

Mei, Zhengrong; Zheng, Peiying; Tan, Xiangping; Wang, Ying; Situ, Bing

2017-12-01

Traumatic brain injury (TBI) may trigger secondary injury cascades including endoplasmic reticulum stress, oxidative stress, and neuroinflammation. Unfortunately, there are no effective treatments targeting either primary or secondary injuries that result in long-term detrimental consequences. Huperzine A (HupA) is a potent acetylcholinesterase inhibitor (AChEI) that has been used treatment of Alzheimer's disease (AD). This study aimed to explore the neuroprotective effects of HupA in TBI and its possible mechanisms. Repetitive mild closed head injury (CHI) model was used to mimic concussive TBI. Mice were randomly assigned into three groups including sham, vehicle-treated and HupA-treated injured mice. The HupA was given at dose of 1.0 mg/kg/day and was initiated 30 min after the first injury, then administered daily for a total of 30 days. The neuronal functions including motor functions, emotion-like behaviors, learning and memory were tested. Axonal injury, reactive oxygen species (ROS), and neuroinflammation were examined as well. The results showed that injured mice treated with HupA had significant improvement in Morris water maze performance compared with vehicle-treated injured mice. HupA treatment significantly attenuated markers of neuroinflammation and oxidative stress in the injured mice. Taken together, HupA was effective in reducing neuroinflammation, oxidative stress and behavioral recovery after TBI. HupA is a promising candidate for treatment of TBI.

Gastrin-releasing peptide receptors in the central nervous system: role in brain function and as a drug target

Directory of Open Access Journals (Sweden)

Rafael eRoesler

2012-12-01

Full Text Available Neuropeptides acting on specific cell membrane receptors of the G protein-coupled receptor (GPCR superfamily regulate a range of important aspects of nervous and neuroendocrine function. Gastrin-releasing peptide (GRP is a mammalian neuropeptide that binds to the GRP receptor (GRPR, BB2. Increasing evidence indicates that GRPR-mediated signaling in the central nervous system (CNS plays an important role in regulating brain function, including aspects related to emotional responses, social interaction, memory, and feeding behavior. In addition, some alterations in GRP or GRPR expression or function have been described in patients with neurodegenerative, neurodevelopmental, and psychiatric disorders, as well as in brain tumors. Findings from preclinical models are consistent with the view that the GRPR might play a role in brain disorders, and raise the possibility that GRPR agonists might ameliorate cognitive and social deficits associated with neurological diseases, while antagonists may reduce anxiety and inhibit the growth of some types of brain cancer. Further preclinical and translational studies evaluating the potential therapeutic effects of GRPR ligands are warranted.

Role of 18F-FDG PET/CT in primary brain lymphoma.

Science.gov (United States)

de-Bonilla-Damiá, Á; Fernández-López, R; Capote-Huelva, F J; de la Cruz-Vicente, F; Egea-Guerrero, J J; Borrego-Dorado, I

To study the usefulness of 18 F-FDG PET/CT in the initial evaluation and in the response assessment in primary brain lymphoma. A retrospective analysis was carried out on 18 patients diagnosed with primary brain lymphoma, a histological subtype of diffuse large B-cell lymphoma, on whom an initial 18 F-FDG PET/CT and MRI was performed, with 7 of the cases being analysed after the completion of treatment in order to assess response and clinical follow up. Initial 18 F-FDG PET/CT showed 26 hypermetabolic foci, whereas 46 lesions were detected by MRI. The average SUV maximum of the lesions was 17.56 with T/N 3.55. The concordance of both tests for identifying the same number of lesions was moderate, obtaining a kappa index of 0.395 (P<.001). In the evaluation of treatment, MRI identified 16 lesions compared to 7 pathological accumulations observed by 18 F-FDG PET/CT. The concordance of both tests to assess type of response to treatment was moderate (kappa index 0.41) (P=.04). In both the initial evaluation and the assessment of the response to treatment, PET/CT led to a change strategy in 22% of patients who had lesions outside the cerebral parenchyma. MRI appears to be the method of choice for detecting brain disease in patients with primary brain lymphoma, whereas 18 F-FDG PET/CT seems to play a relevant role in the assessment of extra-cerebral disease. Copyright © 2017 Elsevier España, S.L.U. y SEMNIM. All rights reserved.

What Should Be the Roles of Conscious States and Brain States in Theories of Mental Activity?**

Science.gov (United States)

Dulany, Donelson E.

2011-01-01

Answers to the title’s question have been influenced by a history in which an early science of consciousness was rejected by behaviourists on the argument that this entails commitment to ontological dualism and “free will” in the sense of indeterminism. This is, however, a confusion of theoretical assertions with metaphysical assertions. Nevertheless, a legacy within computational and information-processing views of mind rejects or de-emphasises a role for consciousness. This paper sketches a mentalistic metatheory in which conscious states are the sole carriers of symbolic representations, and thus have a central role in the explanation of mental activity and action-while specifying determinism and materialism as useful working assumptions. A mentalistic theory of causal learning, experimentally examined with phenomenal reports, is followed by examination of these questions: Are there common roles for phenomenal reports and brain imaging? Is there defensible evidence for unconscious brain states carrying symbolic representations? Are there interesting dissociations within consciousness? PMID:21694964

The role of chemotherapy in the treatment of patients with brain metastases from solid tumors

International Nuclear Information System (INIS)

Walbert, T.; Gilbert, M.R.

2009-01-01

Brain metastases are the most frequent cancer in the central nervous system, being ten times more common than primary brain tumors. Patients generally have a poor outcome with a median survival of 4 months after diagnosis of the metastases. Therapeutic options include surgery, stereotactic, radiosurgery, whole-brain radiotherapy (WBRT), and chemotherapy. Patients with a limited number of brain metastases and well-controlled systemic cancer benefit from brain metastases-specific therapies, including surgery, radiosurgery, and conventional radiation. The role of chemotherapy for brain metastases remains limited. There is concern about drug delivery because of the blood-brain barrier. However, higher response rates are noted with initial therapies, suggesting that part of the poor response rate may be related to the late onset of brain metastases and the use of second- and third-line regimens. Recent studies have demonstrated objective responses with systemic therapy in a variety of cancer types, especially when combined with WBRT. Individual therapeutic strategies for central nervous system metastases must be chosen based on performance status, the extent of intracranial disease, and the chemosensitivity of the underlying tumor, as well as the control of the systemic cancer. In this article we review important prognostic factors and challenges in using chemotherapy. We specifically review recent advances in the treatment of brain metastases from breast and lung cancer as well as melanoma. Future treatment advances will require a multidisciplinary approach integrating surgical, radiation, and chemotherapeutic options to improve neurological function and quality of life, rather than just focusing on survival endpoints. (author)

Matrix metalloproteinases in the brain and blood–brain barrier: Versatile breakers and makers

Science.gov (United States)

Rempe, Ralf G; Hartz, Anika MS

2016-01-01

Matrix metalloproteinases are versatile endopeptidases with many different functions in the body in health and disease. In the brain, matrix metalloproteinases are critical for tissue formation, neuronal network remodeling, and blood–brain barrier integrity. Many reviews have been published on matrix metalloproteinases before, most of which focus on the two best studied matrix metalloproteinases, the gelatinases MMP-2 and MMP-9, and their role in one or two diseases. In this review, we provide a broad overview of the role various matrix metalloproteinases play in brain disorders. We summarize and review current knowledge and understanding of matrix metalloproteinases in the brain and at the blood–brain barrier in neuroinflammation, multiple sclerosis, cerebral aneurysms, stroke, epilepsy, Alzheimer’s disease, Parkinson’s disease, and brain cancer. We discuss the detrimental effects matrix metalloproteinases can have in these conditions, contributing to blood–brain barrier leakage, neuroinflammation, neurotoxicity, demyelination, tumor angiogenesis, and cancer metastasis. We also discuss the beneficial role matrix metalloproteinases can play in neuroprotection and anti-inflammation. Finally, we address matrix metalloproteinases as potential therapeutic targets. Together, in this comprehensive review, we summarize current understanding and knowledge of matrix metalloproteinases in the brain and at the blood–brain barrier in brain disorders. PMID:27323783

Cerebral microdialysis and PtiO2 to decide unilateral decompressive craniectomy after brain gunshot

Directory of Open Access Journals (Sweden)

Boret Henry

2012-01-01

Full Text Available Decompressive craniectomy (DC following brain injury can induce complications (hemorrhage, infection, and hygroma. It is then considered as a last-tier therapy, and can be deleteriously delayed. Focal neuromonitoring (microdialysis and PtiO2 can help clinicians to decide bedside to perform DC in case of intracranial pressure (ICP around 20 to 25 mmHg despite maximal medical treatment. This was the case of a hunter, brain injured by gunshot. DC was performed at day 6, because of unstable ICP, ischemic trend of PtiO2, and decreased cerebral glucose but normal lactate/pyruvate ratio. His evolution was good despite left hemiplegia due to initial injury.

Employer Satisfaction With an Injured Employee's Health Care: How Does It Affect the Selection of an Occupational Health Care Provider?

Science.gov (United States)

Keleher, Myra P; Stanton, Marietta P

2016-01-01

The purpose of this article is to explore the most important factors that an employer utilizes in selecting an occupational health care provider for their employees injured on the job. The primary practice setting is the attending physician's office who is an occupational health care provider. The responding employers deemed "work restrictions given after each office visit" as their most important factor in selecting an occupational health care provider, with a score of 43. This was followed in order in the "very important" category by communication, appointment availability, employee return to work within nationally recognized guidelines, tied were medical provider professionalism and courtesy with diagnostics ordered timely, next was staff professionalism and courtesy, and tied with 20 responses in the "very important" category were wait time and accurate billing by the provider.The selection of an occupational health care provider in the realm of workers' compensation plays a monumental role in the life of a claim for the employer. Safe and timely return to work is in the best interest of the employer and their injured employee. For the employer, it can represent hard dollars saved in indemnity payments and insurance premiums when the employee can return to some form of work. For the injured employee, it can have a positive impact on their attitude of going back to work as they will feel they are a valued asset to their employer. The case managers, who are the "eyes and ears" for the employer in the field of workers' compensation, have a valuable role in a successful outcome of dollars saved and appropriate care rendered for the employees' on the job injury. The employers in the study were looking for case managers who could ensure their employees received quality care but that this care is cost-effective. The case manager can be instrumental in assisting the employer in developing and monitoring a "stay-at-work" program, thereby reducing the financial exposure

Longitudinal volumetric changes following traumatic brain injury: a tensor-based morphometry study.

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Farbota, Kimberly D M; Sodhi, Aparna; Bendlin, Barbara B; McLaren, Donald G; Xu, Guofan; Rowley, Howard A; Johnson, Sterling C

2012-11-01

After traumatic injury, the brain undergoes a prolonged period of degenerative change that is paradoxically accompanied by cognitive recovery. The spatiotemporal pattern of atrophy and the specific relationships of atrophy to cognitive changes are ill understood. The present study used tensor-based morphometry and neuropsychological testing to examine brain volume loss in 17 traumatic brain injury (TBI) patients and 13 controls over a 4-year period. Patients were scanned at 2 months, 1 year, and 4 years post-injury. High-dimensional warping procedures were used to create change maps of each subject's brain for each of the two intervals. TBI patients experienced volume loss in both cortical areas and white matter regions during the first interval. We also observed continuing volume loss in extensive regions of white matter during the second interval. Neuropsychological correlations indicated that cognitive tasks were associated with subsequent volume loss in task-relevant regions. The extensive volume loss in brain white matter observed well beyond the first year post-injury suggests that the injured brain remains malleable for an extended period, and the neuropsychological relationships suggest that this volume loss may be associated with subtle cognitive improvements.

Differential role of tumor necrosis factor receptors in mouse brain inflammatory responses in cryolesion brain injury

DEFF Research Database (Denmark)

Quintana, Albert; Giralt, Mercedes; Rojas, Santiago

2005-01-01

Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via intracell......Tumor necrosis factor-alpha (TNF-alpha) is one of the mediators dramatically increased after traumatic brain injury that leads to the activation, proliferation, and hypertrophy of mononuclear, phagocytic cells and gliosis. Eventually, TNF-alpha can induce both apoptosis and necrosis via...... intracellular signaling. This cytokine exerts its functions via interaction with two receptors: type-1 receptor (TNFR1) and type-2 receptor (TNFR2). In this work, the inflammatory response after a freeze injury (cryolesion) in the cortex was studied in wild-type (WT) animals and in mice lacking TNFR1 (TNFR1 KO...... signaling also affected the expression of apoptosis/cell death-related genes (Fas, Rip, p53), matrix metalloproteinases (MMP3, MMP9, MMP12), and their inhibitors (TIMP1), suggesting a role of TNFR1 in extracellular matrix remodeling after injury. However, GDNF, NGF, and BDNF expression were not affected...

Aluminium and Gamma Irradiation Induced Oxidative Damage in Brain Tissue of Male Rats - Protective Role of Ferulic Acid

International Nuclear Information System (INIS)

Mansour, S.Z.; Hanafi, N.; Noaman, E.

2011-01-01

The current study was carried out to investigate the potential role of ferulic acid (FA) against Aluminium chloride (AlCl 3 ), γ- radiation either alone or combination induced oxidative stress in brain tissue of Wistar rats. The period of the experiment was eight weeks. Animals were administrated by aluminium chloride at a dose of 8.5 mg/kg/day and exposed to a single dose (4 Gy) of γ-radiation. FA was administered orally (50 mg/Kg body weight)/day. Histopathological observations and myeloid protein distribution were recorded in brain tissue. Induction of oxidative stress was recorded after all exposures. Brain tissue of AlCl 3 and γ- irradiation treatments either alone or combined revealed many altered changes and myeloid protein distribution. Also a decrease in serotonin concentration was recorded. An increase in Malonaldialdahyde (MDA) and acetylcholinesterase activity and percentage of saturated fatty acids in plasma and brain tissue was recorded. Reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD) in blood and brain showed a significant decrease. Treatment of AlCl 3 loaded animals by FA showed simple atrophy as shrunken morphology saw in amyotrophic lateral sclerosis and a decrease in myeloid protein deposition. FA treatment of AlCl 3 loaded or irradiated animals represented a significant increase in serotonin concentration and ameliorated affects on oxidative stress markers, acetylcholinesterase activity and percentage of saturated fatty acids in plasma and brain tissue. In conclusion FA has a role in reducing the oxidative stress of AlCl 3 and γ- irradiation on brain tissue of rats

The roles of the amygdala in the affective regulation of body, brain, and behaviour

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Mirolli, Marco; Mannella, Francesco; Baldassarre, Gianluca

2010-09-01

Despite the great amount of knowledge produced by the neuroscientific literature on affective phenomena, current models tackling non-cognitive aspects of behaviour are often bio-inspired but rarely bio-constrained. This paper presents a theoretical account of affective systems centred on the amygdala (Amg). This account aims to furnish a general framework and specific pathways to implement models that are more closely related to biological evidence. The Amg, which receives input from brain areas encoding internal states, innately relevant stimuli, and innately neutral stimuli, plays a fundamental role in the motivational and emotional processes of organisms. This role is based on the fact that Amg implements the two associative processes at the core of Pavlovian learning (conditioned stimulus (CS)-unconditioned stimulus (US) and CS-unconditioned response (UR) associations), and that it has the capacity of modulating these associations on the basis of internal states. These functionalities allow the Amg to play an important role in the regulation of the three fundamental classes of affective responses (namely, the regulation of body states, the regulation of brain states via neuromodulators, and the triggering of a number of basic behaviours fundamental for adaptation) and in the regulation of three high-level cognitive processes (namely, the affective labelling of memories, the production of goal-directed behaviours, and the performance of planning and complex decision-making). Our analysis is conducted within a methodological approach that stresses the importance of understanding the brain within an evolutionary/adaptive framework and with the aim of isolating general principles that can potentially account for the wider possible empirical evidence in a coherent fashion.

Do Health Service Use and Return-to-Work Outcomes Differ with GPs' Injured-Worker Caseload?

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Mazza, Danielle; Brijnath, Bianca; O'Hare, Mary Alice; Ruseckaite, Rasa; Kosny, Agnieszka; Collie, Alex

2018-02-23

Purpose To determine whether healthcare use and return-to-work (RTW) outcomes differ with GPs' injured-worker caseload. Methods Retrospective analyses of the Compensation Research Database, which captures approximately 85% of all injured worker claims in Victoria, Australia was conducted. Four injured-worker caseload groups were examined that represented the 25th, 50th, 75th, and 100th percentiles of claimants seen per GP over the 8-year study period (2003-2010): (i) 1-13 claimants; (ii) 14-26 claimants; (iii) 27-48 claimants; and (iv) 49+ claimants (total claims, n = 124,342; total GPs, n = 9748).The characteristics of claimants in each caseload group, as well as the influence of caseload on three outcomes relevant to RTW (weekly compensation paid, work incapacity days, medical-and-like costs), were examined. Results Distinct profiles for high versus low caseload groups emerged. High caseload GPs treated significantly more men in blue collar occupations and issued significantly more 'alternate duties' certificates. Conversely, low caseload GPs treated significantly more women in white collar occupations, predominantly for mental health injuries, and issued significantly more 'unfit-for-work' certificates. Few significant differences were found between the two intermediate GP caseload groups. High caseload was associated with significantly greater medical-and-like costs, however, no caseload group differences were detected for weekly compensation paid or duration of time-off-work. Conclusions Training GPs who have a low injured-worker caseload in workers' compensation processes, utilising high caseload GPs in initiatives involving peer-to-peer support, or system changes where employers are encouraged to provide preventive or rehabilitative support in the workplace may improve RTW outcomes for injured workers.

Inflaming the diseased brain: a role for tainted melanins.

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Jeitner, T M; Kalogiannis, M; Patrick, P A; Gomolin, I; Palaia, T; Ragolia, L; Brand, D; Delikatny, E J

2015-05-01

Inflammation plays a crucial role in neurodegenerative diseases, but the irritants responsible for this response remain largely unknown. This report addressed the hypothesis that hypochlorous acid reacts with dopamine to produce melanic precipitates that promote cerebral inflammation. Spectrophotometric studies demonstrated that nM amounts of HOCl and dopamine react within seconds. A second-order rate constant for the reaction of HOCl and dopamine of 2.5 × 10(4)M(-1)s(-1) was obtained by measuring loss of dopaminergic fluorescence due to HOCl. Gravimetric measurements, electron microscopy, elemental analysis, and a novel use of flow cytometry confirmed that the major product of this reaction is a precipitate with an average diameter of 1.5 μm. Flow cytometry was also used to demonstrate the preferential reaction of HOCl with dopamine rather than albumin. Engulfment of the chlorodopamine particulates by phagocytes in vitro caused these cells to release TNFα and die. Intrastriatal administration of 10(6) particles also increased the content of TNFα in the brain and led to a 50% loss of the dopaminergic neurons in the nigra. These studies indicate that HOCl and dopamine react quickly and preferentially with each other to produce particles that promote inflammation and neuronal death in the brain. Copyright © 2015 Elsevier B.V. All rights reserved.

Shining light on the head: Photobiomodulation for brain disorders

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Michael R. Hamblin

2016-12-01

Full Text Available Photobiomodulation (PBM describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. One of the organ systems of the human body that is most necessary to life, and whose optimum functioning is most worried about by humankind in general, is the brain. The brain suffers from many different disorders that can be classified into three broad groupings: traumatic events (stroke, traumatic brain injury, and global ischemia, degenerative diseases (dementia, Alzheimer's and Parkinson's, and psychiatric disorders (depression, anxiety, post traumatic stress disorder. There is some evidence that all these seemingly diverse conditions can be beneficially affected by applying light to the head. There is even the possibility that PBM could be used for cognitive enhancement in normal healthy people. In this transcranial PBM (tPBM application, near-infrared (NIR light is often applied to the forehead because of the better penetration (no hair, longer wavelength. Some workers have used lasers, but recently the introduction of inexpensive light emitting diode (LED arrays has allowed the development of light emitting helmets or “brain caps”. This review will cover the mechanisms of action of photobiomodulation to the brain, and summarize some of the key pre-clinical studies and clinical trials that have been undertaken for diverse brain disorders.

‘Studying Injured Minds’ - The Vietnam Head Injury Study and 40 years of brain injury research

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Vanessa eRaymont

2011-03-01

Full Text Available The study of those who have sustained traumatic brain injuries (TBI during military conflicts has greatly facilitated research in the fields of neuropsychology, neurosurgery, psychiatry, neurology and neuroimaging. The Vietnam Head Injury Study (VHIS is a prospective, long-term follow-up study of a cohort of 1,221 Vietnam veterans with mostly penetrating brain injuries, which has stretched over more than 40 years. The scope of this study, both in terms of the types of injury and fields of examination, has been extremely broad. It has been instrumental in extending the field of TBI research and in exposing pressing medical and social issues that affect those who suffer such injuries. This review summarizes the history of conflict-related TBI research and the VHIS to date, as well as the vast range of important findings the VHIS has established.

Caring for the injured child in settings of limited resource.

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Stephenson, Jacob

2016-02-01

Children represent the most vulnerable members of our global society, a truth that is magnified when they are physically wounded. In much of the developed world, society has responded by offering protection in the form of law, injury prevention guidelines, and effective trauma systems to provide care for the injured child. Much of our world, though, remains afflicted by poverty and a lack of protective measures. As the globe becomes smaller by way of ease of travel and technology, surgeons are increasingly able to meet these children where they live and in doing so offer their hands and voices to care and protect these young ones. This article is intended as an overview of current issues in pediatric trauma care in the developing world as well as to offer some tips for the volunteer surgeon who may be involved in the care of the injured child in a setting of limited resource availability. Published by Elsevier Inc.

Respiratory mechanics in brain injury: A review.

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Koutsoukou, Antonia; Katsiari, Maria; Orfanos, Stylianos E; Kotanidou, Anastasia; Daganou, Maria; Kyriakopoulou, Magdalini; Koulouris, Nikolaos G; Rovina, Nikoletta

2016-02-04

Several clinical and experimental studies have shown that lung injury occurs shortly after brain damage. The responsible mechanisms involve neurogenic pulmonary edema, inflammation, the harmful action of neurotransmitters, or autonomic system dysfunction. Mechanical ventilation, an essential component of life support in brain-damaged patients (BD), may be an additional traumatic factor to the already injured or susceptible to injury lungs of these patients thus worsening lung injury, in case that non lung protective ventilator settings are applied. Measurement of respiratory mechanics in BD patients, as well as assessment of their evolution during mechanical ventilation, may lead to preclinical lung injury detection early enough, allowing thus the selection of the appropriate ventilator settings to avoid ventilator-induced lung injury. The aim of this review is to explore the mechanical properties of the respiratory system in BD patients along with the underlying mechanisms, and to translate the evidence of animal and clinical studies into therapeutic implications regarding the mechanical ventilation of these critically ill patients.

HMGB1 a-Box Reverses Brain Edema and Deterioration of Neurological Function in a Traumatic Brain Injury Mouse Model

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Lijun Yang

2018-05-01

Full Text Available Background/Aims: Traumatic brain injury (TBI is a complex neurological injury in young adults lacking effective treatment. Emerging evidences suggest that inflammation contributes to the secondary brain injury following TBI, including breakdown of the blood brain barrier (BBB, subsequent edema and neurological deterioration. High mobility group box-1 (HMGB1 has been identified as a key cytokine in the inflammation reaction following TBI. Here, we investigated the therapeutic efficacy of HMGB1 A-box fragment, an antagonist competing with full-length HMGB1 for receptor binding, against TBI. Methods: TBI was induced by controlled cortical impact (CCI in adult male mice. HMGB1 A-box fragment was given intravenously at 2 mg/kg/day for 3 days after CCI. HMGB1 A-box-treated CCI mice were compared with saline-treated CCI mice and sham mice in terms of BBB disruption evaluated by Evan’s blue extravasation, brain edema by brain water content, cell death by propidium iodide staining, inflammation by Western blot and ELISA assay for cytokine productions, as well as neurological functions by the modified Neurological Severity Score, wire grip and beam walking tests. Results: HMGB1 A-box reversed brain damages in the mice following TBI. It significantly reduced brain edema by protecting integrity of the BBB, ameliorated cell degeneration, and decreased expression of pro-inflammatory cytokines released in injured brain after TBI. These cellular and molecular effects were accompanied by improved behavioral performance in TBI mice. Notably, HMGB1 A-box blocked IL-1β-induced HMGB1 release, and preferentially attenuated TLR4, Myd88 and P65 in astrocyte cultures. Conclusion: Our data suggest that HMGB1 is involved in CCI-induced TBI, which can be inhibited by HMGB1 A-box fragment. Therefore, HMGB1 A-box fragment may have therapeutic potential for the secondary brain damages in TBI.

HMGB1 a-Box Reverses Brain Edema and Deterioration of Neurological Function in a Traumatic Brain Injury Mouse Model.

Science.gov (United States)

Yang, Lijun; Wang, Feng; Yang, Liang; Yuan, Yunchao; Chen, Yan; Zhang, Gengshen; Fan, Zhenzeng

2018-01-01

Traumatic brain injury (TBI) is a complex neurological injury in young adults lacking effective treatment. Emerging evidences suggest that inflammation contributes to the secondary brain injury following TBI, including breakdown of the blood brain barrier (BBB), subsequent edema and neurological deterioration. High mobility group box-1 (HMGB1) has been identified as a key cytokine in the inflammation reaction following TBI. Here, we investigated the therapeutic efficacy of HMGB1 A-box fragment, an antagonist competing with full-length HMGB1 for receptor binding, against TBI. TBI was induced by controlled cortical impact (CCI) in adult male mice. HMGB1 A-box fragment was given intravenously at 2 mg/kg/day for 3 days after CCI. HMGB1 A-box-treated CCI mice were compared with saline-treated CCI mice and sham mice in terms of BBB disruption evaluated by Evan's blue extravasation, brain edema by brain water content, cell death by propidium iodide staining, inflammation by Western blot and ELISA assay for cytokine productions, as well as neurological functions by the modified Neurological Severity Score, wire grip and beam walking tests. HMGB1 A-box reversed brain damages in the mice following TBI. It significantly reduced brain edema by protecting integrity of the BBB, ameliorated cell degeneration, and decreased expression of pro-inflammatory cytokines released in injured brain after TBI. These cellular and molecular effects were accompanied by improved behavioral performance in TBI mice. Notably, HMGB1 A-box blocked IL-1β-induced HMGB1 release, and preferentially attenuated TLR4, Myd88 and P65 in astrocyte cultures. Our data suggest that HMGB1 is involved in CCI-induced TBI, which can be inhibited by HMGB1 A-box fragment. Therefore, HMGB1 A-box fragment may have therapeutic potential for the secondary brain damages in TBI. © 2018 The Author(s). Published by S. Karger AG, Basel.

Brain-to-brain coupling during handholding is associated with pain reduction.

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Goldstein, Pavel; Weissman-Fogel, Irit; Dumas, Guillaume; Shamay-Tsoory, Simone G

2018-03-13

The mechanisms underlying analgesia related to social touch are not clear. While recent research highlights the role of the empathy of the observer to pain relief in the target, the contribution of social interaction to analgesia is unknown. The current study examines brain-to-brain coupling during pain with interpersonal touch and tests the involvement of interbrain synchrony in pain alleviation. Romantic partners were assigned the roles of target (pain receiver) and observer (pain observer) under pain-no-pain and touch-no-touch conditions concurrent with EEG recording. Brain-to-brain coupling in alpha-mu band (8-12 Hz) was estimated by a three-step multilevel analysis procedure based on running window circular correlation coefficient and post hoc power of the findings was calculated using simulations. Our findings indicate that hand-holding during pain administration increases brain-to-brain coupling in a network that mainly involves the central regions of the pain target and the right hemisphere of the pain observer. Moreover, brain-to-brain coupling in this network was found to correlate with analgesia magnitude and observer's empathic accuracy. These findings indicate that brain-to-brain coupling may be involved in touch-related analgesia.

Quantitative Rates of Brain Glucose Metabolism Distinguish Minimally Conscious from Vegetative State Patients

DEFF Research Database (Denmark)

Stender, Johan; Kupers, Ron; Rodell, Anders

2015-01-01

of these patients. However, no quantitative comparisons of cerebral glucose metabolism in VS/UWS and MCS have yet been reported. We calculated the regional and whole-brain CMRglc of 41 patients in the states of VS/UWS (n=14), MCS (n=21) or emergence from MCS (EMCS, n=6), and healthy volunteers (n=29). Global......The differentiation of the vegetative or unresponsive wakefulness syndrome (VS/UWS) from the minimally conscious state (MCS) is an important clinical issue. The cerebral metabolic rate of glucose (CMRglc) declines when consciousness is lost, and may reveal the residual cognitive function...... these results reveal a significant correlation between whole-brain energy metabolism and level of consciousness, suggesting that quantitative values of CMRglc reveal consciousness in severely brain-injured patients.Journal of Cerebral Blood Flow & Metabolism advance online publication, 8 October 2014; doi:10...

Systems biomarkers as acute diagnostics and chronic monitoring tools for traumatic brain injury

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Wang, Kevin K. W.; Moghieb, Ahmed; Yang, Zhihui; Zhang, Zhiqun

2013-05-01

Traumatic brain injury (TBI) is a significant biomedical problem among military personnel and civilians. There exists an urgent need to develop and refine biological measures of acute brain injury and chronic recovery after brain injury. Such measures "biomarkers" can assist clinicians in helping to define and refine the recovery process and developing treatment paradigms for the acutely injured to reduce secondary injury processes. Recent biomarker studies in the acute phase of TBI have highlighted the importance and feasibilities of identifying clinically useful biomarkers. However, much less is known about the subacute and chronic phases of TBI. We propose here that for a complex biological problem such as TBI, multiple biomarker types might be needed to harness the wide range of pathological and systemic perturbations following injuries, including acute neuronal death, neuroinflammation, neurodegeneration and neuroregeneration to systemic responses. In terms of biomarker types, they range from brain-specific proteins, microRNA, genetic polymorphism, inflammatory cytokines and autoimmune markers and neuro-endocrine hormones. Furthermore, systems biology-driven biomarkers integration can help present a holistic approach to understanding scenarios and complexity pathways involved in brain injury.

Behavioral Outcomes Differ Between Rotational Acceleration and Blast Mechanisms of Mild Traumatic Brain Injury

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Brian D. Stemper

2016-03-01

Full Text Available Mild traumatic brain injury (mTBI can result from a number of mechanisms, including blunt impact, head rotational acceleration, exposure to blast, and penetration of projectiles. Mechanism is likely to influence the type, severity, and chronicity of outcomes. The objective of this study was to determine differences in the severity and time-course of behavioral outcomes following blast and rotational mTBI. The Medical College of Wisconsin (MCW Rotational Injury model and a shock tube model of primary blast injury were used to induce mTBI in rats and behavioral assessments were conducted within the first week, as well as 30 and 60 days following injury. Acute recovery time demonstrated similar increases over protocol-matched shams, indicating acute injury severity equivalence between the two mechanisms. Post-injury behavior in the elevated plus maze demonstrated differing trends, with rotationally injured rats acutely demonstrating greater activity, whereas blast-injured rats had decreased activity that developed at chronic time points. Similarly, blast-injured rats demonstrated trends associated with cognitive deficits that were not apparent following rotational injuries. These findings demonstrate that rotational and blast injury result in behavioral changes with different qualitative and temporal manifestations. Whereas rotational injury was characterized by a rapidly emerging phenotype consistent with behavioral disinhibition, blast injury was associated with emotional and cognitive differences that were not evident acutely, but developed later, with an anxiety-like phenotype still present in injured animals at our most chronic measurements.

Procedural and legal status of the injured party according to the new criminal procedure code of the Republic of Serbia

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Grubač Momčilo

2012-01-01

Full Text Available In this article the author is critically analyzing certain solutions of the new Criminal Procedure Code of the Republic of Serbia from 2011 which consider the injured party and their rights in the criminal proceeding. He states that unlike the previous ones, this Code does not improve the status of the injured party but makes it even worse. The author particularly claims that the legislator yet again failed to establish the right of the injured party to be efficiently compensated in the event of a serious offense from a special fund and immediately after the crime has been committed, but prior to the end of the criminal proceeding. In the provision of the Code which states that the injured party may take over the prosecution and become a prosecutor replacing the Public Prosecutor (subsidiary prosecutor only if the Public Prosecutor withdraws after having confirmed the indictment, however not in the cases of rejection of criminal charges or withdrawal from the prosecution in the previous proceeding, the author sees not only the limitation of the rights of the injured party, but also jeopardy of the public interest. This is due to the fact that, freed from a threat of the subsidiary accusation by the injured party, the Public Prosecutor has gained an absolute and uncontrolled monopoly over the initiation of criminal proceeding. According to the author, the subject of the proceedings will not have any substantial use from some rights which the new Code assigns to the injured party (for example the right to appeal against the judgment on the adjudicated property claim. In conclusion, the author stresses out that in spite of his objections against certain provisions in the Code, the legal status of the injured party is more favorable in the criminal law of Serbia then in many other countries.

A role for the serotonin reuptake transporter in the brain and intestinal features of autism spectrum disorders and developmental antidepressant exposure.

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Margolis, Kara Gross

2017-10-01

Many disease conditions considered CNS-predominant harbor significant intestinal comorbidities. Serotonin (5-HT) and the serotonin reuptake transporter (SERT) have increasingly been shown to play important roles in both brain and intestinal development and long-term function. 5-HT and SERT may thus modulate critical functions in the development and perpetuation of brain-gut axis disease. We discuss the potential roles of 5-HT and SERT in the brain and intestinal manifestations of autism spectrum disorders and developmental antidepressant exposure. The potential therapeutic value of 5-HT 4 modulation in the subsequent treatment of these conditions is also addressed. Copyright © 2017 Elsevier B.V. All rights reserved.

Endogenous Nutritive Support after Traumatic Brain Injury: Peripheral Lactate Production for Glucose Supply via Gluconeogenesis.

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Glenn, Thomas C; Martin, Neil A; McArthur, David L; Hovda, David A; Vespa, Paul; Johnson, Matthew L; Horning, Michael A; Brooks, George A

2015-06-01

We evaluated the hypothesis that nutritive needs of injured brains are supported by large and coordinated increases in lactate shuttling throughout the body. To that end, we used dual isotope tracer ([6,6-(2)H2]glucose, i.e., D2-glucose, and [3-(13)C]lactate) techniques involving central venous tracer infusion along with cerebral (arterial [art] and jugular bulb [JB]) blood sampling. Patients with traumatic brain injury (TBI) who had nonpenetrating head injuries (n=12, all male) were entered into the study after consent of patients' legal representatives. Written and informed consent was obtained from healthy controls (n=6, including one female). As in previous investigations, the cerebral metabolic rate (CMR) for glucose was suppressed after TBI. Near normal arterial glucose and lactate levels in patients studied 5.7±2.2 days (range of days 2-10) post-injury, however, belied a 71% increase in systemic lactate production, compared with control, that was largely cleared by greater (hepatic+renal) glucose production. After TBI, gluconeogenesis from lactate clearance accounted for 67.1% of glucose rate of appearance (Ra), which was compared with 15.2% in healthy controls. We conclude that elevations in blood glucose concentration after TBI result from a massive mobilization of lactate from corporeal glycogen reserves. This previously unrecognized mobilization of lactate subserves hepatic and renal gluconeogenesis. As such, a lactate shuttle mechanism indirectly makes substrate available for the body and its essential organs, including the brain, after trauma. In addition, when elevations in arterial lactate concentration occur after TBI, lactate shuttling may provide substrate directly to vital organs of the body, including the injured brain.

Role of Intravenous Levetiracetam in Seizure Prophylaxis of Severe Traumatic Brain Injury Patients

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BATOOL F. KIRMANI

2013-11-01

Full Text Available Traumatic brain injury (TBI can cause seizures and the development of epilepsy. The incidence of seizures varies from 21% in patients with severe brain injuries to 50% in patients with war-related penetrating TBI. In the acute and sub-acute periods following injury, seizures can lead to increased intracranial pressure and cerebral edema, further complicating TBI management. Anticonvulsants should be used for seizure prophylaxis and treatment. Phenytoin is the most widely prescribed anticonvulsant in these patients. Intravenous levetiracetam, made available in 2006, is now being considered as an alternative to phenytoin in acute care settings. When compared with phenytoin, levetiracetam has fewer side-effects and drug-drug interactions. In the following, the role of levetiracetam in TBI care and the supporting evidence is discussed.

Nuclear magnetic resonance studies on brain edema. Time course of /sup 1/H-NMR relaxation times

Energy Technology Data Exchange (ETDEWEB)

Naruse, S; Horikawa, Y; Tanaka, C; Hirakawa, K; Nishikawa, H [Kyoto Prefectural Univ. of Medicine (Japan)

1981-06-01

1. The state of water in normal and edematous brain tissue was studied by measurement of proton longitudinal (T/sub 1/) and transverse (T/sub 2/) relaxation times using pulsed nuclear magnetic resonance (NMR) technique. 2. In control rats, T/sub 1/ and T/sub 2/ of water showed one component, which was more fast in white matter. Those values displayed 1.07 - 1.18 sec. of T/sub 1/ and 75 - 76 msec. of T/sub 2/. 3. When rat brain was injured by cold, T/sub 1/ was observed to become longer (1.18 - 1.27 sec.), and T/sub 2/ was observed be separated into two components, the faster T/sub 2/ (45 - 50 msec.) and slower T/sub 2/ (100 - 105 msec.), in both gray and white matter of the injured side. 4. In triethyltin (TET) induced brain edema, elongation of T/sub 1/ (1.2 sec.) and remarkable separation of T/sub 2/, faster T/sub 2/ (75 msec.) and slower T/sub 2/ (400 - 450 msec.), were observed in white matter. 5. In both cold and TET induced edema, slower T/sub 2/ fraction is suggested to be the extracellular space and faster T/sub 2/ fraction, intracellular. 6. T/sub 2/ changes precede the water content changes in cold injury, and parallel in TET induced edema. Those changes of relaxation times are reversible. 7. T/sub 2/ changes of water is more sensitive than the T/sub 1/ for the detection of production and disappearance of brain edema. 8. These results disclose the dynamic movements of water during the course of brain edema and offered significant information of the clinical application of NMR-CT.

Injured workers' perception of loss and gain in the return to work process.

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Lai, Hon Sun; Szeto, Grace Py; Chan, Chetwyn Ch

2017-01-01

When a worker is injured at work, he has to face a tough decision-making process about when and how to return to work (RTW). This study tests how the prospect theory can be applied to influence the injured workers' perceptions about this important choice. One hundred forty-one injured workers were presented with wage- and pain-related information in four different message framing (negatively or positively) and precision (smaller or larger number) conditions. After exposure to the specific combination of this wage and pain information, the participants were asked to express intentions to RTW in terms of perceived chance, confidence, and anticipated sick leave duration. When asked to predict their RTW outcome, 101 participants (72.3%) responded favorably, whereas only 40 (27.7%) indicated an expectation for staying on sick leave. The present results did not show significant differences in the participants' responses to the positively and negatively framed information about wage and pain. However, it was noted that the control group that was presented with positive framing for both "wage" and "pain" information showed higher scores in expectation and confidence for RTW, whereas the Ambivalent Group that had both negative messages showed lower scores. Seventy-nine participants who had ≥60% perceived improvement in condition were selected for further analysis, and those who were presented with "wage loss" information rated significantly higher perceived chance of RTW than those in the "pain gain" group. More in-depth investigation is warranted on this topic, with a larger sample of injured workers to investigate the effects of message framing on the decision-making process about RTW.

CENTRAL SENSITIZATION AND MEDICATION IN SPINAL CORD INJURED IN-PATIENTS. A CROSS-SECTIONAL CLINICAL STUDY

DEFF Research Database (Denmark)

Rosendahl, A; Kasch, Helge

Background and aims: A major proportion of spinal cord injured subjects (SCIS) suffers from chronic pain. A majority with neuropathic pain, being: shooting, burning and stabbing. Neurological examination reveals signs of central sensitization (CS) e.g. allodynia and hyperalgesia. CS plays...... an important role in maintained neuropathic pain conditions and may lead to or be induced by analgesics. Medication-overuse-headaches (MOH) alter CNS pain processing systems, and the situation is reversed after discontinuation of headache medication. Aim: To determine the occurrence of CS and conditions...... pressure algometry, Von Frey filaments and pinprick test. Patients fulfill McGill Pain Questionnaire and the International SCI pain data-set. All participants undergo examination of the Pressure Pain Detection Threshold, Pressure Pain Tolerance Threshold, Mechanical Detection Threshold, and Wind...

Associations between damage location and five main body region injuries of MAIS 3–6 injured occupants

Science.gov (United States)

Tang, Youming; Cao, Libo; Kan, Steven

2014-01-01

Objectives To examine the damage location distribution of five main body region injuries of maximum abbreviated injury score (MAIS) 3–6 injured occupants for nearside struck vehicle in front-to-side impact crashes. Design and setting MAIS 3–6 injured occupants information was extracted from the US-National Automotive Sampling System/Crashworthiness Data System in the year 2007; it included the head/face/neck, chest, pelvis, upper extremity and lower extremity. Struck vehicle collision damage was classified in a three-dimensional system according to the J224 Collision Deformation Classification of SAE Surface Vehicle Standard. Participants Nearside occupants seated directly adjacent to the struck side of the vehicle with MAIS 3–6 injured, in light truck vehicles–passenger cars (LTV–PC) side impact crashes. Outcome measures Distribution of MAIS 3–6 injured occupants by body regions and specific location of damage (lateral direction, horizontal direction and vertical direction) were examined. Injury risk ratio was also assessed. Results The lateral crush zone contributed to MAIS 3–6 injured occupants (n=705) and 50th centile injury risks when extended into zone 3. When the crush extended to zone 4, the injury risk ratio of MAIS 3–6 injured occupants approached 81%. The horizontal crush zones contributing to the highest injury risk ratio of MAIS 3–6 occupants were zones ‘D’ and ‘Y’, and the injury risk ratios were 25.4% and 36.9%, respectively. In contrast, the lowest injury risk ratio was 5.67% caused by zone ‘B’. The vertical crush zone which contributed to the highest injury risk ratio of MAIS 3–6 occupants was zone ‘E’, whose injury risk ratio was 58%. In contrast, the lowest injury risk ratio was 0.14% caused by zone ‘G+M’. Conclusions The highest injury risk ratio of MAIS 3–6 injured occupants caused by crush intrusion between 40 and 60 cm in LTV–PC nearside impact collisions and the damage region of the struck

Deep pockets or blueprint for change: traumatic brain injury (TBI) proactive strategy.

Science.gov (United States)

Wood, D W; Pohl, S; Lawler, S; Okamoto, G

1998-09-01

The Pacific Conference scheduled for October 1-3, 1988, is a critical event in the development of an integrated community-based plan for a comprehensive continuum of services to address the "silent epidemic," Traumatic Brain Injured (TBI). This paper provides insights of the complex nature and the special problems faced by the TBI survivors; their families, natural supports and caregivers, as well as the health, social and educational care providers in Hawaii. Process for the development of the community plan is presented.

The Effect of Mercury Vapor and the Role of Green Tea Extract on Brain Cells

Directory of Open Access Journals (Sweden)

Dhona Afriza

2013-09-01

Full Text Available Mercury is a wellknown toxic metal that is capable to induce free radical-induced oxidative stress. It can cause human disease including brain disorders. Objective: To identify the effect of mercury vapor inhalation on brain cells and the role of green tea extract (Camellia sinensis as antioxidant on the brain cells exposed to mercury. Methods: Fourty-eight male Mus musculus were divided into 8 groups, which were given treatment for 3 and 6 weeks. Group A did not receive any treatment and served as a negative control. Group B was a positive control exposed to Mercury. Group C was exposed to Mercury and treated with 26μg/g green tea extract. Group D was exposed to mercury and treated with 52μg/g green tea extract. All animals in the Group B, C, D were exposed to mercury through inhalation for 4 hours daily. The effect of mercury on the brain cells were examined histopathologically. Results: The numbers of necrotic cells counted in the green tea-treated mice group were significantly lower than those untreated group (p<0,05. Conclusion: Mercury vapor inhalation may cause necrosis on brain cells. Administration of green tea extract as an antioxidant reduced the amount of mercury-induced necrotic brain cells in mice.DOI: 10.14693/jdi.v20i2.151

Brain lactate metabolism in humans with subarachnoid hemorrhage.

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Oddo, Mauro; Levine, Joshua M; Frangos, Suzanne; Maloney-Wilensky, Eileen; Carrera, Emmanuel; Daniel, Roy T; Levivier, Marc; Magistretti, Pierre J; LeRoux, Peter D

2012-05-01

Lactate is central for the regulation of brain metabolism and is an alternative substrate to glucose after injury. Brain lactate metabolism in patients with subarachnoid hemorrhage has not been fully elucidated. Thirty-one subarachnoid hemorrhage patients monitored with cerebral microdialysis (CMD) and brain oxygen (PbtO(2)) were studied. Samples with elevated CMD lactate (>4 mmol/L) were matched to PbtO(2) and CMD pyruvate and categorized as hypoxic (PbtO(2) 119 μmol/L) versus nonhyperglycolytic. Median per patient samples with elevated CMD lactate was 54% (interquartile range, 11%-80%). Lactate elevations were more often attributable to cerebral hyperglycolysis (78%; interquartile range, 5%-98%) than brain hypoxia (11%; interquartile range, 4%-75%). Mortality was associated with increased percentage of samples with elevated lactate and brain hypoxia (28% [interquartile range 9%-95%] in nonsurvivors versus 9% [interquartile range 3%-17%] in survivors; P=0.02) and lower percentage of elevated lactate and cerebral hyperglycolysis (13% [interquartile range, 1%-87%] versus 88% [interquartile range, 27%-99%]; P=0.07). Cerebral hyperglycolytic lactate production predicted good 6-month outcome (odds ratio for modified Rankin Scale score, 0-3 1.49; CI, 1.08-2.05; P=0.016), whereas increased lactate with brain hypoxia was associated with a reduced likelihood of good outcome (OR, 0.78; CI, 0.59-1.03; P=0.08). Brain lactate is frequently elevated in subarachnoid hemorrhage patients, predominantly because of hyperglycolysis rather than hypoxia. A pattern of increased cerebral hyperglycolytic lactate was associated with good long-term recovery. Our data suggest that lactate may be used as an aerobic substrate by the injured human brain.

The Role of the Brain's Endocannabinoid System in Pain and Its Modulation by Stress.

Science.gov (United States)

Corcoran, Louise; Roche, Michelle; Finn, David P

2015-01-01

Stress has a complex, bidirectional modulatory influence on pain. Stress may either reduce (stress-induced analgesia) or exacerbate (stress-induced hyperalgesia) pain depending on the nature, duration, and intensity of the stressor. The endogenous cannabinoid (endocannabinoid) system is present throughout the neuroanatomical pathways that mediate and modulate responses to painful stimuli. The specific role of the endocannabinoid system in the brain in pain and the modulation of pain by stress is reviewed herein. We first provide a brief overview of the endocannabinoid system, followed by a review of the evidence that the brain's endocannabinoid system modulates pain. We provide a comprehensive evaluation of the role of the endocannabinoid system supraspinally, and particularly in the rostral ventromedial medulla, periaqueductal gray, amygdala, and prefrontal cortex, in pain, stress-induced analgesia, and stress-induced hyperalgesia. Increased understanding of endocannabinoid-mediated regulation of pain and its modulation by stress will inform the development of novel therapeutic approaches for pain and its comorbidity with stress-related disorders. © 2015 Elsevier Inc. All rights reserved.

Deep brain stimulation results in local glutamate and adenosine release: investigation into the role of astrocytes.

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Tawfik, Vivianne L; Chang, Su-Youne; Hitti, Frederick L; Roberts, David W; Leiter, James C; Jovanovic, Svetlana; Lee, Kendall H

2010-08-01

Several neurological disorders are treated with deep brain stimulation; however, the mechanism underlying its ability to abolish oscillatory phenomena associated with diseases as diverse as Parkinson's disease and epilepsy remain largely unknown. To investigate the role of specific neurotransmitters in deep brain stimulation and determine the role of non-neuronal cells in its mechanism of action. We used the ferret thalamic slice preparation in vitro, which exhibits spontaneous spindle oscillations, to determine the effect of high-frequency stimulation on neurotransmitter release. We then performed experiments using an in vitro astrocyte culture to investigate the role of glial transmitter release in high-frequency stimulation-mediated abolishment of spindle oscillations. In this series of experiments, we demonstrated that glutamate and adenosine release in ferret slices was able to abolish spontaneous spindle oscillations. The glutamate release was still evoked in the presence of the Na channel blocker tetrodotoxin, but was eliminated with the vesicular H-ATPase inhibitor bafilomycin and the calcium chelator 2-bis(2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester. Furthermore, electrical stimulation of purified primary astrocytic cultures was able to evoke intracellular calcium transients and glutamate release, and bath application of 2-bis (2-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid tetrakis acetoxymethyl ester inhibited glutamate release in this setting. Vesicular astrocytic neurotransmitter release may be an important mechanism by which deep brain stimulation is able to achieve clinical benefits.

Comparison between capillary, venous and arterial levels of protein S100B in patients with severe brain pathology

DEFF Research Database (Denmark)

Astrand, Ramona; Romner, Bertil; Reinstrup, Peter

2012-01-01

of the study was to investigate the relation between capillary, venous and arterial measurements of protein S100B, primarily by determining whether capillary S100B differ from venous and if capillary S100B can predict venous S100B levels, and secondarily, if arterial S100B samples can substitute venous samples...... in severely brain-injured patients....

The role of crossmodal interaction in psychological and brain organization of mathematical abilities

Directory of Open Access Journals (Sweden)

Nikita A. Khokhlov

2016-12-01

Full Text Available The paper analyzes the work of Russian and foreign scholars devoted to the role of cross analyzer cooperation in developing and implementing mathematical abilities.Crossmodal interaction is considered as an additional category of neuropsychological analysis that allows to extend the existing ideas about the psychological structure and brain providing the mathematical ability. There are data that confirm the relevance of studying the interaction of the senses. Many of the research on this issue are carried out using the synesthesia which is considered a rare phenomenon. However, both Russian and foreign works suggest that the interaction of analyzers is not characteristic only to those whose brain is synesthetic. The joint work of the senses is characteristic of every person since his/her childhood, and is an obligatory condition for cognitive processes. Cross analyzer synthesis is assumed to play an important role in producing spatial representations and the ability to intuitively perceive the notion of quantity (evolutionary foundations of mathematical ability. On the brain level, these processes are provided primarily by functioning of parietal and tertiary cortical areas located at the junctionof cortical analyzer areas and also temporal areas that border on the parahippocampal brain area. When dealing with school mathematics the structure of mathematical abilities is changing due to verbal and symbolic representations of numerical coding. Dealing with symbols opens up new opportunities, but it also narrows the spectrum of modalities involved in doing mathematical sums. Thus, the ability to re-encode information from one modality to another after school mathematics is perceived has an impact on the efficacy of mathematical activity. Doing mathematical sums is accompanied by crossmodal interaction that occurs on the unconscious level. Some problem conditions may be efficiently processed in one modality, others may be solved in other modality

Effect of sildenafil on erectile dysfunction in spinal Cord injured ...

African Journals Online (AJOL)

Effect of sildenafil on erectile dysfunction in spinal Cord injured patients. ... Trauma was the etiology in 87.5% of the cases (44% were road accidents). 12/16 patients were paraplegics (10 above ... in SCI patients. This approach is compatible with the efforts to improve the quality of life and rehabilitation of these patients.

Toxicological findings in fatally injured pilots of 979 amateur-built aircraft accidents.

Science.gov (United States)

2011-12-01

"Biological samples collected from fatally injured pilots in aviation accidents involving all types of aircraft, including : amateur-built aircraft, are submitted to the Civil Aerospace Medical Institute (CAMI) for accident investigation. : These sam...

The role of image registration in brain mapping

Science.gov (United States)

Toga, A.W.; Thompson, P.M.

2008-01-01

Image registration is a key step in a great variety of biomedical imaging applications. It provides the ability to geometrically align one dataset with another, and is a prerequisite for all imaging applications that compare datasets across subjects, imaging modalities, or across time. Registration algorithms also enable the pooling and comparison of experimental findings across laboratories, the construction of population-based brain atlases, and the creation of systems to detect group patterns in structural and functional imaging data. We review the major types of registration approaches used in brain imaging today. We focus on their conceptual basis, the underlying mathematics, and their strengths and weaknesses in different contexts. We describe the major goals of registration, including data fusion, quantification of change, automated image segmentation and labeling, shape measurement, and pathology detection. We indicate that registration algorithms have great potential when used in conjunction with a digital brain atlas, which acts as a reference system in which brain images can be compared for statistical analysis. The resulting armory of registration approaches is fundamental to medical image analysis, and in a brain mapping context provides a means to elucidate clinical, demographic, or functional trends in the anatomy or physiology of the brain. PMID:19890483

Effectiveness of a web-based intervention for injured claimants: a randomized controlled trial.

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Elbers, Nieke A; Akkermans, Arno J; Cuijpers, Pim; Bruinvels, David J

2013-07-20

There is considerable evidence showing that injured people who are involved in a compensation process show poorer physical and mental recovery than those with similar injuries who are not involved in a compensation process. One explanation for this reduced recovery is that the legal process and the associated retraumatization are very stressful for the claimant. The aim of this study was to empower injured claimants in order to facilitate recovery. Participants were recruited by three Dutch claims settlement offices. The participants had all been injured in a traffic crash and were involved in a compensation process. The study design was a randomized controlled trial. An intervention website was developed with (1) information about the compensation process, and (2) an evidence-based, therapist-assisted problem-solving course. The control website contained a few links to already existing websites. Outcome measures were empowerment, self-efficacy, health status (including depression, anxiety, and somatic symptoms), perceived fairness, ability to work, claims knowledge and extent of burden. The outcomes were self-reported through online questionnaires and were measured four times: at baseline, and at 3, 6, and 12 months. In total, 176 participants completed the baseline questionnaire after which they were randomized into either the intervention group (n=88) or the control group (n=88). During the study, 35 participants (20%) dropped out. The intervention website was used by 55 participants (63%). The health outcomes of the intervention group were no different to those of the control group. However, the intervention group considered the received compensation to be fairer (Pwebsite was evaluated positively. Although the web-based intervention was not used enough to improve the health of injured claimants in compensation processes, it increased the perceived fairness of the compensation amount. Netherlands Trial Register NTR2360.

Effects of diabetes on brain metabolism - is brain glycogen a significant player?

DEFF Research Database (Denmark)

Sickmann, Helle M; Waagepetersen, Helle S.

2015-01-01

Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose to the br......Brain glycogen, being an intracellular glucose reservoir, contributes to maintain energy and neurotransmitter homeostasis under physiological as well as pathological conditions. Under conditions with a disturbance in systemic glucose metabolism such as in diabetes, the supply of glucose...... to the brain may be affected and have important impacts on brain metabolism and neurotransmission. This also implies that brain glycogen may serve an essential role in the diabetic state to sustain appropriate brain function. There are two main types of diabetes; type 1 and type 2 diabetes and both types may...... understanding of how brain energy and neurotransmitter metabolism is affected in diabetes. There will be a particular focus on the role of brain glycogen to support glycolytic and TCA cycle activity as well as glutamate-glutamine cycle in type 1 and type 2 diabetes....

Multifunctional roles of enolase in Alzheimer's disease brain: beyond altered glucose metabolism.

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Butterfield, D Allan; Lange, Miranda L Bader

2009-11-01

Enolase enzymes are abundantly expressed, cytosolic carbon-oxygen lyases known for their role in glucose metabolism. Recently, enolase has been shown to possess a variety of different regulatory functions, beyond glycolysis and gluconeogenesis, associated with hypoxia, ischemia, and Alzheimer's disease (AD). AD is an age-associated neurodegenerative disorder characterized pathologically by elevated oxidative stress and subsequent damage to proteins, lipids, and nucleic acids, appearance of neurofibrillary tangles and senile plaques, and loss of synapse and neuronal cells. It is unclear if development of a hypometabolic environment is a consequence of or contributes to AD pathology, as there is not only a significant decline in brain glucose levels in AD, but also there is an increase in proteomics identified oxidatively modified glycolytic enzymes that are rendered inactive, including enolase. Previously, our laboratory identified alpha-enolase as one the most frequently up-regulated and oxidatively modified proteins in amnestic mild cognitive impairment (MCI), early-onset AD, and AD. However, the glycolytic conversion of 2-phosphoglycerate to phosphoenolpyruvate catalyzed by enolase does not directly produce ATP or NADH; therefore it is surprising that, among all glycolytic enzymes, alpha-enolase was one of only two glycolytic enzymes consistently up-regulated from MCI to AD. These findings suggest enolase is involved with more than glucose metabolism in AD brain, but may possess other functions, normally necessary to preserve brain function. This review examines potential altered function(s) of brain enolase in MCI, early-onset AD, and AD, alterations that may contribute to the biochemical, pathological, clinical characteristics, and progression of this dementing disorder.

Photobiomodulation of the brain: a new paradigm (Conference Presentation)

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Hamblin, Michael R.

2017-02-01

Photobiomodulation (PBM) describes the use of red or near-infrared light to stimulate, heal, regenerate, and protect tissue that has either been injured, is degenerating, or else is at risk of dying. One of the organ systems of the human body that is most necessary to life, and whose optimum functioning is most worried about by humankind in general, is the brain. The brain suffers from many different disorders that can be classified into three broad groupings: traumatic events (stroke, traumatic brain injury, and global ischemia), degenerative diseases (dementia, Alzheimer's and Parkinson's), and psychiatric disorders (depression, anxiety, post traumatic stress disorder). There is some evidence that all these seemingly diverse conditions can be beneficially affected by applying light to the head. There is even the possibility that PBM could be used for cognitive enhancement in normal healthy people. In this transcranial PBM (tPBM) application, near-infrared (NIR) light is often applied to the forehead because of the better penetration (no hair, longer wavelength). Some workers have used lasers, but recently the introduction of inexpensive light emitting diode (LED) arrays has allowed the development of light emitting helmets or "brain caps". This presentation will cover the mechanisms of action of photobiomodulation to the brain, and summarize some of the key pre-clinical studies and clinical trials that have been undertaken in this area.

Effect of AVP on brain edema following traumatic brain injury

Institute of Scientific and Technical Information of China (English)

XU Miao; SU Wei; HUANG Wei-dong; LU Yuan-qiang; XU Qiu-ping; CHEN Zhao-jun

2007-01-01

Objective: To evaluate plasma arginine vasopressin (AVP) level in patients with traumatic brain injury and investigate the role of AVP in the process of brain edema. Methods: A total of 30 patients with traumatic brain injury were involved in our study. They were divided into two groups by Glasgow Coma Scale: severe traumatic brain injury group (STBI, GCS≤ 8) and moderate traumatic brain injury group (MTBI, GCS＞8).Samples of venous blood were collected in the morning at rest from 15 healthy volunteers (control group)and within 24 h after traumatic brain injury from these patients for AVP determinations by radioimmunoassay. The severity and duration of the brain edema were estimated by head CT scan.Results: plasma AVP levels (ng/L) were (mean±SD): control, 3.06±1.49; MTBI, 38.12±7.25; and STBI, 66.61±17.10.The plasma level of AVP was significantly increased within 24 h after traumatic brain injury and followed by the reduction of GCS, suggesting the deterioration of cerebral injury (P＜0.01). And the AVP level was correlated with the severity (STBI r=0.919, P＜0.01; MTBI r=0.724, P＜0.01) and the duration of brain edema (STBI r=0.790, P＜0.01; MTBI r=0.712, P＜0.01). Conclusions: The plasma AVP level is closely associated with the severity of traumatic brain injury. AVP may play an important role in pathogenesis of brain edema after traumatic brain injury.

Identification of Potentially Neuroprotective Genes Upregulated by Neurotrophin Treatment of CA3 Neurons in the Injured Brain

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Malik, Saafan Z.; Motamedi, Shahab; Royo, Nicolas C.; LeBold, David

2011-01-01

Abstract Specific neurotrophic factors mediate histological and/or functional improvement in animal models of traumatic brain injury (TBI). In previous work, several lines of evidence indicated that the mammalian neurotrophin NT-4/5 is neuroprotective for hippocampal CA3 pyramidal neurons after experimental TBI. We hypothesized that NT-4/5 neuroprotection is mediated by changes in the expression of specific sets of genes, and that NT-4/5-regulated genes are potential therapeutic targets for blocking delayed neuronal death after TBI. In this study, we performed transcription profiling analysis of CA3 neurons to identify genes regulated by lateral fluid percussion injury, or by treatment with the trkB ligands NT-4/5 or brain-derived neurotrophic factor (BDNF). The results indicate extensive overlap between genes upregulated by neurotrophins and genes upregulated by injury, suggesting that the mechanism behind neurotrophin neuroprotection may mimic the brain's endogenous protective response. A subset of genes selected for further study in vitro exhibited neuroprotection against glutamate excitotoxicity. The neuroprotective genes identified in this study were upregulated at 30 h post-injury, and are thus expected to act during a clinically useful time frame of hours to days after injury. Modulation of these factors and pathways by genetic manipulation or small molecules may confer hippocampal neuroprotection in vivo in preclinical models of TBI. PMID:21083427

Health status recovery at one year in children injured in a road accident: a cohort study.

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Batailler, Pierre; Hours, Martine; Maza, Maud; Charnay, Pierrette; Tardy, Hélène; Tournier, Charlène; Javouhey, Etienne

2014-10-01

Despite the frequency of traumatic injuries due to road accidents and potential importance of identifying children at risk of impaired recovery one year after a road accident, there is a lack of data on long-term recovery of health status, except in children with severe traumatic brain injury. The aim of the present study was to evaluate predictive factors of recovery in children one year after road traffic injuries. The prospective cohort study was composed of children aged road accident. Recovery of health status one year after the accident and information concerning quality of life and the consequences of the accident for the child or family 1 year after the accident were collected by questionnaire, usually completed by the parents. Victims were in majority male (64.6%) and had mild or moderate injuries (81.9% with Maximum Abbreviated Injury Scale (M-AIS) accident, 75.0% of the mild-to-moderate and 34.8% of the severe cases estimated health status as fully recovered. After adjustment, severity score (M-AIS≥3) and lower limb injury (AIS>1) were associated with incomplete recovery of health status: weighted odds ratio (ORw), 4.3 [95% confidence interval (95% CI), 1.3-14.6] and ORw, 6.5 [95% CI, 1.9-21.7], respectively. Recovery status correlated significantly with quality of life physical scores (r=0.46), especially body pain (r=0.48) and role/social-physical (r=0.50) and, to a lesser extent, quality of life psychosocial scores (r=0.21). In a cohort of children injured in a road accident, those with high injury severity score and those with lower limb injuries are less likely to recover full health status by 1 year. Impaired health status was associated with a lower physical quality of life score at 1 year. Copyright © 2014. Published by Elsevier Ltd.

Acute lung injury and the acute respiratory distress syndrome in the injured patient

Directory of Open Access Journals (Sweden)

Bakowitz Magdalena

2012-08-01

Full Text Available Abstract Acute lung injury and acute respiratory distress syndrome are clinical entities of multi-factorial origin frequently seen in traumatically injured patients requiring intensive care. We performed an unsystematic search using PubMed and the Cochrane Database of Systematic Reviews up to January 2012. The purpose of this article is to review recent evidence for the pathophysiology and the management of acute lung injury/acute respiratory distress syndrome in the critically injured patient. Lung protective ventilation remains the most beneficial therapy. Future trials should compare intervention groups to controls receiving lung protective ventilation, and focus on relevant outcome measures such as duration of mechanical ventilation, length of intensive care unit stay, and mortality.

Imatinib preserves blood-brain barrier integrity following experimental subarachnoid hemorrhage in rats.

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Zhan, Yan; Krafft, Paul R; Lekic, Tim; Ma, Qingyi; Souvenir, Rhonda; Zhang, John H; Tang, Jiping

2015-01-01

Blood-brain barrier (BBB) disruption and consequent edema formation contribute to the development of early brain injury following subarachnoid hemorrhage (SAH). Various cerebrovascular insults result in increased platelet-derived growth factor receptor (PDGFR)-α stimulation, which has been linked to BBB breakdown and edema formation. This study examines whether imatinib, a PDGFR inhibitor, can preserve BBB integrity in a rat endovascular perforation SAH model. Imatinib (40 or 120 mg/kg) or a vehicle was administered intraperitoneally at 1 hr after SAH induction. BBB leakage, brain edema, and neurological deficits were evaluated. Total and phosphorylated protein expressions of PDGFR-α, c-Src, c-Jun N-terminal kinase (JNK), and c-Jun were measured, and enzymatic activities of matrix metalloproteinase (MMP)-2 and MMP-9 were determined in the injured brain. Imatinib treatment significantly ameliorated BBB leakage and edema formation 24 hr after SAH, which was paralleled by improved neurological functions. Decreased brain expressions of phosphorylated PDGFR-α, c-Src, JNK, and c-Jun as well as reduced MMP-9 activities were found in treated animals. PDGFR-α inhibition preserved BBB integrity following experimental SAH; however, the protective mechanisms remain to be elucidated. Targeting PDGFR-α signaling might be advantageous to ameliorate early brain injury following SAH. © 2014 Wiley Periodicals, Inc.

Optic nerve sheath diameter: A novel way to monitor the brain

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Seelora Sahu

2017-01-01

Full Text Available Measurement and monitoring of intracranial pressure is pivotal in management of brain injured patients. As a rapid and easily done bed side measurement, ultrasonography of the optic nerve sheath diameter presents itself as a possible replacement of the conventional invasive methods of intracranial pressure management. In this review we go through the evolution of optic nerve sheath diameter measurement as a novel marker of predicting raised intracranial pressure, the modalities by which it can be measured as well as its correlation with the invasive methods of intracranial pressure monitoring.

A cost analysis of conservative management of spinal cord-injured patients in Nigeria.

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Kawu, A A; Olawepo, A; Salami, A O O; Kuranga, S A; Abdulhameed, S; Esenwah, V C

2011-11-01

A prospective study. To determine the cost of acute phase of injury (ASCI) among spinal cord-injured patients managed conservatively in Nigeria. Gwagwalada, Abuja. Over a 1-year period (1 January 2009 to 31 December 2009), the cost of ASCI of consecutive spinal cord-injured patients, gainfully employed preinjury, who paid the hospital bill directly from their purses and could estimate their daily income, and who were managed conservatively for 6 weeks before discharge to rehabilitation, was prospectively examined. A total of 34 cases of spinal cord-injured patients with a mean age of 35.4 ± 12.8 years were included in this study. The mean cost of ASCI over 6 weeks was $1598.29, an average of 6.4-232.8% of patients' annual income where >50% of the people live on less than a dollar a day. The mean cost of hospitalization was 14.9% of the total cost of ASCI in this study. It was significantly more expensive to treat tetraplegics compared with paraplegics. This study identified the cost of acute phase of spinal cord injury in Nigeria to assist clinicians in planning treatment that could reduce financial burden on the patients but optimize patients' care.

[The challenge of adequate reimbursement for the seriously injured patient in the German DRG system].

Science.gov (United States)

Franz, D; Lefering, R; Siebert, H; Windolf, J; Roeder, N; Mahlke, L

2013-02-01

Critically injured patients are a very heterogeneous group, medically and economically. Their treatment is a major challenge for both the medical care and the appropriate financial reimbursement. Systematic underfunding can have a significant impact on the quality of patient care. In 2009 the German Trauma Society and the DRG-Research Group of the University Hospital Muenster initialised a DRG evaluation project to analyse the validity of case allocation of critically injured patients within the German DRG system versions 2008 and 2011 with additional consideration of clinical data from the trauma registry of the German Trauma Society. Severe deficits within the G-DRG structure were identified and specific solutions were designed and realised. A retrospective analysis was undertaken of standardised G-DRG data (§ 21 KHEntgG) including case-related cost data from 3 362 critically injured patients in the periods 2007 and 2008 from 10 university hospitals and 7 large municipal hospitals. For 1 241 cases of the sample, complementary detailed information was available from the trauma registry of the German Trauma Society to monitor the case allocation of critically injured patients within the G-DRG system. Analyses of coding and grouping, performance of case allocation, and the homogeneity of costs in the G-DRG versions 2008 and 2011 were done. The following situations were found: (i) systematic underfunding of trauma patients in the G-DRG-Version 2008, especially trauma patients with acute paraplegia; (ii) participation in the official G-DRG development for 2011 with 13 proposals which were largely realised; (ii) the majority of cases with cost-covering in the G-DRG version 2011; (iv) significant improvements in the quality of statistical criteria; (v) overfunded trauma patients with high intensive care costs; (vi) underfunding for clinically relevant critically injured patients not identified in the G-DRG system. The quality of the G-DRG system is measured by the

Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility

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Eric J. Neuberger

2017-09-01

Full Text Available Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.

Changes in biomechanics and muscle activation in injured ballet dancers during a jump-land task with turnout (Sissonne Fermée).

Science.gov (United States)

Lee, Hsing-Hsan; Lin, Chia-Wei; Wu, Hong-Wen; Wu, Tzu-Chuan; Lin, Cheng-Feng

2012-01-01

Large impact loading with abnormal muscle activity and motion patterns may contribute to lower extremity injuries in ballet dancers. Yet, few studies investigated the influence of injury on the ballet movement. The purpose of this study was to find the neuromuscular and biomechanical characteristics in dancers with and without ankle injury during a jump-landing Sissonne Fermée task. Twenty-two ballet dancers were recruited and divided into the injured group (n = 11) and the uninjured group (n = 11). They performed a ballet movement called "Sissonne Fermée" with reflective markers and electrodes attached to their lower extremities. Ground reaction force, joint kinematics, and muscle activity were measured. The injured dancers had greater peak ankle eversion but smaller hindfoot-to-tibial eversion angles. Also, the injured dancers had greater activity of the hamstring of the dominant leg and tibialis anterior of the non-dominant leg during the pre-landing phase. The injured dancers had greater tibialis anterior activity of the dominant leg but less muscle activity in the medial gastrocnemius of the non-dominant leg during the post-landing phase. The injured dancers had a greater co-contraction index in the non-dominant ankle and a lower loading rate. The higher co-contraction indices showed that the injured dancers required more muscle effort to control ankle stability. Furthermore, the injured dancers used a "load avoidance strategy" to protect themselves from re-injury. Neuromuscular control training of the ankle joint for ballet dancers to prevent injury is necessary.

Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow.

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Linnman, Clas; Catana, Ciprian; Svärdsudd, Kurt; Appel, Lieuwe; Engler, Henry; Långström, Bengt; Sörensen, Jens; Furmark, Tomas; Fredrikson, Mats; Borsook, David; Peterson, Magnus

Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1) receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis) were selected out of a larger (n = 120) randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis). These ten subjects were examined by positron emission tomography (PET) with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA), was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP) / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.

Decreased Brain Neurokinin-1 Receptor Availability in Chronic Tennis Elbow.

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Clas Linnman

Full Text Available Substance P is released in painful and inflammatory conditions, affecting both peripheral processes and the central nervous system neurokinin 1 (NK1 receptor. There is a paucity of data on human brain alterations in NK1 expression, how this system may be affected by treatment, and interactions between central and peripheral tissue alterations. Ten subjects with chronic tennis elbow (lateral epicondylosis were selected out of a larger (n = 120 randomized controlled trial evaluating graded exercise as a treatment for chronic tennis elbow (lateral epicondylosis. These ten subjects were examined by positron emission tomography (PET with the NK1-specific radioligand 11C-GR205171 before, and eight patients were followed up after treatment with graded exercise. Brain binding in the ten patients before treatment, reflecting NK1-receptor availability (NK1-RA, was compared to that of 18 healthy subjects and, longitudinally, to the eight of the original ten patients that agreed to a second PET examination after treatment. Before treatment, patients had significantly lower NK1-RA in the insula, vmPFC, postcentral gyrus, anterior cingulate, caudate, putamen, amygdala and the midbrain but not the thalamus and cerebellum, with the largest difference in the insula contralateral to the injured elbow. No significant correlations between brain NK1-RA and pain, functional severity, or peripheral NK1-RA in the affected limb were observed. In the eight patients examined after treatment, pain ratings decreased in everyone, but there were no significant changes in NK1-RA. These findings indicate a role for the substance P (SP / NK1 receptor system in musculoskeletal pain and tissue healing. As neither clinical parameters nor successful treatment response was reflected in brain NK1-RA after treatment, this may reflect the diverse function of the SP/NK1 system in CNS and peripheral tissue, or a change too small or slow to capture over the three-month treatment.

Increased expression of aquaporin-4 in human traumatic brain injury and brain tumors

Institute of Scientific and Technical Information of China (English)

HuaHu; Wei-PingZhang; LeiZhang; ZhongChen; Er-QingWei

2004-01-01

Aquaporin-4 (AQP4) is one of the aquaporins (AQPs), a water channel family. In the brain, AQP4 is expressed in astroeyte foot processes, and plays an important role in water homeostasis and in the formation of brain edema. In our study, AQP4 expression in human brain specimens from patients with traumatic brain injury or different brain tumors was detected

Perspective of young drivers towards the care of the road traffic injured

African Journals Online (AJOL)

user

2014-12-09

Dec 9, 2014 ... Key words: Young driver, road traffic injured, pre-hospital care, training. INTRODUCTION .... Response time is considered an important criterion in assessing the ... safety was a priority ever before attempting to rescue the ...

Optical microangiography enabling visualization of change in meninges after traumatic brain injury in mice in vivo

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Choi, Woo June; Qin, Wan; Qi, Xiaoli; Wang, Ruikang K.

2016-03-01

Traumatic brain injury (TBI) is a form of brain injury caused by sudden impact on brain by an external mechanical force. Following the damage caused at the moment of injury, TBI influences pathophysiology in the brain that takes place within the minutes or hours involving alterations in the brain tissue morphology, cerebral blood flow (CBF), and pressure within skull, which become important contributors to morbidity after TBI. While many studies for the TBI pathophysiology have been investigated with brain cortex, the effect of trauma on intracranial tissues has been poorly studied. Here, we report use of high-resolution optical microangiography (OMAG) to monitor the changes in cranial meninges beneath the skull of mouse after TBI. TBI is induced on a brain of anesthetized mouse by thinning the skull using a soft drill where a series of drilling exert mechanical stress on the brain through the skull, resulting in mild brain injury. Intracranial OMAG imaging of the injured mouse brain during post-TBI phase shows interesting pathophysiological findings in the meningeal layers such as widening of subdural space as well as vasodilation of subarachnoid vessels. These processes are acute and reversible within hours. The results indicate potential of OMAG to explore mechanism involved following TBI on small animals in vivo.

Magnetic resonance imaging of experimental brain edema

Energy Technology Data Exchange (ETDEWEB)

Tanaka, Chuzo; Naruse, Shoji; Horikawa, Yoshiharu; Higuchi, Toshihiro; Ebisu, Toshihiko; Hirakawa, Kimiyoshi; Ohno, Yoshioki; Maki, Sou

1987-04-01

Experimental brain edema was produced by either cold injury or TET (triethyl-tin) intoxication in twenty-five Wistar rats, weighing about 250 g each, and then analyzed using MRI (magnetic resonance imaging). The MRI was carried out with a 0.1 Tesla clinical apparatus (Asahi Mark J), using a special coil (7 cm in diameter) devised for small animals in order to obtain SR, SE, IR, and calculated T/sub 1/ and T/sub 2/ images. A dose of 0.5 mmol/kg of Gd-DTPA was injected intravenously for the cold-injury edema, and MRIs of the rat brains were started immediately and obtained successively for 3 hours. MRI showed spatial resolution sufficient to differentiate the cortex from the caudate nucleus, even in such a small rat brain. Rat brains with TET intoxication (cytotoxic edema) showed a marked prolongation of T/sub 1/ and T/sub 2/ in the white matter. Consequently, the TET-intoxication images reflected these characteristic findings. Cold-induced edema showed an increased signal intensity in the injured cortex, the white matter, and the opposite white matter when compared with a normal brain. These changes correlate well with the previously reported in vitro data. When Gd-DTPA was administered to the rats with cold-induced edema, the signal intensity of the cold-injury lesion was significantly reduced. These changes were clearly demonstrated by the calculated T/sub 1/ images. To two rats we administered a dose of 0.5 mmol/kg of Gd-DTPA; The T/sub 1/ values for the cold-injury lesions, before and after the injection, were about 445 msec and about 200 msec respectively. These studies were useful not only in evaluating brain edema, but also in analysing the effect of Gd-DTPA on the brain edema.

Posttraumatic stress disorder: the role of medial prefrontal cortex and amygdala.

Science.gov (United States)

Koenigs, Michael; Grafman, Jordan

2009-10-01

Posttraumatic stress disorder (PTSD) is characterized by recurrent distressing memories of an emotionally traumatic event. In this review, the authors present neuroscientific data highlighting the function of two brain areas--the amygdala and ventromedial prefrontal cortex (vmPFC)--in PTSD and related emotional processes. A convergent body of human and nonhuman studies suggests that the amygdala mediates the acquisition and expression of conditioned fear and the enhancement of emotional memory, whereas the vmPFC mediates the extinction of conditioned fear and the volitional regulation of negative emotion. It has been theorized that the vmPFC exerts inhibition on the amygdala, and that a defect in this inhibition could account for the symptoms of PTSD. This theory is supported by functional imaging studies of PTSD patients, who exhibit hypoactivity in the vmPFC but hyperactivity in the amygdala. A recent study of brain-injured and trauma-exposed combat veterans confirms that amygdala damage reduces the likelihood of developing PTSD. But contrary to the prediction of the top-down inhibition model, vmPFC damage also reduces the likelihood of developing PTSD. The putative roles of the amygdala and the vmPFC in the pathophysiology of PTSD, as well as implications for potential treatments, are discussed in light of these results.

Deregulation of brain insulin signaling in Alzheimer's disease.

Science.gov (United States)

Chen, Yanxing; Deng, Yanqiu; Zhang, Baorong; Gong, Cheng-Xin

2014-04-01

Contrary to the previous belief that insulin does not act in the brain, studies in the last three decades have demonstrated important roles of insulin and insulin signal transduction in various functions of the central nervous system. Deregulated brain insulin signaling and its role in molecular pathogenesis have recently been reported in Alzheimer's disease (AD). In this article, we review the roles of brain insulin signaling in memory and cognition, the metabolism of amyloid β precursor protein, and tau phosphorylation. We further discuss deficiencies of brain insulin signaling and glucose metabolism, their roles in the development of AD, and recent studies that target the brain insulin signaling pathway for the treatment of AD. It is clear now that deregulation of brain insulin signaling plays an important role in the development of sporadic AD. The brain insulin signaling pathway also offers a promising therapeutic target for treating AD and probably other neurodegenerative disorders.

Chemotherapy in the management of brain metastases: the emerging role of fotemustine for patients with melanoma and NSCLC.

Science.gov (United States)

Addeo, Raffaele; Zappavigna, Silvia; Luce, Amalia; Facchini, Sergio; Caraglia, Michele

2013-09-01

An estimated 20 - 40% of cancer patients will develop brain metastases that are the most common intracranial tumors in adults. Patients with cerebral metastases represent a variegate group where selection of the most appropriate treatment depends on many patient- and disease-related factors. The impact of therapeutic option on overall survival is lacking and it is important to consider quality of life (QOL) when treating patients with brain metastases. A considerable proportion of patients are treated with palliative approaches such as whole-brain radiotherapy. The role of chemotherapy was limited in the past. Recently, several chemotherapeutic agents have been identified as potentially useful. This article examines the pharmacokinetics, efficacy and safety and tolerability of fotemustine (FTM) for the management of patients with cerebral metastasis from melanoma and non-small cell lung cancer (NSCLC). FTM is a third-generation nitrosourea that has proved its efficacy on brain metastases of melanoma and showed promising results for the treatment of brain metastasis of NSCLC because of its ability to pass the blood-brain barrier.

The evaluation of behavioural changes in brain-injured patients: SOFMER recommendations for clinical practice.

Science.gov (United States)

Prouteau, A; Stéfan, A; Wiart, L; Mazaux, J M

2016-02-01

Behavioural changes are the main cause of difficulties in interpersonal relationships and social integration among traumatic brain injury (TBI) patients. The Société française de médecine physique et réadaptation (SOFMER) decided to develop recommendations for the treatment and care provision for these problem under the auspices of the French health authority, the Haute Autorité de la santé (HAS). Assessment of behaviour is essential to describe, understand and define situations, assess any change and suggest lines for intervention. The relationship of these behavioural changes with the brain lesion is likewise of crucial importance in legal and forensic expertise. Using a literature review and expert opinions, the aim was to define the optimal conditions for the collection of data on behavioural changes in individuals having sustained brain trauma, to identify the situations in which they arise, to review the instruments available, and to suggest lines of intervention. A literature search identified 981 articles, among which 122 on the target subject were selected and analysed in detail and confronted with the experience of professionals and user representatives. A first draft of the recommendations was produced by the working group, and then submitted to a review group for opinions and complements. The literature on this subject is heterogeneous, and presents low levels of evidence. No article enabled the development of recommendations above the "expert opinion" level. After prior clarification of the aims of the evaluation, it is recommended first to carefully describe the changes in behaviour, from patient and third-person narratives, and where possible from direct observations. The information enabling the description of the phenomena occurring should be collected by different individuals (multi-source evaluation): the patient, his or her close circle, and professionals with different training backgrounds (multidisciplinary evaluation). The analysis of

Reconstruction of Injured Carotid Artery in a Comatose Patient

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Arben Zenelaj

2014-06-01

Full Text Available A man 30 years old,was brought to the emergency department after being injured on the left side of the neck area.Massive bleeding from the wound caused by glass was observed.The patient was in cerebral coma and hemorrahagic shock.The eye pupils remained isochoric during and after the operation.He was taken immediately at the surgery room.The bleeding was stopped by using external compression.Exposure of the left neck blood vessels was carried out.The left common carotid artery and internal jugular vein was revealed.A provisory Pruitt-Inahara shunt was put in the common carotid artery,while teh injured vein was ligated.The suture of the left common carotid artery using Prolen 6-0 completed the procedure.After the surgery the patient was transferred to the intensive care unit.About two hours later he woke up,conscious.The left thoracic drainage because of the hemothorax was applied in the second postoperative day.The patient was lively and discharged from the hospitall in the 14-th postoperative day.The right facial paresis and mild left side hemiparesis persisted.Two months after the event no residual neurologic deficits were observed. [Cukurova Med J 2014; 39(3.000: 598-601

Decreased Secondary Lesion Growth and Attenuated Immune Response after Traumatic Brain Injury in Tlr2/4−/− Mice

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Sandro M. Krieg

2017-08-01

Full Text Available Danger-associated molecular patterns are released by damaged cells and trigger neuroinflammation through activation of non-specific pattern recognition receptors, e.g., toll-like receptors (TLRs. Since the role of TLR2 and 4 after traumatic brain injury (TBI is still unclear, we examined the outcome and the expression of pro-inflammatory mediators after experimental TBI in Tlr2/4−/− and wild-type (WT mice. Tlr2/4−/− and WT mice were subjected to controlled cortical injury and contusion volume and brain edema formation were assessed 24 h thereafter. Expression of inflammatory markers in brain tissue was measured by quantitative PCR 15 min, 3 h, 6 h, 12 h, and 24 h after controlled cortical impact (CCI. Contusion volume was significantly attenuated in Tlr2/4−/− mice (29.7 ± 0.7 mm3 as compared to 33.5 ± 0.8 mm3 in WT; p < 0.05 after CCI while brain edema was not affected. Only interleukin (IL-1β gene expression was increased after CCI in the Tlr2/4−/− relative to WT mice. Inducible nitric oxide synthetase, TNF, IL-6, and COX-2 were similar in injured WT and Tlr2/4−/− mice, while the increase in high-mobility group box 1 was attenuated at 6 h. TLR2 and 4 are consequently shown to potentially promote secondary brain injury after experimental CCI via neuroinflammation and may therefore represent a novel therapeutic target for the treatment of TBI.

Functional plasticity in childhood brain disorders: when, what, how, and whom to assess.

Science.gov (United States)

Dennis, Maureen; Spiegler, Brenda J; Simic, Nevena; Sinopoli, Katia J; Wilkinson, Amy; Yeates, Keith Owen; Taylor, H Gerry; Bigler, Erin D; Fletcher, Jack M

2014-12-01

At every point in the lifespan, the brain balances malleable processes representing neural plasticity that promote change with homeostatic processes that promote stability. Whether a child develops typically or with brain injury, his or her neural and behavioral outcome is constructed through transactions between plastic and homeostatic processes and the environment. In clinical research with children in whom the developing brain has been malformed or injured, behavioral outcomes provide an index of the result of plasticity, homeostasis, and environmental transactions. When should we assess outcome in relation to age at brain insult, time since brain insult, and age of the child at testing? What should we measure? Functions involving reacting to the past and predicting the future, as well as social-affective skills, are important. How should we assess outcome? Information from performance variability, direct measures and informants, overt and covert measures, and laboratory and ecological measures should be considered. In whom are we assessing outcome? Assessment should be cognizant of individual differences in gene, socio-economic status (SES), parenting, nutrition, and interpersonal supports, which are moderators that interact with other factors influencing functional outcome.

Epigenetic mechanisms and associated brain circuits in the regulation of positive emotions: A role for transposable elements.

Science.gov (United States)

Gaudi, Simona; Guffanti, Guia; Fallon, James; Macciardi, Fabio

2016-10-15

Epigenetic programming and reprogramming are at the heart of cellular differentiation and represent developmental and evolutionary mechanisms in both germline and somatic cell lines. Only about 2% of our genome is composed of protein-coding genes, while the remaining 98%, once considered "junk" DNA, codes for regulatory/epigenetic elements that control how genes are expressed in different tissues and across time from conception to death. While we already know that epigenetic mechanisms are at play in cancer development and in regulating metabolism (cellular and whole body), the role of epigenetics in the developing prenatal and postnatal brain, and in maintaining a proper brain activity throughout the various stages of life, in addition to having played a critical role in human evolution, is a relatively new domain of knowledge. Here we present the current state-of-the-art techniques and results of these studies within the domain of emotions, and then speculate on how genomic and epigenetic mechanisms can modify and potentially alter our emotional (limbic) brain and affect our social interactions. J. Comp. Neurol. 524:2944-2954, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Treatment for delayed brain injury after pituitary irradiation

International Nuclear Information System (INIS)

Fujii, Takashi; Misumi, Shuzoh; Shibasaki, Takashi; Tamura, Masaru; Kunimine, Hideo; Hayakawa, Kazushige; Niibe, Hideo; Miyazaki, Mizuho; Miyagi, Osamu.

1988-01-01

Treatment for delayed brain injury after pituitary irradiation is discussed. Six cases with delayed brain injury were treated with a combination of dexamethasone or betamethasone, with heparin, glycerol, dextran 40 and some vasodilators. Two cases with temporal lobe syndrome were treated in the early stages of brain injury for a period of over 12 months were almost completely cured, another two cases with chiasma syndrome were treated in the relatively late stages, showed a partial improvement. One case which was irradiated 120 GY during 13 years did not improve. The final case treated with steroids for a short period also resulted in failure and the patient underwent an operation for the removal of the necrotic mass three years after the radiotherapy. Steroid therapy started in the early stages of brain injury after irradiation for over the 12 months is thought to be effective. Heparin therapy was also effective in one out of three cases, but in one of the cases subarachnoid hemorrhage from a traumatic aneurysm occurred during the therapy. In an acute phase, showing edematous change of the injured brain, the administration of glycerol is also thought to be useful. But the effectiveness of the other medicines containing some vasodilators was obscure or doubtful. We propose the following : (1) A meticulous observation is essential for the patients who received high doses of irradiation to diagnose brain injury in the early reversible stage. (2) Steroids should be given immediately in this reversible stage of brain injury before the irreversible ''necrosis'' occurs. (3) Steroids should be maintained for a long period over 12 months. (4) Heparin therapy is also thought to be effective, but careful precautions to avoid hemorrhagic complications before the therapy should be scheduled. This recommended plan may also be used for the treatment of brain injuries after cranial irradiation for other intracranial tumors. (author)

De l'injure en pays maure ou « qui ne loue pas critique »

Directory of Open Access Journals (Sweden)

Catherine Taine-Cheikh

2009-05-01

Full Text Available Catherine Taine-Cheikh, qui s'intéresse au phénomène de l'injure dans la société arabophone de Mauritanie, commence par étudier les différents termes du dialecte hassâniyya qui relèvent de ce champ sémantique. Elle s'attache ensuite à montrer l'importance et la complexité de l'« effet injure », dans cette société fortement imprégnée par les valeurs de l'honneur où non seulement la critique mais aussi la louange peuvent apparaître comme des manifestations de l'injure. Passant en revue diverses situations empruntées à la vie quotidienne ou puisées dans des matériaux littéraires (écrits et surtout oraux, l'auteur relève diverses stratégies adoptées, soit par les injurieurs, soit par les injuriaires, pour tenter de maîtriser les effets des mots (ou gestes « déplacés ». Bien que le problème du contrôle de soi semble presque toujours primordial, la gestion de l'injure laisse apparaître une différenciation importante en fonction du sexe et du statut relatif des acteurs sociaux concernés.

Supervisor Autonomy and Considerate Leadership Style are Associated with Supervisors' Likelihood to Accommodate Back Injured Workers.

Science.gov (United States)

McGuire, Connor; Kristman, Vicki L; Shaw, William; Williams-Whitt, Kelly; Reguly, Paula; Soklaridis, Sophie

2015-09-01

To determine the association between supervisors' leadership style and autonomy and supervisors' likelihood of supporting job accommodations for back-injured workers. A cross-sectional study of supervisors from Canadian and US employers was conducted using a web-based, self-report questionnaire that included a case vignette of a back-injured worker. Autonomy and two dimensions of leadership style (considerate and initiating structure) were included as exposures. The outcome, supervisors' likeliness to support job accommodation, was measured with the Job Accommodation Scale (JAS). We conducted univariate analyses of all variables and bivariate analyses of the JAS score with each exposure and potential confounding factor. We used multivariable generalized linear models to control for confounding factors. A total of 796 supervisors participated. Considerate leadership style (β = .012; 95% CI .009-.016) and autonomy (β = .066; 95% CI .025-.11) were positively associated with supervisors' likelihood to accommodate after adjusting for appropriate confounding factors. An initiating structure leadership style was not significantly associated with supervisors' likelihood to accommodate (β = .0018; 95% CI -.0026 to .0061) after adjusting for appropriate confounders. Autonomy and a considerate leadership style were positively associated with supervisors' likelihood to accommodate a back-injured worker. Providing supervisors with more autonomy over decisions of accommodation and developing their considerate leadership style may aid in increasing work accommodation for back-injured workers and preventing prolonged work disability.

[What kind of health information search the spinal cord injured patients from Spain on the internet?].

Science.gov (United States)

Bea-Muñoz, Manuel; Medina-Sánchez, María; Flórez-García, Mariano

2015-04-16

Internet is an alternative for health education to the population. Spinal cord injured individuals usually consult the Internet about their health problems. To identify the health information sources, the more consulted items and the confidence in Internet information of a group of spinal cord injured individuals from Spain. A survey to spinal cord injured individuals from Spain was conducted, with a questionnaire in Google Drive. It was accessible with a link in ASPAYM-Asturias web page. The questionnaire included epidemiological data and information about Internet use and confidence in its contents. 121 individuals answered the survey, 64% male, with an average age of 45 years. The predominant aetiology was traumatic (70%) and 72% were paraplegics. 83% prefer to consult health care providers directly. More of 70% of the sample searches health problems on the Internet, mostly web pages in Spanish. The preferred item was 'orthopaedic materials and wheelchairs'. 27% of the sample trusts in the Internet information and 32% don't. This research provides information about Internet use of spinal cord injured individuals in Spain. Although we have to admit some bias in the study, more than 70% of the sample searches health problems on the Internet, mostly web pages in Spanish. About one in four individuals trust in information from Internet and most of the sample prefers recommendations directly from healthcare professionals.

Three-dimensional analysis of somatic mitochondrial dynamics in fission-deficient injured motor neurons using FIB/SEM.

Science.gov (United States)

Tamada, Hiromi; Kiryu-Seo, Sumiko; Hosokawa, Hiroki; Ohta, Keisuke; Ishihara, Naotada; Nomura, Masatoshi; Mihara, Katsuyoshi; Nakamura, Kei-Ichiro; Kiyama, Hiroshi

2017-08-01

Mitochondria undergo morphological changes through fusion and fission for their quality control, which are vital for neuronal function. In this study, we examined three-dimensional morphologies of mitochondria in motor neurons under normal, nerve injured, and nerve injured plus fission-impaired conditions using the focused ion beam/scanning electron microscopy (FIB/SEM), because the FIB/SEM technology is a powerful tool to demonstrate both 3D images of whole organelle and the intra-organellar structure simultaneously. Crossing of dynamin-related protein 1 (Drp1) gene-floxed mice with neuronal injury-specific Cre driver mice, Atf3:BAC Tg mice, allowed for Drp1 ablation specifically in injured neurons. FIB/SEM analysis demonstrated that somatic mitochondrial morphologies in motor neurons were not altered before or after nerve injury. However, the fission impairment resulted in prominent somatic mitochondrial enlargement, which initially induced complex morphologies with round regions and long tubular processes, subsequently causing a decrease in the number of processes and further enlargement of the round regions, which eventually resulted in big spheroidal mitochondria without processes. The abnormal mitochondria exhibited several degradative morphologies: local or total cristae collapse, vacuolization, and mitophagy. These suggest that mitochondrial fission is crucial for maintaining mitochondrial integrity in injured motor neurons, and multiple forms of mitochondria degradation may accelerate neuronal degradation. © 2017 Wiley Periodicals, Inc.

Playing with your Brain : Brain-Computer Interfaces and Games

NARCIS (Netherlands)

Nijholt, Anton; Tan, Desney; Bernhaupt, Regina; Tscheligi, Manfred

2007-01-01

In this workshop we investigate a possible role of brain-computer interaction in computer games and entertainment computing. The assumption is that brain activity, whether it is consciously controlled and directed by the user or just recorded in order to obtain information about the user’s affective

Playing with your Brain: Brain-Computer Interfaces and Games

NARCIS (Netherlands)

Nijholt, Antinus; Tan, Desney; Bernhaupt, R.; Tscheligi, M.

2007-01-01

In this workshop we investigate a possible role of brain-computer interaction in computer games and entertainment computing. The assumption is that brain activity, whether it is consciously controlled and directed by the user or just recorded in order to obtain information about the user’s affective

"THE EVALUATION OF THE POSSIBLE EFFECT OF POSITIVE END EXPIRATORY PRESSURE (PEEP) ON PHARMACOKINETICS OF PHENYTOIN IN PATIENTS WITH ACUTE BRAIN INJURY UNDER MECHANICAL VENTILATION."

OpenAIRE

"Elham Hadidi; Mojtaba Mojtahedzadeh; Mohammad Reza Rouini; Behzad Eftekhar; Mohammad Abdollahi; Atabak Najafi; Mohammad R. Khajavi; Saeed Rezaee; Reza Ghaffari; Minoo Afshar"

2005-01-01

Positive ventilation has shown to have an influence on pharmacokinetic and disposition of some drugs.Beacause phenytoin with a narrow therapautic range, is the most commonly used drug for prophylaxis and treatment of early seizures after acute brain injuries, in the present study the effect of short term PEEP (5-10 cm H2O for at least 8 hours) on phenytoin serum concentration and pharmacokinetic parameters such as Vmax and clearance in brain injured patients under mechanical ventilation was e...

Viability of sublethally injured coliform bacteria on fresh-cut cabbage stored in high CO2 atmospheres following rinsing with electrolyzed water.

Science.gov (United States)

Izumi, Hidemi; Inoue, Ayano

2018-02-02

The extent of sublethally injured coliform bacteria on shredded cabbage, either rinsed or not rinsed with electrolyzed water, was evaluated during storage in air and high CO 2 controlled atmospheres (5%, 10%, and 15%) at 5°C and 10°C using the thin agar layer (TAL) method. Sublethally injured coliform bacteria on nonrinsed shredded cabbage were either absent or they were injured at a 64-65% level when present. Rinsing of shredded cabbage with electrolyzed water containing 25ppm available chlorine reduced the coliform counts by 0.4 to 1.1 log and caused sublethal injury ranging from 42 to 77%. Pantoea ananatis was one of the species injured by chlorine stress. When shredded cabbage, nonrinsed or rinsed with electrolyzed water, was stored in air and high CO 2 atmospheres at 5°C for 7days and 10°C for 5days, coliform counts on TAL plates increased from 3.3-4.5 to 6.5-9.0 log CFU/g during storage, with the increase being greater at 10°C than at 5°C. High CO 2 of 10% and 15% reduced the bacterial growth on shredded cabbage during storage at 5°C. Although injured coliform bacteria were not found on nonrinsed shredded cabbage on the initial day, injured coliforms at a range of 49-84% were detected on samples stored in air and high CO 2 atmospheres at 5°C and 10°C. Injured cells were detected more frequently during storage at both temperatures irrespective of the CO 2 atmosphere when shredded cabbage was rinsed with electrolyzed water. These results indicated that injured coliform bacteria on shredded cabbage, either rinsed or not rinsed with electrolyzed water, exhibited different degrees of injury during storage regardless of the CO 2 atmosphere and temperature tested. Copyright © 2017 Elsevier B.V. All rights reserved.

Fluoxetine Increases Hippocampal Neurogenesis and Induces Epigenetic Factors But Does Not Improve Functional Recovery after Traumatic Brain Injury

Science.gov (United States)

Wang, Yonggang; Neumann, Melanie; Hansen, Katharina; Hong, Shuwhey M.; Kim, Sharon; Noble-Haeusslein, Linda J.

2011-01-01

Abstract The selective serotonin reuptake inhibitor fluoxetine induces hippocampal neurogenesis, stimulates maturation and synaptic plasticity of adult hippocampal neurons, and reduces motor/sensory and memory impairments in several CNS disorders. In the setting of traumatic brain injury (TBI), its effects on neuroplasticity and function have yet to be thoroughly investigated. Here we examined the efficacy of fluoxetine after a moderate to severe TBI, produced by a controlled cortical impact. Three days after TBI or sham surgery, mice were treated with fluoxetine (10 mg/kg/d) or vehicle for 4 weeks. To evaluate the effects of fluoxetine on neuroplasticity, hippocampal neurogenesis and epigenetic modification were studied. Stereologic analysis of the dentate gyrus revealed a significant increase in doublecortin-positive cells in brain-injured animals treated with fluoxetine relative to controls, a finding consistent with enhanced hippocampal neurogenesis. Epigenetic modifications, including an increase in histone 3 acetylation and induction of methyl-CpG-binding protein, a transcription factor involved in DNA methylation, were likewise seen by immunohistochemistry and quantitative Western immunoblots, respectively, in brain-injured animals treated with fluoxetine. To determine if fluoxetine improves neurological outcomes after TBI, gait function and spatial learning and memory were assessed by the CatWalk-assisted gait test and Barnes maze test, respectively. No differences in these parameters were seen between fluoxetine- and vehicle-treated animals. Thus while fluoxetine enhanced neuroplasticity in the hippocampus after TBI, its chronic administration did not restore locomotor function or ameliorate memory deficits. PMID:21175261

Cognitive disorder and changes in cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury

Institute of Scientific and Technical Information of China (English)

Weiliang Zhao; Dezhi Kang; Yuanxiang Lin

2008-01-01

BACKGROUND: Learning and memory damage is one of the most permanent and the severest symptoms of traumatic brain injury; it can seriously influence the normal life and work of patients. Some research has demonstrated that cognitive disorder is closely related to nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor. OBJECTIVE: To summarize the cognitive disorder and changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury. RETRIEVAL STRATEGY: A computer-based online search was conducted in PUBMED for English language publications containing the key words "brain injured, cognitive handicap, acetylcholine, N-methyl-D aspartate receptors, neural cell adhesion molecule, brain-derived neurotrophic factor" from January 2000 to December 2007. There were 44 papers in total. Inclusion criteria: ① articles about changes in nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor following brain injury; ② articles in the same researching circle published in authoritative journals or recently published. Exclusion criteria: duplicated articles.LITERATURE EVALUATION: References were mainly derived from research on changes in these four factors following brain injury. The 20 included papers were clinical or basic experimental studies. DATA SYNTHESIS: After craniocerebral injury, changes in these four factors in brain were similar to those during recovery from cognitive disorder, to a certain degree. Some data have indicated that activation of nicotine cholinergic receptors, N-methyl-D aspartate receptors, neural cell adhesion molecule, and brain-derived neurotrophic factor could greatly improve cognitive disorder following brain injury. However, there are still a lot of questions remaining; for example, how do these

Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

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Couraud Pierre-Olivier

2009-07-01

Full Text Available Abstract Background The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BKCa channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BKCa channels in breast cancer metastasis and invasion. Methods We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BKCa channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A, non-metastatic breast cancer (MCF-7, non-brain metastatic breast cancer cells (MDA-MB-231, and brain-specific metastatic breast cancer cells (MDA-MB-361 to study whether BKCa channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX. Results The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BKCa channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Conclusion Determining the relative abundance of BKCa channel expression in breast

Role of KCNMA1 gene in breast cancer invasion and metastasis to brain

International Nuclear Information System (INIS)

Khaitan, Divya; Sankpal, Umesh T; Weksler, Babette; Meister, Edward A; Romero, Ignacio A; Couraud, Pierre-Olivier; Ningaraj, Nagendra S

2009-01-01

The prognosis for patients with breast tumor metastases to brain is extremely poor. Identification of prognostic molecular markers of the metastatic process is critical for designing therapeutic modalities for reducing the occurrence of metastasis. Although ubiquitously present in most human organs, large-conductance calcium- and voltage-activated potassium channel (BK Ca ) channels are significantly upregulated in breast cancer cells. In this study we investigated the role of KCNMA1 gene that encodes for the pore-forming α-subunit of BK Ca channels in breast cancer metastasis and invasion. We performed Global exon array to study the expression of KCNMA1 in metastatic breast cancer to brain, compared its expression in primary breast cancer and breast cancers metastatic to other organs, and validated the findings by RT-PCR. Immunohistochemistry was performed to study the expression and localization of BK Ca channel protein in primary and metastatic breast cancer tissues and breast cancer cell lines. We performed matrigel invasion, transendothelial migration and membrane potential assays in established lines of normal breast cells (MCF-10A), non-metastatic breast cancer (MCF-7), non-brain metastatic breast cancer cells (MDA-MB-231), and brain-specific metastatic breast cancer cells (MDA-MB-361) to study whether BK Ca channel inhibition attenuates breast tumor invasion and metastasis using KCNMA1 knockdown with siRNA and biochemical inhibition with Iberiotoxin (IBTX). The Global exon array and RT-PCR showed higher KCNMA1 expression in metastatic breast cancer in brain compared to metastatic breast cancers in other organs. Our results clearly show that metastatic breast cancer cells exhibit increased BK Ca channel activity, leading to greater invasiveness and transendothelial migration, both of which could be attenuated by blocking KCNMA1. Determining the relative abundance of BK Ca channel expression in breast cancer metastatic to brain and the mechanism of its

Increased sphingosine-1-phosphate improves muscle regeneration in acutely injured mdx mice

Science.gov (United States)

2013-01-01

Background Presently, there is no effective treatment for the lethal muscle wasting disease Duchenne muscular dystrophy (DMD). Here we show that increased sphingosine-1-phoshate (S1P) through direct injection or via the administration of the small molecule 2-acetyl-4(5)-tetrahydroxybutyl imidazole (THI), an S1P lyase inhibitor, has beneficial effects in acutely injured dystrophic muscles of mdx mice. Methods We treated mdx mice with and without acute injury and characterized the histopathological and functional effects of increasing S1P levels. We also tested exogenous and direct administration of S1P on mdx muscles to examine the molecular pathways under which S1P promotes regeneration in dystrophic muscles. Results Short-term treatment with THI significantly increased muscle fiber size and extensor digitorum longus (EDL) muscle specific force in acutely injured mdx limb muscles. In addition, the accumulation of fibrosis and fat deposition, hallmarks of DMD pathology and impaired muscle regeneration, were lower in the injured muscles of THI-treated mdx mice. Furthermore, increased muscle force was observed in uninjured EDL muscles with a longer-term treatment of THI. Such regenerative effects were linked to the response of myogenic cells, since intramuscular injection of S1P increased the number of Myf5nlacz/+ positive myogenic cells and newly regenerated myofibers in injured mdx muscles. Intramuscular injection of biotinylated-S1P localized to muscle fibers, including newly regenerated fibers, which also stained positive for S1P receptor 1 (S1PR1). Importantly, plasma membrane and perinuclear localization of phosphorylated S1PR1 was observed in regenerating muscle fibers of mdx muscles. Intramuscular increases of S1P levels, S1PR1 and phosphorylated ribosomal protein S6 (P-rpS6), and elevated EDL muscle specific force, suggest S1P promoted the upregulation of anabolic pathways that mediate skeletal muscle mass and function. Conclusions These data show that S1P is

Pivotal Role of Brain-Derived Neurotrophic Factor Secreted by Mesenchymal Stem Cells in Severe Intraventricular Hemorrhage in Newborn Rats.

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Ahn, So Yoon; Chang, Yun Sil; Sung, Dong Kyung; Sung, Se In; Ahn, Jee-Yin; Park, Won Soon

2017-01-24

Mesenchymal stem cell (MSC) transplantation protects against neonatal severe intraventricular hemorrhage (IVH)-induced brain injury by a paracrine rather than regenerative mechanism; however, the paracrine factors involved and their roles have not yet been delineated. This study aimed to identify the paracrine mediator(s) and to determine their role in mediating the therapeutic effects of MSCs in severe IVH. We first identified significant upregulation of brain-derived neurotrophic factor (BDNF) in MSCs compared with fibroblasts, in both DNA and antibody microarrays, after thrombin exposure. We then knocked down BDNF in MSCs by transfection with small interfering (si)RNA specific for human BDNF. The therapeutic effects of MSCs with or without BDNF knockdown were evaluated in vitro in rat neuronal cells challenged with thrombin, and in vivo in newborn Sprague-Dawley rats by injecting 200 μl of blood on postnatal day 4 (P4), and transplanting MSCs (1 × 105 cells) intraventricularly on P6. siRNA-induced BDNF knockdown abolished the in vitro benefits of MSCs on thrombin-induced neuronal cell death. BDNF knockdown also abolished the in vivo protective effects against severe IVH-induced brain injuries such as the attenuation of posthemorrhagic hydrocephalus, impaired behavioral test performance, increased astrogliosis, increased number of TUNEL cells, ED-1+ cells, and inflammatory cytokines, and reduced myelin basic protein expression. Our data indicate that BDNF secreted by transplanted MSCs is one of the critical paracrine factors that play a seminal role in attenuating severe IVH-induced brain injuries in newborn rats.

Return to work and quality of life in severely injured patients

NARCIS (Netherlands)

Post, R. B.; Van der Sluis, C. K.; Ten Duis, H. J.

2006-01-01

Background. Little is known about the long-term consequences of severe injuries in terms of return to productivity and quality of life. Methods. In this study we focused on the return to work status and quality of life in 53 severely injured patients (AIS/ISS >= 16, mean ISS 24, range 16 - 54), mean

Return to work and quality of life in severely injured patients

NARCIS (Netherlands)

Post, R. B.; Van der Sluis, C. K.; Ten Duis, H. J.

Background. Little is known about the long-term consequences of severe injuries in terms of return to productivity and quality of life. Methods. In this study we focused on the return to work status and quality of life in 53 severely injured patients (AIS/ISS >= 16, mean ISS 24, range 16 - 54), mean

Injured workers’ perception of loss and gain in the return to work process

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Lai HS

2017-02-01

Full Text Available Hon Sun Lai,1,2 Grace PY Szeto,1 Chetwyn CH Chan3 1Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, 2Total Rehabilitation Management (Hong Kong Limited, 3Applied Cognitive Neuroscience Laboratory, Department of Rehabilitation Sciences, The Hong Kong Polytechnic University, Hong Kong Abstract: When a worker is injured at work, he has to face a tough decision-making process about when and how to return to work (RTW. This study tests how the prospect theory can be applied to influence the injured workers’ perceptions about this important choice. One hundred forty-one injured workers were presented with wage- and pain-related information in four different message framing (negatively or positively and precision (smaller or larger number conditions. After exposure to the specific combination of this wage and pain information, the participants were asked to express intentions to RTW in terms of perceived chance, confidence, and anticipated sick leave duration. When asked to predict their RTW outcome, 101 participants (72.3% responded favorably, whereas only 40 (27.7% indicated an expectation for staying on sick leave. The present results did not show significant differences in the participants’ responses to the positively and negatively framed information about wage and pain. However, it was noted that the control group that was presented with positive framing for both “wage” and “pain” information showed higher scores in expectation and confidence for RTW, whereas the Ambivalent Group that had both negative messages showed lower scores. Seventy-nine participants who had ≥60% perceived improvement in condition were selected for further analysis, and those who were presented with “wage loss” information rated significantly higher perceived chance of RTW than those in the “pain gain” group. More in-depth investigation is warranted on this topic, with a larger sample of injured workers to investigate the

The Relationship between Perceived Sleep Quality, Polysomnographic Measures and Depressive Symptoms in Chemically-Injured Veterans: A Pilot Study

OpenAIRE

Moshkani Farahani, Davood; Tavallaie, Abbas; Vahedi, Ensieh; Rezaiemaram, Peyman; Naderi, Zohreh; Talaie, Akram

2014-01-01

Objective Sleep complaints are common among Iranian chemically-injured veterans. The growing body of research has investigated (in) equalities between such subjective complaints and objective sleep records. Moreover, sleep complaints are associated with depressive symptoms. Depressive symptoms, also, have been frequently reported in chemically-injured veterans. Therefore, the purpose of this pilot study was to investigate the relationship between perceived sleep quality, polysomnographic meas...

Effect of dietary poly unsaturated fatty acids on total brain lipid concentration and anxiety levels of electron beam irradiated mice

International Nuclear Information System (INIS)

Suchetha Kumari; Bekal, Mahesh

2013-01-01

The whole brain irradiation causes injury to the nervous system at various levels. Omega-3 poly unsaturated fatty acids are very much essential for the growth and development of nervous system. Dietary supplementation of these nutrients will promote the development of injured neuronal cells. Therefore this study was undertaken to establish the role of Omega-3 poly unsaturated fatty acids on total brain lipid concentration, lipid peroxidation and anxiety levels in the irradiated mice. The effect of Electron Beam Radiation (EBR) on total brain lipid concentration, lipid peroxidation and anxiety level were investigated in male Swiss albino mice. The study groups were subjected to a sub-lethal dose of EBR and also the flax seed extract and fish oil were given orally to the irradiated mice. Irradiated groups show significant elevation in anxiety levels when compared to control group, indicating the acute radiation effects on the central nervous system. But the oral supplementation of dietary PUFA source decrees the anxiety level in the irradiated group. The analysis of lipid peroxidation showed a significant level of changes when compared between control and radiation groups. Dietary PUFA supplementation showed a significant level of decrease in the lipid peroxidation in the irradiated groups. The observation of total lipids in brain shows decrease in concentration in the irradiated groups, the differences in the variables follow the similar patterns as of that the MDA levels. This study suggests that the dietary intake of PUFAs may help in prevention and recovery of the oxidative stress caused by radiation. (author)

Bone marrow stem cells delivered into the subarachnoid space via cisterna magna improve repair of injured rat spinal cord white matter

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Marcol, Wiesław; Slusarczyk, Wojciech; Sieroń, Aleksander L; Koryciak-Komarska, Halina; Lewin-Kowalik, Joanna

2015-01-01

The influence of bone marrow stem cells on regeneration of spinal cord in rats was investigated. Young adult male Wistar rats were used (n=22). Focal injury of spinal cord white matter at Th10 level was produced using our original non-laminectomy method by means of high-pressured air stream. Cells from tibial and femoral bone marrow of 1-month old rats (n=3) were cultured, labeled with BrdU/Hoechst and injected into cisterna magna (experimental group) three times: immediately after spinal cord injury and 3 as well as 7 days later. Neurons in brain stem and motor cortex were labeled with FluoroGold (FG) delivered caudally from the injury site a week before the end of experiment. Functional outcome and morphological features of regeneration were analyzed during 12-week follow-up. The lesions were characterized by means of MRI. Maximal distance of expansion of implanted cells in the spinal cord was measured and the number of FG-positive neurons in the brain was counted. Rats treated with stem cells presented significant improvement of locomotor performance and spinal cord morphology when compared to the control group. Distance covered by stem cells was 7 mm from the epicenter of the injury. Number of brain stem and motor cortex FG-positive neurons in experimental group was significantly higher than in control. Obtained data showed that bone marrow stem cells are able to induce the repair of injured spinal cord white matter. The route of cells application via cisterna magna appeared to be useful for their delivery in spinal cord injury therapy. PMID:26628950

Supervisor Autonomy and Considerate Leadership Style are Associated with Supervisors’ Likelihood to Accommodate Back Injured Workers

Science.gov (United States)

McGuire, Connor; Kristman, Vicki L; Williams-Whitt, Kelly; Reguly, Paula; Shaw, William; Soklaridis, Sophie

2015-01-01

PURPOSE To determine the association between supervisors’ leadership style and autonomy and supervisors’ likelihood of supporting job accommodations for back-injured workers. METHODS A cross-sectional study of supervisors from Canadian and US employers was conducted using a web-based, self-report questionnaire that included a case vignette of a back-injured worker. Autonomy and two dimensions of leadership style (considerate and initiating structure) were included as exposures. The outcome, supervisors’ likeliness to support job accommodation, was measured with the Job Accommodation Scale. We conducted univariate analyses of all variables and bivariate analyses of the JAS score with each exposure and potential confounding factor. We used multivariable generalized linear models to control for confounding factors. RESULTS A total of 796 supervisors participated. Considerate leadership style (β= .012; 95% CI: .009–.016) and autonomy (β= .066; 95% CI: .025–.11) were positively associated with supervisors’ likelihood to accommodate after adjusting for appropriate confounding factors. An initiating structure leadership style was not significantly associated with supervisors’ likelihood to accommodate (β = .0018; 95% CI: −.0026–.0061) after adjusting for appropriate confounders. CONCLUSIONS Autonomy and a considerate leadership style were positively associated with supervisors’ likelihood to accommodate a back-injured worker. Providing supervisors with more autonomy over decisions of accommodation and developing their considerate leadership style may aid in increasing work accommodation for back-injured workers and preventing prolonged work disability. PMID:25595332

Does brain injury impair speech and gesture differently?

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Tilbe Göksun

2016-09-01

Full Text Available People often use spontaneous gestures when talking about space, such as when giving directions. In a recent study from our lab, we examined whether focal brain-injured individuals’ naming motion event components of manner and path (represented in English by verbs and prepositions, respectively are impaired selectively, and whether gestures compensate for impairment in speech. Left or right hemisphere damaged patients and elderly control participants were asked to describe motion events (e.g., walking around depicted in brief videos. Results suggest that producing verbs and prepositions can be separately impaired in the left hemisphere and gesture production compensates for naming impairments when damage involves specific areas in the left temporal cortex.

The relationship of Chlamydophila pneumoniae with schizophrenia: The role of brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) in this relationship

OpenAIRE

Kalayci, Fatma; Ozdemir, Armagan; Saribas, Suat; Yuksel, Pelin; Ergin, Sevgi; Mert Kuskucu, Ali; Aksoy Poyraz, Cana; Balcioglu, Ibrahim; Alpay, Nihat; Kurt, Aykut; Sezgin, Zeynep; Tufan Kocak, Banu; Sucu Icel, Rana; Can, Gunay; Bahar Tokman, Hrisi

2017-01-01

Several pathogens have been suspected of playing a role in the pathogenesis of schizophrenia. Chronic inflammation has been proposed to occur as a result of persistent infection caused by Chlamydophila pneumoniae cells that reside in brain endothelial cells for many years. It was recently hypothesized that brain-derived neurotrophic factor (BDNF) and neurotrophin-3 (NT-3) may play prominent roles in the development of schizophrenia. NT-3 and BDNF levels have been suggested to change in respon...

Blood borne hormones in a cross-talk between peripheral and brain mechanisms regulating blood pressure, the role of circumventricular organs.

Science.gov (United States)

Ufnal, Marcin; Skrzypecki, Janusz

2014-04-01

Accumulating evidence suggests that blood borne hormones modulate brain mechanisms regulating blood pressure. This appears to be mediated by the circumventricular organs which are located in the walls of the brain ventricular system and lack the blood-brain barrier. Recent evidence shows that neurons of the circumventricular organs express receptors for the majority of cardiovascular hormones. Intracerebroventricular infusions of hormones and their antagonists is one approach to evaluate the influence of blood borne hormones on the neural mechanisms regulating arterial blood pressure. Interestingly, there is no clear correlation between peripheral and central effects of cardiovascular hormones. For example, angiotensin II increases blood pressure acting peripherally and centrally, whereas peripherally acting pressor catecholamines decrease blood pressure when infused intracerebroventricularly. The physiological role of such dual hemodynamic responses has not yet been clarified. In the paper we review studies on hemodynamic effects of catecholamines, neuropeptide Y, angiotensin II, aldosterone, natriuretic peptides, endothelins, histamine and bradykinin in the context of their role in a cross-talk between peripheral and brain mechanisms involved in the regulation of arterial blood pressure. Copyright © 2014 Elsevier Ltd. All rights reserved.

Curcumin plays neuroprotective roles against traumatic brain injury partly via Nrf2 signaling.

Science.gov (United States)

Dong, Wenwen; Yang, Bei; Wang, Linlin; Li, Bingxuan; Guo, Xiangshen; Zhang, Miao; Jiang, Zhenfei; Fu, Jingqi; Pi, Jingbo; Guan, Dawei; Zhao, Rui

2018-05-01

Traumatic brain injury (TBI), which leads to high mortality and morbidity, is a prominent public health problem worldwide with no effective treatment. Curcumin has been shown to be beneficial for neuroprotection in vivo and in vitro, but the underlying mechanism remains unclear. This study determined whether the neuroprotective role of curcumin in mouse TBI is dependent on the NF-E2-related factor (Nrf2) pathway. The Feeney weight-drop contusion model was used to mimic TBI. Curcumin was administered intraperitoneally 15 min after TBI induction, and brains were collected at 24 h after TBI. The levels of Nrf2 and its downstream genes (Hmox-1, Nqo1, Gclm, and Gclc) were detected by Western blot and qRT-PCR at 24 h after TBI. In addition, edema, oxidative damage, cell apoptosis and inflammatory reactions were evaluated in wild type (WT) and Nrf2-knockout (Nrf2-KO) mice to explore the role of Nrf2 signaling after curcumin treatment. In wild type mice, curcumin treatment resulted in reduced ipsilateral cortex injury, neutrophil infiltration, and microglia activation, improving neuron survival against TBI-induced apoptosis and degeneration. These effects were accompanied by increased expression and nuclear translocation of Nrf2, and enhanced expression of antioxidant enzymes. However, Nrf2 deletion attenuated the neuroprotective effects of curcumin in Nrf2-KO mice after TBI. These findings demonstrated that curcumin effects on TBI are associated with the activation the Nrf2 pathway, providing novel insights into the neuroprotective role of Nrf2 and the potential therapeutic use of curcumin for TBI. Copyright © 2018. Published by Elsevier Inc.

Highlighting the Structure-Function Relationship of the Brain with the Ising Model and Graph Theory

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T. K. Das

2014-01-01

Full Text Available With the advent of neuroimaging techniques, it becomes feasible to explore the structure-function relationships in the brain. When the brain is not involved in any cognitive task or stimulated by any external output, it preserves important activities which follow well-defined spatial distribution patterns. Understanding the self-organization of the brain from its anatomical structure, it has been recently suggested to model the observed functional pattern from the structure of white matter fiber bundles. Different models which study synchronization (e.g., the Kuramoto model or global dynamics (e.g., the Ising model have shown success in capturing fundamental properties of the brain. In particular, these models can explain the competition between modularity and specialization and the need for integration in the brain. Graphing the functional and structural brain organization supports the model and can also highlight the strategy used to process and organize large amount of information traveling between the different modules. How the flow of information can be prevented or partially destroyed in pathological states, like in severe brain injured patients with disorders of consciousness or by pharmacological induction like in anaesthesia, will also help us to better understand how global or integrated behavior can emerge from local and modular interactions.

An Evolutionarily Conserved Role of Presenilin in Neuronal Protection in the Aging Drosophila Brain.

Science.gov (United States)

Kang, Jongkyun; Shin, Sarah; Perrimon, Norbert; Shen, Jie

2017-07-01

Mutations in the Presenilin genes are the major genetic cause of Alzheimer's disease. Presenilin and Nicastrin are essential components of γ-secretase, a multi-subunit protease that cleaves Type I transmembrane proteins. Genetic studies in mice previously demonstrated that conditional inactivation of Presenilin or Nicastrin in excitatory neurons of the postnatal forebrain results in memory deficits, synaptic impairment, and age-dependent neurodegeneration. The roles of Drosophila Presenilin ( Psn ) and Nicastrin ( Nct ) in the adult fly brain, however, are unknown. To knockdown (KD) Psn or Nct selectively in neurons of the adult brain, we generated multiple shRNA lines. Using a ubiquitous driver, these shRNA lines resulted in 80-90% reduction of mRNA and pupal lethality-a phenotype that is shared with Psn and Nct mutants carrying nonsense mutations. Furthermore, expression of these shRNAs in the wing disc caused notching wing phenotypes, which are also shared with Psn and Nct mutants. Similar to Nct , neuron-specific Psn KD using two independent shRNA lines led to early mortality and rough eye phenotypes, which were rescued by a fly Psn transgene. Interestingly, conditional KD (cKD) of Psn or Nct in adult neurons using the elav-Gal4 and tubulin-Gal80 ts system caused shortened lifespan, climbing defects, increases in apoptosis, and age-dependent neurodegeneration. Together, these findings demonstrate that, similar to their mammalian counterparts, Drosophila Psn and Nct are required for neuronal survival during aging and normal lifespan, highlighting an evolutionarily conserved role of Presenilin in neuronal protection in the aging brain. Copyright © 2017 by the Genetics Society of America.

Comparative analysis of cervical spine management in a subset of severe traumatic brain injury cases using computer simulation.

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Kimbroe J Carter

Full Text Available BACKGROUND: No randomized control trial to date has studied the use of cervical spine management strategies in cases of severe traumatic brain injury (TBI at risk for cervical spine instability solely due to damaged ligaments. A computer algorithm is used to decide between four cervical spine management strategies. A model assumption is that the emergency room evaluation shows no spinal deficit and a computerized tomogram of the cervical spine excludes the possibility of fracture of cervical vertebrae. The study's goal is to determine cervical spine management strategies that maximize brain injury functional survival while minimizing quadriplegia. METHODS/FINDINGS: The severity of TBI is categorized as unstable, high risk and stable based on intracranial hypertension, hypoxemia, hypotension, early ventilator associated pneumonia, admission Glasgow Coma Scale (GCS and age. Complications resulting from cervical spine management are simulated using three decision trees. Each case starts with an amount of primary and secondary brain injury and ends as a functional survivor, severely brain injured, quadriplegic or dead. Cervical spine instability is studied with one-way and two-way sensitivity analyses providing rankings of cervical spine management strategies for probabilities of management complications based on QALYs. Early collar removal received more QALYs than the alternative strategies in most arrangements of these comparisons. A limitation of the model is the absence of testing against an independent data set. CONCLUSIONS: When clinical logic and components of cervical spine management are systematically altered, changes that improve health outcomes are identified. In the absence of controlled clinical studies, the results of this comparative computer assessment show that early collar removal is preferred over a wide range of realistic inputs for this subset of traumatic brain injury. Future research is needed on identifying factors in

Brain-lung crosstalk in critical care: how protective mechanical ventilation can affect the brain homeostasis.

Science.gov (United States)

Mazzeo, A T; Fanelli, V; Mascia, L

2013-03-01

The maintenance of brain homeostasis against multiple internal and external challenges occurring during the acute phase of acute brain injury may be influenced by critical care management, especially in its respiratory, hemodynamic and metabolic components. The occurrence of acute lung injury represents the most frequent extracranial complication after brain injury and deserves special attention in daily practice as optimal ventilatory strategy for patients with acute brain and lung injury are potentially in conflict. Protecting the lung while protecting the brain is thus a new target in the modern neurointensive care. This article discusses the essentials of brain-lung crosstalk and focuses on how mechanical ventilation may exert an active role in the process of maintaining or treatening brain homeostasis after acute brain injury, highlighting the following points: 1) the role of inflammation as common pathomechanism of both acute lung and brain injury; 2) the recognition of ventilatory induced lung injury as determinant of systemic inflammation affecting distal organs, included the brain; 3) the possible implication of protective mechanical ventilation strategy on the patient with an acute brain injury as an undiscovered area of research in both experimental and clinical settings.

Correlation of glucose metabolism in brain cells and brain morphological changes with clinical typing in children with cerebral palsy

Institute of Scientific and Technical Information of China (English)

Qiongxiang Zhai; Huixian Qiao; Jiqing Liu

2006-01-01

BACKGROUND:It is widely known that fluorino-18-fluorodeoxyglucose positron emission tomography(18F-FDG PET)is commonly used to evaluate and diagnose epilepsy;however,whether it is beneficial to understand functional metabolism of bra in cells so as to reflect injured site and degree of brain cells or not should be studied further.OBJECTIVE:To evaluate the correlation between glucose metabolism and clinical typling as well as the conelation between active function of brain cells and degree of brain injury among children with cerbral palsy with 18F-FDG PET and MRI and compare the results of them.DESIGN:Case analysis.SETTING:Department of Pediatrics,People's Hospital of Guangdong Province.PARTICIPANTS:A total of 31 children with cerebral palsy were selected from Out-patient Clinic and In-patient Department of People's Hospital of Guangdong Province from July 2001 to August 2004.Based on clinical criteria of cerebral palsy,patients were classified into spasm(n=10),gradual movement(n=4),mixed type(n =13)and ataxia(n=4).There were 18 boys and 13 girls aged from 10 months to 4 years.All of them were met the diagnostic criteria of cerebral palsy and all parents of them were told the facts.Exclusion cdteria:Patients who had cerebral palsy caused by genetic metabolism disease were excluded.METHODS:①All children accepted MRI examination after hospitalization with Philips Acs NT 15T superconductling magnetic resonance scanner.②All children were fasted for 4 hours.And then,PET image of brain was collected based on T+EID type.If obvious hypermetabolism or hypometabolism region successively occurred on two layers, the image was regarded as abnormality. ③Different correlations of various abnormal greups of MRI and vadous types of cerebral palsy with PET image were compared and analyzed with Erusal-Willas rank sum test.MAIN OUTCOME MEASURES:①Results of 18F-FDG PET;②Results of MRI examination;③Correlation of variously abnormal groups of MRI and various types of cerebral

HGF mediates the anti-inflammatory effects of PRP on injured tendons.

Directory of Open Access Journals (Sweden)

Jianying Zhang

Full Text Available Platelet-rich plasma (PRP containing hepatocyte growth factor (HGF and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2.

HGF Mediates the Anti-inflammatory Effects of PRP on Injured Tendons

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Zhang, Jianying; Middleton, Kellie K.; Fu, Freddie H.; Im, Hee-Jeong; Wang, James H-C.

2013-01-01

Platelet-rich plasma (PRP) containing hepatocyte growth factor (HGF) and other growth factors are widely used in orthopaedic/sports medicine to repair injured tendons. While PRP treatment is reported to decrease pain in patients with tendon injury, the mechanism of this effect is not clear. Tendon pain is often associated with tendon inflammation, and HGF is known to protect tissues from inflammatory damages. Therefore, we hypothesized that HGF in PRP causes the anti-inflammatory effects. To test this hypothesis, we performed in vitro experiments on rabbit tendon cells and in vivo experiments on a mouse Achilles tendon injury model. We found that addition of PRP or HGF decreased gene expression of COX-1, COX-2, and mPGES-1, induced by the treatment of tendon cells in vitro with IL-1β. Further, the treatment of tendon cell cultures with HGF antibodies reduced the suppressive effects of PRP or HGF on IL-1β-induced COX-1, COX-2, and mPGES-1 gene expressions. Treatment with PRP or HGF almost completely blocked the cellular production of PGE2 and the expression of COX proteins. Finally, injection of PRP or HGF into wounded mouse Achilles tendons in vivo decreased PGE2 production in the tendinous tissues. Injection of platelet-poor plasma (PPP) however, did not reduce PGE2 levels in the wounded tendons, but the injection of HGF antibody inhibited the effects of PRP and HGF. Further, injection of PRP or HGF also decreased COX-1 and COX-2 proteins. These results indicate that PRP exerts anti-inflammatory effects on injured tendons through HGF. This study provides basic scientific evidence to support the use of PRP to treat injured tendons because PRP can reduce inflammation and thereby reduce the associated pain caused by high levels of PGE2. PMID:23840657

Testosterone in the brain: neuroimaging findings and the potential role for neuropsychopharmacology.

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Höfer, Peter; Lanzenberger, Rupert; Kasper, Siegfried

2013-02-01

Testosterone plays a substantial role in a number of physiological processes in the brain. It is able to modulate the expression of certain genes by binding to androgen receptors. Acting via neurotransmitter receptors, testosterone shows the potential to mediate a non-genomic so-called "neuroactive effect". Various neurotransmitter systems are also influenced by the aromatized form of testosterone, estradiol. The following article summarizes the findings of preclinical and clinical neuroimaging studies including structural and functional magnetic resonance imaging (MRI/fMRI), voxel based morphometry (VBM), as well as pharmacological fMRI (phfMRI) and positron emission tomography (PET) regarding the effects of testosterone on the human brain. The impact of testosterone on the pathogenesis of psychiatric disorders and on sex-related prevalence differences have been supported by a wide range of clinical studies. An antidepressant effect of testosterone can be implicitly explained by its effects on the limbic system--especially amygdala, a major target in the treatment of depression--solidly demonstrated by a large body of neuroimaging findings. Copyright © 2012 Elsevier B.V. and ECNP. All rights reserved.

Electrical stimulation enhanced remyelination of injured sciatic nerves by increasing neurotrophins.

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Wan, L D; Xia, R; Ding, W L

2010-09-01

Previous studies have demonstrated that electrical stimulation (ES) enhances axonal regeneration following central and peripheral nerve injury. However, the effect of ES on peripheral remyelination after nerve damage has been investigated less, and the mechanism underlying its action remains unclear. In the present study, neuron/Schwann cell (SC) co-cultures in vitro and crush-injured sciatic nerves in rats were subjected to 1 h of continuous ES (20 Hz, 100 micros, 3 V). Electron microscopy and nerve morphometry were performed to investigate the extent of regenerated nerve myelination. The expression profiles of P0, Par-3 and brain-derived neurotrophic factor (BDNF) in vitro and in vivo were examined by western blotting. We reported that 20 Hz ES increased the number of regenerated and myelinated axons at 4 and 8 weeks after injury. P0 level in the ES-treated groups, as well as myelin sheath thickness, were enhanced compared with the controls. The earlier peak Par-3 in the ES-treated groups indicated earlier initiation of SC myelination. Moreover, the similar results were achieved in the cell co-culture. Additionally, brief ES significantly elevated BDNF expression in co-cultured cells and nerve tissues. In conclusion, ES of the site of nerve injury potentiates axonal regrowth and myelin maturation during peripheral nerve regeneration. Further, the therapeutic actions of ES on myelination that is mediated via enhanced BDNF signals, which driving the promyelination effect on SCs at the onset of myelination. Copyright (c) 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

Crosstalk Between Activated Myofibroblasts and β Cells in Injured Mouse Pancreas.

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Bayan, Jennifer-Ann; Peng, Zhechu; Zeng, Ni; He, Lina; Chen, Jingyu; Stiles, Bangyan L

2015-10-01

In injury conditions, myofibroblasts are induced to lay down matrix proteins and support the repair process. In this study, we investigated the role of myofibroblasts, particularly stellate cells, in the growth and regeneration of pancreatic β cells. We used both in vitro and in vivo approaches to address whether stellate cells may promote the growth of β cells. Our experiments demonstrated that activated stellate cells support the proliferation of β cells in vitro. In vivo, mesenchymals surrounding the pancreatic islets are activated (induced to proliferate) in the islet regeneration model of Pten null mice. These mesenchymals display markers of pancreatic stellate cells, such as desmin and to a lesser extent, smooth muscle actin α. We have shown previously that targeted β-cell deletion of Pten lead to a significant increase in total islet mass. This phenotype was accompanied by an increase in peri-islet mitotic activity, particularly in islets injured by streptozotocin, a β cell-specific toxin. Together with the in vitro observations, our data, here, suggest that that these mesenchymal cells may support the regeneration of the islets. Identifying how the communication occurs may provide clinically relevant mechanism for inducing β-cell regeneration.

Organisation and functional role of the brain angiotensin system

OpenAIRE

Catherine Llorens-Cortes; Frederic AO Mendelsohn

2002-01-01

The discovery that all components of the renin-angiotensin system (RAS) are present in the brain led investigators to postulate the existence of a local brain RAS. Supporting this, angiotensin immunoreactive neurones have been visualised in the brain. Two major pathways were described: a forebrain pathway which connects circumventricular organs to the median preoptic nucleus, paraventricular and supraoptic nuclei, and a second pathway connecting the hypothalamus to the medulla oblongata. Bloo...

Pivotal role of anterior cingulate cortex in working memory after traumatic brain injury in youth

Directory of Open Access Journals (Sweden)

Fabienne eCazalis

2011-01-01

Full Text Available In this fMRI study, the functions of the Anterior Cingulate Cortex were studied in a group of adolescents who had sustained a moderate to severe Traumatic Brain Injury. A spatial working memory task with varying working memory loads, representing experimental conditions of increasing difficulty, was administered.In a cross-sectional comparison between the patients and a matched control group, patients performed worse than Controls, showing longer reaction times and lower response accuracy on the spatial working memory task. Brain imaging findings suggest a possible double-dissociation: activity of the Anterior Cingulate Cortex in the Traumatic Brain Injury group, but not in the Control group, was associated with task difficulty; conversely, activity of the left Sensorimotor Cortex in the Control group, but not in the TBI group, was correlated with task difficulty.In addition to the main cross-sectional study, a longitudinal study of a group of adolescent patients with moderate to severe Traumatic Brain Injury was done using fMRI and the same spatial working memory task. The patient group was studied at two time points: one time point during the post-acute phase and one time point 12 months later, during the chronic phase. Results indicated that patients' behavioral performance improved over time, suggesting cognitive recovery. Brain imaging findings suggest that, over this 12 month period, patients recruited less of the Anterior Cingulate Cortex and more of the left Sensorimotor Cortex in response to increasing task difficulty.The role of Anterior Cingulate Cortex in executive functions following a moderate to severe brain injury in adolescence is discussed within the context of conflicting models of the Anterior Cingulate Cortex functions in the existing literature.

Brain Mapping of Ghrelin O-Acyltransferase in Goldfish (Carassius Auratus): Novel Roles for the Ghrelinergic System in Fish?

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Blanco, Ayelén M; Sánchez-Bretaño, Aída; Delgado, María J; Valenciano, Ana I

2016-06-01

Ghrelin O-acyltransferase (GOAT) is the enzyme responsible for acylation of ghrelin, a gut-brain hormone with important roles in many physiological functions in vertebrates. Many aspects of GOAT remain to be elucidated, especially in fish, and particularly its anatomical distribution within the different brain areas has never been reported to date. The present study aimed to characterize the brain mapping of GOAT using RT-qPCR and immunohistochemistry in a teleost, the goldfish (Carassius auratus). Results show that goat transcripts are expressed in different brain areas of the goldfish, with the highest levels in the vagal lobe. Using immunohistochemistry, we also report the presence of GOAT immunoreactive cells in different encephalic areas, including the telencephalon, some hypothalamic nuclei, pineal gland, optic tectum and cerebellum, although they are especially abundant in the hindbrain. Particularly, an important signal is observed in the vagal lobe and some fiber tracts of the brainstem, such as the medial longitudinal fasciculus, Mauthneri fasciculus, secondary gustatory tract and spinothalamic tract. Most of the forebrain areas where GOAT is detected, particularly the hypothalamic nuclei, also express the ghs-r1a ghrelin receptor and other appetite-regulating hormones (e.g., orexin and NPY), supporting the role of ghrelin as a modulator of food intake and energy balance in fish. Present results are the first report on the presence of GOAT in the brain using imaging techniques. The high presence of GOAT in the hindbrain is a novelty, and point to possible new functions for the ghrelinergic system in fish. Anat Rec, 299:748-758, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Factors affecting directional migration of bone marrow mesenchymal stem cells to the injured spinal cord

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Xia, Peng; Pan, Su; Cheng, Jieping; Yang, Maoguang; Qi, Zhiping; Hou, Tingting; Yang, Xiaoyu

2014-01-01

Microtubule-associated protein 1B plays an important role in axon guidance and neuronal migration. In the present study, we sought to discover the mechanisms underlying microtubule-associated protein 1B mediation of axon guidance and neuronal migration. We exposed bone marrow mesenchymal stem cells to okadaic acid or N-acetyl-D-erythro-sphingosine (an inhibitor and stimulator, respectively, of protein phosphatase 2A) for 24 hours. The expression of the phosphorylated form of type I microtubule-associated protein 1B in the cells was greater after exposure to okadaic acid and lower after N-acetyl-D-erythro-sphingosine. We then injected the bone marrow mesenchymal stem cells through the ear vein into rabbit models of spinal cord contusion. The migration of bone marrow mesenchymal stem cells towards the injured spinal cord was poorer in cells exposed to okadaic acid- and N-acetyl-D-erythro-sphingosine than in non-treated bone marrow mesenchymal stem cells. Finally, we blocked phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase 1/2 (ERK1/2) pathways in rabbit bone marrow mesenchymal stem cells using the inhibitors LY294002 and U0126, respectively. LY294002 resulted in an elevated expression of phosphorylated type I microtubule-associated protein 1B, whereas U0126 caused a reduction in expression. The present data indicate that PI3K and ERK1/2 in bone marrow mesenchymal stem cells modulate the phosphorylation of microtubule-associated protein 1B via a cross-signaling network, and affect the migratory efficiency of bone marrow mesenchymal stem cells towards injured spinal cord. PMID:25374590

Characterization of wound infections among patients injured during the 2011 Libyan conflict.

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Dau, A A; Tloba, S; Daw, M A

2013-04-01

Few studies have analysed the bacterial pathogenesis of infections associated with war-wound in the Eastern Mediterranean region. We analysed surgical wound infections of 1200 patients injured during the Libyan conflict in 2011 and admitted to the emergency services at Tripoli medical centre. Culture swabs or surgical wound debridement samples were collected and cultures were identified and tested for antimicrobial resistance. Of the 1200 patients studied, 498 (42%) were infected with at least 1 pathogen and 57 with >2 pathogens. The most common species were Acinetobacter spp. (isolated from 144 patients), coagulase-negative staphylococci (122), Escherichia coli (107), Pseudomnonas aeruginosa (92) and Klebsiella spp. (86). A high level of resistance to the antibiotics tested was found, especially among Acinetobacter spp. Multi-drug-resistant Gram-negative bacilli were an important complicating factor in wound infections associated with war injuries among injured patients in Libya. Effective policies are needed to control and treat such infections particularly in trauma and emergency services.

Role of mTORC1 Controlling Proteostasis after Brain Ischemia

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Maria J. Perez-Alvarez

2018-02-01

Full Text Available Intense efforts are being undertaken to understand the pathophysiological mechanisms triggered after brain ischemia and to develop effective pharmacological treatments. However, the underlying molecular mechanisms are complex and not completely understood. One of the main problems is the fact that the ischemic damage is time-dependent and ranges from negligible to massive, involving different cell types such as neurons, astrocytes, microglia, endothelial cells, and some blood-derived cells (neutrophils, lymphocytes, etc.. Thus, approaching such a complicated cellular response generates a more complex combination of molecular mechanisms, in which cell death, cellular damage, stress and repair are intermixed. For this reason, animal and cellular model systems are needed in order to dissect and clarify which molecular mechanisms have to be promoted and/or blocked. Brain ischemia may be analyzed from two different perspectives: that of oxygen deprivation (hypoxic damage per se and that of deprivation of glucose/serum factors. For investigations of ischemic stroke, middle cerebral artery occlusion (MCAO is the preferred in vivo model, and uses two different approaches: transient (tMCAO, where reperfusion is permitted; or permanent (pMCAO. As a complement to this model, many laboratories expose different primary cortical neuron or neuronal cell lines to oxygen-glucose deprivation (OGD. This ex vivo model permits the analysis of the impact of hypoxic damage and the specific response of different cell types implicated in vivo, such as neurons, glia or endothelial cells. Using in vivo and neuronal OGD models, it was recently established that mTORC1 (mammalian Target of Rapamycin Complex-1, a protein complex downstream of PI3K-Akt pathway, is one of the players deregulated after ischemia and OGD. In addition, neuroprotective intervention either by estradiol or by specific AT2R agonists shows an important regulatory role for the mTORC1 activity, for

Home Health Care for California's Injured Workers: Options for Implementing a Fee Schedule.

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Wynn, Barbara O; Boustead, Anne

2015-07-15

The California Department of Industrial Relations/Division of Worker's Compensation asked RAND to provide technical assistance in developing a fee schedule for home health services provided to injured workers. The fee schedule needs to address the full spectrum of home health services ranging from skilled nursing and therapy services to unskilled personal care or chore services that may be provided by family members. RAND researchers consulted with stakeholders in the California workers' compensation system to outline issues the fee schedule should address, reviewed home health fee schedules used by other payers, and conducted interviews with WC administrators from other jurisdictions to elicit their experiences. California stakeholders identified unskilled attendant services as most problematic in determining need and payment rates, particularly services furnished by family members. RAND researchers concentrated on fee schedule options that would result in a single fee schedule covering the full range of home health care services furnished to injured workers and made three sets of recommendations. The first set pertains to obtaining additional information that would highlight the policy issues likely to occur with the implementation of the fee schedule and alternatives for assessing an injured worker's home health care needs. Another approach conforms most closely with the Labor Code requirements. It would integrate the fee schedules used by Medicare, In-Home Health Supportive Services, and the federal Office of Workers' Compensation. The third approach would base the home health fee schedule on rules used by the federal Office of Workers' Compensation.

Evaluation of bronchiectasis in war chemically-injured patients via high resolution computed tomography

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Reza Jalli

2017-12-01

Discussion and conclusion: Findings of chest HRCT demonstrated tubular bronchiectasis was the most frequent type of this disease that involve the chemically injured patients and RLL had been the most frequently involved lobe of the lung with bronchiectasis.

Pattern of Pressure Sores in Spinal Injured Patients with in the First ...

African Journals Online (AJOL)

Background: Before 2006, all our spinal injured patients were nursed on conventional form mattress without pressure redistributing support surface. Pressure sore was a common complication and was a major contributing factor to prolonged hospitalization. Aim: The aim of this study is to determine the pattern of pressure ...

Human umbilical cord blood stem cells and brain-derived neurotrophic factor for optic nerve injury: a biomechanical evaluation

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Zhong-jun Zhang

2015-01-01

Full Text Available Treatment for optic nerve injury by brain-derived neurotrophic factor or the transplantation of human umbilical cord blood stem cells has gained progress, but analysis by biomechanical indicators is rare. Rabbit models of optic nerve injury were established by a clamp. At 7 days after injury, the vitreous body received a one-time injection of 50 μg brain-derived neurotrophic factor or 1 × 10 6 human umbilical cord blood stem cells. After 30 days, the maximum load, maximum stress, maximum strain, elastic limit load, elastic limit stress, and elastic limit strain had clearly improved in rabbit models of optical nerve injury after treatment with brain-derived neurotrophic factor or human umbilical cord blood stem cells. The damage to the ultrastructure of the optic nerve had also been reduced. These findings suggest that human umbilical cord blood stem cells and brain-derived neurotrophic factor effectively repair the injured optical nerve, improve biomechanical properties, and contribute to the recovery after injury.

Ang-(1-7) exerts protective role in blood-brain barrier damage by the balance of TIMP-1/MMP-9.

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Wu, Jitao; Zhao, Duo; Wu, Shuang; Wang, Dan

2015-02-05

Cerebrovascular disease (CVD) ranks as the top three health risks, specially cerebral ischemia characterized with the damage of blood-brain barrier (BBB). The angiotensin Ang-(1-7) was proven to have a protective effect on cerebrovascular diseases. However, its role on blood-brain barrier and the underlying molecular mechanism remains unclear. In this study, Ang-(1-7) significantly relieved damage of ischemia reperfusion injury on blood-brain barrier in cerebral ischemia reperfusion injury (IRI) rats. Furthermore, its treatment attenuated BBB permeability and brain edema. Similarly, Ang-(1-7) also decreased the barrier permeability of brain endothelial cell line RBE4. Further analysis showed that Ang-(1-7) could effectively restore tight junction protein (claudin-5 and zonula occludens ZO-1) expression levels both in IRI-rats and hypoxia-induced RBE4 cells. Furthermore, Ang-(1-7) stimulation down-regulated hypoxia-induced matrix metalloproteinase-9 (MMP-9) levels, whose silencing with (matrix metalloproteinase-9 hemopexin domain) MMP9-PEX inhibitor significantly increased the expression of claudin-5 and ZO-1. Further mechanism analysis demonstrated that Ang-(1-7) might junction protein levels by tissue inhibitor of metalloproteinase 1 (TIMP1)-MMP9 pathway, because Ang-(1-7) enhanced TIMP1 expression, whose silencing obviously attenuated the inhibitor effect of Ang-(1-7) on MMP-9 levels and decreased Ang-(1-7)-triggered increase in claudin-5 and ZO-1. Together, this study demonstrated a protective role of Ang-(1-7) in IRI-induced blood-brain barrier damage by TIMP1-MMP9-regulated tight junction protein expression. Accordingly, Ang-(1-7) may become a promising therapeutic agent against IRI and its complications. Copyright © 2014 Elsevier B.V. All rights reserved.

Recent Advances on the Role of Neurogenesis in the Adult Brain: Therapeutic Potential in Parkinson's and Alzheimer's Diseases.

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Radad, Khaled; Moldzio, Rudolf; Al-Shraim, Mubarak; Kranner, Barbara; Krewenka, Christopher; Rausch, Wolf-Dieter

2017-01-01

Generation of nascent functional neurons from neural stem cells in the adult brain has recently become largely accepted by the neuroscience community. In adult mammals including humans, the process of neurogenesis has been well documented in two brain regions; the subventricular zone of the lateral ventricles and the subgranular zone in the dentate gyrus of the hippocampus. Some evidence has indicated neurogenesis in other regions of the adult mammalian brain such as the neocortex, cerebellum, striatum, amygdala and hypothalamus. These discoveries question a long standing dogma on nervous system regeneration and provide medical science with potential new strategies to harness the process of neurogenesis for treating neurological disabilities and neurodegenerative diseases. In this current review, we address the most recent advances on the role of neurogenesis in the adult brain and therapeutic potential in the two most common neurodegenerative disorders, Parkinson's and Alzheimer's diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Direct to Operating Room Trauma Resuscitation Decreases Mortality Among Severely Injured Children.

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Wieck, Minna M; Cunningham, Aaron J; Behrens, Brandon; Ohm, Erika T; Maxwell, Bryan G; Hamilton, Nicholas A; Adams, M Christopher; Cole, Frederick J; Jafri, Mubeen A

2018-03-16

Expediting evaluation and intervention for severely injured patients has remained a mainstay of advanced trauma care. One technique, direct to operating room (DOR) resuscitation, for selective adult patients has demonstrated decreased mortality. We sought to investigate the application of this protocol in children. All DOR pediatric patients from 2009-2016 at a pediatric Level I Trauma Center were identified. DOR criteria included penetrating injury, chest injuries, amputations, significant blood loss, cardiopulmonary resuscitation, and surgeon discretion. Demographics, injury patterns, interventions, and outcomes were analyzed. Observed mortality was compared to expected mortality, calculated using Trauma Injury Severity Score (TRISS) methodology, with two-tailed t-tests and a p-value 15, 33% had GCS≤8, and 9% were hypotensive. The most commonly injured body regions were external (66%), head (34%), chest (30%), and abdomen (27%). Sixty-seven patients (82%) required emergent procedural intervention, most commonly wound exploration/repair (35%), central venous access (22%), tube thoracostomy (19%) and laparotomy (18%). Predictors of intervention were ISS>15 (odds ratio=14, p=0.013) and GCS<9 (odds ratio=8.5, p=0.044). The survival rate to discharge for DOR patients was 84% compared with an expected survival of 79% (TRISS) (p=0.4). The greatest improvement relative to expected mortality was seen in the subgroup with penetrating trauma (84.5% vs. 74.4%, p=0.002). A selective policy of resuscitating the most severely injured children in the operating room can decrease mortality. Patients suffering penetrating trauma with the highest ISS and diminished GCS have the greatest benefit. Trauma centers with appropriate resources should evaluate implementing similar policies. Level II. Diagnostic tests or criteria.

Effect of bulk modulus on deformation of the brain under rotational accelerations

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Ganpule, S.; Daphalapurkar, N. P.; Cetingul, M. P.; Ramesh, K. T.

2018-01-01

Traumatic brain injury such as that developed as a consequence of blast is a complex injury with a broad range of symptoms and disabilities. Computational models of brain biomechanics hold promise for illuminating the mechanics of traumatic brain injury and for developing preventive devices. However, reliable material parameters are needed for models to be predictive. Unfortunately, the properties of human brain tissue are difficult to measure, and the bulk modulus of brain tissue in particular is not well characterized. Thus, a wide range of bulk modulus values are used in computational models of brain biomechanics, spanning up to three orders of magnitude in the differences between values. However, the sensitivity of these variations on computational predictions is not known. In this work, we study the sensitivity of a 3D computational human head model to various bulk modulus values. A subject-specific human head model was constructed from T1-weighted MRI images at 2-mm3 voxel resolution. Diffusion tensor imaging provided data on spatial distribution and orientation of axonal fiber bundles for modeling white matter anisotropy. Non-injurious, full-field brain deformations in a human volunteer were used to assess the simulated predictions. The comparison suggests that a bulk modulus value on the order of GPa gives the best agreement with experimentally measured in vivo deformations in the human brain. Further, simulations of injurious loading suggest that bulk modulus values on the order of GPa provide the closest match with the clinical findings in terms of predicated injured regions and extent of injury.

Cerebral oxygenation in contusioned vs. nonlesioned brain tissue: monitoring of PtiO2 with Licox and Paratrend.

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Sarrafzadeh, A S; Kiening, K L; Bardt, T F; Schneider, G H; Unterberg, A W; Lanksch, W R

1998-01-01

Brain tissue PO2 in severely head injured patients was monitored in parallel with two different PO2-microsensors (Licox and Paratrend). Three different locations of sensor placement were chosen: (1) both catheters into non lesioned tissue (n = 3), (2) both catheters into contusioned tissue (n = 2), and (3) one catheter (Licox) into pericontusional versus one catheter (Paratrend) into non lesioned brain tissue (n = 2). Mean duration of PtiO2-monitoring with both microsensors in parallel was 68.1 hours. Brain tissue PO2 varied when measured in lesioned and nonlesioned tissue. In non lesioned tissue both catheters closely correlated (delta Licox/Paratrend: mean PtiO2 delta lesioned/non lesioned: mean PtiO2: 10.3 mm Hg). In contusioned brain tissue PtiO2 was always below the "hypoxic threshold" of 10 mm Hg, independent of the type of microsensor used. During a critical reduction in cerebral perfusion pressure (PO2, only increased PtiO2 when measured in pericontusional and nonlesioned brain. To recognize critical episodes of hypoxia or ischemia, PtiO2-monitoring of cerebral oxygenation is recommended in nonlesioned brain tissue.

Who benefits? Outcome following a coping skills group intervention for traumatically brain injured individuals.

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Anson, Katie; Ponsford, Jennie

2006-01-01

To investigate the variables associated with positive psychological outcome following a group intervention for 33 individuals with traumatic brain injury. Evaluation study which used multiple regression analysis to examine the variables associated with change in psychological adjustment following a 10-session cognitive behaviour therapy-based group. The predictor variables were age at injury, time since injury, injury severity, self-awareness, pre-morbid intellectual function, memory function, executive function and level of depression and anxiety prior to intervention. The predictor variables contributed a significant proportion of the variance in percentage change in depression. The major finding was that better outcomes following intervention were associated with greater self-awareness of injury-related deficits. The present study identified a number of variables that were associated with improvement in depression following psychological intervention and may assist future treatment resources to be directed most effectively.

Beneficial Roles of Emotion in Decision Making: Functional Association of Brain and Body

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Hideki Ohira

2011-12-01

Full Text Available Though traditional microeconomics has supposed that human decisions are based on logical and exact computation of cost-benefit balances or efficacies, studies in behavioral economics have shown that humans sometimes make seemingly irrational decisions driven by emotions. In our everyday situations, factors related to decisions are complex and which alternative will be the most beneficial is uncertain. In such cases, emotions have been thought adaptive because they can quickly reduce negative alternatives and facilitate fast and effective decision making. Some theorists argued that one of important sources of such emotional drives affecting decision making is bodily responses that are represented in brain regions (Craig, 2009; Damasio, 1994. In this article, empirical evidence for the functional associations of the brain and body accompanying decision making will be shown as follows. (1 Heart rate responses and concentration of inflammatory cytokine (IL-6 can predict acceptance or rejection of an unfair offer in an economical negotiation game, the Ultimatum Game. Activation of the anterior insula mediates relationship between bodily states and decision making. (2 Sympathetic responses reflected by secretion of adrenaline are represented in brain regions such as the midbrain, anterior cingulate cortex, and anterior insula, and furthermore can determine exploration of decision making in a situation where an action-outcome contingency is stochastic and unstable. These findings suggest beneficial roles of emotion and bodily responses in decision making.

Muscle morphometric effect of anterior cruciate ligament injury measured by computed tomography: aspects on using non-injured leg as control

Science.gov (United States)

2013-01-01

Background Anterior cruciate ligament (ACL) tears are common, functionally disabling, and predispose to subsequent injuries and early onset of osteoarthritis in the knee. Injuries result in muscular atrophy and impaired muscular activation. To optimize surgical methods and rehabilitation strategies, knowledge of the effects of ACL injuries on muscles size and function is needed. Asymmetry due to limb dominance implies that the effect of ACL-injury might be different in right-sided and left-sided injuries which, should be taken in account when evaluating the effect of an injury. Evaluation of the effects of injuries is usually made with the contralateral leg as control. The aim of this study is to describe the effect of ACL-injuries on thigh muscle size and also to analyze feasibility of using contralateral limb as control. Methods Sixty-two patients scheduled to undergo ACL reconstruction were examined with computed tomography (CT). Muscle cross sectional area (CSA) was recorded for quadriceps, hamstrings, gracilis and sartorius 15 cm above the knee joint. Comparisons were made between the injured and non-injured side and between individuals separated by gender and side of injury. Comparisons were also made for patients with or without concomitant meniscal tear, for patients differing in time between injury and examinations and for patients with different level of physical activity after the injury. Results Quadriceps CSA was 5% smaller on the injured side. There was an indication that the muscles of the right thigh were generally bigger than those of the left thigh. The difference between the injured and the non-injured side was larger for right-sided injuries than for left-sided. There was also a greater difference in semimembranosus for women than for men. There were no differences related to meniscal injury, time since injury or physical activity. Conclusion The use of contralateral leg for evaluating the effect of ACL-injury is often the only available

Key Considerations for Using No-Harm Contracts with Clients Who Self-Injure

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Hyldahl, Rebecca S.; Richardson, Brent

2011-01-01

One of the more controversial issues in working with people who self-injure is whether counselors should use no-harm contracts. Important therapeutic considerations include the efficacy of such contracts or agreements in preventing self-injury, the emotional and behavioral responses of clients, and the perceived protection these contracts or…

Missed posterior dislocation of the hip in a head-injured patient with ...

African Journals Online (AJOL)

Background: Head injury increases the risk of missed diagnosis by making patient-derived history impossible. The risk of missing a posterior dislocation of the hip in a head-injured patient is aggravated when an ipsilateral femoral shaft fracture co-exists. Adequate radiological evaluation of bone and joints is therefore of ...

Developmental thyroid hormone insufficiency and brain development: A role for brain-derived neurotrophic factor (BDNF)?*

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Thyroid hormones (TH) are essential for normal brain development. Even subclinical hypothyroidism experienced in utero can result in neuropsychological deficits in children despite normal thyroid status at birth. Neurotrophins have been implicated in a host of brain cellular func...

Murine cytomegalovirus infection of neural stem cells alters neurogenesis in the developing brain.

Directory of Open Access Journals (Sweden)

Manohar B Mutnal

2011-01-01

Full Text Available Congenital cytomegalovirus (CMV brain infection causes serious neuro-developmental sequelae including: mental retardation, cerebral palsy, and sensorineural hearing loss. But, the mechanisms of injury and pathogenesis to the fetal brain are not completely understood. The present study addresses potential pathogenic mechanisms by which this virus injures the CNS using a neonatal mouse model that mirrors congenital brain infection. This investigation focused on, analysis of cell types infected with mouse cytomegalovirus (MCMV and the pattern of injury to the developing brain.We used our MCMV infection model and a multi-color flow cytometry approach to quantify the effect of viral infection on the developing brain, identifying specific target cells and the consequent effect on neurogenesis. In this study, we show that neural stem cells (NSCs and neuronal precursor cells are the principal target cells for MCMV in the developing brain. In addition, viral infection was demonstrated to cause a loss of NSCs expressing CD133 and nestin. We also showed that infection of neonates leads to subsequent abnormal brain development as indicated by loss of CD24(hi cells that incorporated BrdU. This neonatal brain infection was also associated with altered expression of Oct4, a multipotency marker; as well as down regulation of the neurotrophins BDNF and NT3, which are essential to regulate the birth and differentiation of neurons during normal brain development. Finally, we report decreased expression of doublecortin, a marker to identify young neurons, following viral brain infection.MCMV brain infection of newborn mice causes significant loss of NSCs, decreased proliferation of neuronal precursor cells, and marked loss of young neurons.

Distribution of the amelogenin protein in developing, injured and carious human teeth

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Thimios eMitsiadis

2014-12-01

Full Text Available Amelogenin is the major enamel matrix protein with key roles in amelogenesis. Although for many decades amelogenin was considered to be exclusively expressed by ameloblasts, more recent studies have shown that amelogenin is also expressed in other dental and no-dental cells. However, amelogenin expression in human tissues remains unclear. Here, we show that amelogenin protein is not only expressed during human embryonic development but also in pathological conditions such as carious lesions and injuries after dental cavity preparation. In developing embryonic teeth, amelogenin stage-specific expression is found in all dental epithelia cell populations but with different instensities. In the different layers of enamel matrix, waves of positive versus negative immunostaining for amelogenin are detected suggesting that the secretion of amelogenin protein is orchestreted by a biological clock. Amelogenin is also expressed transiently in differentiating odontoblasts during predentin formation, but was absent in mature functional odontoblasts. In intact adult teeth, amelogenin was not present in dental pulp, odontoblasts, and dentin. However, in injured and carious adult human teeth amelogenin is strongly re-expressed in newly differentiated odontoblasts and is distributed in the dentinal tubuli under the lesion site. In an in vitro culture system, amelogenin is expressed preferentially in human dental pulp cells that start differentiating into odontoblast-like cells and form mineralization nodules. These data suggest that amelogenin plays important roles not only during cytodifferentiation, but also during tooth repair processes in humans.

Endogenous IL-6 of mesenchymal stem cell improves behavioral outcome of hypoxic-ischemic brain damage neonatal rats by supressing apoptosis in astrocyte.

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