Expression and Localization of TRK-Fused Gene Products in the Rat Brain and Retina

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Maebayashi, Hisae; Takeuchi, Shigako; Masuda, Chiaki; Makino, Satoshi; Fukui, Kenji; Kimura, Hiroshi; Tooyama, Ikuo

2012-01-01

The TRK-fused gene (TFG in human, Tfg in rat) was originally identified in human papillary thyroid cancer as a chimeric form of the NTRK1 gene. It has been reported that the gene product (TFG) plays a role in regulating phosphotyrosine-specific phosphatase-1 activity. However, no information regarding the localization of Tfg in rat tissues is available. In this study, we investigated the expression of Tfg mRNA in normal rat tissues using reverse transcription-polymerase chain reaction (RT-PCR). We also produced an antibody against Tfg gene products and examined the localization of TFG in the rat brain and retina. The RT-PCR experiments demonstrated that two types of Tfg mRNA were expressed in rat tissues: the conventional form of Tfg (cTfg) and a novel variant form, retinal Tfg (rTfg). RT-PCR analyses demonstrated that cTfg was ubiquitously expressed in rat tissues, while rTfg was predominantly expressed in the brain and retina. Western blot analysis demonstrated two bands with molecular weights of about 30 kDa and 50 kDa in the rat brain. Immunohistochemistry indicated that TFG proteins were predominantly expressed by neurons in the brain. In the rat retina, intense TFG-immunoreactivity was detected in the layer of rods and cones and the outer plexiform layer

Changes in Male Rat Sexual Behavior and Brain Activity Revealed by Functional Magnetic Resonance Imaging in Response to Chronic Mild Stress.

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Chen, Guotao; Yang, Baibing; Chen, Jianhuai; Zhu, Leilei; Jiang, Hesong; Yu, Wen; Zang, Fengchao; Chen, Yun; Dai, Yutian

2018-02-01

Non-organic erectile dysfunction (noED) at functional imaging has been related to abnormal brain activity and requires animal models for further research on the associated molecular mechanisms. To develop a noED animal model based on chronic mild stress and investigate brain activity changes. We used 6 weeks of chronic mild stress to induce depression. The sucrose consumption test was used to assess the hedonic state. The apomorphine test and sexual behavior test were used to select male rats with ED. Rats with depression and ED were considered to have noED. Blood oxygen level-dependent-based resting-state functional magnetic resonance imaging (fMRI) studies were conducted on these rats, and the amplitude of low-frequency fluctuations and functional connectivity were analyzed to determine brain activity changes. The sexual behavior test and resting-state fMRI were used for outcome measures. The induction of depression was confirmed by the sucrose consumption test. A low intromission ratio and increased mount and intromission latencies were observed in male rats with depression. No erection was observed in male rats with depression during the apomorphine test. Male rats with depression and ED were considered to have noED. The possible central pathologic mechanism shown by fMRI involved the amygdaloid body, dorsal thalamus, hypothalamus, caudate-putamen, cingulate gyrus, insular cortex, visual cortex, sensory cortex, motor cortex, and cerebellum. Similar findings have been found in humans. The present study provided a novel noED rat model for further research on the central mechanism of noED. The present study developed a novel noED rat model and analyzed brain activity changes based at fMRI. The observed brain activity alterations might not extend to humans. The present study developed a novel noED rat model with brain activity alterations related to sexual arousal and erection, which will be helpful for further research involving the central mechanism of noED. Chen

Repeated administration of almonds increases brain acetylcholine levels and enhances memory function in healthy rats while attenuates memory deficits in animal model of amnesia.

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Batool, Zehra; Sadir, Sadia; Liaquat, Laraib; Tabassum, Saiqa; Madiha, Syeda; Rafiq, Sahar; Tariq, Sumayya; Batool, Tuba Sharf; Saleem, Sadia; Naqvi, Fizza; Perveen, Tahira; Haider, Saida

2016-01-01

Dietary nutrients may play a vital role in protecting the brain from age-related memory dysfunction and neurodegenerative diseases. Tree nuts including almonds have shown potential to combat age-associated brain dysfunction. These nuts are an important source of essential nutrients, such as tocopherol, folate, mono- and poly-unsaturated fatty acids, and polyphenols. These components have shown promise as possible dietary supplements to prevent or delay the onset of age-associated cognitive dysfunction. This study investigated possible protective potential of almond against scopolamine induced amnesia in rats. The present study also investigated a role of acetylcholine in almond induced memory enhancement. Rats in test group were orally administrated with almond suspension (400 mg/kg/day) for four weeks. Both control and almond-treated rats were then divided into saline and scopolamine injected groups. Rats in the scopolamine group were injected with scopolamine (0.5 mg/kg) five minutes before the start of each memory test. Memory was assessed by elevated plus maze (EPM), Morris water maze (MWM) and novel object recognition (NOR) task. Cholinergic function was determined in terms of hippocampal and frontal cortical acetylcholine content and acetylcholinesterase activity. Results of the present study suggest that almond administration for 28 days significantly improved memory retention. This memory enhancing effect of almond was also observed in scopolamine induced amnesia model. Present study also suggests a role of acetylcholine in the attenuation of scopolamine induced amnesia by almond. Copyright © 2015 Elsevier Inc. All rights reserved.

Insulin Protects against Brain Oxidative Stress with an Apparent Effect on Episodic Memory in Doxorubicin-Induced Cognitive Dysfunction in Wistar Rats.

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Ramalingayya, Grandhi Venkata; Sonawane, Vishwajeet; Cheruku, Sri Pragnya; Kishore, Anoop; Nayak, Pawan G; Kumar, Nitesh; Shenoy, Rekha S; Nandakumar, Krishnadas

2017-01-01

The present study was aimed at assessing the protective effect of insulin against doxorubicin (DOX)-induced cognitive dysfunction in Wistar rats. Cognitive function for episodic memory was assessed by a novel object recognition task (NORT) in male Wistar rats. Oxidative stress markers-SOD, catalase, glutathione, and lipid peroxidation-in the hippocampus and frontal cortex were assessed using colorimetric methods. Doxorubicin treatment (2.5 mg/kg, i.p., every 5 days for 50 days) reduced recognition and discriminative indices in NORT with increased oxidative stress in the brain. A nonhypoglycemic dose of insulin (0.5 IU/kg, i.p.) significantly reduced brain oxidative stress (MDA) induced by doxorubicin with an increase in the antioxidant defense systems (SOD, catalase, and GSH). Rats treated with combined insulin and DOX spent comparatively more time with the novel object when compared to the non-novel objects; however, the observed difference was not statistically significant. An apparent improvement (p insulin reduces brain oxidative stress and apparently improves doxorubicin-induced cognitive dysfunction in Wistar rats.

Multidimensional MRI-CT atlas of the naked mole-rat brain

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Fumiko eSeki

2013-12-01

Full Text Available Naked mole-rats have a variety of distinctive features such as the organisation of a hierarchical society (known as eusociality, extraordinary longevity, and cancer resistance; thus, it would be worthwhile investigating these animals in detail. One important task is the preparation of a brain atlas database that provide comprehensive information containing multidimensional data with various image contrasts, which can be achievable using a magnetic resonance imaging (MRI. Advanced MRI techniques such as diffusion tensor imaging (DTI, which generates high contrast images of fibre structures, can characterise unique morphological properties in addition to conventional MRI. To obtain high spatial resolution images, MR histology, DTI, and X-ray computed tomography (CT were performed on the fixed adult brain. Skull and brain structures were segmented as well as reconstructed in stereotaxic coordinates. Data were also acquired for the neonatal brain to allow developmental changes to be observed. Moreover, in vivo imaging of naked mole-rats was established as an evaluation tool of live animals. The data obtained comprised three-dimensional (3D images with high tissue contrast as well as stereotaxic coordinates. Developmental differences in the visual system were highlighted in particular by DTI. Although it was difficult to delineate optic nerves in the mature adult brain, parts of them could be distinguished in the immature neonatal brain. From observation of cortical thickness, possibility of high somatosensory system development replaced to the visual system was indicated. 3D visualisation of brain structures in the atlas as well as the establishment of in vivo imaging would promote neuroimaging researches towards detection of novel characteristics of eusocial naked mole-rats.

A single-neuron tracing study of arkypallidal and prototypic neurons in healthy rats.

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Fujiyama, Fumino; Nakano, Takashi; Matsuda, Wakoto; Furuta, Takahiro; Udagawa, Jun; Kaneko, Takeshi

2016-12-01

The external globus pallidus (GP) is known as a relay nucleus of the indirect pathway of the basal ganglia. Recent studies in dopamine-depleted and healthy rats indicate that the GP comprises two main types of pallidofugal neurons: the so-called "prototypic" and "arkypallidal" neurons. However, the reconstruction of complete arkypallidal neurons in healthy rats has not been reported. Here we visualized the entire axonal arborization of four single arkypallidal neurons and six single prototypic neurons in rat brain using labeling with a viral vector expressing membrane-targeted green fluorescent protein and examined the distribution of axon boutons in the target nuclei. Results revealed that not only the arkypallidal neurons but nearly all of the prototypic neurons projected to the striatum with numerous axon varicosities. Thus, the striatum is a major target nucleus for pallidal neurons. Arkypallidal and prototypic GP neurons located in the calbindin-positive and calbindin-negative regions mainly projected to the corresponding positive and negative regions in the striatum. Because the GP and striatum calbindin staining patterns reflect the topographic organization of the striatopallidal projection, the striatal neurons in the sensorimotor and associative regions constitute the reciprocal connection with the GP neurons in the corresponding regions.

Pomegranate extract protects against cerebral ischemia/reperfusion injury and preserves brain DNA integrity in rats.

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Ahmed, Maha A E; El Morsy, Engy M; Ahmed, Amany A E

2014-08-21

Interruption to blood flow causes ischemia and infarction of brain tissues with consequent neuronal damage and brain dysfunction. Pomegranate extract is well tolerated, and safely consumed all over the world. Interestingly, pomegranate extract has shown remarkable antioxidant and anti-inflammatory effects in experimental models. Many investigators consider natural extracts as novel therapies for neurodegenerative disorders. Therefore, this study was carried out to investigate the protective effects of standardized pomegranate extract against cerebral ischemia/reperfusion-induced brain injury in rats. Adult male albino rats were randomly divided into sham-operated control group, ischemia/reperfusion (I/R) group, and two other groups that received standardized pomegranate extract at two dose levels (250, 500 mg/kg) for 15 days prior to ischemia/reperfusion (PMG250+I/R, and PMG500+I/R groups). After I/R or sham operation, all rats were sacrificed and brains were harvested for subsequent biochemical analysis. Results showed reduction in brain contents of MDA (malondialdehyde), and NO (nitric oxide), in addition to enhancement of SOD (superoxide dismutase), GPX (glutathione peroxidase), and GRD (glutathione reductase) activities in rats treated with pomegranate extract prior to cerebral I/R. Moreover, pomegranate extract decreased brain levels of NF-κB p65 (nuclear factor kappa B p65), TNF-α (tumor necrosis factor-alpha), caspase-3 and increased brain levels of IL-10 (interleukin-10), and cerebral ATP (adenosine triphosphate) production. Comet assay showed less brain DNA (deoxyribonucleic acid) damage in rats protected with pomegranate extract. The present study showed, for the first time, that pre-administration of pomegranate extract to rats, can offer a significant dose-dependent neuroprotective activity against cerebral I/R brain injury and DNA damage via antioxidant, anti-inflammatory, anti-apoptotic and ATP-replenishing effects. Copyright © 2014 Elsevier Inc

Evaluation of JNJ-54717793 a Novel Brain Penetrant Selective Orexin 1 Receptor Antagonist in Two Rat Models of Panic Attack Provocation

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Pascal Bonaventure

2017-06-01

Full Text Available Orexin neurons originating in the perifornical and lateral hypothalamic area are highly reactive to anxiogenic stimuli and have strong projections to anxiety and panic-associated circuitry. Recent studies support a role for the orexin system and in particular the orexin 1 receptor (OX1R in coordinating an integrative stress response. However, no selective OX1R antagonist has been systematically tested in two preclinical models of using panicogenic stimuli that induce panic attack in the majority of people with panic disorder, namely an acute hypercapnia-panic provocation model and a model involving chronic inhibition of GABA synthesis in the perifornical hypothalamic area followed by intravenous sodium lactate infusion. Here we report on a novel brain penetrant, selective and high affinity OX1R antagonist JNJ-54717793 (1S,2R,4R-7-([(3-fluoro-2-pyrimidin-2-ylphenylcarbonyl]-N-[5-(trifluoromethylpyrazin-2-yl]-7-azabicyclo[2.2.1]heptan-2-amine. JNJ-54717793 is a high affinity/potent OX1R antagonist and has an excellent selectivity profile including 50 fold versus the OX2R. Ex vivo receptor binding studies demonstrated that after oral administration JNJ-54717793 crossed the blood brain barrier and occupied OX1Rs in the rat brain. While JNJ-54717793 had minimal effect on spontaneous sleep in rats and in wild-type mice, its administration in OX2R knockout mice, selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. JNJ-54717793 attenuated CO2 and sodium lactate induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. These data confirm that selective OX1R antagonism may represent a novel approach of treating anxiety disorders, with no apparent sedative effects.

Estrogen restores brain insulin sensitivity in ovariectomized non-obese rats, but not in ovariectomized obese rats.

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Pratchayasakul, Wasana; Chattipakorn, Nipon; Chattipakorn, Siriporn C

2014-06-01

We previously demonstrated that obesity caused the reduction of peripheral and brain insulin sensitivity and that estrogen therapy improved these defects. However, the beneficial effect of estrogen on brain insulin sensitivity and oxidative stress in either ovariectomy alone or ovariectomy with obesity models has not been determined. We hypothesized that ovariectomy alone or ovariectomy with obesity reduces brain insulin sensitivity and increases brain oxidative stress, which are reversed by estrogen treatment. Thirty female rats were assigned as either sham-operated or ovariectomized. After the surgery, each group was fed either a normal diet or high-fat diet for 12 weeks. At week 13, rats in each group received either the vehicle or estradiol for 30 days. At week 16, blood and brain were collected for determining the peripheral and brain insulin sensitivity as well as brain oxidative stress. We found that ovariectomized rats and high-fat diet fed rats incurred obesity, reduced peripheral and brain insulin sensitivity, and increased brain oxidative stress. Estrogen ameliorated peripheral insulin sensitivity in these rats. However, the beneficial effect of estrogen on brain insulin sensitivity and brain oxidative stress was observed only in ovariectomized normal diet-fed rats, but not in ovariectomized high fat diet-fed rats. Our results suggested that reduced brain insulin sensitivity and increased brain oxidative stress occurred after either ovariectomy or obesity. However, the reduced brain insulin sensitivity and the increased brain oxidative stress in ovariectomy with obesity could not be ameliorated by estrogen treatment. Copyright © 2014 Elsevier Inc. All rights reserved.

A combined solenoid-surface RF coil for high-resolution whole-brain rat imaging on a 3.0 Tesla clinical MR scanner.

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Underhill, Hunter R; Yuan, Chun; Hayes, Cecil E

2010-09-01

Rat brain models effectively simulate a multitude of human neurological disorders. Improvements in coil design have facilitated the wider utilization of rat brain models by enabling the utilization of clinical MR scanners for image acquisition. In this study, a novel coil design, subsequently referred to as the rat brain coil, is described that exploits and combines the strengths of both solenoids and surface coils into a simple, multichannel, receive-only coil dedicated to whole-brain rat imaging on a 3.0 T clinical MR scanner. Compared with a multiturn solenoid mouse body coil, a 3-cm surface coil, a modified Helmholtz coil, and a phased-array surface coil, the rat brain coil improved signal-to-noise ratio by approximately 72, 61, 78, and 242%, respectively. Effects of the rat brain coil on amplitudes of static field and radiofrequency field uniformity were similar to each of the other coils. In vivo, whole-brain images of an adult male rat were acquired with a T(2)-weighted spin-echo sequence using an isotropic acquisition resolution of 0.25 x 0.25 x 0.25 mm(3) in 60.6 min. Multiplanar images of the in vivo rat brain with identification of anatomic structures are presented. Improvement in signal-to-noise ratio afforded by the rat brain coil may broaden experiments that utilize clinical MR scanners for in vivo image acquisition. 2010 Wiley-Liss, Inc.

Influence of electromagnetic field (1800 MHz on lipid peroxidation in brain, blood, liver and kidney in rats

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Paweł Bodera

2015-08-01

Full Text Available Objectives: The aim of this study is the evaluation of the influence of repeated (5 times for 15 min exposure to electromagnetic field (EMF of 1800 MHz frequency on tissue lipid peroxidation (LPO both in normal and inflammatory state, combined with analgesic treatment. Material and Methods: The concentration of malondialdehyde (MDA as the end-product of the lipid peroxidation (LPO was estimated in blood, liver, kidneys, and brain of Wistar rats, both healthy and those with complete Freund’s adjuvant (CFA-induced persistent paw inflammation. Results: The slightly elevated levels of the MDA in blood, kidney, and brain were observed among healthy rats in electromagnetic field (EMF-exposed groups, treated with tramadol (TRAM/EMF and exposed to the EMF. The malondialdehyde remained at the same level in the liver in all investigated groups: the control group (CON, the exposed group (EMF, treated with tramadol (TRAM as well as exposed to and treated with tramadol (TRAM/EMF. In the group of animals treated with the complete Freund’s adjuvant (CFA we also observed slightly increased values of the MDA in the case of the control group (CON and the exposed groups (EMF and TRAM/EMF. The MDA values concerning kidneys remained at the same levels in the control, exposed, and not-exposed group treated with tramadol. Results for healthy rats and animals with inflammation did not differ significantly. Conclusions: The electromagnetic field exposure (EMF, applied in the repeated manner together with opioid drug tramadol (TRAM, slightly enhanced lipid peroxidation level in brain, blood, and kidneys.

Nutritional Cognitive Neuroscience: Innovations for Healthy Brain Aging

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Marta Karolina Zamroziewicz

2016-06-01

Full Text Available Nutritional cognitive neuroscience is an emerging interdisciplinary field of research that seeks to understand nutrition’s impact on cognition and brain health across the life span. Research in this burgeoning field demonstrates that many aspects of nutrition – from entire diets to specific nutrients – affect brain structure and function, and therefore have profound implications for understanding the nature of healthy brain aging. The aim of this Focused Review is to examine recent advances in nutritional cognitive neuroscience, with an emphasis on methods that enable discovery of nutrient biomarkers that predict healthy brain aging. We propose an integrative framework that calls for the synthesis of research in nutritional epidemiology and cognitive neuroscience, incorporating: (i methods for the precise characterization of nutritional health based on the analysis of nutrient biomarker patterns, along with (ii modern indices of brain health derived from high-resolution magnetic resonance imaging. By integrating cutting-edge techniques from nutritional epidemiology and cognitive neuroscience, nutritional cognitive neuroscience will continue to advance our understanding of the beneficial effects of nutrition on the aging brain and establish effective nutritional interventions to promote healthy brain aging.

Changes in Imaging and Cognition in Juvenile Rats After Whole-Brain Irradiation

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Brown, Robert J.; Jun, Brandon J. [Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California (United States); Advanced Imaging Laboratory, Department of Radiology, Children' s Hospital Los Angeles, Los Angeles, California (United States); Rudi Schulte Research Institute, Santa Barbara, California (United States); Cushman, Jesse D. [Department of Psychology, University of California, Los Angeles, Los Angeles, California (United States); Nguyen, Christine; Beighley, Adam H.; Blanchard, Johnny; Iwamoto, Kei; Schaue, Dorthe [Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California (United States); Harris, Neil G. [UCLA Brain Injury Research Center, Department of Neurosurgery, David Geffen School of Medicine at UCLA Center for the Health Sciences, Los Angeles, California (United States); Jentsch, James D. [Department of Psychology, University of California, Los Angeles, Los Angeles, California (United States); Bluml, Stefan [Advanced Imaging Laboratory, Department of Radiology, Children' s Hospital Los Angeles, Los Angeles, California (United States); Rudi Schulte Research Institute, Santa Barbara, California (United States); McBride, William H., E-mail: wmcbride@mednet.ucla.edu [Division of Molecular and Cellular Oncology, Department of Radiation Oncology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, California (United States)

2016-10-01

Purpose: In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development. Methods and Materials: Juvenile Fischer rats received clinically relevant fractionated doses of WBI or a high-dose exposure. Diffusion tensor imaging and MRS were performed at the time of WBI and during the subacute (3-month) and late (6-month) phases, before behavioral testing. Results: Fractional anisotropy in the splenium of the corpus callosum increased steadily over the study period, reflecting brain development. WBI did not alter the subacute response, but thereafter there was no further increase in fractional anisotropy, especially in the high-dose group. Similarly, the ratios of various MRS metabolites to creatine increased over the study period, and in general, the most significant changes after WBI were during the late phase and with the higher dose. The most dramatic changes observed were in glutamine-creatine ratios that failed to increase normally between 3 and 6 months after either radiation dose. WBI did not affect the ambulatory response to novel open field testing in the subacute phase, but locomotor habituation was impaired and anxiety-like behaviors increased. As for cognitive measures, the most dramatic impairments were in novel object recognition late after either dose of WBI. Conclusions: The developing brains of juvenile rats given clinically relevant fractionated doses of WBI show few abnormalities in the subacute phase but marked late cognitive alterations that may be linked with perturbed MRS signals measured in the corpus callosum. This pathomimetic phenotype of clinically relevant cranial irradiation effects may be useful for modeling, mechanistic

Changes in Imaging and Cognition in Juvenile Rats After Whole-Brain Irradiation

International Nuclear Information System (INIS)

Brown, Robert J.; Jun, Brandon J.; Cushman, Jesse D.; Nguyen, Christine; Beighley, Adam H.; Blanchard, Johnny; Iwamoto, Kei; Schaue, Dorthe; Harris, Neil G.; Jentsch, James D.; Bluml, Stefan; McBride, William H.

2016-01-01

Purpose: In pediatric cancer survivors treated with whole-brain irradiation (WBI), long-term cognitive deficits and morbidity develop that are poorly understood and for which there is no treatment. We describe similar cognitive defects in juvenile WBI rats and correlate them with alterations in diffusion tensor imaging and magnetic resonance spectroscopy (MRS) during brain development. Methods and Materials: Juvenile Fischer rats received clinically relevant fractionated doses of WBI or a high-dose exposure. Diffusion tensor imaging and MRS were performed at the time of WBI and during the subacute (3-month) and late (6-month) phases, before behavioral testing. Results: Fractional anisotropy in the splenium of the corpus callosum increased steadily over the study period, reflecting brain development. WBI did not alter the subacute response, but thereafter there was no further increase in fractional anisotropy, especially in the high-dose group. Similarly, the ratios of various MRS metabolites to creatine increased over the study period, and in general, the most significant changes after WBI were during the late phase and with the higher dose. The most dramatic changes observed were in glutamine-creatine ratios that failed to increase normally between 3 and 6 months after either radiation dose. WBI did not affect the ambulatory response to novel open field testing in the subacute phase, but locomotor habituation was impaired and anxiety-like behaviors increased. As for cognitive measures, the most dramatic impairments were in novel object recognition late after either dose of WBI. Conclusions: The developing brains of juvenile rats given clinically relevant fractionated doses of WBI show few abnormalities in the subacute phase but marked late cognitive alterations that may be linked with perturbed MRS signals measured in the corpus callosum. This pathomimetic phenotype of clinically relevant cranial irradiation effects may be useful for modeling, mechanistic

Development of acute hydrocephalus does not change brain tissue mechanical properties in adult rats, but in juvenile rats.

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Pong, Alice C; Jugé, Lauriane; Bilston, Lynne E; Cheng, Shaokoon

2017-01-01

Regional changes in brain stiffness were previously demonstrated in an experimental obstructive hydrocephalus juvenile rat model. The open cranial sutures in the juvenile rats have influenced brain compression and mechanical properties during hydrocephalus development and the extent by which closed cranial sutures in adult hydrocephalic rat models affect brain stiffness in-vivo remains unclear. The aims of this study were to determine changes in brain tissue mechanical properties and brain structure size during hydrocephalus development in adult rat with fixed cranial volume and how these changes were related to brain tissue deformation. Hydrocephalus was induced in 9 female ten weeks old Sprague-Dawley rats by injecting 60 μL of a kaolin suspension (25%) into the cisterna magna under anaesthesia. 6 sham-injected age-matched female SD rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before and then at 3 days post injection. T2-weighted anatomical MR images were collected to quantify ventricle and brain tissue cross-sectional areas. MR elastography (800 Hz) was used to measure the brain stiffness (G*, shear modulus). Brain tissue in the adult hydrocephalic rats was more compressed than the juvenile hydrocephalic rats because the skulls of the adult hydrocephalic rats were unable to expand like the juvenile rats. In the adult hydrocephalic rats, the cortical gray matter thickness and the caudate-putamen cross-sectional area decreased (Spearman, P hydrocephalus is complex and is not solely dependent on brain tissue deformation. Further studies on the interactions between brain tissue stiffness, deformation, tissue oedema and neural damage are necessary before MRE can be used as a tool to track changes in brain biomechanics in hydrocephalus.

The effects of methylphenidate on cognitive performance of healthy male rats

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Claire Louise Rostron

2013-06-01

Full Text Available We aimed to investigate the effects of methylphenidate (MPH in healthy rats on two distinct radial maze tasks which rely on brain structures and neurotransmitters known to be affected by MPH: the Random Foraging Non-Delay Task (RFNDT and the Delay Spatial Win Shift Task (DSWT. Hooded Lister rats were trained to complete either the RFNDT or the DSWT having received oral treatment of either a vehicle or MPH (3.0 mg/kg and 5.0 mg/kg for RFNDT, 3.0 mg/kg for DSWT. We found no effect of MPH on the RFNDT relative to the control group. However, those treated with 5.0 mg/kg MPH did take significantly longer to reach criterion performance than those treated with the 3.0 mg/kg MPH, suggesting some doses of MPH can have detrimental effects. For the DSWT, if MPH was present in both phases, performance did not differ from when it was absent in both phases. However, when present in only one phase there was an increase in errors made, although this only reached significance for when MPH was present only in the test-phase. These data suggest that MPH may have detrimental effects on task performance and can result in state dependent effects in healthy individuals.

Brain penetrant small molecule 18F-GnRH receptor (GnRH-R) antagonists: Synthesis and preliminary positron emission tomography imaging in rats

International Nuclear Information System (INIS)

Olberg, Dag E.; Bauer, Nadine; Andressen, Kjetil W.; Hjørnevik, Trine; Cumming, Paul; Levy, Finn O.; Klaveness, Jo; Haraldsen, Ira; Sutcliffe, Julie L.

2016-01-01

Introduction: The gonadotropin releasing hormone receptor (GnRH-R) has a well-described neuroendocrine function in the anterior pituitary. However, little is known about its function in the central nervous system (CNS), where it is most abundantly expressed in hippocampus and amygdala. Since peptide ligands based upon the endogenous decapetide GnRH do not pass the blood–brain-barrier, we are seeking a high-affinity small molecule GnRH-R ligand suitable for brain imaging by positron emission tomography. We have previously reported the radiosynthesis and in vitro evaluation of two novel [ 18 F]fluorinated GnRH-R ligands belonging to the furamide class of antagonists, with molecular weight less than 500 Da. We now extend this work using palladium coupling for the synthesis of four novel radioligands, with putatively reduced polar surface area and hydrophilicity relative to the two previously described compounds, and report the uptake of these 18 F-labeled compounds in brain of living rats. Methods: We synthesized reference standards of the small molecule GnRH-R antagonists as well as mesylate precursors for 18 F-labeling. The antagonists were tested for binding affinity for both human and rat GnRH-R. Serum and blood stability in vitro and in vivo were studied. Biodistribution and PET imaging studies were performed in male rats in order to assess brain penetration in vivo. Results: A palladium coupling methodology served for the synthesis of four novel fluorinated furamide GnRH receptor antagonists with reduced heteroatomic count. Radioligand binding assays in vitro revealed subnanomolar affinity of the new fluorinated compounds for both human and rat GnRH-R. The 18 F-GnRH antagonists were synthesized from the corresponding mesylate precursors in 5–15% overall radiochemical yield. The radiolabeled compounds demonstrated good in vivo stability. PET imaging with the 18 F-radiotracers in naive rats showed good permeability into brain and rapid washout, but absence of

MS-377, a novel selective sigma(1) receptor ligand, reverses phencyclidine-induced release of dopamine and serotonin in rat brain.

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Takahashi, S; Horikomi, K; Kato, T

2001-09-21

A novel selective sigma(1) receptor ligand, (R)-(+)-1-(4-chlorophenyl)-3-[4-(2-methoxyethyl)piperazin-1-yl]methyl-2-pyrrolidinone L-tartrate (MS-377), inhibits phencyclidine (1-(1-phenylcyclohexyl)piperidine; PCP)-induced behaviors in animal models. In this study, we measured extracellular dopamine and serotonin levels in the rat brain after treatment with MS-377 alone, using in vivo microdialysis. We also examined the effects of MS-377 on extracellular dopamine and serotonin levels in the rat medial prefrontal cortex after treatment with PCP. MS-377 itself had no significant effects on dopamine release in the striatum (10 mg/kg, p.o.) nor on dopamine or serotonin release in the medial prefrontal cortex (1 and 10 mg/kg, p.o.). PCP (3 mg/kg, i.p.) markedly increased dopamine and serotonin release in the medial prefrontal cortex. MS-377 (1 mg/kg, p.o.), when administered 60 min prior to PCP, significantly attenuated this effect of PCP. These results suggest that the inhibitory effects of MS-377 on PCP-induced behaviors are partly mediated by inhibition of the increase in dopamine and serotonin release in the rat medial prefrontal cortex caused by PCP.

Multidimensional MRI-CT atlas of the naked mole-rat brain (Heterocephalus glaber).

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Seki, Fumiko; Hikishima, Keigo; Nambu, Sanae; Okanoya, Kazuo; Okano, Hirotaka J; Sasaki, Erika; Miura, Kyoko; Okano, Hideyuki

2013-01-01

Naked mole-rats have a variety of distinctive features such as the organization of a hierarchical society (known as eusociality), extraordinary longevity, and cancer resistance; thus, it would be worthwhile investigating these animals in detail. One important task is the preparation of a brain atlas database that provide comprehensive information containing multidimensional data with various image contrasts, which can be achievable using a magnetic resonance imaging (MRI). Advanced MRI techniques such as diffusion tensor imaging (DTI), which generates high contrast images of fiber structures, can characterize unique morphological properties in addition to conventional MRI. To obtain high spatial resolution images, MR histology, DTI, and X-ray computed tomography were performed on the fixed adult brain. Skull and brain structures were segmented as well as reconstructed in stereotaxic coordinates. Data were also acquired for the neonatal brain to allow developmental changes to be observed. Moreover, in vivo imaging of naked mole-rats was established as an evaluation tool of live animals. The data obtained comprised three-dimensional (3D) images with high tissue contrast as well as stereotaxic coordinates. Developmental differences in the visual system were highlighted in particular by DTI. Although it was difficult to delineate optic nerves in the mature adult brain, parts of them could be distinguished in the immature neonatal brain. From observation of cortical thickness, possibility of high somatosensory system development replaced to the visual system was indicated. 3D visualization of brain structures in the atlas as well as the establishment of in vivo imaging would promote neuroimaging researches towards detection of novel characteristics of eusocial naked mole-rats.

Development of antibodies against the rat brain somatostatin receptor.

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Theveniau, M; Rens-Domiano, S; Law, S F; Rougon, G; Reisine, T

1992-05-15

Somatostatin (SRIF) is a neurotransmitter in the brain involved in the regulation of motor activity and cognition. It induces its physiological actions by interacting with receptors. We have developed antibodies against the receptor to investigate its structural properties. Rabbit polyclonal antibodies were generated against the rat brain SRIF receptor. These antibodies (F4) were able to immunoprecipitate solubilized SRIF receptors from rat brain and the cell line AtT-20. The specificity of the interaction of these antibodies with SRIF receptors was further demonstrated by immunoblotting. F4 detected SRIF receptors of 60 kDa from rat brain and adrenal cortex and the cell lines AtT-20, GH3, and NG-108, which express high densities of SRIF receptors. They did not detect immunoreactive material from rat liver or COS-1, HEPG, or CRL cells, which do not express functional SRIF receptors. In rat brain, 60-kDa immunoreactivity was detected by F4 in the hippocampus, cerebral cortex, and striatum, which have high densities of SRIF receptors. However, F4 did not interact with proteins from cerebellum and brain stem, which express few SRIF receptors. Immunoreactive material cannot be detected in rat pancreas or pituitary, which have been reported to express a 90-kDa SRIF receptor subtype. The selective detection of 60-kDa SRIF receptors by F4 indicates that the 60- and 90-kDa SRIF receptor subtypes are immunologically distinct. The availability of antibodies that selectively detect native and denatured brain SRIF receptors provides us with a feasible approach to clone the brain SRIF receptor gene(s).

Brain dysfunctions in Wistar rats exposed to municipal landfill leachates

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Chibuisi G. Alimba

2015-12-01

Full Text Available Brain damage induced by Olusosun and Aba-Eku municipal landfill leachates was investigated in Wistar rats. Male rats were orally exposed to 1–25% concentrations of the leachates for 30 days. Catalase (CAT and superoxide dismutase (SOD activities, and malondialdehyde (MDA concentrations in the brain and serum of rats were evaluated; body and brain weight gain and histopathology were examined. There was significant (p < 0.05 decrease in body weight gain and SOD activity but increase in absolute and relative brain weight gain, MDA concentration and CAT activity in both brain and serum of treated rats. The biochemical parameters, which were more altered in the brain than serum, corroborated the neurologic lesions; neurodegeneration of purkinje cells with loss of dendrites, perineural vacuolations of the neuronal cytoplasm (spongiosis and neuronal necrosis in the brain. The concentrations of Cr, Cu, Pb, As, Cd, Mn, Ni, sulphates, ammonia, chloride and phosphate in the leachate samples were above standard permissible limits. The interactions of the neurotoxic constituents of the leachates induced the observed brain damage in the rats via oxidative damage. This suggests health risk in wildlife and human populations.

Ceftriaxone attenuates hypoxic-ischemic brain injury in neonatal rats

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Huang Yen

2011-09-01

Full Text Available Abstract Background Perinatal brain injury is the leading cause of subsequent neurological disability in both term and preterm baby. Glutamate excitotoxicity is one of the major factors involved in perinatal hypoxic-ischemic encephalopathy (HIE. Glutamate transporter GLT1, expressed mainly in mature astrocytes, is the major glutamate transporter in the brain. HIE induced excessive glutamate release which is not reuptaked by immature astrocytes may induce neuronal damage. Compounds, such as ceftriaxone, that enhance the expression of GLT1 may exert neuroprotective effect in HIE. Methods We used a neonatal rat model of HIE by unilateral ligation of carotid artery and subsequent exposure to 8% oxygen for 2 hrs on postnatal day 7 (P7 rats. Neonatal rats were administered three dosages of an antibiotic, ceftriaxone, 48 hrs prior to experimental HIE. Neurobehavioral tests of treated rats were assessed. Brain sections from P14 rats were examined with Nissl and immunohistochemical stain, and TUNEL assay. GLT1 protein expression was evaluated by Western blot and immunohistochemistry. Results Pre-treatment with 200 mg/kg ceftriaxone significantly reduced the brain injury scores and apoptotic cells in the hippocampus, restored myelination in the external capsule of P14 rats, and improved the hypoxia-ischemia induced learning and memory deficit of P23-24 rats. GLT1 expression was observed in the cortical neurons of ceftriaxone treated rats. Conclusion These results suggest that pre-treatment of infants at risk for HIE with ceftriaxone may reduce subsequent brain injury.

Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats

OpenAIRE

McBride, Devin W.; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H.

2015-01-01

Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected ...

Detection of radiation-induced brain necrosis in live rats using label-free time-resolved fluorescence spectroscopy (TRFS) (Conference Presentation)

Science.gov (United States)

Hartl, Brad A.; Ma, Htet S. W.; Sridharan, Shamira; Hansen, Katherine; Klich, Melanie; Perks, Julian; Kent, Michael; Kim, Kyoungmi; Fragoso, Ruben; Marcu, Laura

2017-02-01

Differentiating radiation-induced necrosis from recurrent tumor in the brain remains a significant challenge to the neurosurgeon. Clinical imaging modalities are not able to reliably discriminate the two tissue types, making biopsy location selection and surgical management difficult. Label-free fluorescence lifetime techniques have previously been shown to be able to delineate human brain tumor from healthy tissues. Thus, fluorescence lifetime techniques represent a potential means to discriminate the two tissues in real-time during surgery. This study aims to characterize the endogenous fluorescence lifetime signatures from radiation induced brain necrosis in a tumor-free rat model. Fischer rats received a single fraction of 60 Gy of radiation to the right hemisphere using a linear accelerator. Animals underwent a terminal live surgery after gross necrosis had developed, as verified with MRI. During surgery, healthy and necrotic brain tissue was measured with a fiber optic needle connected to a multispectral fluorescence lifetime system. Measurements of the necrotic tissue showed a 48% decrease in intensity and 20% increase in lifetimes relative to healthy tissue. Using a support vector machine classifier and leave-one-out validation technique, the necrotic tissue was correctly classified with 94% sensitivity and 97% specificity. Spectral contribution analysis also confirmed that the primary source of fluorescence contrast lies within the redox and bound-unbound population shifts of nicotinamide adenine dinucleotide. A clinical trial is presently underway to measure these tissue types in humans. These results show for the first time that radiation-induced necrotic tissue in the brain contains significantly different metabolic signatures that are detectable with label-free fluorescence lifetime techniques.

A novel rat model of blast-induced traumatic brain injury simulating different damage degree: implications for morphological, neurological, and biomarker changes

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Mengdong eLiu

2015-05-01

Full Text Available In current military conflicts and civilian terrorism, blast-induced traumatic brain injury (bTBI is the primary cause of neurotrauma. However, the effects and mechanisms of bTBI are poorly understood. Although previous researchers have made significant contributions to establishing animal models for the simulation of bTBI, the precision and controllability of blast-induced injury in animal models must be improved. Therefore, we established a novel rat model to simulate blast-wave injury to the brain. To simulate different extents of bTBI injury, the animals were divided into moderate and severe injury groups. The miniature spherical explosives (PETN used in each group were of different sizes (2.5 mm diameter in the moderate injury group and 3.0 mm diameter in the severe injury group. A specially designed apparatus was able to precisely adjust the positions of the miniature explosives and create eight rats with bTBI simultaneously, using a single electric detonator. Neurological functions, gross pathologies, histopathological changes and the expression levels of various biomarkers were examined after the explosion. Compared with the moderate injury group, there were significantly more neurological dysfunctions, cortical contusions, intraparenchymal hemorrhages, cortical expression of S-100β, MBP, NSE, IL-8, IL-10, iNOS and HIF-1α in the severe injury group. These results demonstrate that we have created a reliable and reproducible bTBI model in rats. This model will be helpful for studying the mechanisms of bTBI and developing strategies for clinical bTBI treatment.

Neuroprotective effect of Cucumis melo Var. flexuosus leaf extract on the brains of rats with streptozotocin-induced diabetes.

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Ibrahim, Doaa S

2017-02-01

The central nervous system is one of the most vulnerable organs affected by the oxidative stress associated with diabetes mellitus. Healthy food provides an important source for antioxidants. Therefore, the protective effect of Cucumis melo var. flexuosus (C. melo var. flexuosus) leaf extract on the brains of diabetic rats was investigated. Adult male albino rats divided into 5 groups of 6 rats each were assigned into a normal control group and four diabetic groups. Diabetes was induced in rats by a single intraperitoneal injection of streptozotocin (STZ; 60 mg/kg bw). One of the four diabetic groups was left untreated and was considered as a diabetic control group while the three other groups were treated with C. melo var. flexuosus leaf extract at the doses of 30, 60 and 120 mg/kg bw for a period of 30 days. After completion of experimental duration plasma and brains were used for evaluating biochemical changes. The obtained data showed that C. melo var. flexuosus leaf extract treatment lowered blood glucose, glycated hemoglobin, brain tumor necrosis factor-alpha, interleukin levels, brain malondialdehyde content and caspase-3 activity. Furthermore, the treatment resulted in a marked increase in plasma dopamine, melatonin, brain vascular endothelial growth factor-A levels, brain catalase and superoxide dismutase activities. From the present study, it can be concluded that the C. melo var. flexuosus leaf extract exerts a neuroprotective effect against oxidative damage associated with diabetes.

Extreme hypoxia tolerance of naked mole-rat brain.

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Larson, John; Park, Thomas J

2009-12-09

Mammalian brains have extremely high levels of aerobic metabolism and typically suffer irreversible damage after brief periods of oxygen deprivation such as occur during stroke or cardiac arrest. Here we report that brain tissue from naked mole-rats, rodents that live in a chronically low-oxygen environment, is remarkably resistant to hypoxia: naked mole-rat neurons maintain synaptic transmission much longer than mouse neurons and can recover from periods of anoxia exceeding 30 min. We suggest that brain tolerance to hypoxia may result from slowed or arrested brain development in these extremely long-lived animals.

In vitro comparison of rat and chicken brain neurotoxic esterase

International Nuclear Information System (INIS)

Novak, R.; Padilla, S.

1986-01-01

A systematic comparison was undertaken to characterize neurotoxic esterase (NTE) from rat and chicken brain in terms of inhibitor sensitivities, pH optima, and molecular weights. Paraoxon titration of phenyl valerate (PV)-hydrolyzing carboxylesterases showed that rat esterases were more sensitive than chicken to paraoxon inhibition at concentrations less than or equal to microM and superimposable with chicken esterases at concentrations of 2.5-1000 microM. Mipafox titration of the paraoxon-resistant esterases at a fixed paraoxon concentration of 100 microM (mipafox concentration: 0-1000 microM) resulted in a mipafox I50 of 7.3 microM for chicken brain NTE and 11.6 microM for rat brain NTE. NTE (i.e., paraoxon-resistant, mipafox-sensitive esterase activity) comprised 80% of chicken and 60% of rat brain paraoxon-resistant activity with the specific activity of chicken brain NTE approximately twice that of rat brain NTE. The pH maxima for NTE from both species was similar showing broad, slightly alkaline optima from pH 7.9 to 8.6. [ 3 H]Diisopropyl phosphorofluoridate (DFP)-labeled NTE from the brains of both species had an apparent mol wt of 160,000 measured by sodium dodecyl sulfate polyacrylamide gel electrophoresis. In conclusion, NTE from both species was very similar, with the mipafox I50 for rat NTE within the range of reported values for chicken and human NTE, and the inhibitor parameters of the chicken NTE assay were applicable for the rat NTE assay

An automatic rat brain extraction method based on a deformable surface model.

Science.gov (United States)

Li, Jiehua; Liu, Xiaofeng; Zhuo, Jiachen; Gullapalli, Rao P; Zara, Jason M

2013-08-15

The extraction of the brain from the skull in medical images is a necessary first step before image registration or segmentation. While pre-clinical MR imaging studies on small animals, such as rats, are increasing, fully automatic imaging processing techniques specific to small animal studies remain lacking. In this paper, we present an automatic rat brain extraction method, the Rat Brain Deformable model method (RBD), which adapts the popular human brain extraction tool (BET) through the incorporation of information on the brain geometry and MR image characteristics of the rat brain. The robustness of the method was demonstrated on T2-weighted MR images of 64 rats and compared with other brain extraction methods (BET, PCNN, PCNN-3D). The results demonstrate that RBD reliably extracts the rat brain with high accuracy (>92% volume overlap) and is robust against signal inhomogeneity in the images. Copyright © 2013 Elsevier B.V. All rights reserved.

A Healthy Brain in a Healthy Body: Brain Network Correlates of Physical and Mental Fitness.

NARCIS (Netherlands)

Douw, L.; Nieboer, D.; van Dijk, B.W.; Stam, C.J.; Twisk, J.W.R.

2014-01-01

A healthy lifestyle is an important focus in today's society. The physical benefits of regular exercise are abundantly clear, but physical fitness is also associated with better cognitive performance. How these two factors together relate to characteristics of the brain is still incompletely

Neuronal Rat Brain Damage Caused by Endogenous and Exogenous Hyperthermia

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Mustafa Aydın

2012-03-01

Full Text Available OBJECTIVE: Hyperthermia may induce pathologic alterations within body systems and organs including brain. In this study, neuronal effects of endogenous and exogenous hyperthermia (41°C were studied in rats. METHODS: The endogenous hyperthermia (41°C was induced by lipopolysaccharide and the exogenous by an (electric heater. Possible neuronal damage was evaluated by examining healthy, apoptotic and necrotic cells, and heat shock proteins (HSP 27, HSP 70 in the cerebral cortex, cerebellum and hypothalamus RESULTS: At cellular level, when all neuronal tissues are taken into account; (i a significant increase in the necrotic cells was observed in the both groups (p0.05. CONCLUSION: The neural tissue of brain can show different degree of response to hyperthermia. But we can conclude that endogenous hyperthermia is more harmful to central nervous system than exogenous hyperthermia

Self-assembled polymersomes conjugated with lactoferrin as novel drug carrier for brain delivery.

Science.gov (United States)

Yu, Yuan; Pang, Zhiqing; Lu, Wei; Yin, Qi; Gao, Huile; Jiang, Xinguo

2012-01-01

To develop a novel brain drug delivery system based on self-assembled poly(ethyleneglycol)-poly (D,L-lactic-co-glycolic acid) (PEG-PLGA) polymersomes conjugated with lactoferrin (Lf-POS). The brain delivery properties of Lf-POS were investigated and optimized. Three formulations of Lf-POS, with different densities of lactoferrin on the surface of polymersomes, were prepared and characterized. The brain delivery properties in mice were investigated using 6-coumarin as a fluorescent probe loaded in Lf-POS (6-coumarin-Lf-POS). A neuroprotective peptide, S14G-humanin, was incorporated into Lf-POS (SHN-Lf-POS); a protective effect on the hippocampuses of rats treated by Amyloid-β(25-35) was investigated by immunohistochemical analysis. The results of brain delivery in mice demonstrated that the optimized number of lactoferrin conjugated per polymersome was 101. This obtains the greatest blood-brain barrier (BBB) permeability surface area(PS) product and percentage of injected dose per gram brain (%ID/g brain). Immunohistochemistry revealed the SHN-Lf-POS had a protective effect on neurons of rats by attenuating the expression of Bax and caspase-3 positive cells. Meanwhile, the activity of choline acetyltransferase (ChAT) had been increased compared with negative controls. These results suggest that lactoferrin functionalized self-assembled PEG-PLGA polymersomes could be a promising brain-targeting peptide drug delivery system via intravenous administration.

Neuropeptide Y receptors in rat brain: autoradiographic localization

International Nuclear Information System (INIS)

Martel, J.C.; St-Pierre, S.; Quirion, R.

1986-01-01

Neuropeptide Y (NPY) receptor binding sites have been characterized in rat brain using both membrane preparations and receptor autoradiography. Radiolabelled NPY binds with high affinity and specificity to an apparent single class of sites in rat brain membrane preparations. The ligand selectivity pattern reveals strong similarities between central and peripheral NPY receptors. NPY receptors are discretely distributed in rat brain with high densities found in the olfactory bulb, superficial layers of the cortex, ventral hippocampus, lateral septum, various thalamic nuclei and area postrema. The presence of high densities of NPY and NPY receptors in such areas suggests that NPY could serve important functions as a major neurotransmitter/neuromodulator in the central nervous system

Rat brain CYP2D enzymatic metabolism alters acute and chronic haloperidol side-effects by different mechanisms.

Science.gov (United States)

Miksys, Sharon; Wadji, Fariba Baghai; Tolledo, Edgor Cole; Remington, Gary; Nobrega, Jose N; Tyndale, Rachel F

2017-08-01

Risk for side-effects after acute (e.g. parkinsonism) or chronic (e.g. tardive dyskinesia) treatment with antipsychotics, including haloperidol, varies substantially among people. CYP2D can metabolize many antipsychotics and variable brain CYP2D metabolism can influence local drug and metabolite levels sufficiently to alter behavioral responses. Here we investigated a role for brain CYP2D in acutely and chronically administered haloperidol levels and side-effects in a rat model. Rat brain, but not liver, CYP2D activity was irreversibly inhibited with intracerebral propranolol and/or induced by seven days of subcutaneous nicotine pre-treatment. The role of variable brain CYP2D was investigated in rat models of acute (catalepsy) and chronic (vacuous chewing movements, VCMs) haloperidol side-effects. Selective inhibition and induction of brain, but not liver, CYP2D decreased and increased catalepsy after acute haloperidol, respectively. Catalepsy correlated with brain, but not hepatic, CYP2D enzyme activity. Inhibition of brain CYP2D increased VCMs after chronic haloperidol; VCMs correlated with brain, but not hepatic, CYP2D activity, haloperidol levels and lipid peroxidation. Baseline measures, hepatic CYP2D activity and plasma haloperidol levels were unchanged by brain CYP2D manipulations. Variable rat brain CYP2D alters side-effects from acute and chronic haloperidol in opposite directions; catalepsy appears to be enhanced by a brain CYP2D-derived metabolite while the parent haloperidol likely causes VCMs. These data provide novel mechanistic evidence for brain CYP2D altering side-effects of haloperidol and other antipsychotics metabolized by CYP2D, suggesting that variation in human brain CYP2D may be a risk factor for antipsychotic side-effects. Copyright © 2017 Elsevier Inc. All rights reserved.

ischemic brain injury in neonatal rats

African Journals Online (AJOL)

Pharmacotherapy Group, Faculty of Pharmacy, University of Benin, Benin City, ... Methods: Forty-eight rats (P7-pups) were randomly assigned to one of four groups: ... Keywords: Hypoxic–ischemic brain injury, α-Lipoic acid, Cerebral infarct area, Edema, Antioxidants, .... Of the 48 rats initially used in the current study, 5.

Functional Magnetic Resonance Study of Non-conventional Morphological Brains: malnourished rats

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Martin R.

2015-08-01

Full Text Available Malnutrition during brain development can cause serious problems that can be irreversible. Dysfunctional patterns of brain activity can be detected with functional MRI. We used BOLD functional Magnetic Resonance Imaging (fMRI to investigate region differences of brain activity between control and malnourished rats. The food-competition method was applied to a rat model to induce malnutrition during lactation. A 7T magnet was used to detect changes of the BOLD signal associated with changes in brain activity caused by the trigeminal nerve stimulation in malnourished and control rats. Major neuronal activation was observed in malnourished rats in several brain regions, including cerebellum, somatosensory cortex, hippocampus, and hypothalamus. Statistical analysis of the BOLD signals from various brain areas revealed significant differences in somatosensory cortex between the control and experimental groups, as well as a significant difference between the cerebellum and other structures in the experimental group. This study, particularly in malnourished rats, demonstrates increased BOLD activation in the cerebellum.

Novel Fluorine-Containing NMDA Antagonists for Brain Imaging: In Vitro Evaluation

Energy Technology Data Exchange (ETDEWEB)

Alvarado, M.; Biegon, A.

2001-01-01

The NMDA receptor has been implicated in neuronal death following stroke, brain injury and neurodegenerative disorders (e.g. Alzheimer's, Parkinson's and Huntington's disease) and in physiological functions (e.g. memory and cognition). Non-competitive antagonists, such as MK- 801 and CNS-1102, that block the action of glutamate at the NMDA receptor have been shown to be neuroprotective by blocking the influx of calcium into the cells. As a result, they are being considered as therapeutic agents for the above mentioned diseases. Several Fluorine-containing novel analogs of NMDA channel blockers have been synthesized and evaluated in search of a compound suitable for 18F labeling and Positron Emission Tomography (PET). Based on in vitro binding assay studies on rat brain membranes, the novel compounds examined displayed a range of affinities. Preliminary analyses indicated that chlorine is the best halogen on the ring, and that ethyl fluoro derivatives are more potent than methyl-fluoro compounds. Further analysis based on autoradiography will be needed to examine the regional binding characteristics of the novel compounds examined in this study. Labeling with 18F will allow the use of these compounds in humans, generating new insights into mechanisms and treatment of diseases involving malfunction of the glutamatergic system in the brain.

Comparison of resilience in adolescent survivors of brain tumors and healthy adolescents.

Science.gov (United States)

Chen, Chin-Mi; Chen, Yueh-Chih; Wong, Tai-Tong

2014-01-01

Resilience is essential for the psychological adjustment of adolescents experiencing difficulty. Comparing differences in resilience between adolescent survivors of brain tumors and healthy adolescents may help identify factors related to resilience in adolescents. The purpose of this study was to clarify how illness impacts the normative development of adolescent survivors of brain tumors by comparing them to healthy adolescents in terms of resilience and how it is affected by various health problems. This cross-sectional, case-control study used convenience sampling to recruit 13- to 18-year-old adolescent survivors of brain tumors and healthy adolescents matched by school level, gender, and living area. Data were collected by structured questionnaires. The sample included 60 adolescent survivors and 120 healthy adolescents. Participants in both groups were predominantly male adolescents (63.3%) and junior high school students (55%). The 2 groups did not differ significantly in resilience, but survivors without emotional problems had a higher mean resilience score than did healthy adolescents and survivors with emotional problems (F = 8.65, P adolescent survivors of brain tumors and healthy adolescents. In addition, the impact of emotional problems on resilience was more severe in brain tumor survivors than in healthy adolescents. Our results suggest that pediatric oncology nurses design interdisciplinary school-based interventions to reduce the impact of emotional problems on resilience in both healthy adolescents and those who survived brain tumors.

Biodistribution of 99m technetium labeled creatinine in healthy rats

International Nuclear Information System (INIS)

Yilmaz, O.; Soylu, A.; Kavukcu, S.; Lambrecht, F. Yurt; Durkan, K.

2007-01-01

The distribution of creatinine, one of the toxic guanidine compounds, in various tissues has not been studied in detail by using radiolabeled creatinine. Our objective was to investigate the biodistribution of creatinine labeled with 99m technetium ( 99m Tc) by the stannous (II) chloride method in healthy male Wistar rats. Quality controls were carried out by radio thin layer chromatography, high-performance liquid chromatography, and paper electrophoresis. The labeling yield was 85 ± 2% under optimum conditions (pH 7 and 100 μg stannous chloride). Rats (N 12) were injected intravenously with 99m Tc creatinine and their blood and visceral organs were evaluated for 99m Tc-creatinine uptake as percent of the injected dose per gram wet weight of each tissue (%ID/g). The lowest amount of uptake was detected in the brain and testis. When the rate of uptake was evaluated, only the kidney showed increasing rates of uptake of 99m Tc-creatinine throughout the study. Kidneys showed the highest amount of uptake throughout the study (P < 0.001 compared to all other organs), followed by liver, spleen and lung tissue. (author)

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

Science.gov (United States)

Wang, Feng; Li, Yong-hong

2010-02-01

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

A Novel Dynamic Neonatal Blood-Brain Barrier on a Chip.

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Sudhir P Deosarkar

Full Text Available Studies of neonatal neural pathologies and development of appropriate therapeutics are hampered by a lack of relevant in vitro models of neonatal blood-brain barrier (BBB. To establish such a model, we have developed a novel blood-brain barrier on a chip (B3C that comprises a tissue compartment and vascular channels placed side-by-side mimicking the three-dimensional morphology, size and flow characteristics of microvessels in vivo. Rat brain endothelial cells (RBEC isolated from neonatal rats were seeded in the vascular channels of B3C and maintained under shear flow conditions, while neonatal rat astrocytes were cultured under static conditions in the tissue compartment of the B3C. RBEC formed continuous endothelial lining with a central lumen along the length of the vascular channels of B3C and exhibited tight junction formation, as measured by the expression of zonula occludens-1 (ZO-1. ZO-1 expression significantly increased with shear flow in the vascular channels and with the presence of astrocyte conditioned medium (ACM or astrocytes cultured in the tissue compartment. Consistent with in vivo BBB, B3C allowed endfeet-like astrocyte-endothelial cell interactions through a porous interface that separates the tissue compartment containing cultured astrocytes from the cultured RBEC in the vascular channels. The permeability of fluorescent 40 kDa dextran from vascular channel to the tissue compartment significantly decreased when RBEC were cultured in the presence of astrocytes or ACM (from 41.0 ± 0.9 x 10-6 cm/s to 2.9 ± 1.0 x 10-6 cm/s or 1.1±0.4 x 10-6 cm/s, respectively. Measurement of electrical resistance in B3C further supports that the addition of ACM significantly improves the barrier function in neonatal RBEC. Moreover, B3C exhibits significantly improved barrier characteristics compared to the transwell model and B3C permeability was not significantly different from the in vivo BBB permeability in neonatal rats. In summary, we

Brain inflammation enhances 1-methyl-4-phenylpyridinium-evoked neurotoxicity in rats

International Nuclear Information System (INIS)

Goralski, Kerry B.; Renton, Kenneth W.

2004-01-01

Experimental Parkinson's disease and Parkinson's disease in humans include a CNS inflammatory component that may contribute to the pathogenesis of the disease. CNS inflammation produces a loss in cytochrome P450 metabolism and may impair the brain's protection against neurotoxins. We have examined if preexisting inflammation in the brain could increase the toxicity of the dopaminergic toxin 1-methyl-4-phenylpyridinium (MPP + ). Lipopolysaccharide (LPS, 25 μg) or saline (control) was injected into the left lateral cerebral ventricle. A single injection of MPP + into the median forebrain bundle followed 48 h later and produced a reduction in striatal dopamine content that was dose and time dependant. Two-days after 5 μg of MPP + was administered, a 90% decrease in striatal dopamine content was observed in saline- and LPS-pretreated rats. However, 4 and 7 days after 5 μg MPP + treatment, striatal dopamine recovered up to 70-80% of control values in saline-pretreated rats but remained depressed (80-90%) in rats treated with LPS. These results suggested that CNS inflammation might create an increased risk factor for drug-induced CNS toxicity or chemically mediated Parkinson's disease. The prolonged toxicity of MPP + may be due to a decrease in brain cytochrome P450 metabolism that occurs during inflammation. As a second objective for the study, we examined if the CNS lesion produced by MPP + altered cytochrome P450 metabolic activity in the liver, kidney, and lung. We have demonstrated a novel mechanism whereby the brain pathology produced by MPP + treatment contributes to a reduction in cytochrome P450 metabolism in the kidney but not the liver or lung. Therefore, a chemically evoked CNS disorder with a chronic inflammatory component might have major effects on the renal metabolism of drugs or endogenous substrates

Novel selective PDE type 1 inhibitors cause vasodilatation and lower blood pressure in rats

DEFF Research Database (Denmark)

Laursen, Morten; Beck, Lilliana; Kehler, Jan

2017-01-01

BACKGROUND AND PURPOSE: The PDE enzymes (PDE1-11) hydrolyse and thus inactivate cyclic nucleotides and are important in the regulation of the cardiovascular system. Here,we have investigated the effects on the cardiovascular system, of two novel selective PDE1 inhibitors, Lu AF41228 and Lu AF58027...... and Lu AF58027 inhibited PDE1A, PDE1B and PDE1C enzyme activity, while micromolar concentrations were required to observe inhibitory effects at other PDEs. RT-PCR revealed expression of PDE1A, PDE1B and PDE1C in rat brain, heart and aorta, but only PDE1A and PDE1B in mesenteric arteries. In rat isolated...... and Lu AF58027 dose-dependently lowered mean BP and increased heart rate. In conscious rats with telemetric pressure transducers, repeated dosing with Lu AF41228 lowered mean arterial BP 10-15 mmHg and increased heart rate. CONCLUSIONS AND IMPLICATIONS: These novel PDE1 inhibitors induce vasodilation...

Brain glucose content in fetuses of ethanol-fed rats

Energy Technology Data Exchange (ETDEWEB)

Pullen, G.; Singh, S.P.; Snyder, A.K.; Hoffen, B.

1986-03-01

The authors have previously demonstrated impaired placental glucose transfer and fetal hypoglycemia in association with ethanol ingestion by pregnant rats. The present study examines the relationship between glucose availability and fetal brain growth under the same conditions. Rats (EF) were fed ethanol (30% of caloric intake) in liquid diet throughout gestation. Controls received isocaloric diet without ethanol by pair-feeding (PF) or ad libitum (AF). On the 22nd day of gestation fetuses were obtained by cesarean section. Fetal brains were removed and freeze-clamped. Brain weight was significantly reduced (p < 0.001) by maternal ethanol ingestion (206 +/- 2, 212 +/- 4 and 194 +/- 2 mg in AF, FP and EF fetuses respectively). Similarly, fetal brain glucose content was lower (p < 0.05) in the EF group (14.3 +/- 0.9 mmoles/g dry weight) than in the PF (18.6 +/- 1.0) or the AF (16.2 +/- 0.9) groups. The protein: DNA ratio, an indicator of cell size, correlated positively (r = 0.371, p < 0.005) with brain glucose content. In conclusion, maternal ethanol ingestion resulted in lower brain weight and reduced brain glucose content. Glucose availability may be a significant factor in the determination of cell size in the fetal rat brain.

Third Trimester Brain Growth in Preterm Infants Compared With In Utero Healthy Fetuses.

Science.gov (United States)

Bouyssi-Kobar, Marine; du Plessis, Adré J; McCarter, Robert; Brossard-Racine, Marie; Murnick, Jonathan; Tinkleman, Laura; Robertson, Richard L; Limperopoulos, Catherine

2016-11-01

Compared with term infants, preterm infants have impaired brain development at term-equivalent age, even in the absence of structural brain injury. However, details regarding the onset and progression of impaired preterm brain development over the third trimester are unknown. Our primary objective was to compare third-trimester brain volumes and brain growth trajectories in ex utero preterm infants without structural brain injury and in healthy in utero fetuses. As a secondary objective, we examined risk factors associated with brain volumes in preterm infants over the third-trimester postconception. Preterm infants born before 32 weeks of gestational age (GA) and weighing <1500 g with no evidence of structural brain injury on conventional MRI and healthy pregnant women were prospectively recruited. Anatomic T2-weighted brain images of preterm infants and healthy fetuses were parcellated into the following regions: cerebrum, cerebellum, brainstem, and intracranial cavity. We studied 205 participants (75 preterm infants and 130 healthy control fetuses) between 27 and 39 weeks' GA. Third-trimester brain volumes were reduced and brain growth trajectories were slower in the ex utero preterm group compared with the in utero healthy fetuses in the cerebrum, cerebellum, brainstem, and intracranial cavity. Clinical risk factors associated with reduced brain volumes included dexamethasone treatment, the presence of extra-axial blood on brain MRI, confirmed sepsis, and duration of oxygen support. These preterm infants exhibited impaired third-trimester global and regional brain growth in the absence of cerebral/cerebellar parenchymal injury detected by using conventional MRI. Copyright © 2016 by the American Academy of Pediatrics.

Hydrophilic solute transport across the rat blood-brain barrier

International Nuclear Information System (INIS)

Lucchesi, K.J.

1987-01-01

Brain capillary permeability-surface area products (PS) of hydrophilic solutes ranging in size from 180 to 5,500 Daltons were measured in rats according to the method of Ohno, Pettigrew and Rapoport. The distribution volume of 70 KD dextran at 10 minutes after i.v. injection was also measured to determine the residual volume of blood in brain tissue at the time of sacrifice. Small test solutes were injected in pairs in order to elucidate whether their transfer into the brain proceeds by diffusion through water- or lipid-filled channels or by vesicular transport. This issue was examined in rats whose blood-brain barrier (BBB) was presumed to be intact (untreated) and in rats that received intracarotid infusions to open the BBB (isosmotic salt (ISS) and hyperosmolar arabinose). Ohno PS values of 3 H-inulin and 14 C-L-glucose in untreated rats were found to decrease as the labelling time was lengthened. This was evidence that a rapidly equilibrating compartment exists between blood and brain that renders the Ohno two-compartment model inadequate for computing true transfer rate constants. When the data were reanalyzed using a multi-compartment graphical analysis, solutes with different molecular radii were found to enter the brain at approximately equal rates. Furthermore, unidirectional transport is likely to be initiated by solute adsorption to a glycocalyx coat on the luminal surface of brain capillary endothelium. Apparently, more inulin than L-glucose was adsorbed, which may account for its slightly faster transfer across the BBB. After rats were treated with intracarotid infusions of ISS or hyperosmolar arabinose, solute PS values were significantly increased, but the ratio of PS for each of the solute pairs approached that of their free-diffusion coefficients

Testosterone supplementation restores vasopressin innervation in the senescent rat brain

NARCIS (Netherlands)

Goudsmit, E.; Fliers, E.; Swaab, D. F.

1988-01-01

The vasopressin (AVP) innervation in the male rat brain is decreased in senescence. This decrease is particularly pronounced in brain regions where AVP fiber density is dependent on plasma levels of sex steroids. Since plasma testosterone levels decrease progressively with age in the rat, the

Chronic choline supplementation improves cognitive and motor performance via modulating oxidative and neurochemical status in rats.

Science.gov (United States)

Tabassum, Saiqa; Haider, Saida; Ahmad, Saara; Madiha, Syeda; Parveen, Tahira

2017-08-01

Choline, an essential nutrient, accounts for multiple functions in the body and brain. While its beneficial effects on healthy adults are not clear, choline supplementation is important during pregnancy for brain development, in elderly patients for support of cognitive performance and in patients with neurological disorders to reduce memory deficits. Thus, the aim of this study is to investigate whether choline administration in healthy adult rats beneficially impacts cognitive and locomotor performance, and associated oxidative and neurochemical outcomes. Two groups, control and choline, received tap water and choline bitartrate, respectively at the dose equivalent to adequate intake for five weeks. Food intake and body weight were monitored daily. Behavioral analysis comprising assessment of cognitive performance (by novel object recognition, passive avoidance and Morris Water Maze test) and locomotor performance (by Open field, Kondziela's inverted screen and beam walking test) were performed. Following testing, rats were decapitated and brain samples were collected for estimation of acetylcholine, redox profile and monoamine measurements. The results showed that chronic choline administration significantly improves cognitive and locomotor performance accompanied by a reduction in oxidative stress, enhanced cholinergic neurotransmission and monoamine levels in the brain of healthy adult rats. Hence, chronic choline intake was found to improve behavioral, oxidative and neurochemical outcomes in the normal population, so it can be suggested that choline tablets can be used as a safe and effective supplement for improving the neurological health of normal individuals and that they might also be beneficial in preventing cognitive and motor disorders later in life. Copyright © 2017 Elsevier Inc. All rights reserved.

Age Dependent Hypothalamic and Pituitary Responses to Novel Environment Stress or Lipopolysaccharide in Rats

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Sandy Koenig

2018-03-01

Full Text Available Previously, we have shown that the transcription factor nuclear factor interleukin (NF-IL6 can be used as an activation marker for inflammatory lipopolysaccharide (LPS-induced and psychological novel environment stress (NES in the rat brain. Here, we aimed to investigate age dependent changes of hypothalamic and pituitary responses to NES (cage switch or LPS (100 μg/kg in 2 and 24 months old rats. Animals were sacrificed at specific time points, blood and brains withdrawn and analyzed using immunohistochemistry, RT-PCR and bioassays. In the old rats, telemetric recording revealed that NES-induced hyperthermia was enhanced and prolonged compared to the young group. Plasma IL-6 levels remained unchanged and hypothalamic IL-6 mRNA expression was increased in the old rats. Interestingly, this response was accompanied by a significant upregulation of corticotropin-releasing hormone mRNA expression only in young rats after NES and overall higher plasma corticosterone levels in all aged animals. Immunohistochemical analysis revealed a significant upregulation of NF-IL6-positive cells in the pituitary after NES or LPS-injection. In another important brain structure implicated in immune-to-brain communication, namely, in the median eminence (ME, NF-IL6-immunoreactivity was increased in aged animals, while the young group showed just minor activation after LPS-stimulation. Interestingly, we found a higher amount of NF-IL6-CD68-positive cells in the posterior pituitary of old rats compared to the young counterparts. Moreover, aging affected the regulation of cytokine interaction in the anterior pituitary lobe. LPS-treatment significantly enhanced the secretion of the cytokines IL-6 and TNFα into supernatants of primary cell cultures of the anterior pituitary. Furthermore, in the young rats, incubation with IL-6 and IL-10 antibodies before LPS-stimulation led to a robust decrease of IL-6 production and an increase of TNFα production by the pituitary

A novel antipyretic action of 15-deoxy-Delta12,14-prostaglandin J2 in the rat brain.

Science.gov (United States)

Mouihate, Abdeslam; Boissé, Lysa; Pittman, Quentin J

2004-02-11

Fever is an important part of the host defense response, yet fever can be detrimental if it is uncontrolled. We provide the first evidence that 15-deoxy-Delta12,14-prostaglandin J2 (15d-PGJ2), an endogenous ligand for peroxisome proliferator-activated receptor gamma (PPARgamma), can attenuate the febrile response to lipopolysaccharide (LPS) in rats via an action on the brain. Furthermore, we show that PPARgamma is expressed in the hypothalamus, an important locus in the brain for fever generation. In addition, 15d-PGJ2 and its synthesizing enzyme (PGD2 synthase) were present in rat cerebrospinal fluid, and their levels were enhanced in response to systemic injection of LPS. The antipyretic effect of 15d-PGJ2 was associated with reduction in LPS-stimulated cyclooxygenase-2 expression in the hypothalamus but not in p44/p42 mitogen-activated protein kinase phosphorylation or in the expression of the PPARgamma. Thus it is likely that there is a parallel induction of an endogenous prostanoid pathway in the brain capable of limiting deleterious actions of the proinflammatory prostaglandin E2-dependent pathway.

In vivo bioimpedance measurement of healthy and ischaemic rat brain: implications for stroke imaging using electrical impedance tomography

International Nuclear Information System (INIS)

Dowrick, T; Blochet, C; Holder, D

2015-01-01

In order to facilitate the imaging of haemorrhagic and ischaemic stroke using frequency difference electrical impedance tomography (EIT), impedance measurements of normal and ischaemic brain, and clotted blood during haemorrhage, were gathered using a four-terminal technique in an in vivo animal model, a first for ischaemic measurements. Differences of 5–10% in impedance were seen between the frequency spectrums of healthy and ischaemic brain, over the frequency range 0–3 kHz, while the spectrum of blood was predominately uniform. The implications of imaging blood/ischaemia in the brain using electrical impedance tomography are discussed, supporting the notion that it will be possible to differentiate stroke from haemorrhage. (paper)

Antitumor efficacy of a novel CLA-PTX microemulsion against brain tumors: in vitro and in vivo findings.

Science.gov (United States)

Li, Dan; Yang, Ke; Li, Jie-Si; Ke, Xi-Yu; Duan, Yu; Du, Ruo; Song, Ping; Yu, Ke-Fu; Ren, Wei; Huang, Dan; Li, Xing-Huo; Hu, Xin; Zhang, Xuan; Zhang, Qiang

2012-01-01

Considering the observations that linoleic acid conjugated with paclitaxel (CLA-PTX) possesses antitumor activity against brain tumors, is able to cross the blood-brain barrier, but has poor water solubility, the purpose of this study was to prepare a novel CLA-PTX microemulsion and evaluate its activity against brain tumors in vitro and in vivo. The in vitro cytotoxicity of a CLA-PTX microemulsion was investigated in C6 glioma cells. The in vivo antitumor activity of the CLA-PTX microemulsion was evaluated in tumor-bearing nude mice and rats. The pharmacokinetics of the CLA-PTX microemulsion were investigated in rats, and its safety was also evaluated in mice. The average droplet size of the CLA-PTX microemulsion was approximately 176.3 ± 0.8 nm and the polydispersity index was 0.294 ± 0.024. In vitro cytotoxicity results showed that the IC(50) of the CLA-PTX microemulsion was 1.61 ± 0.83 μM for a C6 glioma cell line, which was similar to that of free paclitaxel and CLA-PTX solution (P > 0.05). The antitumor activity of the CLA-PTX microemulsion against brain tumors was confirmed in our in vivo C6 glioma tumor-bearing nude mice as well as in a rat model. In contrast, Taxol(®) had almost no significant antitumor effect in C6 glioma tumor-bearing rats, but could markedly inhibit growth of C6 tumors in C6 glioma tumor-bearing nude mice. The pharmacokinetic results indicated that CLA-PTX in solution has a much longer circulation time and produces higher drug plasma concentrations compared with the CLA-PTX microemulsion. The results of the acute toxicity study showed that the LD(50) of CLA-PTX solution was 103.9 mg/kg. In contrast, the CLA-PTX microemulsion was well tolerated in mice when administered at doses up to 200 mg/kg. CLA-PTX microemulsion is a novel formulation with significant antitumor efficacy in the treatment of brain tumors, and is safer than CLA-PTX solution.

Glucose and amino acid metabolism in rat brain during sustained hypoglycemia

International Nuclear Information System (INIS)

Wong, K.L.; Tyce, G.M.

1983-01-01

The metabolism of glucose in brains during sustained hypoglycemia was studied. [U- 14 C]Glucose (20 microCi) was injected into control rats, and into rats at 2.5 hr after a bolus injection of 2 units of insulin followed by a continuous infusion of 0.2 units/100 g rat/hr. This regimen of insulin injection was found to result in steady-state plasma glucose levels between 2.5 and 3.5 mumol per ml. In the brains of control rats carbon was transferred rapidly from glucose to glutamate, glutamine, gamma-aminobutyric acid and aspartate and this carbon was retained in the amino acids for at least 60 min. In the brains of hypoglycemic rats, the conversion of carbon from glucose to amino acids was increased in the first 15 min after injection. After 15 min, the specific activity of the amino acids decreased in insulin-treated rats but not in the controls. The concentrations of alanine, glutamate, and gamma-amino-butyric acid decreased, and the concentration of aspartate increased, in the brains of the hypoglycemic rats. The concentration of pyridoxal-5'-phosphate, a cofactor in many of the reactions whereby these amino acids are formed from tricarboxylic acid cycle intermediates, was less in the insulin-treated rats than in the controls. These data provide evidence that glutamate, glutamine, aspartate, and GABA can serve as energy sources in brain during insulin-induced hypoglycemia

Thymoquinone ameliorates lead-induced brain damage in Sprague Dawley rats.

Science.gov (United States)

Radad, Khaled; Hassanein, Khaled; Al-Shraim, Mubarak; Moldzio, Rudolf; Rausch, Wolf-Dieter

2014-01-01

The present study aims to investigate the protective effects of thymoquinone, the major active ingredient of Nigella sativa seeds, against lead-induced brain damage in Sprague-Dawley rats. In which, 40 rats were divided into four groups (10 rats each). The first group served as control. The second, third and fourth groups received lead acetate, lead acetate and thymoquinone, and thymoquinone only, respectively, for one month. Lead acetate was given in drinking water at a concentration of 0.5 g/l (500 ppm). Thymoquinone was given daily at a dose of 20mg/kg b.w. in corn oil by gastric tube. Control and thymoquinone-treated rats showed normal brain histology. Treatment of rats with lead acetate was shown to produce degeneration of endothelial lining of brain blood vessels with peri-vascular cuffing of mononuclear cells consistent to lymphocytes, congestion of choroid plexus blood vessels, ischemic brain infarction, chromatolysis and neuronal degeneration, microglial reaction and neuronophagia, degeneration of hippocampal and cerebellar neurons, and axonal demyelination. On the other hand, co-administration of thymoquinone with lead acetate markedly decreased the incidence of lead acetate-induced pathological lesions. Thus the current study shed some light on the beneficial effects of thymoquinone against neurotoxic effects of lead in rats. Copyright © 2013 Elsevier GmbH. All rights reserved.

Brain perfusion in acute and chronic hyperglycemia in rats

International Nuclear Information System (INIS)

Kikano, G.E.; LaManna, J.C.; Harik, S.I.

1989-01-01

Recent studies show that acute and chronic hyperglycemia cause a diffuse decrease in regional cerebral blood flow and that chronic hyperglycemia decreases the brain L-glucose space. Since these changes can be caused by a decreased density of perfused brain capillaries, we used 30 adult male Wistar rats to study the effect of acute and chronic hyperglycemia on (1) the brain intravascular space using radioiodinated albumin, (2) the anatomic density of brain capillaries using alkaline phosphatase histochemistry, and (3) the fraction of brain capillaries that are perfused using the fluorescein isothiocyanate-dextran method. Our results indicate that acute and chronic hyperglycemia do not affect the brain intravascular space nor the anatomic density of brain capillaries. Also, there were no differences in capillary recruitment among normoglycemic, acutely hyperglycemic, and chronically hyperglycemic rats. These results suggest that the shrinkage of the brain L-glucose space in chronic hyperglycemia is more likely due to changes in the blood-brain barrier permeability to L-glucose

Radioimmunoassay of met-enkephalin in microdissected areas of paraformaldehyde-fixed rat brain

International Nuclear Information System (INIS)

Correa, F.M.A.; Saavedra, J.M.

1984-01-01

The effects were studied of various sample preparation procedures on rat brain met-enkephalin content, measured by radioimmunoassay. Whole brain met-enkephalin content of rats killed by decapitation followed by immediate tissue freezing was similar to that of rats killed by microwave irradiation and to those of rats anesthetized with pentobarbital or halothane before killing, whether previously perfused with paraformaldehyde or not. In contrast, a decrease (up to 80%) in met-enkephalin concentrations was observed when brain samples were frozen and thawed to mimic the procedure utilized in the ''punch'' technique for analysis of discrete brain nuclei. This decrease was totally prevented by paraformaldehyde perfusion of the brain prior to sacrifice. Brain perfusion did not alter the amount of immunoassayable met-enkephalin extracted from tissue or its profile after Sephadex chromatography. Paraformaldehyde perfusion results in better morphological tissue preservation and facilitates the ''punch'' dissecting technique. Paraformaldehyde perfusion may be the procedure of choice for the measurement of neuropeptides in specific brain nuclei dissected by the ''punch'' technique

Incidence of brain tumours in rats exposed to an aerosol of 239PuO2

International Nuclear Information System (INIS)

Sanders, C.L.; Dagle, G.E.; Mahaffey, J.A.

1992-01-01

Incidence of brain tumours was investigated in 3390 female and male Wistar rats exposed to an aerosol of 239 PuO 2 , or as sham-exposed controls. Lung doses ranged from 0.05 to 22 Gy. In females, six brain tumours were found in 1058 control rats (incidence, 0.6%) and 24 brain tumours in 2134 rats exposed to Pu (incidence, 1.1%); the survival-adjusted level of significance was p = 0.29 for comparing control with exposed females. In males, two brain tumours were found in 60 control rats (incidence, 3.3%) and seven brain tumours in 138 rats exposed to Pu (incidence, 5.1%); the survival-adjusted level of significance was p = 0.33. Brain tumour incidence was about five times greater in male than in female rats (p = 0.0001), a highly significant sex difference in brain tumour incidence. Tumour types were distributed similarly among control and Pu-exposed groups of both sexes; most were astrocytomas. Mean lifespans for rats with brain tumours were not significantly different between control and Pu-exposed rats. (author)

Biodistribution of {sup 99m} technetium labeled creatinine in healthy rats

Energy Technology Data Exchange (ETDEWEB)

Yilmaz, O. [Dokuz Eylul University, Narlidere, Izmir (Turkey). Medical Faculty. Dept. of Animal Research Center; Soylu, A.; Kavukcu, S. [Dokuz Eylul University, Narlidere, Izmir (Turkey). Medical Faculty. Dept. of Pediatrics; Lambrecht, F. Yurt; Durkan, K. [Ege University, Bornova, Izmir (Turkey). Institute of Nuclear Sciences. Dept. of Nuclear Applications]. E-mail: s.kavukcu@deu.edu.tr

2007-06-15

The distribution of creatinine, one of the toxic guanidine compounds, in various tissues has not been studied in detail by using radiolabeled creatinine. Our objective was to investigate the biodistribution of creatinine labeled with {sup 99m}technetium ({sup 99m} Tc) by the stannous (II) chloride method in healthy male Wistar rats. Quality controls were carried out by radio thin layer chromatography, high-performance liquid chromatography, and paper electrophoresis. The labeling yield was 85 {+-} 2% under optimum conditions (pH 7 and 100 {mu}g stannous chloride). Rats (N 12) were injected intravenously with {sup 99m} Tc creatinine and their blood and visceral organs were evaluated for {sup 99m} Tc-creatinine uptake as percent of the injected dose per gram wet weight of each tissue (%ID/g). The lowest amount of uptake was detected in the brain and testis. When the rate of uptake was evaluated, only the kidney showed increasing rates of uptake of {sup 99m} Tc-creatinine throughout the study. Kidneys showed the highest amount of uptake throughout the study (P < 0.001 compared to all other organs), followed by liver, spleen and lung tissue. (author)

Scale-free functional connectivity of the brain is maintained in anesthetized healthy participants but not in patients with unresponsive wakefulness syndrome.

Directory of Open Access Journals (Sweden)

Xiaolin Liu

Full Text Available Loss of consciousness in anesthetized healthy participants and in patients with unresponsive wakefulness syndrome (UWS is associated with substantial alterations of functional connectivity across large-scale brain networks. Yet, a prominent distinction between the two cases is that after anesthesia, brain connectivity and consciousness are spontaneously restored, whereas in patients with UWS this restoration fails to occur, but why? A possible explanation is that the self-organizing capability of the brain is compromised in patients with UWS but not in healthy participants undergoing anesthesia. According to the theory of self-organized criticality, many natural complex systems, including the brain, evolve spontaneously to a critical state wherein system behaviors display spatial and/or temporal scale-invariant characteristics. Here we tested the hypothesis that the scale-free property of brain network organization is in fact fundamentally different between anesthetized healthy participants and UWS patients. We introduced a novel, computationally efficient approach to determine anatomical-functional parcellation of the whole-brain network at increasingly finer spatial scales. We found that in healthy participants, scale-free distributions of node size and node degree were present across wakefulness, propofol sedation, and recovery, despite significant propofol-induced functional connectivity changes. In patients with UWS, the scale-free distribution of node degree was absent, reflecting a fundamental difference between the two groups in adaptive reconfiguration of functional interaction between network components. The maintenance of scale-invariance across propofol sedation in healthy participants suggests the presence of persistent, on-going self-organizing processes to a critical state--a capacity that is compromised in patients with UWS.

Microwave hyperthermia enhancement of methotrexate absorption in rat brains

International Nuclear Information System (INIS)

Lin, J.C.; Yuen, M.K.; Jung, D.T.

1987-01-01

The author studied enhanced absorption of methotrexate (MTX) in brains of male Wistar (10 weeks old, 500g) subjected to microwave hyperthermia. The rat was anesthetized using 40 mg/kg of sodium pentobarbital, IP and was placed in a stereotaxic head holder. Microwave energy (2450 MHz, 2.6 W/cm/sup 2/, CW) were applied directly to the left side of the rat's head by a coaxial applicator for 20 min. The body temperature was kept at 37.8 0 C. The brain temperature recorded in a similar group of animals using a Vitek probe was about 45 0 C. Three different MTX dosages, 50, 100 and 200 mg/kg, were injected intravenously immediately following microwave irradiation into three groups of rats in 1.5, 3 and 6 min., respectively. MTX was allowed to circulate for five min. before brains were removed for analysis. Standard HPLC procedures were applied to samples from anterior and posterior left hemisphere of the cerebrum, and the cerebellum. Samples from the right hemisphere were used for controls. The average absorption at the posterior left hemisphere was found to be 2.4, 9.6 and 12.4μg of MTX/g of brain tissue for 50, 100 and 200 mg/kg, respectively. These results indicate that MTX absorption is significantly increased in rat brains subjected to microwave hyperthermia treatment

Neuroanatomy-based matrix-guided trimming protocol for the rat brain.

Science.gov (United States)

Defazio, Rossella; Criado, Ana; Zantedeschi, Valentina; Scanziani, Eugenio

2015-02-01

Brain trimming through defined neuroanatomical landmarks is recommended to obtain consistent sections in rat toxicity studies. In this article, we describe a matrix-guided trimming protocol that uses channels to reproduce coronal levels of anatomical landmarks. Both setup phase and validation study were performed on Han Wistar male rats (Crl:WI(Han)), 10-week-old, with bodyweight of 298 ± 29 (SD) g, using a matrix (ASI-Instruments(®), Houston, TX) fitted for brains of rats with 200 to 400 g bodyweight. In the setup phase, we identified eight channels, that is, 6, 8, 10, 12, 14, 16, 19, and 21, matching the recommended landmarks midway to the optic chiasm, frontal pole, optic chiasm, infundibulum, mamillary bodies, midbrain, middle cerebellum, and posterior cerebellum, respectively. In the validation study, we trimmed the immersion-fixed brains of 60 rats using the selected channels to determine how consistently the channels reproduced anatomical landmarks. Percentage of success (i.e., presence of expected targets for each level) ranged from 89 to 100%. Where 100% success was not achieved, it was noted that the shift in brain trimming was toward the caudal pole. In conclusion, we developed and validated a trimming protocol for the rat brain that allow comparable extensiveness, homology, and relevance of coronal sections as the landmark-guided trimming with the advantage of being quickly learned by technicians. © 2014 by The Author(s).

The effect of infectious brain edema on NMDA receptor binding in rat's brain

International Nuclear Information System (INIS)

Cheng Guansheng; Chen Jianfang; Chen Xiang

1997-01-01

PURPOSE: The effect of the infectious brain edema (IBE) induced by Bordetella Pertussis (BP) on the specific binding of 3 H MK-801 in rat's brain in vivo was determined. METHODS: BP was injected via left internal carotid artery in rat model of infectious brain edema. Male SD rats were divided into three groups: 1) Group control (NS, n = 11); 2) Group IBF (BP, n = 12); 3) Group pretreatment of MK-801 + PB (MK-801, n = 4). Normal saline or BP 0.2 ml/kg was injected into left internal carotid artery in NS and BP group respectively. MK-801 0.5 mg/kg per day was injected i.p. two days before injection of BP in group MK-801. Rats were killed by decapitation at 24 hours after injection of BP. The specific binding of N-methyl-D-aspartate (NMDA) receptor were measured with 3 H-MK-801 in the neuronal membrane of cerebral cortex. The Scatchard plots were performed. RESULTS: The B max values were 0.623 +- 0.082 and 0.606 +- 0.087 pmol/mg protein in group NS and BP respectively (t = 0.48, P>0.05). The Kd values were 43.1 +- 4.2 and 30.5 +- 3.0 nmol/L in group NS and BP respectively (t = 7.8, P<0.05). The specific binding of NMDA receptor was decreased by pretreatment of MK-801. CONCLUSIONS: The total number of NMDA receptor had not changed, whereas its affinity increased significantly in the model of brain edema induced by pertussis bacilli in rat. The increase of affinity of NMDA receptor can be blockaded by MK-801 pretreatment in vivo

Decreased α1-adrenergic receptor-mediated inositide hydrolysis in neurons from hypertensive rat brain

International Nuclear Information System (INIS)

Feldstein, J.B.; Gonzales, R.A.; Baker, S.P.; Sumners, C.; Crews, F.T.; Raizada, M.K.

1986-01-01

The expression of α 1 -adrenergic receptors and norepinephrine (NE)-stimulated hydrolysis of inositol phospholipid has been studied in neuronal cultures from the brains of normotensive (Wistar-Kyoto, WKY) and spontaneously hypertensive (SH) rats. Binding of 125 I-1-[β-(4-hydroxyphenyl)-ethyl-aminomethyl] tetralone (HEAT) to neuronal membranes was 68-85% specific and was rapid. Competition-inhibition experiments with various agonists and antagonists suggested that 125 I-HEAT bound selectively to α 1 -adrenergic receptors. Specific binding of 125 I-HEAT to neuronal membranes from SH rat brain cultures was 30-45% higher compared with binding in WKY normotensive controls. This increase was attributed to an increase in the number of α 1 -adrenergic receptors on SH rat brain neurons. Incubation of neuronal cultures of rat brain from both strains with NE resulted in a concentration-dependent stimulation of release of inositol phosphates, although neurons from SH rat brains were 40% less responsive compared with WKY controls. The decrease in responsiveness of SH rat brain neurons to NE, even though the α 1 -adrenergic receptors are increased, does not appear to be due to a general defect in membrane receptors and postreceptor signal transduction mechanisms. This is because neither the number of muscarinic-cholinergic receptors nor the carbachol-stimulated release of inositol phosphates is different in neuronal cultures from the brains of SH rats compared with neuronal cultures from the brains of WKY rats. These observations suggest that the increased expression of α 1 -adrenergic receptors does not parallel the receptor-mediated inositol phosphate hydrolysis in neuronal cultures from SH rat brain

Stereological brain volume changes in post-weaned socially isolated rats

DEFF Research Database (Denmark)

Fabricius, Katrine; Helboe, Lone; Steiniger-Brach, Björn

2010-01-01

Rearing rats in isolation after weaning is an environmental manipulation that leads to behavioural and neurochemical alterations that resemble what is seen in schizophrenia. The model is neurodevelopmental in origin and has been used as an animal model of schizophrenia. However, only a few studies...... Lister Hooded rats isolated from postnatal day 25 for 15 weeks. We observed the expected gender differences in total brain volume with males having larger brains than females. Further, we found that isolated males had significantly smaller brains than group-housed controls and larger lateral ventricles...... than controls. However, this was not seen in female rats. Isolated males had a significant smaller hippocampus, dentate gyrus and CA2/3 where isolated females had a significant smaller CA1 compared to controls. Thus, our results indicate that long-term isolation of male rats leads to neuroanatomical...

Studies on estradiol-2/4-hydroxylase activity in rat brain and liver

International Nuclear Information System (INIS)

Theron, C.N.

1985-03-01

A sensitive and specific radio-enzymatic assay was used to study estradiol-2/4-hydroxylase activity in rat liver microsomes and in microsomes obtained from 6 discrete brain areas of the rat. Kinetic parameters were determined for these enzyme activities. The effects of different P-450 inhibitors on estradiol-2/4-hydroxylase activity in brain and liver microsomes were also studied. In both organs these enzyme activities were found to be located mainly in the microsomal fraction and were inhibited by the 3 P-450 inhibitors tested. The hepatic estradiol-2/4-hydroxylase activity in adult male rats was significantly higher than that of females, but the enzyme activity in the brain did not exhibit a similar sex difference. Furthermore, estradiol-2/4-hydroxylase activity in rat liver was strongly induced by phenobarbitone treatment, but not in the brain. The phenobarbitone-induced activity in male and female rats exhibited significant kinetic differences. In female rats sexual maturation was associated with significant changes in the apparent Km of estradiol-2/4-hydroxylases in the liver and hypothalamus. Evidence was found that the in vitro estradiol-2/4-hydroxylase activity in rat brain and liver is due to more than one form of microsomal P-450. Kinetic studies showed important differences between the estradiol-2/4-hydroxylase activities in the hippocampus and hypothalamus. Significant differences in estradiol-2/4-hydroxylase activities were observed in the 6 brain areas studied, with the hippocampus showing the highest, and the hypothalamus the lowest activity at all developmental stages in both male and female rats

Impact of benzodiazepines on brain FDG-PET quantification after single-dose and chronic administration in rats

International Nuclear Information System (INIS)

Silva-Rodríguez, Jesús; García-Varela, Lara; López-Arias, Esteban; Domínguez-Prado, Inés; Cortés, Julia; Pardo-Montero, Juan; Fernández-Ferreiro, Anxo

2016-01-01

Introduction: Current guidelines for brain PET imaging advice against the injection of diazepam prior to brain FDG-PET examination in order to avoid possible interactions of benzodiazepines with the radiotracer uptake. Nevertheless, many patients undergoing PET studies are likely to be under chronic treatment with benzodiazepines, for example due to the use of different medications such as sleeping pills. Animal studies may provide an extensive and accurate estimation of the effect of benzodiazepines on brain metabolism in a well-defined and controlled framework. Aim: This study aims at evaluating the impact of benzodiazepines on brain FDG uptake after single-dose administration and chronic treatment in rats. Methods: Twelve Sprague–Dawley healthy rats were randomly divided into two groups, one treated with diazepam and the other used as control group. Both groups underwent PET/CT examinations after single-dose and chronic administration of diazepam (treated) or saline (controls) during twenty-eight days. Different atlas-based quantification methods were used to explore differences on the total uptake and uptake patterns of FDG between both groups. Results: Our analysis revealed a significant reduction of global FDG uptake after acute (−16.2%) and chronic (−23.2%) administration of diazepam. Moreover, a strong trend pointing to differences between acute and chronic administrations (p < 0.08) was also observed. Uptake levels returned to normal after interrupting the administration of diazepam. On the other hand, patterns of FDG uptake were not affected by the administration of diazepam. Conclusions: The administration of diazepam causes a progressive decrease of the FDG global uptake in the rat brain, but it does not change local patterns within the brain. Under these conditions, visual assessment and quantification methods based on regional differences such as asymmetry indexes or SPM statistical analysis would still be valid when administrating this

Stereological brain volume changes in post-weaned socially isolated rats

DEFF Research Database (Denmark)

Fabricius, Katrine; Helboe, Lone; Steiniger-Brach, Björn

2010-01-01

Lister Hooded rats isolated from postnatal day 25 for 15 weeks. We observed the expected gender differences in total brain volume with males having larger brains than females. Further, we found that isolated males had significantly smaller brains than group-housed controls and larger lateral ventricles...... have evaluated the neuroanatomical changes in this animal model in comparison to changes seen in schizophrenia. In this study, we applied stereological volume estimates to evaluate the total brain, the ventricular system, and the pyramidal and granular cell layers of the hippocampus in male and female...... than controls. However, this was not seen in female rats. Isolated males had a significant smaller hippocampus, dentate gyrus and CA2/3 where isolated females had a significant smaller CA1 compared to controls. Thus, our results indicate that long-term isolation of male rats leads to neuroanatomical...

Increased Oxidative Stress and Mitochondrial Dysfunction in Zucker Diabetic Rat Liver and Brain

Directory of Open Access Journals (Sweden)

Haider Raza

2015-02-01

Full Text Available Background/Aims: The Zucker diabetic fatty (ZDF, FA/FA rat is a genetic model of type 2 diabetes, characterized by insulin resistance with progressive metabolic syndrome. We have previously demonstrated mitochondrial dysfunction and oxidative stress in the heart, kidneys and pancreas of ZDF rats. However, the precise molecular mechanism of disease progression is not clear. Our aim in the present study was to investigate oxidative stress and mitochondrial dysfunction in the liver and brain of ZDF rats. Methods: In this study, we have measured mitochondrial oxidative stress, bioenergetics and redox homeostasis in the liver and brain of ZDF rats. Results: Our results showed increased reactive oxygen species (ROS production in the ZDF rat brain compared to the liver, while nitric oxide (NO production was markedly increased both in the brain and liver. High levels of lipid and protein peroxidation were also observed in these tissues. Glutathione metabolism and mitochondrial respiratory functions were adversely affected in ZDF rats when compared to Zucker lean (ZL, +/FA control rats. Reduced ATP synthesis was also observed in the liver and brain of ZDF rats. Western blot analysis confirmed altered expression of cytochrome P450 2E1, iNOS, p-JNK, and IκB-a confirming an increase in oxidative and metabolic stress in ZDF rat tissues. Conclusions: Our data shows that, like other tissues, ZDF rat liver and brain develop complications associated with redox homeostasis and mitochondrial dysfunction. These results, thus, might have implications in understanding the etiology and pathophysiology of diabesity which in turn, would help in managing the disease associated complications.

A wireless beta-microprobe based on pixelated silicon for in vivo brain studies in freely moving rats

Science.gov (United States)

Märk, J.; Benoit, D.; Balasse, L.; Benoit, M.; Clémens, J. C.; Fieux, S.; Fougeron, D.; Graber-Bolis, J.; Janvier, B.; Jevaud, M.; Genoux, A.; Gisquet-Verrier, P.; Menouni, M.; Pain, F.; Pinot, L.; Tourvielle, C.; Zimmer, L.; Morel, C.; Laniece, P.

2013-07-01

The investigation of neurophysiological mechanisms underlying the functional specificity of brain regions requires the development of technologies that are well adjusted to in vivo studies in small animals. An exciting challenge remains the combination of brain imaging and behavioural studies, which associates molecular processes of neuronal communications to their related actions. A pixelated intracerebral probe (PIXSIC) presents a novel strategy using a submillimetric probe for beta+ radiotracer detection based on a pixelated silicon diode that can be stereotaxically implanted in the brain region of interest. This fully autonomous detection system permits time-resolved high sensitivity measurements of radiotracers with additional imaging features in freely moving rats. An application-specific integrated circuit (ASIC) allows for parallel signal processing of each pixel and enables the wireless operation. All components of the detector were tested and characterized. The beta+ sensitivity of the system was determined with the probe dipped into radiotracer solutions. Monte Carlo simulations served to validate the experimental values and assess the contribution of gamma noise. Preliminary implantation tests on anaesthetized rats proved PIXSIC's functionality in brain tissue. High spatial resolution allows for the visualization of radiotracer concentration in different brain regions with high temporal resolution.

Studies of aluminum in rat brain

Energy Technology Data Exchange (ETDEWEB)

Lipman, J.J.; Brill, A.B.; Som, P.; Jones, K.W.; Colowick, S.; Cholewa, M.

1985-01-01

The effects of high aluminum concentrations in rat brains were studied using /sup 14/C autoradiography to measure the uptake of /sup 14/C 2-deoxy-D-glucose (/sup 14/C-2DG) and microbeam proton-induced x-ray emission (microPIXE) with a 20-..mu..m resolution to measure concentrations of magnesium, aluminum, potassium, and calcium. The aluminum was introduced intracisternally in the form of aluminum tartrate (Al-T) while control animals were given sodium tartrate (Na-T). The /sup 14/C was administered intravenously. The animals receiving Al-T developed seizure disorders and had pathological changes that included cerebral cortical atrophy. The results showed that there was a decreased uptake of /sup 14/C-2DG in cortical regions in which increased aluminum levels were measured, i.e., there is a correlation between the aluminum in the rat brain and decreased brain glucose metabolism. A minimum detection limit of about 16 ppM (mass fraction) or 3 x 10/sup 9/ Al atoms was obtained for Al under the conditions employed. 14 refs., 4 figs., 1 tab.

Studies of aluminum in rat brain

International Nuclear Information System (INIS)

Lipman, J.J.; Brill, A.B.; Som, P.; Jones, K.W.; Colowick, S.; Cholewa, M.

1985-01-01

The effects of high aluminum concentrations in rat brains were studied using 14 C autoradiography to measure the uptake of 14 C 2-deoxy-D-glucose ( 14 C-2DG) and microbeam proton-induced x-ray emission (microPIXE) with a 20-μm resolution to measure concentrations of magnesium, aluminum, potassium, and calcium. The aluminum was introduced intracisternally in the form of aluminum tartrate (Al-T) while control animals were given sodium tartrate (Na-T). The 14 C was administered intravenously. The animals receiving Al-T developed seizure disorders and had pathological changes that included cerebral cortical atrophy. The results showed that there was a decreased uptake of 14 C-2DG in cortical regions in which increased aluminum levels were measured, i.e., there is a correlation between the aluminum in the rat brain and decreased brain glucose metabolism. A minimum detection limit of about 16 ppM (mass fraction) or 3 x 10 9 Al atoms was obtained for Al under the conditions employed. 14 refs., 4 figs., 1 tab

Brain biochemistry of infant mice and rats exposed to lead

Energy Technology Data Exchange (ETDEWEB)

Berber, G.B.; Maes, J.; Gilliavod, N.; Casale, G.

1978-05-01

Brains of rats and mice exposed to lead from birth receive biochemical examinations. Mice are given drinking water with lead and are studied until they are 17 days old. Rats ae given lead in the diet and followed for more than a year. In mice a retardation in body growth and development in brain DNA is found. In rats, cathepsin is enhanced at almost all times. An important role of proteolytic processes and biogenic animes is suggested in lead encephalopathy. (33 references, 7 tables)

Risperidone treatment increases CB1 receptor binding in rat brain

DEFF Research Database (Denmark)

Secher, Anna; Husum, Henriette; Holst, Birgitte

2010-01-01

, the ghrelin receptor, neuropeptide Y, adiponectin and proopiomelanocortin. We investigated whether the expression of these factors was affected in rats chronically treated with the antipsychotic risperidone. METHODS: Male Sprague-Dawley rats were treated with risperidone (1.0 mg/kg/day) or vehicle (20...... showed that risperidone treatment altered CB(1) receptor binding in the rat brain. Risperidone-induced adiposity and metabolic dysfunction in the clinic may be explained by increased CB(1) receptor density in brain regions involved in appetite and regulation of metabolic function....

Effect of ketamine on aquaporin-4 expression and neuronal apoptosis in brain tissues following brain injury in rats

Institute of Scientific and Technical Information of China (English)

Zangong Zhou; Xiangyu Ji; Li Song; Jianfang Song; Shiduan Wang; Yanwei Yin

2006-01-01

BACKGROUND: Aquaporin-4 (AQP-4) is closely related to the formation of brain edema. Neuronal apoptosis plays an important part in the conversion of swelled neuron following traumatic brain injury. At present, the studies on the protective effect of ketamine on brain have involved in its effect on aquaporin-4 expression and neuronal apoptosis in the brain tissues following brain injury in rats.OBJECTIVE: To observe the effect of ketamine on AQP-4 expression and neuronal apoptosis in the brain tissue following rat brain injury, and analyze the time-dependence of ketamine in the treatment of brain injury.DESIGN: Randomized grouping design, controlled animal trial.SETTING: Department of Anesthesiology, the Medical School Hospital of Qingdao University.MATERIALS: Totally 150 rats of clean grade, aged 3 months, were involved and randomized into control group and ketamine-treated group, with 75 rats in each. Each group was divided into 5 subgroups separately at 6,12, 24, 48 and 72 hours after injury, with 15 rats at each time point. Main instruments and reagents:homemade beat machine, ketamine hydrochloride (Hengrui Pharmaceutical Factory, Jiangsu), rabbit anti-rat AQP-4 polyclonal antibody, SABC immunohistochemical reagent kit and TUNEL reagent kit (Boster Co.,Ltd.,Wuhan).METHODS: This trial was carried out in the Institute of Cerebrovascular Disease, Medical College of Qingdao University during March 2005 to February 2006. A weight-dropping rat model of brain injury was created with Feeney method. The rats in the ketamine-treated group were intraperitoneally administered with 50 g/L ketamine (120 mg/kg) one hour after injury, but ketamine was replaced by normal saline in the control group. In each subgroup, the water content of cerebral hemisphere was measured in 5 rats chosen randomly. The left 10 rats in each subgroup were transcardiacally perfused with ketamine, then the brain tissue was made into paraffin sections and stained by haematoxylin and eosin. Neuronal

Intracarotid injection of 195mPt-CDDP on rat brain tumors

International Nuclear Information System (INIS)

Ikawa, Eishi; Kamitani, Hideki; Hori, Tomokatsu; Akaboshi, Mitsuhiko.

1995-01-01

We began to try intracarotid injection of 195m Pt-CDDP on transplanted rats of C6 glioma. As a control, normal rats were also treated with intracarotid injection of 195m Pt-CDDP. After injection, the tumor, the normal brain of injected site, the brain of contralateral site, and the blood were sampled for the measurement of the Pt uptake. On normal rats, the ratio of the Pt uptake of the brain to that of the blood was highest in 20 minutes after injection. The ratio of the Pt uptake of the brain of injected site to that of the blood was almost same as that of the brain of contralateral site, so it seemed that the Pt uptake was not so enhanced with intracarotid injection on the normal brain. On the other hand, the ratio of the Pt uptake of the transplanted brain tumor to that of the blood was greatly higher than that of the normal brain. So it seemed that the intracarotid injection of CDDP may have some activities against brain tumors. This study was now started, so we continue this study further more. (author)

Effects of enriched uranium on developing brain damage of neonatal rats

International Nuclear Information System (INIS)

Gu Guixiong; Zhu Shoupeng; Wang Liuyi; Yang Shuqin; Zhu Lingli

2001-01-01

The model of irradiation-induced brain damage in vivo was settled first of all. The micro-auto-radiographic tracing showed that when the rat's brain at postnatal day after lateral ventricle injection with enriched uranium 235 U the radionuclides were mainly accumulated in the nucleus. At the same time autoradiographic tracks appeared in the cytoplasm and interval between cells. The effects of cerebrum exposure to alpha irradiation by enriched uranium on somatic growth and neuro-behavior development of neonatal rats were examined by determination of multiple parameters. In the growth and development of the neonatal rat's cerebrum exposure to enriched uranium, the somatic growth such as body weight and brain weight increase was lower significantly. The data indicated that the neonatal wistar rats having cerebrum exposure to alpha irradiation by enriched uranium showed delayed growth and abnormal neuro-behavior. The changes of neuron specific enolase (NSE), interleukin-1 β (IL- β), superoxide dismutase (SOD), and endothelin (ET) in cerebellum, cerebral cortex, hippocampus, diencephalons of the rat brain after expose to alpha irradiation by enriched uranium were examined with radioimmunoassay. The results showed that SOD and ET can be elevated by the low dose irradiation of enriched uranium, and can be distinctly inhibited by the high dose. The data in view of biochemistry indicated firstly that alpha irradiation from enriched uranium on the developing brain damage of neonatal rats were of sensibility, fragility and compensation in nervous cells

Effects of enriched uranium on developing brain damage of neonatal rats

Energy Technology Data Exchange (ETDEWEB)

Guixiong, Gu; Shoupeng, Zhu; Liuyi, Wang; Shuqin, Yang; Lingli, Zhu [Suzhou Medical College, Suzhou (China)

2001-04-01

The model of irradiation-induced brain damage in vivo was settled first of all. The micro-auto-radiographic tracing showed that when the rat's brain at postnatal day after lateral ventricle injection with enriched uranium {sup 235}U the radionuclides were mainly accumulated in the nucleus. At the same time autoradiographic tracks appeared in the cytoplasm and interval between cells. The effects of cerebrum exposure to alpha irradiation by enriched uranium on somatic growth and neuro-behavior development of neonatal rats were examined by determination of multiple parameters. In the growth and development of the neonatal rat's cerebrum exposure to enriched uranium, the somatic growth such as body weight and brain weight increase was lower significantly. The data indicated that the neonatal wistar rats having cerebrum exposure to alpha irradiation by enriched uranium showed delayed growth and abnormal neuro-behavior. The changes of neuron specific enolase (NSE), interleukin-1 {beta} (IL- {beta}), superoxide dismutase (SOD), and endothelin (ET) in cerebellum, cerebral cortex, hippocampus, diencephalons of the rat brain after expose to alpha irradiation by enriched uranium were examined with radioimmunoassay. The results showed that SOD and ET can be elevated by the low dose irradiation of enriched uranium, and can be distinctly inhibited by the high dose. The data in view of biochemistry indicated firstly that alpha irradiation from enriched uranium on the developing brain damage of neonatal rats were of sensibility, fragility and compensation in nervous cells.

A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion

Science.gov (United States)

Mitsios, Nick; Saka, Mohamad; Krupinski, Jerzy; Pennucci, Roberta; Sanfeliu, Coral; Wang, Qiuyu; Rubio, Francisco; Gaffney, John; Kumar, Pat; Kumar, Shant; Sullivan, Matthew; Slevin, Mark

2007-01-01

Background Altered gene expression is an important feature of ischemic cerebral injury and affects proteins of many functional classes. We have used microarrays to investigate the changes in gene expression at various times after middle cerebral artery occlusion in human and rat brain. Results Our results demonstrated a significant difference in the number of genes affected and the time-course of expression between the two cases. The total number of deregulated genes in the rat was 335 versus 126 in the human, while, of 393 overlapping genes between the two array sets, 184 were changed only in the rat and 36 in the human with a total of 41 genes deregulated in both cases. Interestingly, the mean fold changes were much higher in the human. The expression of novel genes, including p21-activated kinase 1 (PAK1), matrix metalloproteinase 11 (MMP11) and integrase interactor 1, was further analyzed by RT-PCR, Western blotting and immunohistochemistry. Strong neuronal staining was seen for PAK1 and MMP11. Conclusion Our findings confirmed previous studies reporting that gene expression screening can detect known and unknown transcriptional features of stroke and highlight the importance of research using human brain tissue in the search for novel therapeutic agents. PMID:17997827

Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats.

Science.gov (United States)

McBride, Devin W; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H

2015-09-01

Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 h after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in significantly elevated frontal lobe brain water content 24 and 72 h after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study's results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 h post-SBI. Copyright © 2015 Elsevier B.V. All rights reserved.

Correlation between subacute sensorimotor deficits and brain water content after surgical brain injury in rats

Science.gov (United States)

McBride, Devin W.; Wang, Yuechun; Sherchan, Prativa; Tang, Jiping; Zhang, John H.

2015-01-01

Brain edema is a major contributor to poor outcome and reduced quality of life after surgical brain injury (SBI). Although SBI pathophysiology is well-known, the correlation between cerebral edema and neurological deficits has not been thoroughly examined in the rat model of SBI. Thus, the purpose of this study was to determine the correlation between brain edema and deficits in standard sensorimotor neurobehavior tests for rats subjected to SBI. Sixty male Sprague-Dawley rats were subjected to either sham surgery or surgical brain injury via partial frontal lobectomy. All animals were tested for neurological deficits 24 post-SBI and fourteen were also tested 72 hours after surgery using seven common behavior tests: modified Garcia neuroscore (Neuroscore), beam walking, corner turn test, forelimb placement test, adhesive removal test, beam balance test, and foot fault test. After assessing the functional outcome, animals were euthanized for brain water content measurement. Surgical brain injury resulted in a significantly elevated frontal lobe brain water content 24 and 72 hours after surgery compared to that of sham animals. In all behavior tests, significance was observed between sham and SBI animals. However, a correlation between brain water content and functional outcome was observed for all tests except Neuroscore. The selection of behavior tests is critical to determine the effectiveness of therapeutics. Based on this study’s results, we recommend using beam walking, the corner turn test, the beam balance test, and the foot fault test since correlations with brain water content were observed at both 24 and 72 hours post-SBI. PMID:25975171

Radiation therapy of 9L rat brain tumors

International Nuclear Information System (INIS)

Henderson, S.D.; Kimler, B.F.; Morantz, R.A.

1981-01-01

The effects of radiation therapy on normal rats and on rats burdened with 9L brain tumors have been studied. The heads of normal rats were x-irradiated with single exposures ranging from 1000 R to 2700 R. Following acute exposures greater than 2100 R, all animals died in 8 to 12 days. Approximately 30% of the animals survived beyond 12 days over the range of 1850 to 1950 R; following exposures less than 1850 R, all animals survived the acute radiation effects, and median survival times increased with decreasing exposure. Three fractionated radiation schedules were also studied: 2100 R or 3000 R in 10 equal fractions, and 3000 R in 6 equal fractions, each schedule being administered over a 2 week period. The first schedule produced a MST of greater than 1 1/2 years; the other schedules produced MSTs that were lower. It was determined that by applying a factor of 1.9, similar survival responses of normal rats were obtained with single as with fractionated radiation exposures. Animals burdened with 9L gliosarcoma brain tumors normally died of the disease process within 18 to 28 days ater tumor inoculation. Both single and fractionated radiation therapy resulted in a prolongation of survival of tumor-burdened rats. This prolongation was found to be linearly dependent upon the dose; but only minimally dependent upon the time after inoculation at which therapy was initiated, or upon the fractionation schedule that was used. As with normal animals, similar responses were obtained with single as with fractionated exposures when a factor (1.9) was applied. All tumor-bearing animals died prior to the time that death was observed in normal, irradiated rats. Thus, the 9L gliosarcoma rat brain tumor model can be used for the pre-clinical experimental investigation of new therapeutic schedules involving radiation therapy and adjuvant therapies

Regional brain glucose use in unstressed rats after two days of starvation

International Nuclear Information System (INIS)

Mans, A.M.; Davis, D.W.; Hawkins, R.A.

1987-01-01

Regional brain glucose use was measured in conscious, unrestrained, fed rats and after 2 days of starvation, using quantitative autoradiography and [6- 14 C]glucose. Plasma glucose, lactate, and ketone body concentrations and brain glucose and lactate content were measured in separate groups of rats. Glucose concentrations were lower in starved rats in both plasma and brain; plasma ketone body concentrations were elevated. Glucose use was found to be lower throughout the brain by about 12%. While some areas seemed to be affected more than others, statistical analysis showed that none were exceptionally different. The results could not be explained by increased loss of 14 C as lactate or pyruvate during the experimental period, because the arteriovenous differences of these species were insignificant. The calculated contribution by ketone bodies to the total energy consumption was between 3 and 9% for the brain as a whole in the starved rats and could, therefore, partially account for the depression seen in glucose use. It was concluded that glucose oxidation is slightly depressed throughout the brain after 2 days of starvation

Induction by mercury compounds of brain metallothionein in rats: Hg{sup 0} exposure induces long-lived brain metallothionein

Energy Technology Data Exchange (ETDEWEB)

Yasutake, Akira; Nakano, Atsuhiro [Biochemistry Section, National Institute for Minamata Disease, Kumamoto (Japan); Hirayama, Kimiko [Kumamoto University, College of Medical Science (Japan)

1998-03-01

Metallothionein (MT) is one of the stress proteins which can easily be induced by various kind of heavy metals. However, MT in the brain is difficult to induce because of blood-brain barrier impermeability to most heavy metals. In this paper, we have attempted to induce brain MT in rats by exposure to methylmercury (MeHg) or metallic mercury vapor, both of which are known to penetrate the blood-brain barrier and cause neurological damage. Rats treated with MeHg (40 {mu}mol/kg per day x 5 days, p.o.) showed brain Hg levels as high as 18 {mu}g/g with slight neurological signs 10 days after final administration, but brain MT levels remained unchanged. However, rats exposed to Hg vapor for 7 days showed 7-8 {mu}g Hg/g brain tissue 24 h after cessation of exposure. At that time brain MT levels were about twice the control levels. Although brain Hg levels fell gradually with a half-life of 26 days, MT levels induced by Hg exposure remained unchanged for >2 weeks. Gel fractionation revealed that most Hg was in the brain cytosol fraction and thus bound to MT. Hybridization analysis showed that, despite a significant increase in MT-I and -II mRNA in brain, MT-III mRNA was less affected. Although significant Hg accumulation and MT induction were observed also in kidney and liver of Hg vapor-exposed rats, these decreased more quickly than in brain. The long-lived MT in brain might at least partly be accounted for by longer half-life of Hg accumulated there. The present results showed that exposure to Hg vapor might be a suitable procedure to provide an in vivo model with enhanced brain MT. (orig.) With 4 figs., 1 tab., 27 refs.

The observation of blood-brain barrier of organic mercury poisoned rat

International Nuclear Information System (INIS)

Kuwabara, Takeo; Yuasa, Tatsuhiko; Hidaka, Kazuyuki; Igarashi, Hironaka; Kaneko, Kiyotoshi; Miyatake, Tadashi

1989-01-01

Permeability of the blood-brain barrier (BBB) of methymercury chrolide (MMC) intoxicated rat brain was studied in vivo by gadlinium diethylenetriamine pentaacetic acid (Gd-DTPA) enhanced magnetic resonance imaging (MRI), measuring the longitudinal relaxation time (T 1 ) and the transverse relaxation time (T 2 ). MMC intoxicated rat brain showed the prolonged T 1 in the cerebral white matter and prolonged T 2 in the cerebellar cortex. After Gd-DTPA administration, T 1 of cerebral and cerebellar white matter shortened from 1.647 to 1.344 sec., and 1.290 to 1.223 sec. respectively. On the contrary, T 2 showed no change after Gd-DTPA injection. It was concluded that, although the shortening of T 1 after Gd-DTPA enhancement was rather little when compared with experimental brain ischemia, the shortening of the relaxation time of the MMC intoxicated rat brain was caused by the increased permeability of BBB. (author)

A Microarray Study of Middle Cerebral Occlusion Rat Brain with Acupuncture Intervention

Directory of Open Access Journals (Sweden)

Chao Zhang

2015-01-01

Full Text Available Microarray analysis was used to investigate the changes of gene expression of ischemic stroke and acupuncture intervention in middle cerebral artery occlusion (MCAo rat brain. Results showed that acupuncture intervention had a remarkable improvement in neural deficit score, cerebral blood flow, and cerebral infarction volume of MCAo rats. Microarray analysis showed that a total of 627 different expression genes were regulated in ischemic stroke. 417 genes were upregulated and 210 genes were downregulated. A total of 361 different expression genes were regulated after acupuncture intervention. Three genes were upregulated and 358 genes were downregulated. The expression of novel genes after acupuncture intervention, including Tph1 and Olr883, was further analyzed by Real-Time Quantitative Polymerase Chain Reaction (RT-PCR. Upregulation of Tph1 and downregulation of Olr883 indicated that the therapeutic effect of acupuncture for ischemic stroke may be closely related to the suppression of poststroke depression and regulation of olfactory transduction. In conclusion, the present study may enrich our understanding of the multiple pathological process of ischemic brain injury and indicate possible mechanisms of acupuncture on ischemic stroke.

MRI-based Brain Healthcare Quotients: A bridge between neural and behavioral analyses for keeping the brain healthy.

Science.gov (United States)

Nemoto, Kiyotaka; Oka, Hiroki; Fukuda, Hiroki; Yamakawa, Yoshinori

2017-01-01

Neurological and psychiatric disorders are a burden on social and economic resources. Therefore, maintaining brain health and preventing these disorders are important. While the physiological functions of the brain are well studied, few studies have focused on keeping the brain healthy from a neuroscientific viewpoint. We propose a magnetic resonance imaging (MRI)-based quotient for monitoring brain health, the Brain Healthcare Quotient (BHQ), which is based on the volume of gray matter (GM) and the fractional anisotropy (FA) of white matter (WM). We recruited 144 healthy adults to acquire structural neuroimaging data, including T1-weighted images and diffusion tensor images, and data associated with both physical (BMI, blood pressure, and daily time use) and social (subjective socioeconomic status, subjective well-being, post-materialism and Epicureanism) factors. We confirmed that the BHQ was sensitive to an age-related decline in GM volume and WM integrity. Further analysis revealed that the BHQ was critically affected by both physical and social factors. We believe that our BHQ is a simple yet highly sensitive, valid measure for brain health research that will bridge the needs of the scientific community and society and help us lead better lives in which we stay healthy, active, and sharp.

MRI-based Brain Healthcare Quotients: A bridge between neural and behavioral analyses for keeping the brain healthy.

Directory of Open Access Journals (Sweden)

Kiyotaka Nemoto

Full Text Available Neurological and psychiatric disorders are a burden on social and economic resources. Therefore, maintaining brain health and preventing these disorders are important. While the physiological functions of the brain are well studied, few studies have focused on keeping the brain healthy from a neuroscientific viewpoint. We propose a magnetic resonance imaging (MRI-based quotient for monitoring brain health, the Brain Healthcare Quotient (BHQ, which is based on the volume of gray matter (GM and the fractional anisotropy (FA of white matter (WM. We recruited 144 healthy adults to acquire structural neuroimaging data, including T1-weighted images and diffusion tensor images, and data associated with both physical (BMI, blood pressure, and daily time use and social (subjective socioeconomic status, subjective well-being, post-materialism and Epicureanism factors. We confirmed that the BHQ was sensitive to an age-related decline in GM volume and WM integrity. Further analysis revealed that the BHQ was critically affected by both physical and social factors. We believe that our BHQ is a simple yet highly sensitive, valid measure for brain health research that will bridge the needs of the scientific community and society and help us lead better lives in which we stay healthy, active, and sharp.

Cyclosporin safety in a simplified rat brain tumor implantation model

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Francisco H. C. Felix

2012-01-01

Full Text Available Brain cancer is the second neurological cause of death. A simplified animal brain tumor model using W256 (carcinoma 256, Walker cell line was developed to permit the testing of novel treatment modalities. Wistar rats had a cell tumor solution inoculated stereotactically in the basal ganglia (right subfrontal caudate. This model yielded tumor growth in 95% of the animals, and showed absence of extracranial metastasis and systemic infection. Survival median was 10 days. Estimated tumor volume was 17.08±6.7 mm³ on the 7th day and 67.25±19.8 mm³ on 9th day post-inoculation. Doubling time was 24.25 h. Tumor growth induced cachexia, but no hematological or biochemical alterations. This model behaved as an undifferentiated tumor and can be promising for studying tumor cell migration in the central nervous system. Dexamethasone 3.0 mg/kg/day diminished significantly survival in this model. Cyclosporine 10 mg/kg/day administration was safely tolerated.

Brain and Serum Androsterone is Elevated in Response to Stress in Rats with Mild Traumatic Brain Injury

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Richard J Servatius

2016-08-01

Full Text Available Exposure to lateral fluid percussion (LFP injury consistent with mild traumatic brain injury (mTBI persistently attenuates acoustic startle responses (ASRs in rats. Here, we examined whether the experience of head trauma affects stress reactivity. Male Sprague-Dawley rats were matched for ASRs and randomly assigned to receive mTBI through LFP or experience a sham surgery (SHAM. ASRs were measured post injury days (PIDs 1, 3, 7, 14, 21 and 28. To assess neurosteroids, rats received a single 2.0 mA, 0.5 s foot shock on PID 34 (S34, PID 35 (S35, on both days (2S, or the experimental context (CON. Levels of the neurosteroids pregnenolone (PREG, allopregnanolone (ALLO, and androsterone (ANDRO were determined for the prefrontal cortex, hippocampus and cerebellum. For 2S rats, repeated blood samples were obtained at 15, 30 and 60 min post-stressor for determination of corticosterone (CORT levels after stress or context on PID 34. Similar to earlier work, ASRs were severely attenuated in mTBI rats without remission for 28 days after injury. No differences were observed between mTBI and SHAM rats in basal CORT, peak CORT levels or its recovery. In serum and brain, ANDRO levels were the most stress-sensitive. Stress-induced ANDRO elevations were greater than those in mTBI rats. As a positive allosteric modulator of gamma-aminobutyric acid (GABAA receptors, increased brain ANDRO levels are expected to be anxiolytic. The impact of brain ANDRO elevations in the aftermath of mTBI on coping warrants further elaboration.

Cognitive dysfunction and histological findings in adult rats one year after whole brain irradiation

International Nuclear Information System (INIS)

Akiyama, Katsuhiko; Tanaka, Ryuichi; Sato, Mitsuya; Takeda, Norio

2001-01-01

Cognitive dysfunction and histological changes in the brain were investigated following irradiation in 20 Fischer 344 rats aged 6 months treated with whole brain irradiation (WBR) (25 Gy/single dose), and compared with the same number of sham-irradiated rats as controls. Performance of the Morris water maze task and the passive avoidance task were examined one year after WBR. Finally, histological and immunohistochemical examinations using antibodies to myelin basic protein (MBP), glial fibrillary acidic protein (GFAP), and neurofilament (NF) were performed of the rat brains. The irradiated rats continued to gain weight 7 months after WBR whereas the control rats stopped gaining weight. Cognitive functions in both the water maze task and the passive avoidance task were lower in the irradiated rats than in the control rats. Brain damage consisting of demyelination only or with necrosis was found mainly in the body of the corpus callosum and the parietal white matter near the corpus callosum in the irradiated rats. Immunohistochemical examination of the brains without necrosis found MBP-positive fibers were markedly decreased in the affected areas by irradiation; NF-positive fibers were moderately decreased and irregularly dispersed in various shapes in the affected areas; and GFAP-positive fibers were increased, with gliosis in those areas. These findings are similar to those in clinically accelerated brain aging in conditions such as Alzheimer's disease, Binswanger's disease, and multiple sclerosis. (author)

Glucose metabolism of fetal rat brain in utero, measured with labeled deoxyglucose

Energy Technology Data Exchange (ETDEWEB)

Dyve, S [Department of General Physiology and Biophysics, Panum Institute, Copenhagen (Denmark); Gjedde, A [Positron Imaging Laboratories, McConnell Brain Imaging Center, Montreal, Quebec (Canada)

1991-01-01

Mammals have low cerebral metabolic rates immediately after birth and, by inference, also before birth. In this study, we extended the deoxyglucose method to the fetal rat brain in utero. Rate constants for deoxyglucose transfer across the maternal placental and fetal blood-brain barriers, and lumped constant, have not been reported. Therefore, we applied a new method of determining the lumped constant regionally to the fetal rat brain in utero. The lumped constant averaged 0.55 +- 0.15 relative to the maternal circulation. On this basis, we determined the glucose metabolic rate of the fetal rat brain to be one third of the corresponding maternal value, or 19 +- 2 {mu}mol hg{sup -1} min{sup -1}. (author).

Global Proteomic Analysis of Brain Tissues in Transient Ischemia Brain Damage in Rats

Directory of Open Access Journals (Sweden)

Jiann-Hwa Chen

2015-05-01

Full Text Available Ischemia-reperfusion injury resulting from arterial occlusion or hypotension in patients leads to tissue hypoxia with glucose deprivation, which causes endoplasmic reticulum (ER stress and neuronal death. A proteomic approach was used to identify the differentially expressed proteins in the brain of rats following a global ischemic stroke. The mechanisms involved the action in apoptotic and ER stress pathways. Rats were treated with ischemia-reperfusion brain injuries by the bilateral occlusion of the common carotid artery. The cortical neuron proteins from the stroke animal model (SAM and the control rats were separated using two-dimensional gel electrophoresis (2-DE to purify and identify the protein profiles. Our results demonstrated that the SAM rats experienced brain cell death in the ischemic core. Fifteen proteins were expressed differentially between the SAM rats and control rats, which were assayed and validated in vivo and in vitro. Interestingly, the set of differentially expressed, down-regulated proteins included catechol O-methyltransferase (COMT and cathepsin D (CATD, which are implicated in oxidative stress, inflammatory response and apoptosis. After an ischemic stroke, one protein spot, namely the calretinin (CALB2 protein, showed increased expression. It mediated the effects of SAM administration on the apoptotic and ER stress pathways. Our results demonstrate that the ischemic injury of neuronal cells increased cell cytoxicity and apoptosis, which were accompanied by sustained activation of the IRE1-alpha/TRAF2, JNK1/2, and p38 MAPK pathways. Proteomic analysis suggested that the differential expression of CALB2 during a global ischemic stroke could be involved in the mechanisms of ER stress-induced neuronal cell apoptosis, which occurred via IRE1-alpha/TRAF2 complex formation, with activation of JNK1/2 and p38 MAPK. Based on these results, we also provide the molecular evidence supporting the ischemia

Brain energy metabolism and blood flow differences in healthy aging

DEFF Research Database (Denmark)

Aanerud, Joel; Borghammer, Per; Chakravarty, M Mallar

2012-01-01

Cerebral metabolic rate of oxygen consumption (CMRO(2)), cerebral blood flow (CBF), and oxygen extraction fraction (OEF) are important indices of healthy aging of the brain. Although a frequent topic of study, changes of CBF and CMRO(2) during normal aging are still controversial, as some authors......, and in the temporal cortex. Because of the inverse relation between OEF and capillary oxygen tension, increased OEF can compromise oxygen delivery to neurons, with possible perturbation of energy turnover. The results establish a possible mechanism of progression from healthy to unhealthy brain aging, as the regions...

Radio frequency radiation effects on protein kinase C activity in rats' brain

International Nuclear Information System (INIS)

Paulraj, R.; Behari, J.

2004-01-01

The present work describes the effect of amplitude modulated radio frequency (rf) radiation (112 MHz amplitude-modulated at 16 Hz) on calcium-dependent protein kinase C (PKC) activity on developing rat brain. Thirty-five days old Wistar rats were used for this study. The rats were exposed 2 h per day for 35 days at a power density of 1.0 mW/cm 2 (SAR=1.48 W/kg). After exposure, rats were sacrificed and PKC was determined in whole brain, hippocampus and whole brain minus hippocampus separately. A significant decrease in the enzyme level was observed in the exposed group as compared to the sham exposed group. These results indicate that this type of radiation could affect membrane bound enzymes associated with cell signaling, proliferation and differentiation. This may also suggest an affect on the behavior of chronically exposed rats

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.

A diet enriched with Mugil cephalus processed roes modulates the tissue lipid profile in healthy rats: a biochemical and chemometric assessment.

Science.gov (United States)

Rosa, A; Atzeri, A; Putzu, D; Scano, P

2016-01-01

The effect of a diet enriched with mullet bottarga on the lipid profile (total lipids, total cholesterol, unsaturated fatty acids, α-tocopherol, and hydroperoxides) of plasma, liver, kidney, brain, and perirenal adipose tissues of healthy rats was investigated. Rats fed a 10% bottarga enriched-diet for 5 days showed body weights and tissue total lipid and cholesterol levels similar to those of animals fed control diet. Univariate and multivariate results showed that bottarga enriched-diet modified the fatty acid profile in all tissues, except brain. Significant increases of n-3 PUFA, particularly EPA, were observed together with a 20:4 n-6 decrease in plasma, liver, and kidney. Perirenal adipose tissue showed a fat accumulation that reflected the diet composition. The overall data suggest that mullet bottarga may be considered as a natural bioavailable source of n-3 PUFA and qualify it as a traditional food product with functional properties and a potential functional ingredient for preparation of n-3 PUFA enriched foods.

Free-Radical Scavenger Edaravone Treatment Confers Neuroprotection Against Traumatic Brain Injury in Rats

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Wang, Guo-Hua; Li, Yong-Cai; Li, Xia; Shi, Hong; Gao, Yan-Qin; Vosler, Peter S.

2011-01-01

Abstract Traumatic brain injury (TBI) is one of the leading causes of neurological disability in young adults. Edaravone, a novel synthetic small-molecule free-radical scavenger, has been shown to have a neuroprotective effect in both animal models of cerebral ischemia and stroke patients; however, the underlying mechanism is poorly understood. In this report, we investigated the potential mechanisms of edaravone treatment in a rat model of TBI. TBI was induced in the right cerebral cortex of male adult rats using Feeney's weight-drop method. Edaravone (0.75, 1.5, or 3 mg/kg) or vehicle (normal saline) was intravenously administered at 2 and 12 h after TBI. Edaravone treatment significantly decreased hippocampal CA3 neuron loss, reduced oxidative stress, and decreased neuronal programmed cell death compared to vehicle treatment. The protective effects of edaravone treatment were also related to the pathology of TBI on non-neuronal cells, as edaravone decreased astrocyte and glial activation. Lastly, edaravone treatment significantly reduced the presence of inflammatory cytokines, cerebral edema, blood–brain barrier (BBB) permeability, and, importantly, neurological deficits following TBI. Our results suggest that edaravone exerts a neuroprotective effect in the rat model of TBI. The likely mechanism is via inhibiting oxidative stress, leading to a decreased inflammatory response and glial activation, and thereby reducing neuronal death and improving neurological function. PMID:21732763

Elemental concentration analysis in the brain of young and old Wistar rats by total reflection X-ray fluorescence spectrometry

International Nuclear Information System (INIS)

Serpa, Renata F.B.; Jesus, Edgar F.O. de; Lopes, Ricardo T.; Anjos, Marcelino J. dos; Carmo, Maria G.T. do; Rocha, Monica S.; Moreira, Silvana; Martinez, Ana M.B.

2007-01-01

It is well known that aging is associated with neurobehavioral deficits. The aging process of human brain is characterized by progressive neuronal loss. Furthermore, certain brain areas are more vulnerable to neuronal degeneration than others, reflecting an altered resistance to stress of the tissue itself and/or the lack of adequate immunological defense mechanisms in these regions. About the elemental levels in the brain, it is known that the excess ou deficiency of some elements are toxic for human healthy, being also related to several neurodegenerative diseases. In this way, the main goal of this work was to determine the elemental concentration in the hippocampus of young and old male (n = 10) and female (n = 10) Wistar rats by total reflection X-ray fluorescence spectrometry with synchrotron radiation (SR-TXRF). These measurements were carried out at XRF beam line at Light Synchrotron Brazilian Laboratory, Campinas, Brazil. About the results, we could observe that Al, Fe, Cu, Zn and Br levels were higher in the hippocampus of the old female rats than the young ones. On the other hand, only Cu levels were higher in the hippocampus of the old male rats than the young ones. Therefore, the aging of the hippocampus of the female rats can be characterized by an accumulate for Al, Fe, Cu, Zn and Br. The excess in these elements levels are also associated with several neurodegenerative disorders, such as Alzheimer' disease, Parkinson's disease and Huntington's disease. (author)

Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats

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Jian-Qin Wang

2014-01-01

Full Text Available Objective. Numerous epidemiological studies have linked diabetes mellitus (DM with an increased risk of developing Alzheimer’s disease (AD. However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ- induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC. Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies.

Brain Aging and AD-Like Pathology in Streptozotocin-Induced Diabetic Rats

Science.gov (United States)

Wang, Jian-Qin; Yin, Jie; Song, Yan-Feng; Zhang, Lang; Ren, Ying-Xiang; Wang, De-Gui; Gao, Li-Ping; Jing, Yu-Hong

2014-01-01

Objective. Numerous epidemiological studies have linked diabetes mellitus (DM) with an increased risk of developing Alzheimer's disease (AD). However, whether or not diabetic encephalopathy shows AD-like pathology remains unclear. Research Design and Methods. Forebrain and hippocampal volumes were measured using stereology in serial coronal sections of the brain in streptozotocin- (STZ-) induced rats. Neurodegeneration in the frontal cortex, hypothalamus, and hippocampus was evaluated using Fluoro-Jade C (FJC). Aβ aggregation in the frontal cortex and hippocampus was tested using immunohistochemistry and ELISA. Dendritic spine density in the frontal cortex and hippocampus was measured using Golgi staining, and western blot was conducted to detect the levels of synaptophysin. Cognitive ability was evaluated through the Morris water maze and inhibitory avoidant box. Results. Rats are characterized by insulin deficiency accompanied with polydipsia, polyphagia, polyuria, and weight loss after STZ injection. The number of FJC-positive cells significantly increased in discrete brain regions of the diabetic rats compared with the age-matched control rats. Hippocampal atrophy, Aβ aggregation, and synapse loss were observed in the diabetic rats compared with the control rats. The learning and memory of the diabetic rats decreased compared with those of the age-matched control rats. Conclusions. Our results suggested that aberrant metabolism induced brain aging as characterized by AD-like pathologies. PMID:25197672

Correlation Between Subacute Sensorimotor Deficits and Brain Edema in Rats after Surgical Brain Injury.

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McBride, Devin W; Wang, Yuechun; Adam, Loic; Oudin, Guillaume; Louis, Jean-Sébastien; Tang, Jiping; Zhang, John H

2016-01-01

No matter how carefully a neurosurgical procedure is performed, it is intrinsically linked to postoperative deficits resulting in delayed healing caused by direct trauma, hemorrhage, and brain edema, termed surgical brain injury (SBI). Cerebral edema occurs several hours after SBI and is a major contributor to patient morbidity, resulting in increased postoperative care. Currently, the correlation between functional recovery and brain edema after SBI remains unknown. Here we examine the correlation between neurological function and brain water content in rats 42 h after SBI. SBI was induced in male Sprague-Dawley rats via frontal lobectomy. Twenty-four hours post-ictus animals were subjected to four neurobehavior tests: composite Garcia neuroscore, beam walking test, corner turn test, and beam balance test. Animals were then sacrificed for right-frontal brain water content measurement via the wet-dry method. Right-frontal lobe brain water content was found to significantly correlate with neurobehavioral deficits in the corner turn and beam balance tests: the number of left turns (percentage of total turns) for the corner turn test and distance traveled for the beam balance test were both inversely proportional with brain water content. No correlation was observed for the composite Garcia neuroscore or the beam walking test.

CNS-syndrome. Characterization of rat brain intermediate filaments

International Nuclear Information System (INIS)

Nedzvetskij, V.S.; Busygina, S.G.; Berezin, V.A.; Dvoretskij, A.I.

1990-01-01

A study was made of the effect of ionizing radiation on the content and polypeptide composition of filamentous and soluble glial fibrillary acidic protein (GFAP) in different regions of rat brain. Ionizing radiation was shown to decrease considerably the level of soluble GFAP in cerebral cortex, cerebellum, middle brain and hippocampus. Polypeptide composition of soluble GFAP detected by the immonublot-method was found to be changed considerably in different brain areas of irradiated animals

Changes of interleukin-1β, tumor necrosis factor α and interleukin-6 in brain and plasma after brain injury in rats

Institute of Scientific and Technical Information of China (English)

朱涛; 姚智; 袁汉娜; 陆伯刚; 杨树源

2004-01-01

Objective: To study the changes of interleukin-1 β (IL-1β), tumor necrosis factor α (TNFα) and interleukin-6 (IL-6) levels in brain and plasma after brain injury and to assess the relationship between the cytokine levels and injury severity in rats. Methods: A total of 51 male Wistar rats, weighing 280-340 g, were anesthetized with chloral hydrate (400 mg/kg body weight) through intraperitoneal injection and fixed on a stereotaxic instrument. Severe brain injury was created in 16 rats (severe injury group) and moderate brain injury in 18 rats (moderate injury group) by a fluid percussion model, and cytokine levels of IL-1β, TNFα and IL-6 were measured with biological assay. And sham operation was made on the other 17 rats (control group). Results: In the control group, the levels of IL-1β, TNFα and IL-6 were hardly detected in the cortex of the rats, but in the ipsilateral cortex of the rats in both injury groups, they increased obviously at 8 hours after injury. The increasing degree of these cytokines had no significant difference between the two injury groups. The levels of IL-6 in the plasma of all the rats increased slightly, whereas the levels of IL-1β and TNFα were undetectable. Conclusions: The increase of IL-1β, TNFα and IL-6 levels is closely related to brain injury. The increased cytokine levels in the central nervous system are not parallel to those in the peripheral blood. It suggests that inflammatory cytokines play important roles in the secondary neural damage after brain injury.

In vivo imaging of brain androgen receptors in rats: a [18F]FDHT PET study

International Nuclear Information System (INIS)

Khayum, M.A.; Doorduin, J.; Antunes, I.F.; Kwizera, C.; Zijlma, R.; Boer, J.A. den; Dierckx, R.A.J.O.; Vries, E.F.J. de

2015-01-01

Introduction: Steroid hormones like androgens play an important role in the development and maintenance of several brain functions. Androgens can act through androgen receptors (AR) in the brain. This study aims to demonstrate the feasibility of positron emission tomography (PET) with 16β-[ 18 F]fluoro-5α-dihydrotestosterone ([ 18 F]FDHT) to image AR expression in the brain. Methods: Male Wistar rats were either orchiectomized to inhibit endogenous androgen production or underwent sham-surgery. Fifteen days after surgery, rats were subjected to a 90-min dynamic [ 18 F]FDHT PET scan with arterial blood sampling. In a subset of orchiectomized rats, 1 mg/kg dihydrotestosterone was co-injected with the tracer in order to saturate the AR. Plasma samples were analyzed for the presence of radioactive metabolites by radio-TLC. Pharmacokinetic modeling was performed to quantify brain kinetics of the tracer. After the PET scan, the animals were terminated for ex-vivo biodistribution. Results: PET imaging and ex vivo biodistribution studies showed low [ 18 F]FDHT uptake in all brain regions, except pituitary. [ 18 F]FDHT uptake in the surrounding cranial bones was high and increased over time. [ 18 F]FDHT was rapidly metabolized in rats. Metabolism was significantly faster in orchiectomized rats than in sham-orchiectomized rats. Quantitative analysis of PET data indicated substantial spill-over of activity from cranial bones into peripheral brain regions, which prevented further analysis of peripheral brain regions. Logan graphical analysis and kinetic modeling using 1- and 2-tissue compartment models showed reversible and homogenously distributed tracer uptake in central brain regions. [ 18 F]FDHT uptake in the brain could not be blocked by endogenous androgens or administration of dihydrotestosterone. Conclusion: The results of this study indicate that imaging of AR availability in rat brain with [ 18 F]FDHT PET is not feasible. The low AR expression in the brain, the

Outer brain barriers in rat and human development

DEFF Research Database (Denmark)

Brøchner, Christian B; Holst, Camilla Bjørnbak; Møllgård, Kjeld

2015-01-01

Complex barriers at the brain's surface, particularly in development, are poorly defined. In the adult, arachnoid blood-cerebrospinal fluid (CSF) barrier separates the fenestrated dural vessels from the CSF by means of a cell layer joined by tight junctions. Outer CSF-brain barrier provides...... diffusion restriction between brain and subarachnoid CSF through an initial radial glial end feet layer covered with a pial surface layer. To further characterize these interfaces we examined embryonic rat brains from E10 to P0 and forebrains from human embryos and fetuses (6-21st weeks post...

Trillium tschonoskii maxim saponin mitigates D-galactose-induced brain aging of rats through rescuing dysfunctional autophagy mediated by Rheb-mTOR signal pathway.

Science.gov (United States)

Wang, Lingjie; Du, Junlong; Zhao, Fangyu; Chen, Zonghai; Chang, Jingru; Qin, Furong; Wang, Zili; Wang, Fengjie; Chen, Xianbing; Chen, Ning

2018-02-01

During the expansion of aging population, the study correlated with brain aging is one of the important research topics. Developing novel and effective strategies for delaying brain aging is highly desired. Brain aging is characteristics of impaired cognitive capacity due to dysfunctional autophagy regulated by Rheb-mTOR signal pathway in hippocampal tissues. In the present study, we have established a rat model with brain aging through subcutaneous injection of D-galactose (D-gal). Upon the intervention of Trillium tschonoskii Maxim (TTM) saponin, one of bioactive components from local natural herbs in China, the learning and memory capacity of D-gal-induced aging rats was evaluated through Morris water maze test, and the regulation of Rheb-mTOR signal pathway and functional status of autophagy in hippocampal tissues of D-gal-induced aging rats was explored by Western blot. TTM saponin revealed an obvious function to improve learning and memory capacity of D-gal-induced aging rats through up-regulating Rheb and down-regulating mTOR, thereby rescuing dysfunctional autophagy to execute anti-aging role. Meanwhile, this study confirmed the function of TTM saponin for preventing and treating brain aging, and provided a reference for the development and utilization of natural products in health promotion and aging-associated disease treatment. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Curcumin pretreatment attenuates brain lesion size and improves neurological function following traumatic brain injury in the rat.

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Samini, Fariborz; Samarghandian, Saeed; Borji, Abasalt; Mohammadi, Gholamreza; bakaian, Mahdi

2013-09-01

Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow coloring principle in turmeric, is a polyphenolic and a major active constituent. Besides anti-inflammatory, thrombolytic and anti-carcinogenic activities, curcumin also possesses strong antioxidant property. The neuroprotective effects of curcumin were evaluated in a weight drop model of cortical contusion trauma in rat. Male Wistar rats (350-400 g, n=9) were anesthetized with sodium pentobarbital (60 mg/kg i.p.) and subjected to head injury. Five days before injury, animals randomly received an i.p. bolus of either curcumin (50 and 100 mg/kg/day, n=9) or vehicle (n=9). Two weeks after the injury and drug treatment, animals were sacrificed and a series of brain sections, stained with hematoxylin and eosin (H&E) were evaluated for quantitative brain lesion volume. Two weeks after the injury, oxidative stress parameter (malondialdehyde) was also measured in the brain. Curcumin (100 mg/kg) significantly reduced the size of brain injury-induced lesions (Pcurcumin (100 mg/kg). Curcumin treatment significantly improved the neurological status evaluated during 2 weeks after brain injury. The study demonstrates the protective efficacy of curcumin in rat traumatic brain injury model. © 2013 Elsevier Inc. All rights reserved.

Carnosine supplementation protects rat brain tissue against ethanol-induced oxidative stress.

Science.gov (United States)

Ozel Turkcu, Ummuhani; Bilgihan, Ayşe; Biberoglu, Gursel; Mertoglu Caglar, Oznur

2010-06-01

Ethanol causes oxidative stress and tissue damage. The aim of this study was to investigate the effect of antioxidant carnosine on the oxidative stress induced by ethanol in the rat brain tissue. Forty male rats were divided equally into four groups as control, carnosine (CAR), ethanol (EtOH), and ethanol plus carnosine (EtOH + CAR). Rats in the control group (n = 10) were injected intraperitoneally (i.p.) with 0.9% saline; EtOH group (n = 10) with 2 g/kg/day ethanol, CAR group (n = 10) received carnosine at a dose of 1 mg/kg/day and EtOH + CAR group (n = 10) received carnosine (orally) and ethanol (i.p.). All animals were sacrificed using ketamine and brain tissues were removed. Malondialdehyde (MDA), protein carbonyl (PCO) and tissue carnosine levels, and superoxide dismutase (SOD) activities were measured. Endogenous CAR levels in the rat brain tissue specimens were significantly increased in the CAR and EtOH groups when compared to the control animals. MDA and PCO levels in the EtOH group were significantly increased as compared to the other groups (P < 0.05). CAR treatment also decreased MDA levels in the CAR group as compared to the control group. Increased SOD activities were obtained in the EtOH + CAR group as compared to the control (P < 0.05). CAR levels in the rat brain were significantly increased in the CAR, EtOH and CAR + EtOH groups when compared to the control animals. These findings indicated that carnosine may appear as a protective agent against ethanol-induced brain damage.

BIOLOGICAL EFFECTS OF MICROWAVE RADIATION ON BRAIN TISSUE IN RATS

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Boris Đinđić

2003-04-01

Full Text Available Exposure to microwave radiation induces multiple organ dysfunctions, especially in CNS.The aim of this work was investigation of biological effects of microwave radiation on rats' brain and determination of increased oxidative stress as a possible pathogenetic's mechanism.Wis tar rats 3 months old were divided in experimental (4 female and 4 male animal and control group (5 female and 4 male. This experimental group was constantly exposed to a magnetic field of 5 mG. We simulated using of mobile phones 30 min every day. The source of NIR emitted MF that was similar to mobile phones at 900 MHz. The rats were killed after 2 months. Biological effects were determined by observation of individual and collective behavior and body mass changes. Lipid per oxidation was determined by measuring quantity of malondialdehyde (MDA in brain homogenate.The animals in experimental group exposed to EMF showed les weight gain. The most important observations were changing of basic behavior models and expression of aggressive or panic behavior. The content of MDA in brain tissue is singificantly higher (1.42 times in rats exposed to electromagnetic fields (3,82±0.65 vs. control 2.69±0.42 nmol/mg proteins, p<0.01.Increased oxidative stress and lipid peroxidation after exposition in EM fields induced disorders of function and structure of brain.

Dietary Virgin Olive Oil Reduces Blood Brain Barrier Permeability, Brain Edema, and Brain Injury in Rats Subjected to Ischemia-Reperfusion

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Fatemeh Mohagheghi

2010-01-01

Full Text Available Recent studies suggest that dietary virgin olive oil (VOO reduces hypoxia-reoxygenation injury in rat brain slices. We sought to extend these observations in an in vivo study of rat cerebral ischemia-reperfusion injury. Four groups, each consisting of 18 Wistar rats, were studied. One group (control received saline, while three treatment groups received oral VOO (0.25, 0.5, and 0.75 mL/kg/day, respectively. After 30 days, blood lipid profiles were determined, before a 60-min period of middle cerebral artery occlusion (MCAO. After 24-h reperfusion, neurological deficit scores, infarct volume, brain edema, and blood brain barrier permeability were each assessed in subgroups of six animals drawn from each main group. VOO reduced the LDL/HDL ratio in doses of 0.25, 0.5, and 0.75 mL/kg/day in comparison to the control group (p < 0.05, and offered cerebroprotection from ischemia-reperfusion. For controls vs. doses of 0.25 vs. 0.5 vs. 0.75 mL/kg/day, attenuated corrected infarct volumes were 207.82 ± 34.29 vs. 206.41 ± 26.23 vs. 124.21 ± 14.73 vs. 108.46 ± 31.63 mm3; brain water content of the infarcted hemisphere was 82 ±± 0.25 vs. 81.5 ± 0.56 vs. 80.5 ± 0.22 vs. 80.5 ± 0.34%; and blood brain barrier permeability of the infarcted hemisphere was 11.31 ± 2.67 vs. 9.21 ± 2.28 vs. 5.83 ± 1.6 vs. 4.43 ± 0.93 µg/g tissue (p < 0.05 for measures in doses 0.5 and 0.75 mL/kg/day vs. controls. Oral administration of VOO reduces infarct volume, brain edema, blood brain barrier permeability, and improves neurologic deficit scores after transient MCAO in rats.

Pharmacological manipulation of serotonin receptors during brain embryogenesis favours stress resiliency in female rats

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Gianluca Lavanco

2018-02-01

Full Text Available Manipulations of the serotonin transmission during early development induce long-lasting changes in the serotonergic circuitry throughout the brain. However, little is known on the developmental consequences in the female progeny. Therefore, this study aimed at exploring the behavioural effects of pre- and postnatal stimulation of the serotonergic system by 5-methoxytryptamine in adolescent female rats on behavioural reactivity and anxiety- like phenotype. Our results show that perinatal 5- methoxythyptamine decreased total distance travelled and rearing frequency in the novel enviroment, and increased the preference for the centre of the arena in the open field test. Moreover, perinatal 5-methoxytryptamine increased the percentages of entries and time spent on the open arms of the elevated plus maze, with respect to perinatally vehicle-exposed rats. Thus, perinatal stimulation of serotonin receptors does not impair the functional response to the emotional challenges in female rats, favouring the occurrence of a stress-resilient phenotype.

Rat Brain Biogenic Amine Levels during Acute and Sub- acute ...

African Journals Online (AJOL)

User

2011-05-20

May 20, 2011 ... substances in rat brain regions are altered during acute and sub-acute .... Different areas of the brain such as cerebral cortex (CC), cerebellum (CB), .... dopamine metabolism and differential motor behavioral tolerance.

Quantitative autoradiography of [3H]corticosterone receptors in rat brain

International Nuclear Information System (INIS)

Sapolsky, R.M.; McEwen, B.S.; Rainbow, T.C.

1983-01-01

The authors have quantified corticosterone receptors in rat brain by optical density measurements of tritium-film autoradiograms. Rats were injected i.v. with 500 μCi [ 3 H]corticosterone to label brain receptors. Frozen sections of brain were cut with a cryostat and exposed for 2 months against tritium-sensitive sheet film (LKB Ultrofilm). Tritium standards were used to convert optical density readings into molar concentrations of receptor. High levels of corticosterone receptors were present throughout the pyramidal and granule cell layers of the hippocampus. Moderate levels of receptors were found in the neuropil of the hippocampus, the lateral septum, the cortical nucleus of the amygdala and the entorhinal cortex. All other brain regions had low levels of receptors. These results extend previous non-quantitative autoradigraphic studies of corticosterone receptors and provide a general procedure for the quantitative autoradiography of steroid hormone receptors in brain tissue. (Auth.)

MR brain volumetric measurements are predictive of neurobehavioral impairment in the HIV-1 transgenic rat.

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Casas, Rafael; Muthusamy, Siva; Wakim, Paul G; Sinharay, Sanhita; Lentz, Margaret R; Reid, William C; Hammoud, Dima A

2018-01-01

HIV infection is known to be associated with brain volume loss, even in optimally treated patients. In this study, we assessed whether dynamic brain volume changes over time are predictive of neurobehavorial performance in the HIV-1 transgenic (Tg) rat, a model of treated HIV-positive patients. Cross-sectional brain MRI imaging was first performed comparing Tg and wild type (WT) rats at 3 and 19 months of age. Longitudinal MRI and neurobehavioral testing of another group of Tg and WT rats was then performed from 5 to 23 weeks of age. Whole brain and subregional image segmentation was used to assess the rate of brain growth over time. We used repeated-measures mixed models to assess differences in brain volumes and to establish how predictive the volume differences are of specific neurobehavioral deficits. Cross-sectional imaging showed smaller whole brain volumes in Tg compared to WT rats at 3 and at 19 months of age. Longitudinally, Tg brain volumes were smaller than age-matched WT rats at all time points, starting as early as 5 weeks of age. The Tg striatal growth rate delay between 5 and 9 weeks of age was greater than that of the whole brain. Striatal volume in combination with genotype was the most predictive of rota-rod scores and in combination with genotype and age was the most predictive of total exploratory activity scores in the Tg rats. The disproportionately delayed striatal growth compared to whole brain between 5 and 9 weeks of age and the role of striatal volume in predicting neurobehavioral deficits suggest an important role of the dopaminergic system in HIV associated neuropathology. This might explain problems with motor coordination and executive decisions in this animal model. Smaller brain and subregional volumes and neurobehavioral deficits were seen as early as 5 weeks of age, suggesting an early brain insult in the Tg rat. Neuroprotective therapy testing in this model should thus target this early stage of development, before brain

Lifelong consumption of sodium selenite: gender differences on blood-brain barrier permeability in convulsive, hypoglycemic rats.

Science.gov (United States)

Seker, F Burcu; Akgul, Sibel; Oztas, Baria

2008-07-01

The aim of this study was to compare the effects of hypoglycemia and induced convulsions on the blood-brain barrier permeability in rats with or without lifelong administration of sodium selenite. There is a significant decrease of the blood-brain barrier permeability in three brain regions of convulsive, hypoglycemic male rats treated with sodium selenite when compared to sex-matched untreated rats (p0.05). The blood-brain barrier permeability of the left and right hemispheres of untreated, moderately hypoglycemic convulsive rats of both genders was better than their untreated counterparts (peffect against blood-brain barrier permeability during convulsions and that the effects of sodium selenite are gender-dependent.

Identification of blood-brain barrier function following subarachnoid hemorrhage in rats at different stages

Institute of Scientific and Technical Information of China (English)

Zongyi Xie; Weiwei Shen; Ying Ma; Yuan Cheng

2008-01-01

BACKGROUND: Recent studies have indicated that blood-brain barrier (BBB) disruption following subarachnoid hemorrhage (SAH) significantly correlates with the development of brain injury and poor prognosis of patients subjected to SAH. OBJECTIVE: To investigate both functional and structural changes related to BBB in various phases after SAH in rats through quantitative and qualitative methods.DESIGN, TIME AND SETTING: This experiment, a completely randomized design and controlled experiment, was performed at the Department of Neurosurgery, the Second Affiliated Hospital of Chongqing University of Medical Sciences from June 2006 to March 2007.MATERIALS: A total of 128 female, healthy, Sprague-Dawley rats were selected for this study. Main reagents and instruments: Evans Blue dye (Sigma Company, USA), fluorescence spectrophotometer (Shimadzu Company, Japan), and transmission electron microscope (Olympus Company, Japan). MAIN OUTCOME MEASURES: Brain tissue water content was determined by the wet-dry method. BBB permeability in the cerebral cortex was determined by Evans Blue dye and fluorescent spectrophotometer. The ultrastructural changes in BBB were observed with transmission electron microscope.RESULTS: Compared with the sham-operated group, SAH induced a significant increase in brain water content between 24 and 60 hours (F = 888.32, P 0.05). Electron microscopy demonstrated only a mild perivascular edema at 24 hours after SAH. By 36 hours, a notable perivascular edema was associated with a collapse of the capillary. Astrocytic endfeet surrounding the capillary were prominently swollen in the edematous areas. The above-mentioned abnormal ultrastructural changes in the BBB were reversed by 72 hours after SAH. No obvious morphological changes in the BBB were detected in the sham-operated rats.CONCLUSION: These results directly suggest that SAH could induce rapid changes in BBB function and structure during the acute phases of BBB breakdown. Moreover, these dynamic

Brain receptors for thyrotropin releasing hormone in morphine tolerant-dependent rats

Energy Technology Data Exchange (ETDEWEB)

Bhargava, H.N.; Das, S.

1986-03-01

The effect of chronic treatment of rats with morphine and its subsequent withdrawal on the brain receptors for thyrotropin releasing hormone (TRH) labeled with /sup 3/H-(3MeHis/sup 2/)TRH (MeTRH). Male Sprague Dawley rats were implanted with 4 morphine pellets (each containing 75 mg morphine base) during a 3-day period. Placebo pellet implanted rats served as controls. Both tolerance to and dependence on morphine developed as a result of this procedure. For characterization of brain TRH receptors, the animals were sacrificed 72 h after the implantation of first pellet. In another set of animals the pellets were removed and were sacrificed 24 h later. The binding of /sup 3/H-MeTRH to membranes prepared from brain without the cerebellum was determined. /sup 3/H-MeTRH bound to brain membranes prepared from placebo pellet implanted rats at a single high affinity site with a B/sub max/ value of 33.50 +/- 0.97 fmol/mg protein and a K/sub d/ of 5.18 +/- 0.21 nM. Implantation of morphine pellets did not alter the B/sub max/ value of /sup 3/H-MeTRH but decreased the K/sub d/ value significantly. Abrupt or naloxone precipitated withdrawal of morphine did not alter B/sub max/ or the K/sub d/ values. The binding of /sup 3/H-MeTRH to brain areas was also determined. The results suggest that the development of tolerance to morphine is associated with enhanced sensitivity of brain TRH receptors, however abrupt withdrawal of morphine does not change the characteristics of brain TRH receptors.

Characteristic effects of heavy ion irradiation on the rat brain

International Nuclear Information System (INIS)

Sun, X.Z.; Takahashi, S.; Kubota, Y.; Yoshida, S.; Takeda, H.; Zhang, R.; Fukui, Y.

2005-01-01

Heavy ion irradiation has the feature to administer a large radiation dose in the vicinity of the endpoint in the beam range, and its irradiation system and biophysical characteristics are different from ordinary irradiation instruments like X- or gamma-rays. Using this special feature, heavy ion irradiation has been applied for cancer treatment. The safety and efficacy of heavy ion irradiator have been demonstrated to a great extent. For instance, brain tumors treated by heavy-ion beams became smaller or disappearance. However, fundamental research related to such clinical phenotypes and their underlying mechanisms are little known. In order to clarify characteristic effects of heavy ion irradiation on the brain, we developed an experimental system for irradiating a restricted region of the rat brain using heavy ion beams. The characteristics of the heavy ion beams, histological, behavioral and elemental changes were studied in the rat following heavy ion irradiation. Adult male Sprague-Dawley rats, aged 12 weeks and weighing 260-340 g (Shizuoka Laboratory Animal Center, Hamamatsu, Japan) were used. Rats were deeply anesthetized 10-15 minutes before irradiation with ketamine (40 mg/kg) and xylazine (10 mg/kg), immobilized in a specifically designed jig, and irradiated with 290 MeV/nucleon charged carbon beams in a dorsal-to ventral direction, The left cerebral hemispheres of the brain were irradiated at doses of 100 Gy charged carbon particles. The depth-dose distribution of the heavy ion beams was modified to make a spread-out bragg peak of 5 mm wide with a range modulator. The characteristics of the heavy-ion beams (field and depth of the heavy-ion beams) were examined by a measuring paraffin section of rat brain at different thickness. That extensive necrosis was observed between 2.5 mm and 7.5 mm depth from the surface of the rat head, suggesting a relatively high dose and uniform dose was delivered among designed depths and the spread-out bragg peak used here

Development of I-123-labeled amines for brain studies: localization of I-123 iodophenylalkyl amines in rat brain

International Nuclear Information System (INIS)

Winchell, H.S.; Baldwin, R.M.; Lin, T.H.

1980-01-01

Localization in rat brain of forty iodophenylalkyl amines labeled with I-123 was evaluated in an attempt to develop I-123-labeled amines useful for brain studies. For the amines studied, the highest activity in brain and the brain-to-blood activity ratios ranked p > m > o as related to iodine position on the benzene ring: for alkyl groups the rank order was α-methylethyl > ethyl > methyl > none; for N additions it was single lipophilic group > H > two lipophilic groups. It is suggested that introduction of a halogen into the ring structure of many amines results in greater concentration of the agent in brain than is seen with the nonhalogenated parent compound. The agent N-isopropyl-p-iodoamphetamine was chosen for further study because, in the rat, it showed high brain activity (1.57%/g) and brain-blood ratio (12.6) at 5 min

Photoacoustic imaging to detect rat brain activation after cocaine hydrochloride injection

Science.gov (United States)

Jo, Janggun; Yang, Xinmai

2011-03-01

Photoacoustic imaging (PAI) was employed to detect small animal brain activation after the administration of cocaine hydrochloride. Sprague Dawley rats were injected with different concentrations (2.5, 3.0, and 5.0 mg per kg body) of cocaine hydrochloride in saline solution through tail veins. The brain functional response to the injection was monitored by photoacoustic tomography (PAT) system with horizontal scanning of cerebral cortex of rat brain. Photoacoustic microscopy (PAM) was also used for coronal view images. The modified PAT system used multiple ultrasonic detectors to reduce the scanning time and maintain a good signal-to-noise ratio (SNR). The measured photoacoustic signal changes confirmed that cocaine hydrochloride injection excited high blood volume in brain. This result shows PAI can be used to monitor drug abuse-induced brain activation.

Salvia officinalis l. (sage) Ameliorates Radiation-Induced Oxidative Brain Damage In Rats

International Nuclear Information System (INIS)

Osman, N. N.; Abd El Azime, A.Sh.

2013-01-01

The present study was designed to investigate the oxidative stress and the role of antioxidant system in the management of gamma irradiation induced whole brain damage in rats . Also, to elucidate the potential role of Salvia officinalis (sage) in alleviating such negative effects. Rats were subjected to gamma radiation (6 Gy). Sage extract was daily given to rats during 14 days before starting irradiation and continued after radiation exposure for another 14 days. The results revealed that the levels of thiobarbituric acid reactive substances (TBARS), protein carbonyl content (PCC) and nitric oxide (NO) content were significantly increased, while the activities of superoxide dismutase (SOD) and catalase (CAT) as well as the reduced glutathione (GSH) content were significantly decreased in the brain homogenate of irradiated rats. Additionally, brain acetylcholinesterase (AChE) as well as alkaline phosphatase (ALP), acid phosphatase (ACP) and lactate dehydrogenase (LDH) activities were significantly increased. On the other hand, the results showed that, administration of sage extract to rats was able to ameliorate the mentioned parameters and the values returned close to the normal ones. It could be concluded that sage extract, by its antioxidant constituents, could modulate radiation induced oxidative stress and enzyme activities in the brain.

[Expression of aquaporin-4 during brain edema in rats with thioacetamide-induced acute encephalopathy].

Science.gov (United States)

Wang, Li-Qing; Zhu, Sheng-Mei; Zhou, Heng-Jun; Pan, Cai-Fei

2011-09-27

To investigate the expression of aquaporin-4 (AQP4) during brain edema in rats with thioacetamide-induced acute liver failure and encephalopathy. The rat model of acute hepatic failure and encephalopathy was induced by intraperitoneal injection of thioacetamide (TAA) at a 24-hour interval for 2 consecutive days. Thirty-two SD rats were randomly divided into the model group (n = 24) and the control group (normal saline, n = 8). And then the model group was further divided into 3 subgroups by the timepoint of decapitation: 24 h (n = 8), 48 h (n = 8) and 60 h (n = 8). Then we observed their clinical symptoms and stages of HE, indices of liver function and ammonia, liver histology and brain water content. The expression of AQP4 protein in brain tissues was measured with Western blot and the expression of AQP4mRNA with RT-PCR (reverse transcription-polymerase chain reaction). Typical clinical manifestations of hepatic encephalopathy occurred in all TAA-administrated rats. The model rats showed the higher indices of ALT (alanine aminotransferase), AST (aspartate aminotransferase), TBIL (total bilirubin) and ammonia than the control rats (P liver failure and encephalopathy plays a significant role during brain edema. AQP4 is one of the molecular mechanisms for the occurrence of brain edema in hepatic encephalopathy.

Reduction in brain immunoreactive corticotropin-releasing factor (CRF) in spontaneously hypertensive rats

International Nuclear Information System (INIS)

Hashimoto, K.; Hattori, T.; Murakami, K.; Suemaru, S.; Kawada, Y.; Kageyama, J.; Ota, Z.

1985-01-01

The brain CRF concentration of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY) was examined by rat CRF radioimmunoassay. Anti-CRF serum was developed by immunizing rabbits with synthetic rat CRF. Synthetic rat CRF was also used as tracer and standard. The displacement of 125 I-rat CRF by serially diluted extracts of male Wistar rats hypothalamus, thalamus, midbrain, pons, medulla oblongata, cerebral cortex, cerebellum and neurointermediate lobe was parallel to the displacement of synthetic rat CRF. In both WKY and SHR the highest levels of CRF immunoreactivity were shown by the hypothalamus and neurointermediate lobe, and considerable CRF immunoreactivity was also detected in other brain regions. The CRF immunoreactivity in the hypothalamus, neurointermediate lobe, midbrain, medulla oblongata and cerebral cortex was significantly reduced in SHR and it may suggest that CRF abnormality may be implicated in the reported abnormalities in the pituitary-adrenal axis, autonomic response and behavior of SHR

Magnetic resonance spectroscopy of traumatic brain in SD rats model

International Nuclear Information System (INIS)

Li Ke; Li Yangbin; Li Zhiming; Huang Yong; Li Bin; Lu Guangming

2009-01-01

Objective: To assess the value and prospect of magnetic resonance spectroscopy (MRS) in early diagnosis of traumatic brain with traumatic brain model in SD rats. Methods: Traumatic brain modal was established in 40 male SD rats utilizing a weigh-drop device, and MRS was performed before trauma and 4,8,24 and 48 hours after trauma. The ratio of N-acetylaspartate/creatine (NAA/Ct) and choline/creatine (Cho/Cr) were calculated and compared with pathological findings respectively. Results: Axonal changes were confirmed in microscopic study 4 hours after injury. The ratio of NAA/Ct decreased distinctly at 4 hours after trauma, followed by a steadily recover at 8 hours, and no significant change from 24h to 48h. There was no significant change in the ratio of Cho/Cr before and after trauma. Conclusion: MRS can be used to monitor the metabolic changes of brain non-invasively. MRS could play a positive role in early diagnosis, prognosis and follow-up of traumatic brain. (authors)

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

Science.gov (United States)

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.

Aging and sex influence the permeability of the blood-brain barrier in the rat

International Nuclear Information System (INIS)

Saija, A.; Princi, P.; D'Amico, N.; De Pasquale, R.; Costa, G.

1990-01-01

The aim of the present study was to investigate the existence of aging- and sex-related alterations in the permeability of the blood-brain barrier (BBB) in the rat, by calculating a unidirectional blood-to-brain transfer constant (Ki) for the circulating tracer [ 14 C]-α-aminoisobutyric acid. The authors observed that: (a) the permeability of the BBB significantly increased within the frontal and temporo-parietal cortex, hypothalamus and cerebellum in 28-30 week old rats, in comparison with younger animals; (b) in several brain areas of female intact rats higher Ki values (even though not significantly different) were calculated at oestrus than at proestrus; (c) in 1-week ovariectomized rats there was a marked increase of Ki values at the level of the frontal, temporo-parietal and occipital cortex, cerebellum and brain-stem. One can speculate that aging and sex-related alterations in thee permeability of the BBB reflect respectively changes in brain neurochemical system activity and in plasma steroid hormone levels

Oxidative stress and superoxide dismutase activity in brain of rats ...

African Journals Online (AJOL)

JTEkanem

effect of superoxide dismutase (SOD) activity in brain homogenates of Wistar rats. Oxidative stress measured as ..... on the brain and nervous system of humans as handlers and ... environment may be at higher health risk in that their internal ...

Neurons derived from different brain regions are inherently different in vitro: a novel multiregional brain-on-a-chip.

Science.gov (United States)

Dauth, Stephanie; Maoz, Ben M; Sheehy, Sean P; Hemphill, Matthew A; Murty, Tara; Macedonia, Mary Kate; Greer, Angie M; Budnik, Bogdan; Parker, Kevin Kit

2017-03-01

Brain in vitro models are critically important to developing our understanding of basic nervous system cellular physiology, potential neurotoxic effects of chemicals, and specific cellular mechanisms of many disease states. In this study, we sought to address key shortcomings of current brain in vitro models: the scarcity of comparative data for cells originating from distinct brain regions and the lack of multiregional brain in vitro models. We demonstrated that rat neurons from different brain regions exhibit unique profiles regarding their cell composition, protein expression, metabolism, and electrical activity in vitro. In vivo, the brain is unique in its structural and functional organization, and the interactions and communication between different brain areas are essential components of proper brain function. This fact and the observation that neurons from different areas of the brain exhibit unique behaviors in vitro underline the importance of establishing multiregional brain in vitro models. Therefore, we here developed a multiregional brain-on-a-chip and observed a reduction of overall firing activity, as well as altered amounts of astrocytes and specific neuronal cell types compared with separately cultured neurons. Furthermore, this multiregional model was used to study the effects of phencyclidine, a drug known to induce schizophrenia-like symptoms in vivo, on individual brain areas separately while monitoring downstream effects on interconnected regions. Overall, this work provides a comparison of cells from different brain regions in vitro and introduces a multiregional brain-on-a-chip that enables the development of unique disease models incorporating essential in vivo features. NEW & NOTEWORTHY Due to the scarcity of comparative data for cells from different brain regions in vitro, we demonstrated that neurons isolated from distinct brain areas exhibit unique behaviors in vitro. Moreover, in vivo proper brain function is dependent on the

Iodine 125-lysergic acid diethylamide binds to a novel serotonergic site on rat choroid plexus epithelial cells

International Nuclear Information System (INIS)

Yagaloff, K.A.; Hartig, P.R.

1985-01-01

125 I-Lysergic acid diethylamide ( 125 I-LSD) binds with high affinity to serotonergic sites on rat choroid plexus. These sites were localized to choroid plexus epithelial cells by use of a novel high resolution stripping film technique for light microscopic autoradiography. In membrane preparations from rat choroid plexus, the serotonergic site density was 3100 fmol/mg of protein, which is 10-fold higher than the density of any other serotonergic site in brain homogenates. The choroid plexus site exhibits a novel pharmacology that does not match the properties of 5-hydroxytryptamine-1a (5-HT1a), 5-HT1b, or 5-HT2 serotonergic sites. 125 I-LSD binding to the choroid plexus site is potently inhibited by mianserin, serotonin, and (+)-LSD. Other serotonergic, dopaminergic, and adrenergic agonists and antagonists exhibit moderate to weak affinities for this site. The rat choroid plexus 125 I-LSD binding site appears to represent a new type of serotonergic site which is located on non-neuronal cells in this tissue

Effect of MgSO4 on the contents of Ca2+ in brain cell and NO in brain tissue of rats with radiation-induced acute brain injury

International Nuclear Information System (INIS)

Yuan Wenjia; Cui Fengmei; Liu Ping; He Chao; Tu Yu; Wang Lili

2009-01-01

The work is to explore the protection of magnesium sulfate(MgSO 4 ) on radiation-induced acute brain injury. Thirty six mature Sprague-Dawley(SD) rats were randomly divided into 3 groups of control, experimental control and experimental therapy group. The whole brains of SD rats of experimental control and experimental therapy group were irradiated with a dose of 20 Gy using 6 MeV electron beam. MgSO 4 was injected into the abdomen of experimental therapy rats group 1 day before, immediately and continue for 5 days after irradiation respectively. The brain tissues were taken on 3, 10, 17 and 24 d after irradiation. Ca 2+ content in brain cell was measured by laser scanning confocal microscopy, and the NO content in brain tissue was detected by the method of nitric acid reductase. Compared with the blank control group, the contents of Ca 2+ in brain cell and NO in brain tissue of the experimental control group increase (P 4 used in early stage can inhibit the contents of Ca 2+ in brain cell and NO in brain tissue after radiation-induced acute brain injury. It means that MgSO 4 has a protective effect on radiation-induced acute brain injury. (authors)

Complex Trajectories of Brain Development in the Healthy Human Fetus.

Science.gov (United States)

Andescavage, Nickie N; du Plessis, Adre; McCarter, Robert; Serag, Ahmed; Evangelou, Iordanis; Vezina, Gilbert; Robertson, Richard; Limperopoulos, Catherine

2017-11-01

This study characterizes global and hemispheric brain growth in healthy human fetuses during the second half of pregnancy using three-dimensional MRI techniques. We studied 166 healthy fetuses that underwent MRI between 18 and 39 completed weeks gestation. We created three-dimensional high-resolution reconstructions of the brain and calculated volumes for left and right cortical gray matter (CGM), fetal white matter (FWM), deep subcortical structures (DSS), and the cerebellum. We calculated the rate of growth for each tissue class according to gestational age and described patterns of hemispheric growth. Each brain region demonstrated major increases in volume during the second half of gestation, the most pronounced being the cerebellum (34-fold), followed by FWM (22-fold), CGM (21-fold), and DSS (10-fold). The left cerebellar hemisphere, CGM, and DSS had larger volumes early in gestation, but these equalized by term. It has been increasingly recognized that brain asymmetry evolves throughout the human life span. Advanced quantitative MRI provides noninvasive measurements of early structural asymmetry between the left and right fetal brain that may inform functional and behavioral laterality differences seen in children and young adulthood. © The Author 2016. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

Increased Arousal Levels and Decreased Sleep by Brain Music in Rats

Institute of Scientific and Technical Information of China (English)

Guang-Zhan Fang; Chun-Peng Zhang; Dan Wu; Yang Xia; Yong-Xiu Lai; De-Zhong Yao

2009-01-01

More and more studies have been reported on whether music and other types of auditory stimulation would improve the quality of sleep.Many of these studies have found significant results,but others argue that music is not significantly better than the tones or control conditions in improving sleep.For further understanding the relationship between music and sleep or music and arousal,the present study therefore examines the effects of brain music on sleep and arousal by means of biofeedback.The music is from the transformation of rapid eye movement (REM) sleep electroencephalogram (EEG) of rats using an algorithm in the Chengdu Brain Music (CBM) system.When the brain music was played back to rats,EEG data were recorded to assess the efficacy of music to induce or improve sleep,or increase arousal levels by sleep staging,etc.Our results demonstrate that exposure to the brain music increases arousal levels and decreases sleep in rats,and the underlying mechanism of decreased non-rapid eye movement (NREM) and REM sleep may be different.

Rapamycin suppresses brain aging in senescence-accelerated OXYS rats.

Science.gov (United States)

Kolosova, Nataliya G; Vitovtov, Anton O; Muraleva, Natalia A; Akulov, Andrey E; Stefanova, Natalia A; Blagosklonny, Mikhail V

2013-06-01

Cellular and organismal aging are driven in part by the MTOR (mechanistic target of rapamycin) pathway and rapamycin extends life span inC elegans, Drosophila and mice. Herein, we investigated effects of rapamycin on brain aging in OXYS rats. Previously we found, in OXYS rats, an early development of age-associated pathological phenotypes similar to several geriatric disorders in humans, including cerebral dysfunctions. Behavioral alterations as well as learning and memory deficits develop by 3 months. Here we show that rapamycin treatment (0.1 or 0.5 mg/kg as a food mixture daily from the age of 1.5 to 3.5 months) decreased anxiety and improved locomotor and exploratory behavior in OXYS rats. In untreated OXYS rats, MRI revealed an increase of the area of hippocampus, substantial hydrocephalus and 2-fold increased area of the lateral ventricles. Rapamycin treatment prevented these abnormalities, erasing the difference between OXYS and Wister rats (used as control). All untreated OXYS rats showed signs of neurodegeneration, manifested by loci of demyelination. Rapamycin decreased the percentage of animals with demyelination and the number of loci. Levels of Tau and phospho-Tau (T181) were increased in OXYS rats (compared with Wistar). Rapamycin significantly decreased Tau and inhibited its phosphorylation in the hippocampus of OXYS and Wistar rats. Importantly, rapamycin treatment caused a compensatory increase in levels of S6 and correspondingly levels of phospo-S6 in the frontal cortex, indicating that some downstream events were compensatory preserved, explaining the lack of toxicity. We conclude that rapamycin in low chronic doses can suppress brain aging.

Circulating and brain BDNF levels in stroke rats. Relevance to clinical studies.

Directory of Open Access Journals (Sweden)

Yannick Béjot

Full Text Available BACKGROUND: Whereas brain-derived neurotrophic factor (BDNF levels are measured in the brain in animal models of stroke, neurotrophin levels in stroke patients are measured in plasma or serum samples. The present study was designed to investigate the meaning of circulating BDNF levels in stroke patients. METHODS AND RESULTS: Unilateral ischemic stroke was induced in rats by the injection of various numbers of microspheres into the carotid circulation in order to mimic the different degrees of stroke severity observed in stroke patients. Blood was serially collected from the jugular vein before and after (4 h, 24 h and 8 d embolization and the whole brains were collected at 4, 24 h and 8 d post-embolization. Rats were then selected from their degree of embolization, so that the distribution of stroke severity in the rats at the different time points was large but similar. Using ELISA tests, BDNF levels were measured in plasma, serum and brain of selected rats. Whereas plasma and serum BDNF levels were not changed by stroke, stroke induced an increase in brain BDNF levels at 4 h and 24 h post-embolization, which was not correlated with stroke severity. Individual plasma BDNF levels did not correlate with brain levels at any time point after stroke but a positive correlation (r = 0.67 was observed between individual plasma BDNF levels and stroke severity at 4 h post-embolization. CONCLUSION: Circulating BDNF levels do not mirror brain BDNF levels after stroke, and severe stroke is associated with high plasma BDNF in the very acute stage.

Regional brain distribution of toluene in rats and in a human autopsy

Energy Technology Data Exchange (ETDEWEB)

Ameno, Kiyoshi; Kiriu, Takahiro; Fuke, Chiaki; Ameno, Setsuko; Shinohara, Toyohiko; Ijiri, Iwao (Kagawa Medical School (Japan). Dept. of Forensic Medicine)

1992-02-01

Toluene concentrations in 9 brain regions of acutely exposed rats and that in 11 brain regions of a human case who inhaled toluene prior to death are described. After exposure to toluene by inhalation (2000 or 10 000 ppm) for 0.5 h or by oral dosing (400 mg/kg.), rats were killed by decapitation 0.5 and 4 h after onset of inhalation and 2 and 10 h after oral ingestion. After each experimental condition the highest range of brain region/blood toluene concentration ratio (BBCR) was in the brain stem regions (2.85-3.22) such as the pons and medulla oblongata, the middle range (1.77-2.12) in the midbrain, thalamus, caudate-putamen, hypothalamus and cerebellum, and the lowest range (1.22-1.64) in the hippocampus and cerebral cortex. These distribution patterns were quite constant. Toluene concentration in various brain regions were unevenly distributed and directly related blood levels. In a human case who had inhaled toluene vapor, the distribution among brain regions was relatively similar to that in rats, the highest concentration ratios being in the corpus callosum (BBCR:2.66) and the lowest in the hippocampus (BBCR:1.47). (orig.).

Long-term BPA infusions. Evaluation in the rat brain tumor and rat spinal cord models

International Nuclear Information System (INIS)

Coderre, J.A.; Micca, P.L.; Nawrocky, M.M.; Joel, D.D.; Morris, G.M.

2000-01-01

In the BPA-based dose escalation clinical trial, the observations of tumor recurrence in areas of extremely high calculated tumor doses suggest that the BPA distribution is non-uniform. Longer (6-hour) i.v. infusions of BPA are evaluated in the rat brain tumor and spinal cord models to address the questions of whether long-term infusions are more effective against the tumor and whether long-term infusions are detrimental in the central nervous system. In the rat spinal cord, the 50% effective doses (ED 50 ) for myeloparesis were not significantly different after a single i.p. injection of BPA-fructose or a 6 hour i.v. infusion. In the rat 9L gliosarcoma brain tumor model, BNCT following 2-hr or 6-hr infusions of BPA-F produced similar levels of long term survival. (author)

Improved apparatus for neutron capture therapy of rat brain tumors

International Nuclear Information System (INIS)

Liu, Hungyuan B.; Joel, D.D.; Slatkin, D.N.; Coderre, J.A.

1994-01-01

The assembly for irradiating tumors in the rat brain at the thermal neutron beam port of the Brookhaven Medical Research Reactor was redesigned to lower the average whole-body dose from different components of concomitant radiation without changing the thermal neutron fluence at the brain tumor. At present, the tumor-bearing rat is positioned in a rat holder that functions as a whole-body radiation shield. A 2.54 cm-thick collimator with a centered conical aperture, 6 cm diameter tapering to 2 cm diameter, is used to restrict the size of the thermal neutron field. Using the present holder and collimator as a baseline design, Monte Carlo calculations and mixed-field dosimetry were used to assess new designs. The computations indicate that a 0.5 cm-thick plate, made of 6 Li 2 CO 3 dispersed in polyethylene (Li-poly), instead of the existing rat holder, will reduce the whole-body radiation dose. Other computations show that a 10.16 cm-thick (4 inches) Li-poly collimator, having a centered conical aperture of 12 cm diameter tapering to 2 cm diameter, would further reduce the whole-body dose. The proposed irradiation apparatus of tumors in the rat brain, although requiring a 2.3-fold longer irradiation time, would reduce the average whole-body dose to less than half of that from the existing irradiation assembly. 7 refs., 4 figs., 7 tabs

Cloning and expression of a rat brain α2B-adrenergic receptor

International Nuclear Information System (INIS)

Flordellis, C.S.; Handy, D.E.; Bresnahan, M.R.; Zannis, V.I.; Gavras, H.

1991-01-01

The authors isolated a cDNA clone (RBα 2B ) and its homologous gene (GRα 2B ) encoding an α 2B -adrenergic receptor subtype by screening a rat brain cDNA and a rat genomic library. Nucleotide sequence analysis showed that both clones code for a protein of 458 amino acids, which is 87% homologous to the human kidney glycosylated adrenergic receptor (α 2 -C4) and divergent from the rat kidney nonglycosylated α 2B subtype (RNGα 2 ). Transient expression of RBα 2B in COS-7 cells resulted in high-affinity saturable binding for [ 3 H]rauwolscine and a high receptor number in the membranes of transfected COS-7 cells. Pharmacological analysis demonstrated that the expressed receptor bound adrenergic ligands with the following order of potency: rauwolscine > yohimbine > prazosin > oxymetazoline, with a prazosin-to-oxymetazoline K i ratio of 0.34. This profile is characteristic of the α 2B -adrenergic receptor subtype. Blotting analysis of rat brain mRNA gave one major and two minor mRNA species, and hybridization with strand-specific probes showed that both DNA strands of GRα 2B may be transcriptionally active. These findings show that rat brain expresses an α 2B -adrenergic receptor subtype that is structurally different from the rat kidney nonglycosylated α 2B subtype. Thus the rat expresses at least two divergent α 2B -adrenergic receptors

Volumetric abnormalities of the brain in a rat model of recurrent headache.

Science.gov (United States)

Jia, Zhihua; Tang, Wenjing; Zhao, Dengfa; Hu, Guanqun; Li, Ruisheng; Yu, Shengyuan

2018-01-01

Voxel-based morphometry is used to detect structural brain changes in patients with migraine. However, the relevance of migraine and structural changes is not clear. This study investigated structural brain abnormalities based on voxel-based morphometry using a rat model of recurrent headache. The rat model was established by infusing an inflammatory soup through supradural catheters in conscious male rats. Rats were subgrouped according to the frequency and duration of the inflammatory soup infusion. Tactile sensory testing was conducted prior to infusion of the inflammatory soup or saline. The periorbital tactile thresholds in the high-frequency inflammatory soup stimulation group declined persistently from day 5. Increased white matter volume was observed in the rats three weeks after inflammatory soup stimulation, brainstem in the in the low-frequency inflammatory soup-infusion group and cortex in the high-frequency inflammatory soup-infusion group. After six weeks' stimulation, rats showed gray matter volume changes. The brain structural abnormalities recovered after the stimulation was stopped in the low-frequency inflammatory soup-infused rats and persisted even after the high-frequency inflammatory soup stimulus stopped. The changes of voxel-based morphometry in migraineurs may be the result of recurrent headache. Cognition, memory, and learning may play an important role in the chronification of migraines. Reducing migraine attacks has the promise of preventing chronicity of migraine.

Study of five novel non-synonymous polymorphisms in human brain-expressed genes in a Colombian sample.

Science.gov (United States)

Ojeda, Diego A; Forero, Diego A

2014-10-01

Non-synonymous single nucleotide polymorphisms (nsSNPs) in brain-expressed genes represent interesting candidates for genetic research in neuropsychiatric disorders. To study novel nsSNPs in brain-expressed genes in a sample of Colombian subjects. We applied an approach based on in silico mining of available genomic data to identify and select novel nsSNPs in brain-expressed genes. We developed novel genotyping assays, based in allele-specific PCR methods, for these nsSNPs and genotyped them in 171 Colombian subjects. Five common nsSNPs (rs6855837; p.Leu395Ile, rs2305160; p.Thr394Ala, rs10503929; p.Met289Thr, rs2270641; p.Thr4Pro and rs3822659; p.Ser735Ala) were studied, located in the CLOCK, NPAS2, NRG1, SLC18A1 and WWC1 genes. We reported allele and genotype frequencies in a sample of South American healthy subjects. There is previous experimental evidence, arising from genome-wide expression and association studies, for the involvement of these genes in several neuropsychiatric disorders and endophenotypes, such as schizophrenia, mood disorders or memory performance. Frequencies for these nsSNPSs in the Colombian samples varied in comparison to different HapMap populations. Future study of these nsSNPs in brain-expressed genes, a synaptogenomics approach, will be important for a better understanding of neuropsychiatric diseases and endophenotypes in different populations.

Effects of post mortem interval and gender in DNA base excision repair activities in rat brains

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Soltys, Daniela Tathiana; Pereira, Carolina Parga Martins; Ishibe, Gabriela Naomi; Souza-Pinto, Nadja Cristhina de, E-mail: nadja@iq.usp.br

2015-06-15

Most human tissues used in research are of post mortem origin. This is the case for all brain samples, and due to the difficulty in obtaining a good number of samples, especially in the case of neurodegenerative diseases, male and female samples are often included in the same experimental group. However, the effects of post mortem interval (PMI) and gender differences in the endpoints being analyzed are not always fully understood, as is the case for DNA repair activities. To investigate these effects, in a controlled genetic background, base excision repair (BER) activities were measured in protein extracts obtained from Wistar rat brains from different genders and defined PMI up to 24 hours, using a novel fluorescent-based in vitro incision assay. Uracil and AP-site incision activity in nuclear and mitochondrial extracts were similar in all groups included in this study. Our results show that gender and PMI up to 24 hours have no influence in the activities of the BER proteins UDG and APE1 in rat brains. These findings demonstrate that these variables do not interfere on the BER activities included in these study, and provide a security window to work with UDG and APE1 proteins in samples of post mortem origin.

Effects of post mortem interval and gender in DNA base excision repair activities in rat brains

International Nuclear Information System (INIS)

Soltys, Daniela Tathiana; Pereira, Carolina Parga Martins; Ishibe, Gabriela Naomi; Souza-Pinto, Nadja Cristhina de

2015-01-01

Most human tissues used in research are of post mortem origin. This is the case for all brain samples, and due to the difficulty in obtaining a good number of samples, especially in the case of neurodegenerative diseases, male and female samples are often included in the same experimental group. However, the effects of post mortem interval (PMI) and gender differences in the endpoints being analyzed are not always fully understood, as is the case for DNA repair activities. To investigate these effects, in a controlled genetic background, base excision repair (BER) activities were measured in protein extracts obtained from Wistar rat brains from different genders and defined PMI up to 24 hours, using a novel fluorescent-based in vitro incision assay. Uracil and AP-site incision activity in nuclear and mitochondrial extracts were similar in all groups included in this study. Our results show that gender and PMI up to 24 hours have no influence in the activities of the BER proteins UDG and APE1 in rat brains. These findings demonstrate that these variables do not interfere on the BER activities included in these study, and provide a security window to work with UDG and APE1 proteins in samples of post mortem origin

11C-ORM-13070, a novel PET ligand for brain α2C-adrenoceptors: radiometabolism, plasma pharmacokinetics, whole-body distribution and radiation dosimetry in healthy men

International Nuclear Information System (INIS)

Luoto, Pauliina; Oikonen, Vesa; Arponen, Eveliina; Helin, Semi; Virta, Jere; Virtanen, Kirsi; Roivainen, Anne; Suilamo, Sami; Herttuainen, Jukka; Hietamaeki, Johanna; Holopainen, Aila; Rouru, Juha; Sallinen, Jukka; Kailajaervi, Marita; Peltonen, Juha M.; Scheinin, Mika; Volanen, Iina; Rinne, Juha O.

2014-01-01

11 C-labelled 1-[(S)-1-(2,3-dihydrobenzo[1,2]dioxin-2-yl)methyl] -4-(3-methoxy-methylpyridin-2- yl)-piperazine ( 11 C-ORM-13070) is a novel PET tracer for imaging of α 2C -adrenoceptors in the human brain. Brain α 2C -adrenoceptors may be therapeutic targets in several neuropsychiatric disorders, including depression, schizophrenia and Alzheimer's disease. To validate the use of 11 C-ORM-13070 in humans, we investigated its radiometabolism, pharmacokinetics, whole-body distribution and radiation dose. Radiometabolism was studied in a test-retest setting in six healthy men. After intravenous injection of 11 C-ORM-13070, blood samples were drawn over 60 min. Plasma samples were analysed by radio-HPLC for intact tracer and its radioactive metabolites. Metabolite-corrected plasma time-activity curves were used for calculation of pharmacokinetics. In a separate group of 12 healthy men, the whole-body distribution of 11 C-ORM-13070 and radiation exposure were investigated by dynamic PET/CT imaging without blood sampling. Two radioactive metabolites of 11 C-ORM-13070 were detected in human arterial plasma. The proportion of unchanged 11 C-ORM-13070 decreased from 81 ± 4 % of total radioactivity at 4 min after tracer injection to 23 ± 4 % at 60 min. At least one of the radioactive metabolites penetrated into red blood cells, while the parent tracer remained in plasma. The apparent elimination rate constant and corresponding half-life of unchanged 11 C-ORM-13070 in arterial plasma were 0.0117 ± 0.0056 min -1 and 73.6 ± 35.8 min, respectively. The organs with the highest absorbed doses were the liver (12 μSv/MBq), gallbladder wall (12 μSv/MBq) and pancreas (9.1 μSv/MBq). The mean effective dose was 3.9 μSv/MBq, with a range of 3.6 - 4.2 μSv/MBq. 11 C-ORM-13070 was rapidly metabolized in human subjects after intravenous injection. The effective radiation dose of 11 C-ORM-13070 was in the same range as that of other 11 C-labelled brain receptor tracers. An injection

Oxidative stress induces the decline of brain EPO expression in aging rats.

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Li, Xu; Chen, Yubao; Shao, Siying; Tang, Qing; Chen, Weihai; Chen, Yi; Xu, Xiaoyu

2016-10-01

Brain Erythropoietin (EPO), an important neurotrophic factor and neuroprotective factor, was found to be associated with aging. Studies found EPO expression was significantly decreased in the hippocampus of aging rat compared with that of the youth. But mechanisms of the decline of the brain EPO during aging remain unclear. The present study utilized a d-galactose (d-gal)-induced aging model in which the inducement of aging was mainly oxidative injury, to explore underlying mechanisms for the decline of brain EPO in aging rats. d-gal-induced aging rats (2months) were simulated by subcutaneously injecting with d-gal at doses of 50mg·kg(-1), 150mg·kg(-1) and 250mg·kg(-1) daily for 8weeks while the control group received vehicle only. These groups were all compared with the aging rats (24months) which had received no other treatment. The cognitive impairment was assessed using Morris water maze (MWM) in the prepared models, and the amount of β-galactosidase, the lipid peroxidation product malondialdehyde (MDA) level and the superoxide dismutase (SOD) activity in the hippocampus was examined by assay kits. The levels of EPO, EPOR, p-JAK2 and hypoxia-inducible factor-2α (HIF-2α) in the hippocampus were detected by western blot. Additionally, the correlation coefficient between EPO/EPOR expression and MDA level was analyzed. The MWM test showed that compared to control group, the escape latency was significantly extended and the times of crossing the platform was decreased at the doses of 150mg·kg(-1) and 250mg·kg(-1) (paging rats, the expressions of EPO, EPOR, p-JAK2, and HIF-2αin the brain of d-gal-treated rats were significantly decreased (paging could result in the decline of EPO in the hippocampus and oxidative stress might be the main reason for the decline of brain EPO in aging rats, involved with the decrease of HIF-2α stability. Copyright © 2016 Elsevier Inc. All rights reserved.

Blood-ocular and blood-brain barrier function in streptozocin-induced diabetes in rats

International Nuclear Information System (INIS)

Maeepea, O.; Karlsson, C.; Alm, A.

1984-01-01

Edetic acid labeled with chromium 51 was injected intravenously in normal rats and in rats with streptozocin-induced diabetes. One hour after the injection the animals were killed and the concentrations of edetic acid 51Cr in vitreous body, retina, and brain were determined. No significant difference was observed between the two groups for either tissue. In a second series, a mixture of tritiated 1-glucose and aminohippuric acid tagged with carbon 14 was injected instead of edetic acid. A substantial accumulation of aminohippuric acid 14C compared with tritiated 1-glucose was observed in the vitreous body and the brain of diabetic rats in comparison with the control group. It is concluded that untreated streptozocin-induced diabetes in rats for one to two weeks will not cause a generalized increase in the permeability of the blood-ocular or the blood-brain barriers, but organic acids may accumulate in the vitreous body as well as in the brain as a consequence of reduced outward transport through these barriers

Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats

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Schwartz, M.W.; Figlewicz, D.F.; Kahn, S.E.; Baskin, D.G.; Greenwood, M.R.; Porte, D. Jr.

1990-01-01

In order to study the role of plasma insulin in regulating the binding of insulin to the endothelium of the blood-brain barrier (BBB), insulin binding to a purified preparation of brain capillaries was measured in both genetically obese Zucker rats and lean Zucker controls. We found a reduction of 65% in brain capillary insulin binding site number in the obese compared to lean rats with no change in receptor affinity. Furthermore, specific insulin binding to brain capillaries was negatively correlated (p less than 0.05) to the plasma insulin level, suggesting a role for plasma insulin in regulating insulin binding. A similar relationship was observed between insulin receptor number in liver membranes and the plasma insulin level. We conclude that obese, hyperinsulinemic Zucker rats exhibit a reduction in the number of BBB insulin receptors, which parallels the reduction seen in other peripheral tissues. Since insulin receptors have been hypothesized to participate in the transport of insulin across the BBB, the reduction observed in the obese rats may account for the decrease in cerebrospinal fluid insulin uptake previously demonstrated in these animals

Comparison of Trazodone, Diazepame and Dibenzepine Influences on Rat Brain Beta-Endorphins Content

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Radivoj Jadrić

2007-08-01

Full Text Available The aim of our study was to establish the extent of influence of different psychotropic drugs to brain β-endorphins in experimental animals. The study was performed on albino Wistar rats (weight 250 g, treated with different psychoactive drugs. RIA technique was employed for quantification of brain β-endorphins. Brain β-endorphins were higher in experiment group treated with trazodone (929 pg/g ± 44,43; X±SD, and dibenzepine (906,63 pg/g ± 74,06, yet with lower brain content in rats treated with diazepame (841,55 pg/g ± 68,47, compared to brain β-endorphins content of control group treated with saline solution (0,95% NaCl (873,5 pg/g ± 44,89. Significant differences were obtained comparing brain β-endorphins of trazodone vs. diaze-pame treated animals, with diazepame group having lower values (p<0,02. This study showed differences in changes of rat brain β-endorphins contents when different psy-choactive drugs are used. Therefore, we consider that β-endorphins could be used for evaluation of effects of psychoactive drugs, as a useful parameter in therapy with these psycho pharmaceuticals.

Confocal laser endomicroscopy for diagnosis and histomorphologic imaging of brain tumors in vivo.

Directory of Open Access Journals (Sweden)

Sebastian Foersch

Full Text Available Early detection and evaluation of brain tumors during surgery is crucial for accurate resection. Currently cryosections during surgery are regularly performed. Confocal laser endomicroscopy (CLE is a novel technique permitting in vivo histologic imaging with miniaturized endoscopic probes at excellent resolution. Aim of the current study was to evaluate CLE for in vivo diagnosis in different types and models of intracranial neoplasia. In vivo histomorphology of healthy brains and two different C6 glioma cell line allografts was evaluated in rats. One cell line expressed EYFP, the other cell line was used for staining with fluorescent dyes (fluorescein, acriflavine, FITC-dextran and Indocyanine green. To evaluate future application in patients, fresh surgical resection specimen of human intracranial tumors (n = 15 were examined (glioblastoma multiforme, meningioma, craniopharyngioma, acoustic neurinoma, brain metastasis, medulloblastoma, epidermoid tumor. Healthy brain tissue adjacent to the samples served as control. CLE yielded high-quality histomorphology of normal brain tissue and tumors. Different fluorescent agents revealed distinct aspects of tissue and cell structure (nuclear pattern, axonal pathways, hemorrhages. CLE discrimination of neoplastic from healthy brain tissue was easy to perform based on tissue and cellular architecture and resemblance with histopathology was excellent. Confocal laser endomicroscopy allows immediate in vivo imaging of normal and neoplastic brain tissue at high resolution. The technology might be transferred to scientific and clinical application in neurosurgery and neuropathology. It may become helpful to screen for tumor free margins and to improve the surgical resection of malignant brain tumors, and opens the door to in vivo molecular imaging of tumors and other neurologic disorders.

[11C]befloxatone brain kinetics is not influenced by Bcrp function at the blood-brain barrier: A PET study using Bcrp TGEM knockout rats

International Nuclear Information System (INIS)

Hosten, Benoit; Jacob, Aude; Saubamea, Bruno; Scherrmann, Jean-Michel; Boisgard, Raphael; Goutal, Sebastien; Dolle, Frederic; Tournier, Nicolas; Cisternino, Salvatore

2013-01-01

Knockout (KO) animals are useful tools with which to assess the interplay between P-glycoprotein (P-gp; Abcb1) and the breast cancer resistance protein (Bcrp, Abcg2), two major ABC-transporters expressed at the blood-brain barrier (BBB). However, one major drawback of such deficient models is the possible involvement of compensation between transporters. In the present study, P-gp and Bcrp distribution in the brain as well as P-gp expression levels at the BBB were compared between the Bcrp TGEM KO rat model and the wild-type (WT) strain. Therefore, we used confocal microscopy of brain slices and western blot analysis of the isolated brain microvessels forming the BBB. This deficient rat model was used to assess the influence of Bcrp on the brain and peripheral kinetics of its substrate [ 11 C]befloxatone using positron emission tomography (PET). The influence of additional P-gp inhibition was tested using elacridar (GF120918) 2 mg/kg in Bcrp KO rats. The distribution pattern of P-gp in the brain as well as P-gp expression levels at the BBB was similar in Bcrp-deficient and WT rats. Brain and peripheral kinetics of [ 11 C]befloxatone were not influenced by the lack of Bcrp. Neither was the brain uptake of [ 11 C]befloxatone in Bcrp-deficient rats influenced by the inhibition of P-gp. In conclusion, the Bcrp-deficient rat strain, in which we detected no compensatory mechanism or modification of P-gp expression as compared to WT rats, is a suitable model to study Bcrp function separately from that of P-gp at the BBB. However, although selectively transported by BCRP in vitro, our results suggest that [ 11 C]befloxatone PET imaging might not be biased by impaired function of this transporter in vivo. (authors)

Naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein partially purified from rat liver and rat brain membranes: an opioid/sigma receptor?

Science.gov (United States)

Tsao, L I; Su, T P

1997-02-01

A naloxone-sensitive, haloperidol-sensitive, [3H](+)SKF-10047-binding protein was partially purified from rat liver and rat brain membranes in an affinity chromatography originally designed to purify sigma receptors. Detergent-solubilized extracts from membranes were adsorbed to Sephadex G-25 resin containing an affinity ligand for sigma receptors: N-(2- 3,4-dichlorophenyl]ethyl)-N-(6-aminohexyl)-(2-[1-pyrrolidinyl]) ethylamine (DAPE). After eluting the resin with haloperidol, a protein that bound [3H](+)SKF-10047 was detected in the eluates. However, the protein was not the sigma receptor. [3H](+)SKF-10047 binding to the protein was inhibited by the following compounds in the order of decreasing potency: (+)pentazocine > (-) pentazocine > (+/-)cyclazocine > (-)morphine > (-)naloxone > haloperidol > (+)SKF-10047 > DADLE > (-)SKF-10047. Further, the prototypic sigma receptor ligands, such as 1,3-di-o-tolylguanidine (DTG), (+)3-PPP, and progesterone, bound poorly to the protein. Tryptic digestion and heat treatment of the affinity-purified protein abolished radioligand binding. Sodium dodecyl sulfate/polyacrylamide gel electrophoresis (SDS/PAGE) of the partially-purified protein from the liver revealed a major diffuse band with a molecular mass of 31 kDa, a polypeptide of 65 kDa, and another polypeptide of > 97 kDa. This study demonstrates the existence of a novel protein in the rat liver and rat brain which binds opioids, benzomorphans, and haloperidol with namomolar affinity. The protein resembles the opioid/sigma receptor originally proposed by Martin et al. [(1976): J. Pharmacol. Exp. Ther., 197:517-532.]. A high degree of purification of this protein has been achieved in the present study.

A novel nicotinic agonist facilitates induction of long-term potentiation in the rat hippocampus.

Science.gov (United States)

Hunter, B E; de Fiebre, C M; Papke, R L; Kem, W R; Meyer, E M

1994-02-28

Long-term potentiation (LTP) can be modulated by a number of neurotransmitter receptors including muscarinic and GABAergic receptor types. We have found that a novel nicotinic agonist, 2,4-dimethoxybenzylidene anabaseine (DMXB), facilitated the induction of LTP in the hippocampus in a dose-dependent and mecamylamine-sensitive manner. DMXB displaced high affinity nicotinic [125I]alpha-bungarotoxin and [3H]acetylcholine binding in rat brain. Xenopus oocyte studies demonstrated that DMXB has agonist activity at alpha 7 but not alpha 4/beta 2 nicotinic receptor subtypes. These results indicated that DMXB is a novel nicotinic agonist with apparent specificity for the alpha 7/alpha-bungarotoxin nicotinic receptor subtype and indicate that nicotinic receptor activation is capable of modulating the induction of long-term potentiation.

Anti-correlated cortical networks of intrinsic connectivity in the rat brain.

Science.gov (United States)

Schwarz, Adam J; Gass, Natalia; Sartorius, Alexander; Risterucci, Celine; Spedding, Michael; Schenker, Esther; Meyer-Lindenberg, Andreas; Weber-Fahr, Wolfgang

2013-01-01

In humans, resting-state blood oxygen level-dependent (BOLD) signals in the default mode network (DMN) are temporally anti-correlated with those from a lateral cortical network involving the frontal eye fields, secondary somatosensory and posterior insular cortices. Here, we demonstrate the existence of an analogous lateral cortical network in the rat brain, extending laterally from anterior secondary sensorimotor regions to the insular cortex and exhibiting low-frequency BOLD fluctuations that are temporally anti-correlated with a midline "DMN-like" network comprising posterior/anterior cingulate and prefrontal cortices. The primary nexus for this anti-correlation relationship was the anterior secondary motor cortex, close to regions that have been identified with frontal eye fields in the rat brain. The anti-correlation relationship was corroborated after global signal removal, underscoring this finding as a robust property of the functional connectivity signature in the rat brain. These anti-correlated networks demonstrate strong anatomical homology to networks identified in human and monkey connectivity studies, extend the known preserved functional connectivity relationships between rodent and primates, and support the use of resting-state functional magnetic resonance imaging as a translational imaging method between rat models and humans.

Brain protection by methylprednisolone in rats with spinal cord injury.

Science.gov (United States)

Chang, Chia-Mao; Lee, Ming-Hsueh; Wang, Ting-Chung; Weng, Hsu-Huei; Chung, Chiu-Yen; Yang, Jen-Tsung

2009-07-01

Traumatic spinal cord injury is clinically treated by high doses of methylprednisolone. However, the effect of methylprednisolone on the brain in spinal cord injury patients has been little investigated. This experimental study examined Bcl-2 and Bax protein expression and Nissl staining to evaluate an apoptosis-related intracellular signaling event and final neuron death, respectively. Spinal cord injury produced a significant apoptotic change and cell death not only in the spinal cord but also in the supraventricular cortex and hippocampal cornu ammonis 1 region in the rat brains. The treatment of methylprednisolone increased the Bcl-2/Bax ratio and prevented neuron death for 1-7 days after spinal cord injury. These findings suggest that rats with spinal cord injury show ascending brain injury that could be restricted through methylprednisolone management.

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.

Novel whole brain segmentation and volume estimation using quantitative MRI

International Nuclear Information System (INIS)

West, J.; Warntjes, J.B.M.; Lundberg, P.

2012-01-01

Brain segmentation and volume estimation of grey matter (GM), white matter (WM) and cerebro-spinal fluid (CSF) are important for many neurological applications. Volumetric changes are observed in multiple sclerosis (MS), Alzheimer's disease and dementia, and in normal aging. A novel method is presented to segment brain tissue based on quantitative magnetic resonance imaging (qMRI) of the longitudinal relaxation rate R 1 , the transverse relaxation rate R 2 and the proton density, PD. Previously reported qMRI values for WM, GM and CSF were used to define tissues and a Bloch simulation performed to investigate R 1 , R 2 and PD for tissue mixtures in the presence of noise. Based on the simulations a lookup grid was constructed to relate tissue partial volume to the R 1 -R 2 -PD space. The method was validated in 10 healthy subjects. MRI data were acquired using six resolutions and three geometries. Repeatability for different resolutions was 3.2% for WM, 3.2% for GM, 1.0% for CSF and 2.2% for total brain volume. Repeatability for different geometries was 8.5% for WM, 9.4% for GM, 2.4% for CSF and 2.4% for total brain volume. We propose a new robust qMRI-based approach which we demonstrate in a patient with MS. (orig.)

Novel whole brain segmentation and volume estimation using quantitative MRI

Energy Technology Data Exchange (ETDEWEB)

West, J. [Linkoeping University, Radiation Physics, Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoeping (Sweden); Linkoeping University, Center for Medical Imaging Science and Visualization (CMIV), Linkoeping (Sweden); SyntheticMR AB, Linkoeping (Sweden); Warntjes, J.B.M. [Linkoeping University, Center for Medical Imaging Science and Visualization (CMIV), Linkoeping (Sweden); SyntheticMR AB, Linkoeping (Sweden); Linkoeping University and Department of Clinical Physiology UHL, County Council of Oestergoetland, Clinical Physiology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoeping (Sweden); Lundberg, P. [Linkoeping University, Center for Medical Imaging Science and Visualization (CMIV), Linkoeping (Sweden); Linkoeping University and Department of Radiation Physics UHL, County Council of Oestergoetland, Radiation Physics, Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoeping (Sweden); Linkoeping University and Department of Radiology UHL, County Council of Oestergoetland, Radiology, Department of Medical and Health Sciences, Faculty of Health Sciences, Linkoeping (Sweden)

2012-05-15

Brain segmentation and volume estimation of grey matter (GM), white matter (WM) and cerebro-spinal fluid (CSF) are important for many neurological applications. Volumetric changes are observed in multiple sclerosis (MS), Alzheimer's disease and dementia, and in normal aging. A novel method is presented to segment brain tissue based on quantitative magnetic resonance imaging (qMRI) of the longitudinal relaxation rate R{sub 1}, the transverse relaxation rate R{sub 2} and the proton density, PD. Previously reported qMRI values for WM, GM and CSF were used to define tissues and a Bloch simulation performed to investigate R{sub 1}, R{sub 2} and PD for tissue mixtures in the presence of noise. Based on the simulations a lookup grid was constructed to relate tissue partial volume to the R{sub 1}-R{sub 2}-PD space. The method was validated in 10 healthy subjects. MRI data were acquired using six resolutions and three geometries. Repeatability for different resolutions was 3.2% for WM, 3.2% for GM, 1.0% for CSF and 2.2% for total brain volume. Repeatability for different geometries was 8.5% for WM, 9.4% for GM, 2.4% for CSF and 2.4% for total brain volume. We propose a new robust qMRI-based approach which we demonstrate in a patient with MS. (orig.)

Impairments of learning and memory in the rats after brain irradiation

Energy Technology Data Exchange (ETDEWEB)

Takai, Nobuhiko [National Inst. of Radiological Sciences, Chiba (Japan)

2002-06-01

Clinical trials of hadrontherapy have been carried out world wide at several facilities including National Institute of Radiological Sciences (NIRS). Cerebral dysfunction is one of the major concerns associated with radiotherapy of brain tumors. However, little is known about the neurochemical basis of brain dysfunction induced by proton irradiation. We investigated and reported here the early consequences of brain damages caused by proton beam. The animals that had memorized the location of the standard position were locally irradiated to brain with either 70 MeV protons or 290 MeV carbon ions. At 24 hr after irradiation, impairment of the long-term memory was not observed in the irradiated rats compared to control. Irradiated animals, however, required substantially longer time finding out the standard position than control rats when the standard platform displaced to a position different from memorized position. This follows that a single doses of 30 Gy, either protons or carbon ions, impairs the working memory of animals. Function of muscarinic acetylcholine receptors was analyzed by an in vivo binding assay using radioligand quinuclidinyl benzilate (QNB). Irradiated rats were intravenously injected with 5.5 MBq of {sup 3}H-QNB 24 hr after the irradiation, and decapitated 60 min after tracer injection. The autoradiographic studies showed an transitional increase of {sup 3}H-QNB in vivo binding in the early phase after proton irradiation, even though no change in in-vitro {sup 3}H-QNB binding was see in brain autoradiograms of irradiated rats. The cerebral blood flow and the histrogical features of brain were also changed at 3 months post-irradiation. These results indicate that the memory impairment caused by radiation is closely related to the early change of acetylcholine receptor in vivo. (author)

Impairments of learning and memory in the rats after brain irradiation

International Nuclear Information System (INIS)

Takai, Nobuhiko

2002-01-01

Clinical trials of hadrontherapy have been carried out world wide at several facilities including National Institute of Radiological Sciences (NIRS). Cerebral dysfunction is one of the major concerns associated with radiotherapy of brain tumors. However, little is known about the neurochemical basis of brain dysfunction induced by proton irradiation. We investigated and reported here the early consequences of brain damages caused by proton beam. The animals that had memorized the location of the standard position were locally irradiated to brain with either 70 MeV protons or 290 MeV carbon ions. At 24 hr after irradiation, impairment of the long-term memory was not observed in the irradiated rats compared to control. Irradiated animals, however, required substantially longer time finding out the standard position than control rats when the standard platform displaced to a position different from memorized position. This follows that a single doses of 30 Gy, either protons or carbon ions, impairs the working memory of animals. Function of muscarinic acetylcholine receptors was analyzed by an in vivo binding assay using radioligand quinuclidinyl benzilate (QNB). Irradiated rats were intravenously injected with 5.5 MBq of 3 H-QNB 24 hr after the irradiation, and decapitated 60 min after tracer injection. The autoradiographic studies showed an transitional increase of 3 H-QNB in vivo binding in the early phase after proton irradiation, even though no change in in-vitro 3 H-QNB binding was see in brain autoradiograms of irradiated rats. The cerebral blood flow and the histrogical features of brain were also changed at 3 months post-irradiation. These results indicate that the memory impairment caused by radiation is closely related to the early change of acetylcholine receptor in vivo. (author)

Novel flurbiprofen derivatives with improved brain delivery: synthesis, in vitro and in vivo evaluations.

Science.gov (United States)

Zheng, Dan; Shuai, Xiao; Li, Yanping; Zhou, Peng; Gong, Tao; Sun, Xun; Zhang, Zhirong

2016-09-01

Tarenflurbil (R-flurbiprofen) was acknowledged as a promising candidate in Alzheimer's disease (AD) therapy. However, the Phase III study of tarenflurbil was extremely restricted by its poor delivery efficiency to the brain. To tackle this problem, the novel carriers for tarenflurbil, racemic flurbiprofen (FLU) derivatives (FLU-D1 and FLU-D2) modified by N,N-dimethylethanolamine-related structures were synthesized and characterized. These derivatives showed good safety level in vitro and they possessed much higher cellular uptake efficiency in brain endothelial cells than FLU did. More importantly, the uptake experiments suggested that they were internalized via active transport mechanisms. Biodistribution studies in rats also illustrated a remarkably enhanced accumulation of these derivatives in the brain. FLU-D2, the ester linkage form of these derivatives, achieved a higher brain-targeting efficiency. Its C max and AUC 0- t were enhanced by 12.09-fold and 4.61-fold, respectively compared with those of FLU. Additionally, it could be hydrolyzed by esterase in the brain to release the parent FLU, which might facilitate its therapeutic effect. These in vitro and in vivo results highlighted the improvement of the brain-targeted delivery of FLU by making use of N,N-dimethylethanolamine ligand, with which an active transport mechanism was involved.

Comparison of brain activation to purposefully activate a tool in healthy subjects and brain tumor patients using fMRI

International Nuclear Information System (INIS)

Nishimura, Masahiko; Yoshii, Yoshihiko; Hyodo, Akio; Sugimoto, Koichi; Tsuchida, Yukihiro; Yonaha, Hirokatsu; Ito, Koichi

2007-01-01

The purpose of this study was to determine the functional organization of the human brain involved in tool-manipulation. Blood Oxygen Level Dependent was measured by functional magnetic resonance imaging in seventeen right-handed healthy volunteers and two brain tumor patients during two tool-manipulation tasks: simulated tightening a bolt with a screwdriver (Simulation), and tightening a bolt with a screwdriver (Real). Subjects performed the experiment without watching the tasks. Bilateral pre-supplementary motor areas, bilateral cerebellar posterior lobes, right ventral premotor area, right calcarine sulcus, and cerebellar vermis were activated during Real but not during Simulation tasks in healthy volunteers. In addition, brain tumor patients activated the prefrontal areas. Our results suggest that the human brain mechanisms for tool-manipulation have a neural-network comprised of presupplementary motor area, ventral premotor area, and bilateral cerebellar posterior lobes. In the patients with brain dusfurction diee to tumors, activation at the prefrontal area provided function compensation without motor paralysis. (author)

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

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

2013-01-01

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

Autoradiographic visualization of insulin-like growth factor-II receptors in rat brain

International Nuclear Information System (INIS)

Mendelsohn, L.G.; Kerchner, G.A.; Clemens, J.A.; Smith, M.C.

1986-01-01

The documented presence of IGF-II in brain and CSF prompted us to investigate the distribution of receptors for IGF-II in rat brain slices. Human 125 -I-IGF-II (10 pM) was incubated for 16 hrs at 4 0 C with slide-mounted rat brain slices in the absence and presence of unlabeled human IGF-II (67 nM) or human insulin (86 nM). Slides were washed, dried, and exposed to X-ray film for 4-7 days. The results showed dense labeling in the granular layers of the olfactory bulbs, deep layers of the cerebral cortex, pineal gland, anterior pituitary, hippocampus (pyramidal cells CA 1 -CA 2 and dentate gyrus), and the granule cell layers of the cerebellum. Unlabeled IGF-II eliminated most of the binding of these brain regions while insulin produced only a minimal reduction in the amount of 125 I-IGF-II bound. These results indicate that a specific neural receptor for IGS-II is uniquely distributed in rat brain tissue and supports the notion that this peptide might play an important role in normal neuronal functioning

[Alterations of glial fibrillary acidic protein in rat brain after gamma knife irradiation].

Science.gov (United States)

Ma, Z M; Jiang, B; Ma, J R

2001-08-28

To study glial fibrillary acidic protein (GFAP) immunoreactivity in different time and water content of the rat brain treated with gamma knife radiotherapy and to understand the alteration course of the brain lesion after a single high dose radiosurgical treatment. In the brains of the normal rats were irradiated by gamma knife with 160 Gy-high dose. The irradiated rats were then killed on the 1st day, 7th day, 14th day, and 28th day after radiotherapy, respectively. The positive cells of GFAP in brain tissue were detected by immunostaining; the water content of the brain tissue was measured by microgravimetry. The histological study of the irradiated brain tissue was performed with H.E. and examined under light microscope. The numbers of GFAP-positive astrocytes began to increase on the 1st day after gamma knife irradiation. It was enlarged markedly in the number and size of GFAP-stained astrocytes over the irradiated areas. Up to the 28th day, circumscribed necrosis foci (4 mm in diameter) was seen in the central area of the target. In the brain tissue around the necrosis, GFAP-positive astrocytes significantly increased (P gravity in the irradiated brain tissue the 14th and 28th day after irradiation. The results suggest that GFAP can be used as a marker for the radiation-induced brain injury. The brain edema and disruption of brain-blood barrier can be occurred during the acute stage after irradiation.

Restoring susceptibility induced MRI signal loss in rat brain at 9.4 T: A step towards whole brain functional connectivity imaging.

Directory of Open Access Journals (Sweden)

Rupeng Li

Full Text Available The aural cavity magnetic susceptibility artifact leads to significant echo planar imaging (EPI signal dropout in rat deep brain that limits acquisition of functional connectivity fcMRI data. In this study, we provide a method that recovers much of the EPI signal in deep brain. Needle puncture introduction of a liquid-phase fluorocarbon into the middle ear allows acquisition of rat fcMRI data without signal dropout. We demonstrate that with seeds chosen from previously unavailable areas, including the amygdala and the insular cortex, we are able to acquire large scale networks, including the limbic system. This tool allows EPI-based neuroscience and pharmaceutical research in rat brain using fcMRI that was previously not feasible.

Brain regional differences in social encounter-induced Fos expression in male and female rats after post-weaning social isolation.

Science.gov (United States)

Ahern, Megan; Goodell, Dayton J; Adams, Jessica; Bland, Sondra T

2016-01-01

Early life adversity has been related to a number of psychological disorders including mood and other disorders that can manifest as inappropriate or aggressive responses to social challenges. The present study used post-weaning social isolation (PSI) in rats, a model of early life adversity, to examine its effects on Fos protein expression produced by exposure to a novel social encounter. We have previously reported that the social encounter-induced increase in Fos expression in the medial prefrontal cortex observed in group-housed controls (GRP) was attenuated in rats that had experienced PSI. Here we assessed Fos expression in other brain regions thought to be involved in emotion regulation and social behavior. Male and female rats were housed in same-sex groups or in isolation (ISO) for 4 weeks beginning on postnatal day (P) 21 and were exposed to a single 15 min social encounter with a novel same-sex conspecific on P49. Fos positive cells were assessed using immunohistochemistry in 16 regions within the forebrain. Exposure to a novel conspecific increased Fos expression in the forebrain of GRP rats in a region- and sex-specific fashion. This increase was blunted or absent in ISO rats within many regions including cortical regions, thalamus, habenula, dentate gyrus, lateral septum, and basolateral amygdala. In several regions, the increase in Fos was greater in male than in female group housed rats. Negative relationships were observed between social interactions and Fos in some regions. Forebrain hypofunction produced by early-life adversity may be involved in socially inappropriate behavior. Copyright © 2015 Elsevier B.V. All rights reserved.

Agonist and antagonist binding to rat brain muscarinic receptors: influence of aging

International Nuclear Information System (INIS)

Gurwitz, D.; Egozi, Y.; Henis, Y.I.; Kloog, Y.; Sokolovsky, M.

1987-01-01

The objective of the present study was to determine the binding properties of muscarinic receptors in six brain regions in mature and old rats of both sexes by employing direct binding of [ 3 H]-antagonist as well as of the labeled natural neurotransmitter, [ 3 H]-acetylcholine [( 3 H]-AcCh). In addition, age-related factors were evaluated in the modulation processes involved in agonist binding. The results indicate that as the rat ages the density of the muscarinic receptors is altered differently in the various brain regions: it is decreased in the cerebral cortex, hippocampus, striatum and olfactory bulb of both male and female rats, but is increased (58%) in the brain stem of senescent males while no significant change is observed for females. The use of the highly sensitive technique measuring direct binding of [ 3 H]-AcCh facilitated the separate detection of age-related changes in the two classes (high- and low-affinity) of muscarinic agonist binding sites. In old female rats the density of high-affinity [ 3 H]-AcCh binding sites was preserved in all tissues studied, indicating that the decreases in muscarinic receptor density observed with [ 3 H]-antagonist represent a loss of low-affinity agonist binding sites. In contrast, [ 3 H]-AcCh binding is decreased in the hypothalamus and increased in the brain stem of old male rats. These data imply sexual dimorphism of the aging process in central cholinergic mechanisms

Psychological stress, cocaine and natural reward each induce endoplasmic reticulum stress genes in rat brain.

Science.gov (United States)

Pavlovsky, A A; Boehning, D; Li, D; Zhang, Y; Fan, X; Green, T A

2013-08-29

Our prior research has shown that the transcription of endoplasmic reticulum (ER) stress transcription factors activating transcription factor 3 (ATF3) and ATF4 are induced by amphetamine and restraint stress in rat striatum. However, presently the full extent of ER stress responses to psychological stress or cocaine, and which of the three ER stress pathways is activated is unknown. The current study examines transcriptional responses of key ER stress target genes subsequent to psychological stress or cocaine. Rats were subjected to acute or repeated restraint stress or cocaine treatment and mRNA was isolated from dorsal striatum, medial prefrontal cortex and nucleus accumbens brain tissue. ER stress gene mRNA expression was measured using quantitative polymerase chain reaction (PCR) and RNA sequencing. Restraint stress and cocaine-induced transcription of the classic ER stress-induced genes (BIP, CHOP, ATF3 and GADD34) and of two other ER stress components x-box binding protein 1 (XBP1) and ATF6. In addition, rats living in an enriched environment (large group cage with novel toys changed daily) exhibited rapid induction of GADD34 and ATF3 after 30 min of exploring novel toys, suggesting these genes are also involved in normal non-pathological signaling. However, environmental enrichment, a paradigm that produces protective addiction and depression phenotypes in rats, attenuated the rapid induction of ATF3 and GADD34 after restraint stress. These experiments provide a sensitive measure of ER stress and, more importantly, these results offer good evidence of the activation of ER stress mechanisms from psychological stress, cocaine and natural reward. Thus, ER stress genes may be targets for novel therapeutic targets for depression and addiction. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of anesthesia on [11C]raclopride binding in the rat brain

DEFF Research Database (Denmark)

Alstrup, Aage Kristian Olsen; Simonsen, Mette; Møller, Arne

Background Very often rats are anesthetized prior to micro positron emission tomography (microPET) brain imaging in order to prevent head movements. Anesthesia can be administered by inhalation agents, such as isoflurane, or injection mixtures, such as fentanyl-fluanisone-midazolam. Unfortunately......, anesthesia affects a variety of physiological variables, including in the brain. Aim The aim of this study was to compare the effects of inhalation and injection anesthesia on the binding potential of the dopaminergic D2/3 tracer [11C]raclopride used for PET brain imaging in human and animal studies....... Materials & Methods Nine male Lew/Mol rats were assigned to either inhalation (isoflurane; N=4) or injection (fentanyl-fluanisone-midazolam; N=5) anesthesia. Catheters were surgically placed in femoral arteries and veins for blood sampling and tracer injection. After a short attenuation scan, the rats were...

Simultaneous measurement of glucose blood–brain transport constants and metabolic rate in rat brain using in-vivo 1H MRS

Science.gov (United States)

Du, Fei; Zhang, Yi; Zhu, Xiao-Hong; Chen, Wei

2012-01-01

Cerebral glucose consumption and glucose transport across the blood–brain barrier are crucial to brain function since glucose is the major energy fuel for supporting intense electrophysiological activity associated with neuronal firing and signaling. Therefore, the development of noninvasive methods to measure the cerebral metabolic rate of glucose (CMRglc) and glucose transport constants (KT: half-saturation constant; Tmax: maximum transport rate) are of importance for understanding glucose transport mechanism and neuroenergetics under various physiological and pathological conditions. In this study, a novel approach able to simultaneously measure CMRglc, KT, and Tmax via monitoring the dynamic glucose concentration changes in the brain tissue using in-vivo 1H magnetic resonance spectroscopy (MRS) and in plasma after a brief glucose infusion was proposed and tested using an animal model. The values of CMRglc, Tmax, and KT were determined to be 0.44±0.17 μmol/g per minute, 1.35±0.47 μmol/g per minute, and 13.4±6.8 mmol/L in the rat brain anesthetized with 2% isoflurane. The Monte-Carlo simulations suggest that the measurements of CMRglc and Tmax are more reliable than that of KT. The overall results indicate that the new approach is robust and reliable for in-vivo measurements of both brain glucose metabolic rate and transport constants, and has potential for human application. PMID:22714049

Metabolic enhancer piracetam attenuates rotenone induced oxidative stress: a study in different rat brain regions.

Science.gov (United States)

Verma, Dinesh Kumar; Joshi, Neeraj; Raju, Kunumuri Sivarama; Wahajuddin, Muhammad; Singh, Rama Kant; Singh, Sarika

2015-01-01

Piracetam is clinically being used nootropic drug but the details of its neuroprotective mechanism are not well studied. The present study was conducted to assess the effects of piracetam on rotenone induced oxidative stress by using both ex vivo and in vivo test systems. Rats were treated with piracetam (600 mg/kg b.w. oral) for seven constitutive days prior to rotenone administration (intracerebroventricular, 12 µg) in rat brain. Rotenone induced oxidative stress was assessed after 1 h and 24 h of rotenone administration. Ex vivo estimations were performed by using two experimental designs. In one experimental design the rat brain homogenate was treated with rotenone (1 mM, 2 mM and 4 mM) and rotenone+piracetam (10 mM) for 1 h. While in second experimental design the rats were pretreated with piracetam for seven consecutive days. On eighth day the rats were sacrificed, brain homogenate was prepared and treated with rotenone (1 mM, 2 mM and 4mM) for 1h. After treatment the glutathione (GSH) and malondialdehyde (MDA) levels were estimated in brain homogenate. In vivo study showed that pretreatment of piracetam offered significant protection against rotenone induced decreased GSH and increased MDA level though the protection was region specific. But the co-treatment of piracetam with rotenone did not offer significant protection against rotenone induced oxidative stress in ex vivo study. Whereas ex vivo experiments in rat brain homogenate of piracetam pretreated rats, showed the significant protection against rotenone induced oxidative stress. Findings indicated that pretreatment of piracetam significantly attenuated the rotenone induced oxidative stress though the protection was region specific. Piracetam treatment to rats led to its absorption and accumulation in different brain regions as assessed by liquid chromatography mass spectrometry/mass spectrometry. In conclusion, study indicates the piracetam is able to enhance the antioxidant capacity in brain cells

[11C]TASP457, a novel PET ligand for histamine H3 receptors in human brain

International Nuclear Information System (INIS)

Kimura, Yasuyuki; Seki, Chie; Ikoma, Yoko; Ichise, Masanori; Kawamura, Kazunori; Takahata, Keisuke; Moriguchi, Sho; Nagashima, Tomohisa; Ishii, Tatsuya; Kitamura, Soichiro; Niwa, Fumitoshi; Endo, Hironobu; Yamada, Makiko; Higuchi, Makoto; Zhang, Ming-Rong; Suhara, Tetsuya

2016-01-01

The histamine H 3 receptors are presynaptic neuroreceptors that inhibit the release of histamine and other neurotransmitters. The receptors are considered a drug target for sleep disorders and neuropsychiatric disorders with cognitive decline. We developed a novel PET ligand for the H 3 receptors, [ 11 C]TASP0410457 ([ 11 C]TASP457), with high affinity, selectivity and favorable kinetic properties in the monkey, and evaluated its kinetics and radiation safety profile for quantifying the H 3 receptors in human brain. Ten healthy men were scanned for 120 min with a PET scanner for brain quantification and three healthy men were scanned for radiation dosimetry after injection of 386 ± 6.2 MBq and 190 ± 7.5 MBq of [ 11 C]TASP457, respectively. For brain quantification, arterial blood sampling and metabolite analysis were performed using high-performance liquid chromatography. Distribution volumes (V T ) in brain regions were determined by compartment and graphical analyses using the Logan plot and Ichise multilinear analysis (MA1). For dosimetry, radiation absorbed doses were estimated using the Medical Internal Radiation Dose scheme. [ 11 C]TASP457 PET showed high uptake (standardized uptake values in the range of about 3 - 6) in the brain and fast washout in cortical regions and slow washout in the pallidum. The two-tissue compartment model and graphical analyses estimated V T with excellent identification using 60-min scan data (about 16 mL/cm 3 in the pallidum, 9 - 14 in the basal ganglia, 6 - 9 in cortical regions, and 5 in the pons), which represents the known distribution of histamine H 3 receptors. For parametric imaging, MA1 is recommended because of minimal underestimation with small intersubject variability. The organs with the highest radiation doses were the pancreas, kidneys, and liver. The effective dose delivered by [ 11 C]TASP457 was 6.9 μSv/MBq. [ 11 C]TASP457 is a useful novel PET ligand for the investigation of the density of histamine H 3

Insulin-like growth factor-II (IGF II) receptor from rat brain is of lower apparent molecular weight than the IGF II receptor from rat liver

International Nuclear Information System (INIS)

McElduff, A.; Poronnik, P.; Baxter, R.C.

1987-01-01

The binding subunits of the insulin and insulin-like growth factor-I (IGF I) receptors from rat brain are of lower molecular weight than the corresponding receptor in rat liver, possibly due to variations in sialic acid content. We have compared the IGF II receptor from rat brain and rat liver. The brain receptor is of smaller apparent mol wt (about 10 K) on sodium dodecyl sulfate polyacrylamide gel electrophoresis. This size difference is independent of ligand binding as it persists in iodinated and specifically immunoprecipitated receptors. From studies of wheat germ agglutinin binding and the effect of neuraminidase on receptor mobility, we conclude that this difference is not simply due to variations in sialic acid content. Treatment with endoglycosidase F results in reduction in the molecular size of both liver and brain receptors and after this treatment the aglycoreceptors are of similar size. We conclude that in rat brain tissue the IGF II receptor like the binding subunits of the insulin and IGF I receptors is of lower molecular size than the corresponding receptors in rat liver. This difference is due to differences in N-linked glycosylation

Effects of the Acute and Chronic Ethanol Intoxication on Acetate Metabolism and Kinetics in the Rat Brain.

Science.gov (United States)

Hsieh, Ya-Ju; Wu, Liang-Chih; Ke, Chien-Chih; Chang, Chi-Wei; Kuo, Jung-Wen; Huang, Wen-Sheng; Chen, Fu-Du; Yang, Bang-Hung; Tai, Hsiao-Ting; Chen, Sharon Chia-Ju; Liu, Ren-Shyan

2018-02-01

Ethanol (EtOH) intoxication inhibits glucose transport and decreases overall brain glucose metabolism; however, humans with long-term EtOH consumption were found to have a significant increase in [1- 11 C]-acetate uptake in the brain. The relationship between the cause and effect of [1- 11 C]-acetate kinetics and acute/chronic EtOH intoxication, however, is still unclear. [1- 11 C]-acetate positron emission tomography (PET) with dynamic measurement of K 1 and k 2 rate constants was used to investigate the changes in acetate metabolism in different brain regions of rats with acute or chronic EtOH intoxication. PET imaging demonstrated decreased [1- 11 C]-acetate uptake in rat brain with acute EtOH intoxication, but this increased with chronic EtOH intoxication. Tracer uptake rate constant K 1 and clearance rate constant k 2 were decreased in acutely intoxicated rats. No significant change was noted in K 1 and k 2 in chronic EtOH intoxication, although 6 of 7 brain regions showed slightly higher k 2 than baseline. These results indicate that acute EtOH intoxication accelerated acetate transport and metabolism in the rat brain, whereas chronic EtOH intoxication status showed no significant effect. In vivo PET study confirmed the modulatory role of EtOH, administered acutely or chronically, in [1- 11 C]-acetate kinetics and metabolism in the rat brain. Acute EtOH intoxication may inhibit the transport and metabolism of acetate in the brain, whereas chronic EtOH exposure may lead to the adaptation of the rat brain to EtOH in acetate utilization. [1- 11 C]-acetate PET imaging is a feasible approach to study the effect of EtOH on acetate metabolism in rat brain. Copyright © 2017 by the Research Society on Alcoholism.

Fragmentation of Protein Kinase N (PKN) in the Hydrocephalic Rat Brain

International Nuclear Information System (INIS)

Okii, Norifumi; Amano, Taku; Seki, Takahiro; Matsubayashi, Hiroaki; Mukai, Hideyuki; Ono, Yoshitaka; Kurisu, Kaoru; Sakai, Norio

2007-01-01

PKN (protein kinase N; also called protein kinase C-related kinase (PRK-1)), is a serine/threonine protein kinase that is ubiquitously expressed in several organs, including the brain. PKN has a molecular mass of 120 kDa and has two domains, a regulatory and a catalytic domain, in its amino-terminals and carboxyl-terminus, respectively. Although the role of PKN has not been fully elucidated, previous studies have revealed that PKN is cleaved to a constitutively active catalytic fragment of 55 kDa in response to apoptotic signals. Hydrocephalus is a pathological condition caused by insufficient cerebrospinal fluid (CSF) circulation and subsequent excess of CSF in the brain. In this study, in order to elucidate the role of PKN in the pathophysiology of hydrocephalus, we examined PKN fragmentation in hydrocephalic model rats. Hydrocephalus was induced in rats by injecting kaolin into the cisterna magna. Kaolin-induced rats (n=60) were divided into three groups according to the observation period after treatment (group 1: 3–6 weeks, group 2: 7–12 weeks, and group 3: 13–18 weeks). Sham-treated control rats, injected with sterile saline (n=20), were similarly divided into three groups. Spatial learning ability was estimated by a modified water maze test. Thereafter, brains were cut into slices and ventricular dilatation was estimated. Fragmentation of PKN was observed by Western blotting in samples collected from the parietal cortex, striatum, septal nucleus, hippocampus, and periaqueductal gray matter. All kaolin-induced rats showed ventricular dilatation. Most of them showed less spatial learning ability than those of sham-treated controls. In most regions, fragmentation of PKN had occurred in a biphasic manner more frequently than that in controls. The appearance of PKN fragmentation in periaqueductal gray matter was correlated with the extent of ventricular dilation and spatial learning disability. These results revealed that PKN fragmentation was observed in

Effects of nanoparticle zinc oxide on emotional behavior and trace elements homeostasis in rat brain.

Science.gov (United States)

Amara, Salem; Slama, Imen Ben; Omri, Karim; El Ghoul, Jaber; El Mir, Lassaad; Rhouma, Khemais Ben; Abdelmelek, Hafedh; Sakly, Mohsen

2015-12-01

Over recent years, nanotoxicology and the potential effects on human body have grown in significance, the potential influences of nanosized materials on the central nervous system have received more attention. The aim of this study was to determine whether zinc oxide (ZnO) nanoparticles (NPs) exposure cause alterations in emotional behavior and trace elements homeostasis in rat brain. Rats were treated by intraperitoneal injection of ZnO NPs (20-30 nm) at a dose of 25 mg/kg body weight. Sub -: acute ZnO NPs treatment induced no significant increase in the zinc content in the homogenate brain. Statistically significant decreases in iron and calcium concentrations were found in rat brain tissue compared to control. However, sodium and potassium contents remained unchanged. Also, there were no significant changes in the body weight and the coefficient of brain. In the present study, the anxiety-related behavior was evaluated using the plus-maze test. ZnO NPs treatment modulates slightly the exploratory behaviors of rats. However, no significant differences were observed in the anxious index between ZnO NP-treated rats and the control group (p > 0.05). Interestingly, our results demonstrated minimal effects of ZnO NPs on emotional behavior of animals, but there was a possible alteration in trace elements homeostasis in rat brain. © The Author(s) 2012.

Imaging of water distribution in the rat brain by activation autoradiography

International Nuclear Information System (INIS)

Kogure, K.; Kawashima, K.; Iwata, R.; Ido, T.

1990-01-01

Regional water distribution in the rat brain was obtained autoradiographically by activation analysis. The autoradiogram obtained for the normal rat brain showed high accumulation of water in the areas of sensory-motor cortex, hippocampus, thalamus, and amygdaloid cortex, whereas corpus callosum and internal capsule showed low water contents as expected. The estimated values of water content were 78.6 +/- 4.9 weight % for gray matter, and 73.5 +/- 4.9 weight % for white matter, respectively. The mean values of the water content were consistent with those obtained by a conventional drying-weighing method

Influence of age on the passage of paraquat through the blood-brain barrier in rats: a distribution and pathological examination

International Nuclear Information System (INIS)

Widdowson, P.S.; Farnworth, M.J.; Simpson, M.G.; Lock, E.A.

1996-01-01

Experiments were performed to determine the extent of paraquat entry into the brain of neonatal and elderly rats, as compared with adult rats, which may be dependent on the efficacy of the blood-brain barrier. A single, median lethal dose (20 mg/kg s.c.) of paraquat containing [14C]paraquat was administered to neonatal (10 day old), adult (3 month old) and elderly (18 month old) rats. In contrast to the adult and elderly rats where paraquat levels fell over the 24 h post-dosing period to negligible levels, paraquat concentrations in neonatal brains did not decrease with time between 0.5 and 24 h following dosing. The distribution of [14C]paraquat was measured in selective brain regions using quantitative autoradiography in all three age groups of rats, 30 min and 24 h following dosing. Autoradiography demonstrated that brain paraquat distributions were similar in the rat age groups. Most of the paraquat was confined to regions outside the blood-brain barrier and to brain regions that lack a complete blood-brain barrier e.g. dorsal hypothalamus, area postrema and the anterior olfactory bulb. Between 0.5 h and 24 h following dosing, paraquat concentrations in deeper brain structures, some distance away from the sites of entry, began to slowly increase in all the rat age groups. By 24 h following dosing, a majority of brain regions examined using quantitative autoradiography revealed significantly higher paraquat concentrations in neonatal brains as compared to brain regions of adult and elderly rats. Despite increased paraquat entry into neonatal brain, we could find no evidence for paraquat-induced neuronal cell damage following a detailed histopathological examination of perfused-fixed brains. In conclusion, impaired blood-brain barrier integrity in neonatal brain thus permitting more paraquat to enter than in adult brain, did not result in neuronal damage

A Novel Audiovisual Brain-Computer Interface and Its Application in Awareness Detection

Science.gov (United States)

Wang, Fei; He, Yanbin; Pan, Jiahui; Xie, Qiuyou; Yu, Ronghao; Zhang, Rui; Li, Yuanqing

2015-01-01

Currently, detecting awareness in patients with disorders of consciousness (DOC) is a challenging task, which is commonly addressed through behavioral observation scales such as the JFK Coma Recovery Scale-Revised. Brain-computer interfaces (BCIs) provide an alternative approach to detect awareness in patients with DOC. However, these patients have a much lower capability of using BCIs compared to healthy individuals. This study proposed a novel BCI using temporally, spatially, and semantically congruent audiovisual stimuli involving numbers (i.e., visual and spoken numbers). Subjects were instructed to selectively attend to the target stimuli cued by instruction. Ten healthy subjects first participated in the experiment to evaluate the system. The results indicated that the audiovisual BCI system outperformed auditory-only and visual-only systems. Through event-related potential analysis, we observed audiovisual integration effects for target stimuli, which enhanced the discriminability between brain responses for target and nontarget stimuli and thus improved the performance of the audiovisual BCI. This system was then applied to detect the awareness of seven DOC patients, five of whom exhibited command following as well as number recognition. Thus, this audiovisual BCI system may be used as a supportive bedside tool for awareness detection in patients with DOC. PMID:26123281

Development and validation of a sensitive UPLC-MS/MS method for the quantitation of [(13)C]sucrose in rat plasma, blood, and brain: Its application to the measurement of blood-brain barrier permeability.

Science.gov (United States)

Miah, Mohammad K; Bickel, Ulrich; Mehvar, Reza

2016-03-15

Accurate and reproducible measurement of blood-brain barrier (BBB) integrity is critical in the assessment of the pathophysiology of the central nervous system disorders and in monitoring therapeutic effects. The widely-used low molecular weight marker [(14)C]sucrose is non-specific in the absence of chromatographic separation. The purpose of this study was to develop and validate a sensitive and reproducible LC-MS/MS method for the analysis of stable isotope-modified [(13)C12]sucrose in brain, plasma, and blood to determine BBB permeability to sucrose. After addition of internal standard (IS, [(13)C6]sucrose), the marker and IS were recovered from diluted rat blood, plasma, and brain homogenate by protein precipitation using acetonitrile. The recovery of the marker and IS was almost quantitative (90-106%) for all three matrices. The recovered samples were directly injected into an isocratic UPLC system with a run time of 6 min. Mass spectrometry was conducted using multiple reaction monitoring in negative mode. The method was linear (r(2)≥0.99) in the concentration ranges tested for the diluted blood and plasma (10-1000 ng/mL) and brain homogenate (1-200 ng/mL). The lower limit of quantitation of the assay was 0.5 pg injected on column. The assay was validated (n=5) based on acceptable intra- and inter-run accuracy and precision values. The method was successfully used for the measurement of serial blood and plasma and terminal brain concentrations of [(13)C12]sucrose after a single intravenous dose (10 mg/kg) of the marker to rats. As expected, the apparent brain uptake clearance values of [(13)C12]sucrose were low in healthy rats. The method may be useful for determination of the BBB integrity in animal models. Copyright © 2016 Elsevier B.V. All rights reserved.

Biodistribution and PET Imaging of a Novel [(68)Ga]-Anti-CD163-Antibody Conjugate in Rats with Collagen-Induced Arthritis and in Controls

DEFF Research Database (Denmark)

Eichendorff, Sascha; Svendsen, Pia; Bender, Dirk

2015-01-01

-68 and evaluated stability and binding specificity of the conjugate ([(68)Ga]ED2) in vitro. Furthermore, tracer biodistribution was assessed in vivo in healthy rats and rats with acute collagen-induced arthritis (CIA) by MicroPET and tissue analysis. RESULTS: Radiosynthesis of [(68)Ga]ED2 antibody...... was also changed in the sense that a significantly higher liver uptake and lower spleen uptake of [(68)Ga]ED2 was measured in CIA rats that accordingly showed a corresponding change in level of CD163 expression. CONCLUSIONS: [(68)Ga]ED2 specifically binds CD163 in vitro and in vivo. Biodistribution studies...... in CIA rats suggest that this novel tool may have applications in studies of inflammatory diseases....

Aging-Dependent Changes in the Radiation Response of the Adult Rat Brain

International Nuclear Information System (INIS)

Schindler, Matthew K.; Forbes, M. Elizabeth; Robbins, Mike E.; Riddle, David R.

2008-01-01

Purpose: To assess the impact of aging on the radiation response in the adult rat brain. Methods and Materials: Male rats 8, 18, or 28 months of age received a single 10-Gy dose of whole-brain irradiation (WBI). The hippocampal dentate gyrus was analyzed 1 and 10 weeks later for sensitive neurobiologic markers associated with radiation-induced damage: changes in density of proliferating cells, immature neurons, total microglia, and activated microglia. Results: A significant decrease in basal levels of proliferating cells and immature neurons and increased microglial activation occurred with normal aging. The WBI induced a transient increase in proliferation that was greater in older animals. This proliferation response did not increase the number of immature neurons, which decreased after WBI in young rats, but not in old rats. Total microglial numbers decreased after WBI at all ages, but microglial activation increased markedly, particularly in older animals. Conclusions: Age is an important factor to consider when investigating the radiation response of the brain. In contrast to young adults, older rats show no sustained decrease in number of immature neurons after WBI, but have a greater inflammatory response. The latter may have an enhanced role in the development of radiation-induced cognitive dysfunction in older individuals

Utilization of 14C-tyrosine in brain and peripheral tissues of developmentally protein malnourished rats

International Nuclear Information System (INIS)

Miller, M.; Leahy, J.P.; McConville, F.; Morgane, P.J.; Resnick, O.

1978-01-01

Prior studies of developmentally protein malnourished rats have reported substantial changes in brain and peripheral utilization of 14 C-leucine, 14 C-phenylalanine, and 14 C-tryptophan. In the present study rats born to dams fed a low protein diet (8% casein) compared to the offspring of control rats fed a normal diet (25% casein) showed few significant differences in the uptake and incorporation of 14 C-tyrosine into brain and peripheral tissues from birth to age 21 days. At birth, the 8% casein pups exhibited significant decreases in brain and peripheral tissue incorporation of tracer only at short post-injection times (10 and 20 min), but not at longer intervals (90 and 180 min). During ontogenetic development (Days 5-21), the 8% casein rats showed significant increases in uptake of 14 C-tyrosine into the brain and peripheral tissues on Day 11 and a significantly higher percent incorporation of tracer into brain protein on Day 21 as compared to the 25% casein rats. For the most part, there were no significant changes in incorporation of radioactivity in peripheral tissues for the 2 diet groups on these post-birth days. Overall, the data indicates that developmental protein malnutrition causes relatively fewer changes in brain and peripheral utilization of the semi-essential amino acid tyrosine than those observed in previous studies with essential amino acids

In vivo deep brain imaging of rats using oral-cavity illuminated photoacoustic computed tomography

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Lin, Li; Xia, Jun; Wong, Terence T. W.; Zhang, Ruiying; Wang, Lihong V.

2015-03-01

We demonstrate, by means of internal light delivery, photoacoustic imaging of the deep brain of rats in vivo. With fiber illumination via the oral cavity, we delivered light directly into the bottom of the brain, much more than can be delivered by external illumination. The study was performed using a photoacoustic computed tomography (PACT) system equipped with a 512-element full-ring transducer array, providing a full two-dimensional view aperture. Using internal illumination, the PACT system provided clear cross sectional photoacoustic images from the palate to the middle brain of live rats, revealing deep brain structures such as the hypothalamus, brain stem, and cerebral medulla.

Disruption of behavior and brain metabolism in artificially reared rats.

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Aguirre-Benítez, Elsa L; Porras, Mercedes G; Parra, Leticia; González-Ríos, Jacquelina; Garduño-Torres, Dafne F; Albores-García, Damaris; Avendaño, Arturo; Ávila-Rodríguez, Miguel A; Melo, Angel I; Jiménez-Estrada, Ismael; Mendoza-Garrido, Ma Eugenia; Toriz, César; Diaz, Daniel; Ibarra-Coronado, Elizabeth; Mendoza-Ángeles, Karina; Hernández-Falcón, Jesús

2017-12-01

Early adverse life stress has been associated to behavioral disorders that can manifest as inappropriate or aggressive responses to social challenges. In this study, we analyzed the effects of artificial rearing on the open field and burial behavioral tests and on GFAP, c-Fos immunoreactivity, and glucose metabolism measured in anxiety-related brain areas. Artificial rearing of male rats was performed by supplying artificial milk through a cheek cannula and tactile stimulation, mimicking the mother's licking to rat pups from the fourth postnatal day until weaning. Tactile stimulation was applied twice a day, at morning and at night, by means of a camel brush on the rat anogenital area. As compared to mother reared rats, greater aggressiveness, and boldness, stereotyped behavior (burial conduct) was observed in artificially reared rats which occurred in parallel to a reduction of GFAP immunoreactivity in somatosensory cortex, c-Fos immunoreactivity at the amygdala and primary somatosensory cortex, and lower metabolism in amygdala (as measured by 2-deoxi-2-[ 18 fluoro]-d-glucose uptake, assessed by microPET imaging). These results could suggest that tactile and/or chemical stimuli from the mother and littermates carry relevant information for the proper development of the central nervous system, particularly in brain areas involved with emotions and social relationships of the rat. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1413-1429, 2017. © 2017 Wiley Periodicals, Inc.

Quantitative determination of deoxyribonucleic acid in rat brain

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Penn, N. W.; Suwalski, R.

1969-01-01

1. A procedure is given for spectrophotometric analysis of rat brain DNA after its resolution into component bases. Amounts of tissue in the range 50–100mg. can be used. 2. The amount of DNA obtained by the present method is 80% greater than that reported for rat brain by a previous procedure specific for DNA thymine. Identity of the material is established by the base ratios of purines and pyrimidines. The features responsible for the higher yield are the presence of dioxan during alkaline hydrolysis of tissue, the determination of the optimum concentration of potassium hydroxide in this step and omission of organic washes of the initial acid-precipitated residues. 3. The requirement for dioxan during alkaline hydrolysis suggests a possible association of brain DNA with lipid. The concentration of potassium hydroxide that gives maximum yield is 0·1m, indicating that there may be internucleotide linkages in this DNA that are more sensitive to alkali than those of liver or thymus DNA. 4. This procedure gives low yields of DNA from liver. It is not suitable for analysis of the DNA from this tissue. PMID:5353529

Effect of sildenafil citrate (Viagra®) on trace element concentration in serum and brain of rats.

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Fayed, Abdel-Hasseb A; Gad, Shereen B

2011-12-01

As a vasodilator with good hemodynamic effects, sildenafil has been successfully used in the treatment of patients with pulmonary hypertension and cardiovascular diseases. By selectively inhibiting phosphodiestrase type 5 (PDE-5) and thus effectively reducing the breakdown of c GMP, sildenafil administration can markedly improve the erectile dysfunction. Sildenafil also elevates localized cerebral blood flow in rat brain. The objective of the present study was to investigate the effect of sildenafil on the level of trace elements (Zinc (Zn), copper (Cu), iron (Fe), selenium (Se), cobalt (Co), and chromium (Cr)) in blood and brain of rats. Sixteen male albino rats weighing 180-200 g were divided into two groups (8 rats/group). Sildenafil (Viagra, Pfizer Inc.) was dissolved in saline and administered at a dose of 10mg/kg i.p. (0.5 ml volume) to rats in the treated group every 72 h for 12 injections. Rats in the control group were administered the same volume of saline as in treated group. All rats were sacrificed 24h after the last injection. Blood samples were collected and serum was separated and stored at -20°C. Brains were dissected and stored frozen until analysis. Trace elements concentrations were determined by flame emission atomic absorption spectrophotometer. Results showed that sildenafil injection significantly (P<0.05) increased serum and brain Se and Cu concentrations. Moreover, sildenafil increased the Cr concentration in the brain tissue. It was concluded that sildenafil citrate administration increased serum Se and Cu as well as, increased brain Se, Cu, and Cr concentrations in rats. Copyright © 2011 Elsevier GmbH. All rights reserved.

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

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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.

Brain Insulin Administration Triggers Distinct Cognitive and Neurotrophic Responses in Young and Aged Rats.

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Haas, Clarissa B; Kalinine, Eduardo; Zimmer, Eduardo R; Hansel, Gisele; Brochier, Andressa W; Oses, Jean P; Portela, Luis V; Muller, Alexandre P

2016-11-01

Aging is a major risk factor for cognitive deficits and neurodegenerative disorders, and impaired brain insulin receptor (IR) signaling is mechanistically linked to these abnormalities. The main goal of this study was to investigate whether brain insulin infusions improve spatial memory in aged and young rats. Aged (24 months) and young (4 months) male Wistar rats were intracerebroventricularly injected with insulin (20 mU) or vehicle for five consecutive days. The animals were then assessed for spatial memory using a Morris water maze. Insulin increased memory performance in young rats, but not in aged rats. Thus, we searched for cellular and molecular mechanisms that might account for this distinct memory response. In contrast with our expectation, insulin treatment increased the proliferative activity in aged rats, but not in young rats, implying that neurogenesis-related effects do not explain the lack of insulin effects on memory in aged rats. Furthermore, the expression levels of the IR and downstream signaling proteins such as GSK3-β, mTOR, and presynaptic protein synaptophysin were increased in aged rats in response to insulin. Interestingly, insulin treatment increased the expression of the brain-derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) receptors in the hippocampus of young rats, but not of aged rats. Our data therefore indicate that aged rats can have normal IR downstream protein expression but failed to mount a BDNF response after challenge in a spatial memory test. In contrast, young rats showed insulin-mediated TrkB/BDNF response, which paralleled with improved memory performance.

A biphasic and brain-region selective down-regulation of cyclic adenosine monophosphate concentrations supports object recognition in the rat.

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Maïte Hotte

Full Text Available BACKGROUND: We aimed to further understand the relationship between cAMP concentration and mnesic performance. METHODS AND FINDINGS: Rats were injected with milrinone (PDE3 inhibitor, 0.3 mg/kg, i.p., rolipram (PDE4 inhibitor, 0.3 mg/kg, i.p. and/or the selective 5-HT4R agonist RS 67333 (1 mg/kg, i.p. before testing in the object recognition paradigm. Cyclic AMP concentrations were measured in brain structures linked to episodic-like memory (i.e. hippocampus, prefrontal and perirhinal cortices before or after either the sample or the testing phase. Except in the hippocampus of rolipram treated-rats, all treatment increased cAMP levels in each brain sub-region studied before the sample phase. After the sample phase, cAMP levels were significantly increased in hippocampus (1.8 fold, prefrontal (1.3 fold and perirhinal (1.3 fold cortices from controls rat while decreased in prefrontal cortex (∼0.83 to 0.62 fold from drug-treated rats (except for milrinone+RS 67333 treatment. After the testing phase, cAMP concentrations were still increased in both the hippocampus (2.76 fold and the perirhinal cortex (2.1 fold from controls animals. Minor increase were reported in hippocampus and perirhinal cortex from both rolipram (respectively, 1.44 fold and 1.70 fold and milrinone (respectively 1.46 fold and 1.56 fold-treated rat. Following the paradigm, cAMP levels were significantly lower in the hippocampus, prefrontal and perirhinal cortices from drug-treated rat when compared to controls animals, however, only drug-treated rats spent longer time exploring the novel object during the testing phase (inter-phase interval of 4 h. CONCLUSIONS: Our results strongly suggest that a "pre-sample" early increase in cAMP levels followed by a specific lowering of cAMP concentrations in each brain sub-region linked to the object recognition paradigm support learning efficacy after a middle-term delay.

Beneficial psychological effects of novel psychobiotics in diabetic rats: the interaction among the gut, blood and amygdala.

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Morshedi, Mohammad; Valenlia, Khadijeh Bavafa; Hosseinifard, Elaheh Sadat; Shahabi, Parviz; Abbasi, Mehran Mesgari; Ghorbani, Meysam; Barzegari, Abolfazl; Sadigh-Eteghad, Saeed; Saghafi-Asl, Maryam

2018-04-03

Type 2 diabetes mellitus (T2DM) can lead to major complications such as psychiatric disorders which include depressive and anxiety-like behaviors. The association of the gut-brain axis in the development of such disorders, especially in T2DM, has been elucidated; however, gut dysbiosis is also reported in patients with T2DM. Hence, the regulation of the gut-brain axis, in particular, the gut-amygdala, as a vital region for the regulation of behavior is essential. Thirty-five male Wistar rats were divided into six groups. To induce T2DM, treatment groups received high-fat diet and 35 mg/kg streptozotocin. Then, supplements of Lactobacillus plantarum, inulin or their combination were administered to each group for 8 weeks. Finally, the rats were sacrificed for measurement of blood and tissue parameters after behavioral testing. The findings demonstrated the favorable effects of the psychobiotics (L. plantarum, inulin or their combination) on oxidative markers of the blood and amygdala (superoxide dismutase, glutathione peroxidase, malondialdehyde and total antioxidant capacity), as well as on concentrations of amygdala serotonin and brain-derived neurotrophic factor, in the diabetic rats. In addition, beneficial effects were observed on the elevated plus maze and forced swimming tests with no change in locomotor activity of the rats. There was a strong correlation between the blood and amygdala oxidative markers, insulin and fasting blood sugar with depressive and anxiety-like behaviors. Our results identified L. plantarum ATCC 8014 and inulin or their combination as novel psychobiotics that could improve the systemic and nervous antioxidant status and improve amygdala performance and beneficial psychotropic effects. Copyright © 2018 Elsevier Inc. All rights reserved.

Effect of naturally mouldy wheat or fungi administration on metallothioneins level in brain tissues of rats.

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Vasatkova, Anna; Krizova, Sarka; Krystofova, Olga; Adam, Vojtech; Zeman, Ladislav; Beklova, Miroslava; Kizek, Rene

2009-01-01

The aim of this study is to determine level of metallothioneins (MTs) in brain tissues of rats administered by feed mixtures with different content of mouldy wheat or fungi. Selected male laboratory rats of Wistar albino at age of 28 days were used in our experiments. The rats were administered by feed mixtures with different content of vitamins, naturally mouldy wheat or fungi for 28 days. At the very end of the experiment, the animals were put to death and brains were sampled. MT level was determined by differential pulse voltammetry Brdicka reaction. We found that MTs' level in brain tissues from rats administered by standard feed mixtures was significantly higher compared to the level of MTs in rats supplemented by vitamins. Further we studied the effect of supplementation of naturally mouldy wheat on MTs level in rats. In mouldy wheat we detected the presence of following fungi species: Mucor spp., Absidia spp., Penicillium spp., Aspergillus spp. and Fusarium spp. Moreover we also identified and quantified following mycotoxins - deoxynivalenol, zearalenone, T2-toxin and aflatoxins. Level of MTs determined in rats treated with 33 or 66% of mouldy wheat was significantly lower compared to control ones. On the other hand rats treated with 100% of mouldy wheat had less MTs but not significantly. Supplementation of vitamins to rats fed by mouldy wheat had adverse effect on MTs level compared to rats with no other supplementation by vitamins. Moreover vitamins supplementation has no effect on MTs level in brain tissues of rats treated or non-treated with Ganoderma lucidum L. Both mycotoxins and vitamins have considerable effect on level of MTs in brain tissues. It can be assumed that the administered substances markedly influence redox metabolism, which could negatively influence numerous biochemical pathways including those closely related with MTs.

Proteomic analysis of proteins expressing in regions of rat brain by a combination of SDS-PAGE with nano-liquid chromatography-quadrupole-time of flight tandem mass spectrometry

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Maekawa Tsuyoshi

2010-07-01

Full Text Available Abstract Background Most biological functions controlled by the brain and their related disorders are closely associated with activation in specific regions of the brain. Neuroproteomics has been applied to the analysis of whole brain, and the general pattern of protein expression in all regions has been elucidated. However, the comprehensive proteome of each brain region remains unclear. Results In this study, we carried out comparative proteomics of six regions of the adult rat brain: thalamus, hippocampus, frontal cortex, parietal cortex, occipital cortex, and amygdala using semi-quantitative analysis by Mascot Score of the identified proteins. In order to identify efficiently the proteins that are present in the brain, the proteins were separated by a combination of SDS-PAGE on a C18 column-equipped nano-liquid chromatograph, and analyzed by quadrupole-time of flight-tandem-mass spectrometry. The proteomic data show 2,909 peptides in the rat brain, with more than 200 identified as region-abundant proteins by semi-quantitative analysis. The regions containing the identified proteins are membrane (20.0%, cytoplasm (19.5%, mitochondrion (17.1%, cytoskeleton (8.2%, nucleus (4.7%, extracellular region (3.3%, and other (18.0%. Of the identified proteins, the expressions of glial fibrillary acidic protein, GABA transporter 3, Septin 5, heat shock protein 90, synaptotagmin, heat shock protein 70, and pyruvate kinase were confirmed by immunoblotting. We examined the distributions in rat brain of GABA transporter 3, glial fibrillary acidic protein, and heat shock protein 70 by immunohistochemistry, and found that the proteins are localized around the regions observed by proteomic analysis and immunoblotting. IPA analysis indicates that pathways closely related to the biological functions of each region may be activated in rat brain. Conclusions These observations indicate that proteomics in each region of adult rat brain may provide a novel way to

Insulin-like growth factor II messenger ribonucleic acids are synthesized in the choroid plexus of the rat brain

International Nuclear Information System (INIS)

Hynes, M.A.; Brooks, P.J.; Van Wyk, J.J.; Lund, P.K.

1988-01-01

Previous studies demonstrating the presence of immunoreactive insulin-like growth factors (IGFs) and their receptors in the brain suggest a role of the IGFs in the central nervous system. IGF-II has been implicated as the predominant IGF in brain of mature animals based on studies of immunoreactive peptide and of IGF-II mRNAs. To obtain information about the sites of synthesis of IGF-II in adult rat brain, a 32 P-labeled 31 base long synthetic oligodeoxyribonucleotide complementary in sequence to trailer peptide coding sequences in rat IGF-II mRNA (IGF-II 31 mer) was hybridized with coronal sections of fixed rat brain. The IGF-II 31 mer showed specific hybridization with the choroid plexus throughout rat brain, whereas in other brain regions, structures or cells, hybridization was not discernibly above background. These findings suggest that the choroid plexus is a primary site of synthesis of IGF-II, a probable source of IGF-II in cerebrospinal fluid, and a potential source of IGF-II for actions on target cells within the adult rat brain

Resuscitation therapy for traumatic brain injury-induced coma in rats: mechanisms of median nerve electrical stimulation

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Zhen Feng

2015-01-01

Full Text Available In this study, rats were put into traumatic brain injury-induced coma and treated with median nerve electrical stimulation. We explored the wake-promoting effect, and possible mechanisms, of median nerve electrical stimulation. Electrical stimulation upregulated the expression levels of orexin-A and its receptor OX1R in the rat prefrontal cortex. Orexin-A expression gradually increased with increasing stimulation, while OX1R expression reached a peak at 12 hours and then decreased. In addition, after the OX1R antagonist, SB334867, was injected into the brain of rats after traumatic brain injury, fewer rats were restored to consciousness, and orexin-A and OXIR expression in the prefrontal cortex was downregulated. Our findings indicate that median nerve electrical stimulation induced an up-regulation of orexin-A and OX1R expression in the prefrontal cortex of traumatic brain injury-induced coma rats, which may be a potential mechanism involved in the wake-promoting effects of median nerve electrical stimulation.

In vitro assessment of the agonist properties of the novel 5-HT1A receptor ligand, CUMI-101 (MMP), in rat brain tissue

International Nuclear Information System (INIS)

Hendry, Nicola; Christie, Isabel; Rabiner, Eugenii Alfredovich; Laruelle, Marc; Watson, Jeannette

2011-01-01

Introduction: Development of agonist positron emission tomography (PET) radioligands for the 5-HT neurotransmitter system is an important target to enable the understanding of human 5-HT function in vivo. [ 11 C]CUMI-101, proposed as the first 5-HT 1A receptor agonist PET ligand, has been reported to behave as a potent 5-HT 1A agonist in a cellular system stably expressing human recombinant 5-HT 1A receptors. In this study, we investigate the agonist properties of CUMI-101 in rat brain tissue. Methods: [ 35 S]-GTPγS binding studies were used to determine receptor function in HEK (human embryonic kidney) 293 cells transfected with human recombinant 5-HT 1A receptors and in rat cortex and rat hippocampal tissue, following administration of CUMI-101 and standard 5-HT1A antagonists (5-HT, 5-CT and 8-OH-DPAT). Results: CUMI-101 behaved as an agonist at human recombinant 5-HT 1A receptors (pEC 50 9.2). However, CUMI-101 did not show agonist activity in either rat cortex or hippocampus at concentrations up to 10 μM. In these tissues, CUMI-behaved as an antagonist with pK B s of 9.2 and 9.3, respectively. Conclusions: Our studies demonstrate that as opposed to its behavior in human recombinant system, in rat brain tissue CUMI-101 behaves as a potent 5-HT 1A receptor antagonist.

Antihypertensive activity of blueberries fermented by Lactobacillus plantarum DSM 15313 and effects on the gut microbiota in healthy rats.

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Ahrén, Irini Lazou; Xu, Jie; Önning, Gunilla; Olsson, Crister; Ahrné, Siv; Molin, Göran

2015-08-01

The aim of the present animal study was to examine the anti-hypertensive capacity of two probiotic products combining blueberries and the tannase producing probiotic bacteria Lactobacillus plantarum DSM 15313 and to investigate if such an effect is linked to a change in the gut microbiota. Male Sprague Dawley rats were randomly divided into six groups of nine each. Three groups of the animals were treated with N(G)-nitro-L-arginine methyl ester (L-NAME) in the drinking water (40 mg/L) to induce a hypertensive state, and the other three groups were not treated with L-NAME (healthy rats). Two blueberry products differing in their phenolic acid content were tested and each rat received 2 g/day of the fermented blueberry powders for 4 weeks. The effects of the study products on the blood pressure, blood lipids, inflammatory markers, organ weights as well as caecal microbiota of the healthy (non-L-NAME-treated) rats were analyzed. After four weeks, healthy rats consuming freeze dried fermented blueberries with probiotics had a significant reduction in blood pressure compared to the control rats. In rats with L-NAME induced hypertension there was a significant reduction of the blood pressure after two weeks treatment. The probiotic product with a higher content of phenolic acids reduced ALAT in the healthy rats. Furthermore, ingestion of the probiotic blueberry products resulted in changes of the gut microbiota in the healthy rats. Blueberries fermented with the tannase producing bacteria L. plantarum DSM 15313 have anti-hypertensive properties and may reduce the risk for cardiovascular diseases. Copyright © 2014 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.

Relationship between catalase activity and uptake of elemental mercury by rat brain

International Nuclear Information System (INIS)

Eide, I.; Syversen, T.L.M.

1983-01-01

Uptake of mercury by brain after intravenous injection of elemental mercury was investigated in the rat. Catalase activity was inhibited by aminotriazole either by intraperitoneal affecting catalase in most tissues of the animal or by intraventricular injections affecting catalase in the brain selectively. Uptake of elemental mercury by rat brain was not influenced by intraperitoneal administration of aminotriazole resulting in 50% inhibition of brain catalase. However, when the inhibitor was injected intraventricularly in concentrations to give a 50% inhibition of brain catalase, it was shown that the mercury uptake by brain was significantly decreased. In the latter case when only brain catalase was inhibited and the supply of elemtal mercury to brain was maintained, mercury uptake by brain was proportional to the activity of catalase in brain tissue and to the injected amount of elemental mercury. Contrary to the intraventricular injection of aminotriazole, in animals recieving aminotriazole intraperitoneally prior to elemental mercury injection, we suggest that the lower activity of brain catalse is compensated by an increased supply of elemtal mercury caused by the generally lower oxidation rate in the animal. This view is supported by the finding that mercury uptake by liver increased due to aminotriazole intraperitoneally although activity of catalase was depressed. (author)

Demonstration of endogenous imipramine like material in rat brain

International Nuclear Information System (INIS)

Rehavi, M.; Ventura, I.; Sarne, Y.

1985-01-01

The extraction and partial purification of an endogenous imipramine-like material from rat brain is described. The endogenous factor obtained after gel filtration and silica chromatography inhibits [ 3 H] imipramine specific binding and mimics the inhibitory effect of imipramine on [ 3 H] serotonin uptake in both brain and platelet preparations. The effects of the endogenous material are dose-dependent and it inhibits [ 3 H] imipramine binding in a competitive fashion. The factor is unevenly distributed in the brain with high concentration in the hypothalamus and low concentration in the cerebellum

Measurement of tritiated norepinephrine metabolism in intact rat brain

International Nuclear Information System (INIS)

Levitt, M.; Kowalik, S.; Barkai, A.I.

1983-01-01

A procedure for the study of NE metabolism in the intact rat brain is described. The method involves ventriculocisternal perfusion of the adult male rat with artificial CSF containing [ 3 H]NE. Radioactivity in the perfusate associated with NE and its metabolites 3,4-dihydroxymandelic acid (DOMA), 3,4-dihydroxphenylethyleneglycol (DHPG), 3-methoxy-4-hydroxymandelic acid (VMA), 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG), and normetanephrine (NMN) is separated using high-performance liquid chromatography (HPLC). After 80 min the radioactivity in the perfusate reaches an apparent steady-state. Analysis of the steady-state samples shows higher activity in the fractions corresponding to DHPG and MHPG than in those corresponding to DOMA and VMA, confirming glycol formation as the major pathway of NE metabolism in rat brain. Pretreatment with an MAO inhibitor (tranylcypromine) results in a marked decrease in the deaminated metabolites DHPG and MHPG and a concurrent increase in NMN. The results indicate this to be a sensitive procedure for the in vivo determination of changes in NE metabolism. (Auth.)

Effects of acupuncture on tissue oxygenation of the rat brain.

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Chen, G S; Erdmann, W

1978-04-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by smypathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture points (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible and was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase in inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes increased brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients.

Metabolic mapping of the effects of the antidepressant fluoxetine on the brains of congenitally helpless rats.

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Shumake, Jason; Colorado, Rene A; Barrett, Douglas W; Gonzalez-Lima, F

2010-07-09

Antidepressants require adaptive brain changes before efficacy is achieved, and they may impact the affectively disordered brain differently than the normal brain. We previously demonstrated metabolic disturbances in limbic and cortical regions of the congenitally helpless rat, a model of susceptibility to affective disorder, and we wished to test whether administration of fluoxetine would normalize these metabolic differences. Fluoxetine was chosen because it has become a first-line drug for the treatment of affective disorders. We hypothesized that fluoxetine antidepressant effects may be mediated by decreasing metabolism in the habenula and increasing metabolism in the ventral tegmental area. We measured the effects of fluoxetine on forced swim behavior and regional brain cytochrome oxidase activity in congenitally helpless rats treated for 2 weeks with fluoxetine (5mg/kg, i.p., daily). Fluoxetine reduced immobility in the forced swim test as anticipated, but congenitally helpless rats responded in an atypical manner, i.e., increasing climbing without affecting swimming. As hypothesized, fluoxetine reduced metabolism in the habenula and increased metabolism in the ventral tegmental area. In addition, fluoxetine reduced the metabolism of the hippocampal dentate gyrus and dorsomedial prefrontal cortex. This study provided the first detailed mapping of the regional brain effects of an antidepressant drug in congenitally helpless rats. All of the effects were consistent with previous studies that have metabolically mapped the effects of serotonergic antidepressants in the normal rat brain, and were in the predicted direction of metabolic normalization of the congenitally helpless rat for all affected brain regions except the prefrontal cortex. Copyright (c) 2010 Elsevier B.V. All rights reserved.

Treatment planning and 3D dose verification of whole brain radiation therapy with hippocampal avoidance in rats

International Nuclear Information System (INIS)

Yoon, S W; Miles, D; Reinsvold, M; Kirsch, D; Oldham, M; Cramer, C

2017-01-01

Despite increasing use of stereotactic radiosurgery, whole brain radiotherapy (WBRT) continues to have a therapeutic role in a selected subset of patients. Selectively avoiding the hippocampus during such treatment (HA-WBRT) emerged as a strategy to reduce the cognitive morbidity associated with WBRT and gave rise to a recently published the phase II trial (RTOG 0933) and now multiple ongoing clinical trials. While conceptually hippocampal avoidance is supported by pre-clinical evidence showing that the hippocampus plays a vital role in memory, there is minimal pre-clinic data showing that selectively avoiding the hippocampus will reduce radiation-induced cognitive decline. Largely the lack of pre-clinical evidence can be attributed to the technical hurdles associated with delivering precise conformal treatment the rat brain. In this work we develop a novel conformal HA-WBRT technique for Wistar rats, utilizing a 225kVp micro-irradiator with precise 3D-printed radiation blocks designed to spare hippocampus while delivering whole brain dose. The technique was verified on rodent-morphic Presage ® 3D dosimeters created from micro-CT scans of Wistar rats with Duke Large Field-of-View Optical Scanner (DLOS) at 1mm isotropic voxel resolution. A 4-field box with parallel opposed AP-PA and two lateral opposed fields was explored with conformal hippocampal sparing aided by 3D-printed radiation blocks. The measured DVH aligned reasonably well with that calculated from SmART Plan Monte Carlo simulations with simulated blocks for 4-field HA-WBRT with both demonstrating hippocampal sparing of 20% volume receiving less than 30% the prescription dose. (paper)

Bidirectional Microglia-Neuron Communication in the Healthy Brain

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Ukpong B. Eyo

2013-01-01

Full Text Available Unlike other resident neural cells that are of neuroectodermal origin, microglia are resident neural cells of mesodermal origin. Traditionally recognized for their immune functions during disease, new roles are being attributed to these cells in the development and maintenance of the central nervous system (CNS including specific communication with neurons. In this review, we highlight some of the recent findings on the bidirectional interaction between neurons and microglia. We discuss these interactions along two lines. First, we review data that suggest that microglial activity is modulated by neuronal signals, focusing on evidence that (i neurons are capable of regulating microglial activation state and influence basal microglial activities; (ii classic neurotransmitters affect microglial behavior; (iii chemotactic signals attract microglia during acute neuronal injury. Next, we discuss some of the recent data on how microglia signal to neurons. Signaling mechanisms include (i direct physical contact of microglial processes with neuronal elements; (ii microglial regulation of neuronal synapse and circuit by fractalkine, complement, and DAP12 signaling. In addition, we discuss the use of microglial depletion strategies in studying the role of microglia in neuronal development and synaptic physiology. Deciphering the mechanisms of bidirectional microglial-neuronal communication provides novel insights in understanding microglial function in both the healthy and diseased brain.

Blood-brain barrier permeability and brain uptake mechanism of kainic Acid and dihydrokainic Acid

DEFF Research Database (Denmark)

Gynther, Mikko; Petsalo, Aleksanteri; Hansen, Steen Honoré

2015-01-01

tools in various in vivo central nervous system disease models in rodents, as well as being templates in the design of novel ligands affecting the glutamatergic system. Both molecules are highly polar but yet capable of crossing the blood-brain barrier (BBB). We used an in situ rat brain perfusion...... technique to determine the brain uptake mechanism and permeability across the BBB. To determine KA and DHK concentrations in the rat brain, simple and rapid sample preparation and liquid chromatography mass spectrometer methods were developed. According to our results the BBB permeability of KA and DHK...... is low, 0.25 × 10(-6) and 0.28 × 10(-6) cm/s for KA and DHK, respectively. In addition, the brain uptake is mediated by passive diffusion, and not by active transport. Furthermore, the non-specific plasma and brain protein binding of KA and DHK was determined to be low, which means that the unbound drug...

Low glucose utilization and neurodegenerative changes caused by sodium fluoride exposure in rat's developmental brain.

Science.gov (United States)

Jiang, Chunyang; Zhang, Shun; Liu, Hongliang; Guan, Zhizhong; Zeng, Qiang; Zhang, Cheng; Lei, Rongrong; Xia, Tao; Wang, Zhenglun; Yang, Lu; Chen, Yihu; Wu, Xue; Zhang, Xiaofei; Cui, Yushan; Yu, Linyu; Wang, Aiguo

2014-03-01

Fluorine, a toxic and reactive element, is widely prevalent throughout the environment and can induce toxicity when absorbed into the body. This study was to explore the possible mechanisms of developmental neurotoxicity in rats treated with different levels of sodium fluoride (NaF). The rats' intelligence, as well as changes in neuronal morphology, glucose absorption, and functional gene expression within the brain were determined using the Morris water maze test, transmission electron microscopy, small-animal magnetic resonance imaging and Positron emission tomography and computed tomography, and Western blotting techniques. We found that NaF treatment-impaired learning and memory in these rats. Furthermore, NaF caused neuronal degeneration, decreased brain glucose utilization, decreased the protein expression of glucose transporter 1 and glial fibrillary acidic protein, and increased levels of brain-derived neurotrophic factor in the rat brains. The developmental neurotoxicity of fluoride may be closely associated with low glucose utilization and neurodegenerative changes.

Oxytocin biotransformation in the rat limbic brain

NARCIS (Netherlands)

Burbach, J.P.H.; Schotman, P.; Kloet, E.R. de

2006-01-01

Two peptide fragments of oxytocin were isolated by high-pressure liquid chromatography from digests of oxytocin obtained after exposure to a SPM preparation of the rat limbic brain. The structures of these peptides, being Gln-Asn-Cys(O)x-Pro-Leu-GlyNH2 and Gln-Asn-Cys(-S-S-Cys)-Pro-Leu-GlyNH2, were

Identification of a novel CoA synthase isoform, which is primarily expressed in Brain

International Nuclear Information System (INIS)

Nemazanyy, Ivan; Panasyuk, Ganna; Breus, Oksana; Zhyvoloup, Alexander; Filonenko, Valeriy; Gout, Ivan T.

2006-01-01

CoA and its derivatives Acetyl-CoA and Acyl-CoA are important players in cellular metabolism and signal transduction. CoA synthase is a bifunctional enzyme which mediates the final stages of CoA biosynthesis. In previous studies, we have reported molecular cloning, biochemical characterization, and subcellular localization of CoA synthase (CoASy). Here, we describe the existence of a novel CoA synthase isoform, which is the product of alternative splicing and possesses a 29aa extension at the N-terminus. We termed it CoASy β and originally identified CoA synthase, CoASy α. The transcript specific for CoASy β was identified by electronic screening and by RT-PCR analysis of various rat tissues. The existence of this novel isoform was further confirmed by immunoblot analysis with antibodies directed to the N-terminal peptide of CoASy β. In contrast to CoASy α, which shows ubiquitous expression, CoASy β is primarily expressed in Brain. Using confocal microscopy, we demonstrated that both isoforms are localized on mitochondria. The N-terminal extension does not affect the activity of CoA synthase, but possesses a proline-rich sequence which can bring the enzyme into complexes with signalling proteins containing SH3 or WW domains. The role of this novel isoform in CoA biosynthesis, especially in Brain, requires further elucidation

A novel herbal treatment reduces depressive-like behaviors and increases brain-derived neurotrophic factor levels in the brain of type 2 diabetic rats

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Luo C

2016-11-01

Full Text Available Chun Luo,1,* Yuting Ke,1,* Yanyan Yuan,1 Ming Zhao,1 Fuyan Wang,1 Yisheng Zhang,2 Shizhong Bu1 1Runliang Diabetes Laboratory, Diabetes Research Center, Ningbo University, 2Department of Gynaecology and Obstetrics, Ningbo Medical Center, Li Huili Eastern Hospital, Ningbo, Zhejiang, People’s Republic of China *These authors contributed equally to this work Background: Radix Puerariae and hawthorn fruit have been demonstrated to treat diabetes. They offer potential benefits for preventing depression in diabetes. Objective: The aim of this study was to investigate whether the combination of Radix Puerariae and hawthorn fruit (CRPHF could prevent depression in a diabetic rat model generated by feeding the rats with a high-fat diet and a low-dose streptozotocin (STZ. Methods: The CRPHF was provided by the Shanghai Chinese Traditional Medical University. Twenty-four rats were randomly divided into four groups: normal control, normal-given-CRPHF (NC, diabetic control, and diabetic-given-CRPHF (DC groups. The type 2 diabetic model was created by feeding the rats with a high-fat diet for 4 weeks followed by injection of 25 mg/kg STZ. CRPHF was given at 2 g/kg/d to the rats of NC and DC groups by intragastric gavage daily for 4 weeks after the type 2 diabetic model was successfully created. Body weight, random blood glucose (RBG, oral glucose tolerance test, total cholesterol (TC, triglyceride (TG, high-density lipoprotein cholesterol (HDL-C, and low-density lipoprotein cholesterol (LDL-C were measured during the study. Depressive-like behavior was evaluated at the end of the treatment by using the open field test (OFT, the elevated plus-maze test (EPMT, locomotor activity test (LAT, and forced swimming test (FST. Levels of extracellular signal-regulated protein kinase (ERK and brain-derived neurotrophic factor (BDNF in the prefrontal cortex were evaluated by using Western blot. Results: 1 CRPHF reduced RBG and improved glucose tolerance in diabetic rats

Pathological and MRI study on experimental heroin-induced brain damage in rats

International Nuclear Information System (INIS)

Long Yu; Kong Xiangquan; Xu Haibo; Liu Dingxi; Yuan Ren; Yu Qun; Xiong Yin; Deng Xianbo

2005-01-01

Objective: To study the pathological characteristics of the heroin-induced brain damage in rats, and to assess the diagnostic value of MRI. Methods: A total of 40 adult Wistar rats were studied, 32 rats were used for injecting heroin as heroin group and 8 were used for injecting saline as control group. The heroin dependent rat model was established by administering heroin (ip) in the ascending dosage schedule (0.5 mg/kg), three times a day (at 8:00, 12:00, and 18:00). The control group was established by the same way by injection with saline. The withdrawal scores were evaluated with imp roved criterion in order to estimate the degree of addiction after administering naloxone. Based on the rat model of heroin dependence, the rat model of heroin-induced brain damage was established by the same way with increasing heroin dosage everyday. Two groups were examined by using MRI, light microscope, and electron microscope, respectively in different heroin accumulated dosage (918, 1580, 2686, 3064, 4336, and 4336 mg/kg withdrawal after 2 weeks). Results: There was statistically significant difference (t=9.737, P<0.01) of the withdrawal scores between the heroin dependent group and the saline group (23.0 ± 4.4 and 1.4 ± 0.5, respectively). It suggested that the heroin dependent rat model be established successfully. In different accumulated dosage ( from 1580 mg/kg to 4336 mg/kg), there were degeneration and death of nerve cells in cerebrum and cerebellum of heroin intoxicated rats, and it suggested that the rat model of heroin-induced brain damage was established successfully. The light microscope and electron microscope features of heroin-induced brain damage in rats included: (1) The nerve cells of cerebral cortex degenerated and died. According to the heroin accumulated dosage, there were statistically significant difference of the nerve cell deaths between 4336 mg/kg group and 1580 mg/kg group or control group (P=0.024 and P=0.032, respectively); (2) The main

Vitamin-C protect ethanol induced apoptotic neuro degeneration in postnatal rat brain

International Nuclear Information System (INIS)

Naseer, M.I.; Najeebullah; Ikramullah; Zubair, H.; Hassan, M.; Yang, B.C.

2010-01-01

Objective: To evaluate ethanol effects to induced activation of caspsae-3, and to observe the protective effects of Vitamin C (vit-C) on ethanol-induced apoptotic neuro degeneration in rat cortical area of brain. Methodology: Administration of a single dose of ethanol in 7-d postnatal (P7) rats triggers activation of caspase-3 and widespread apoptotic neuronal death. Western blot analysis, cells counting and Nissl staining were used to elucidate possible protective effect of vit-C against ethanol-induced apoptotic neuro degeneration in brain. Results: The results showed that ethanol significantly increased caspase-3 expression and neuronal apoptosis. Furthermore, the co-treatment of vit-C along with ethanol showed significantly decreased expression of caspase-3 as compare to control group. Conclusion: Our findings indicate that vit-C can prevent some of the deleterious effect of ethanol on developing rat brain when given after ethanol exposure and can be used as an effective protective agent for Fetal Alcohol Syndrome (FAS). (author)

MR elastography study of the brain in healthy volunteers

International Nuclear Information System (INIS)

Liu Guangrui; Gao Peiyi; Lin Yan; Wang Xiaochun; Xue Jing; Sui Bingbing; Ma Li; Wang Chen; Shen Mi

2009-01-01

Objective: To evaluate the shear stiffness of brain by MR elastography (MRE) in healthy Chinese volunteers and to assess the association between the cerebral shear stiffness and age. Methods: Brain MRE studies were performed on 105 healthy volunteers. The shear stiffness of brain parenchyma was measured by local frequency estimation (LFE) algorithm. The differences of the shear stiffness between white matter (WM) and grey matter (GM) were analyzed by independent sample t test; the differences of brain parenchyma shear stiffness between male and female were estimated by independent sample t test. Spearman test was used to analyze the correlation between age and the shear stiffness of parenchyma; the volunteers were divided into two groups (age ≤40 and age > 40) and the correlation between age and shear stiffness of parenchyma in each group were analyzed separately. Results: The shear stiffness of whiter matter [(23.1±5.7) kPa] was higher than that of grey matter [(11.3±2.6) kPa], and the difference was significant (t=19.34, P 0.05). An age-dependent trend was observed in the stiffness of grey matter (r= 0.315, P 0.05). When the shear stiffness of subjects no more than 40 years old was analysed, the age-dependent trend of shear stiffness was found both in white matter and gray matter (r=0.251, 0.235, P 0.05). Conclusions: The shear stiffness of WM is significantly higher than that of GM. No obvious sex difference was found in the stiffness of brain parenchyma. The shear stiffness of GM increases with age; the age-related increase of shear stiffness of WM was only found in subjects under 40 years old. (authors)

Specific binding of 125I-salmon calcitonin to rat brain

International Nuclear Information System (INIS)

Nakamuta, Hiromichi; Furukawa, Shinichi; Koida, Masao; Yajima, Haruaki; Orlowski, R.C.

1981-01-01

Rat brain particulate fraction was found to contain binding sites for 125 I-Salmon Calcitonin-I ( 125 I-SCT). Maximum binding occurred in the physiological pH range of 7.25 - 7.5. The binding reaction proceeded in a temperature-dependent manner. Binding sites were broadly distributed among the various rat brain regions and considerable regional differences existed in the affinity and density as detected by Scatchard analysis. The highest affinity was recorded in the case of the hypothalamus and the lowest in the case of the cerebellum. The KD (nM) and Bmax (pmole/mg protein) estimated for the binding to four regions were as follows: hypothalamus: 1.4 and 0.19, midbrain, hippocampus plus striatum: 1.5 and 0.08, pon plus medulla oblongata: 3.0 and 0.15 and cerebellum: 8.3 and 0.20. Using a particulate fraction of rat brain void of cerebellum and cortices, a binding assay for calcitonins was developed. Binding of 125 I-SCT was inhibited by unlabeled salmon, [Asu sup(1,7)]-eel and porcine calcitonins in a dose-dependent manner and the IC50s were 2.0, 8.0 and 30 nM, respectively. The IC50s were comparable to those estimated using a kidney particulate fraction. Human calcitonin, β-endorphin and substance P were weak inhibitors of the binding. Other peptides, drugs and putative neurotransmitters tested (totally 23 substances) failed to inhibit the binding at concentrations of 1.0 μM. The physiological significance of brain binding sites for calcitonin, with the possibility that the brain may possess endogenous ligands for these sites are discussed. (author)

Quantitative autoradiography of the binding sites for [125I] iodoglyburide, a novel high-affinity ligand for ATP-sensitive potassium channels in rat brain

International Nuclear Information System (INIS)

Gehlert, D.R.; Gackenheimer, S.L.; Mais, D.E.; Robertson, D.W.

1991-01-01

We have developed a high specific activity ligand for localization of ATP-sensitive potassium channels in the brain. When brain sections were incubated with [ 125 I]iodoglyburide (N-[2-[[[(cyclohexylamino)carbonyl]amino]sulfonyl]ethyl]-5- 125 I-2- methoxybenzamide), the ligand bound to a single site with a KD of 495 pM and a maximum binding site density of 176 fmol/mg of tissue. Glyburide was the most potent inhibitor of specific [ 125 I]iodoglyburide binding to rat forebrain sections whereas iodoglyburide and glipizide were slightly less potent. The binding was also sensitive to ATP which completely inhibited binding at concentrations of 10 mM. Autoradiographic localization of [ 125 I]iodoglyburide binding indicated a broad distribution of the ATP-sensitive potassium channel in the brain. The highest levels of binding were seen in the globus pallidus and ventral pallidum followed by the septohippocampal nucleus, anterior pituitary, the CA2 and CA3 region of the hippocampus, ventral pallidum, the molecular layer of the cerebellum and substantia nigra zona reticulata. The hilus and dorsal subiculum of the hippocampus, molecular layer of the dentate gyrus, cerebral cortex, lateral olfactory tract nucleus, olfactory tubercle and the zona incerta contained relatively high levels of binding. A lower level of binding (approximately 3- to 4-fold) was found throughout the remainder of the brain. These results indicate that the ATP-sensitive potassium channel has a broad presence in the rat brain and that a few select brain regions are enriched in this subtype of neuronal potassium channels

Neuroprotective Effect of Dexmedetomidine on Hyperoxia-Induced Toxicity in the Neonatal Rat Brain

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Marco Sifringer

2015-01-01

Full Text Available Dexmedetomidine is a highly selective agonist of α2-receptors with sedative, anxiolytic, analgesic, and anesthetic properties. Neuroprotective effects of dexmedetomidine have been reported in various brain injury models. In the present study, we investigated the effects of dexmedetomidine on neurodegeneration, oxidative stress markers, and inflammation following the induction of hyperoxia in neonatal rats. Six-day-old Wistar rats received different concentrations of dexmedetomidine (1, 5, or 10 µg/kg bodyweight and were exposed to 80% oxygen for 24 h. Sex-matched littermates kept in room air and injected with normal saline or dexmedetomidine served as controls. Dexmedetomidine pretreatment significantly reduced hyperoxia-induced neurodegeneration in different brain regions of the neonatal rat. In addition, dexmedetomidine restored the reduced/oxidized glutathione ratio and attenuated the levels of malondialdehyde, a marker of lipid peroxidation, after exposure to high oxygen concentration. Moreover, administration of dexmedetomidine induced downregulation of IL-1β on mRNA and protein level in the developing rat brain. Dexmedetomidine provides protections against toxic oxygen induced neonatal brain injury which is likely associated with oxidative stress signaling and inflammatory cytokines. Our results suggest that dexmedetomidine may have a therapeutic potential since oxygen administration to neonates is sometimes inevitable.

Soft-food diet induces oxidative stress in the rat brain.

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Yoshino, Fumihiko; Yoshida, Ayaka; Hori, Norio; Ono, Yumie; Kimoto, Katsuhiko; Onozuka, Minoru; Lee, Masaichi Chang-il

2012-02-02

Decreased dopamine (DA) release in the hippocampus may be caused by dysfunctional mastication, although the mechanisms involved remain unclear. The present study examined the effects of soft- and hard-food diets on oxidative stress in the brain, and the relationship between these effects and hippocampal DA levels. The present study showed that DA release in the hippocampus was decreased in rats fed a soft-food diet. Electron spin resonance studies using the nitroxyl spin probe 3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl directly demonstrated a high level of oxidative stress in the rat brain due to soft-food diet feeding. In addition, we confirmed that DA directly react with reactive oxygen species such as hydroxyl radical and superoxide. These observations suggest that soft-food diet feeding enhances oxidative stress, which leads to oxidation and a decrease in the release of DA in the hippocampus of rats. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Response of rat brain protein synthesis to ethanol and sodium barbital

International Nuclear Information System (INIS)

Tewari, S.; Greenberg, S.A.; Do, K.; Grey, P.A.

1987-01-01

Central nervous system (CNS) depressants such as ethanol and barbiturates under acute or chronic conditions can induce changes in rat brain protein synthesis. While these data demonstrate the individual effects of drugs on protein synthesis, the response of brain protein synthesis to alcohol-drug interactions is not known. The goal of the present study was to determine the individual and combined effects of ethanol and sodium barbital on brain protein synthesis and gain an understanding of the mechanisms by which these alterations in protein synthesis are produced. Specifically, the in vivo and in vitro effects of sodium barbital (one class of barbiturates which is not metabolized by the hepatic tissue) were examined on brain protein synthesis in rats made physically dependent upon ethanol. Using cell free brain polysomal systems isolated from Control, Ethanol and 24 h Ethanol Withdrawn rats, data show that sodium barbital, when intubated intragastrically, inhibited the time dependent incorporation of 14 C) leucine into protein by all three groups of ribosomes. Under these conditions, the Ethanol Withdrawn group displayed the largest inhibition of the 14 C) leucine incorporation into protein when compared to the Control and Ethanol groups. In addition, sodium barbital when added at various concentrations in vitro to the incubation medium inhibited the incorporation of 14 C) leucine into protein by Control and Ethanol polysomes. The inhibitory effects were also obtained following preincubation of ribosomes in the presence of barbital but not cycloheximide. Data suggest that brain protein synthesis, specifically brain polysomes, through interaction with ethanol or barbital are involved in the functional development of tolerance. These interactions may occur through proteins or polypeptide chains or alterations in messenger RNA components associated with the ribosomal units

Metabolic fate of 13N-labeled ammonia in rat brain

International Nuclear Information System (INIS)

Cooper, A.J.L.; McDonald, J.M.; Gelbard, A.S.; Gledhill, R.F.; Duffy, T.E.

1979-01-01

After infusion of physiological concentrations of [ 13 N]ammonia for 10 min via one internal carotid artery, the relative specific activities of glutamate, glutamine (α-amino), and glutamine (amide) in rat brain were approximately 1:5:400, respectively. Analysis of metabolites, after infusion of [ 13 N]ammonia into one lateral cerebral ventricle, indicated that ammonia entering the brain from the cerebrospinal fluid is also metabolized in a small glutamate pool. Pretreatment with methionine sulfoximine led to a decrease in the label present in brain glutamine following carotid artery infusion of [ 13 N]ammonia. 13 N activity in brain glutamate was greater than in the α-amino group of glutamine. The amount of label recovered in the right cerebral hemisphere, 5 s after a rapid bolus injection of [ 13 N]ammonia via the right common carotid artery, was independent of concentration within the bolus over a 1000-fold range indicating that ammonia enters the brain largely by diffusion. In normal rats approximately 60% of the label recovered in brain was incorporated into glutamine, indicating that the t 1 /sub// 2 for conversion of ammonia to glutamine in the small pool is in the range of 1 to 3 s or less. The data emphasize the importance of the small pool glutamine synthetase as a metabolic trap for the detoxification of blood-borne and endogenously produced brain ammonia. The possibility that the astrocytes represent the anatomical site of the small pool is considered

Effect of maternal excessive sodium intake on postnatal brain development in rat offspring.

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Shin, Jung-a; Ahn, Young-mo; Lee, Hye-ah; Park, Hyesook; Kim, Young-ju; Lee, Hwa-young

2015-04-01

Postnatal brain development is affected by the in utero environment. Modern people usually have a high sodium intake. The aim of this study was to investigate the effect of sodium hyperingestion during pregnancy on the postnatal brain development of rat offspring. The sodium-overloaded rats received 1.8% NaCl in their drinking water for 7 days during the last week of gestation. Their body weight, urine, and blood levels of sodium and other parameters were measured. Some rats were sacrificed at pregnancy day 22 and the weight and length of the placenta and foetus were measured. The cerebral cortex and hippocampus were obtained from their offspring at postnatal day 1 and at postnatal weeks 1, 2, 4, and 8. Western blot analyses were conducted with brain tissue lysates. The sodium-overloaded animals had decreased weight gain in the last week of gestation as well as decreased food intake, increased water intake, urine volume, urine sodium, and serum sodium. There were no differences in placental weight and length. The foetuses of sodium-overloaded rats showed decreased body weight and size, and this difference was maintained postnatally for 2 weeks. In the cerebral cortex and hippocampus of the offspring, the protein levels of myelin basic protein, calmodulin/calcium-dependent protein kinase II, and brain-derived neurotrophic factor were decreased or aberrantly expressed. The present data suggest that increased sodium intake during pregnancy affects the brain development of the offspring.

Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

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Najmeh Kabiri

2016-09-01

Full Text Available The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99. Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly higher than the Sham group, although right hemispheres in all of the treated groups illustrated higher brain water content than the left ones. Brain anti-oxidant capacity elevated in the ischemic rats treated with Kombucha and in the Sham group. Brain and plasma malondialdehyde concentrations significantly decreased in both of the ischemic groups injected with Kombucha. The findings suggest that Kombucha tea could be useful for the prevention of cerebral damage.

The Effect of Hydroxylated Fullerene Nanoparticles on Antioxidant Defense System in Brain Ischemia Rat

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2017-05-01

Full Text Available Background and Objectives: According to the previous findings, brain ischemia attenuates the brain antioxidant defense system. This study aimed to investigate the effect of hydroxylated fullerene nanoparticle on antioxidant defense system in ischemic brain rat. Methods: In this Experimental study, rats were divided into three groups (n=6 in each group: sham, ischemic control, and ischemic treatment group. Brain ischemia was induced by middle cerebral artery (MCA occlusion for 90 minutes followed by a 24-hour reperfusion. Ischemic treatment animals received fullerene nanoparticles intraperitoneally at a dose of 10mg/kg immediately after the end of MCA occlusion. After 24-h reperfusion period, brain catalase and superoxide dismutase (SOD, and glutathione activities were assessed by biochemical methods. The data were analyzed using one-way ANOVA and Tukey post-hoc test. Results: The mean glutathione level and catalase and SOD activities in sham animals were 1±0.18%, 1±0.20%, and 1±0.04%, respectively. Induction of brain ischemia decreased the value of glutathione level and catalase and SOD activities in control ischemic rats and their values were obtained to be 0.55±0.09%, 0.44±0.05%, and 0.86±0.02%, respectively. Fullerene significantly increased the activities of catalase (0.93±0.29% and SOD (1.33±0.22% in ischemic treatment group compared to ischemic control rats, but did not change the glutathione level (0.52±0.25%. Conclusion: The results of this study showed that treatment with fullerene nanoparticles improves the brain antioxidant defense system, which is weakened during brain ischemia, through increasing catalase and SOD activities.

Effects of acupuncture on tissue-oxygenation of the rat brain.

Science.gov (United States)

Chen, G S; Erdmann, W

1977-01-01

Acupuncture has been claimed to be effective in restoring consciousness in some comatose patients. Possible mechanisms to explain alleged acupuncture-induced arousal may include vasodilatory effects caused by sympathetic stimulation which leads to an augmentation of cerebral microcirculation and thereby improves oxygen supply to the brain tissue. Experiments were performed in ten albino rats (Wistar) employing PO2 microelectrodes which were inserted into the cortex of the animals through small burholes. Brain tissue PO2 was continuously recorded before, during, and after acupuncture. Stimulation of certain acupuncture loci (Go-26) resulted in immediate increase of PO2 in the frontal cortex of the rat brain. This effect was reproducible. The effect was comparable to that obtained with increase of inspiratory CO2 known to induce arterial vasodilatation and thus capillary perfusion pressure. The effect was more significant as compared to tissue PO2 increases obtained after increase of inspiratory oxygen concentration from 21% to 100%. It appears that acupuncture causes an increase of brain tissue perfusion which may be, at least in part, responsible for arousal of unconscious patients. Dilatation of cerebral vascular vessels and improvement of autoregulation in the brain by acupuncture stimulation may also explain the effectiveness of acupuncture in the treatment of migraine headache.

Longitudinal Whole-Brain N-acetylaspartate Concentration in Healthy Adults

Science.gov (United States)

Rigotti, Daniel J.; Kirov, Ivan I.; Djavadi, Bejan; Perry, Nissa N.; Babb, James S.; Gonen, Oded

2011-01-01

BACKGROUND AND PURPOSE Though N-acetylaspartate (NAA) is often used as a marker of neural integrity and health in different neurological disorders, the temporal behavior of its whole-brain concentration (WBNAA) is not well characterized. Our goal, therefore, was to establish its normal variations in a cohort of healthy adults over typical clinical trial periods. METHODS Baseline amount of brain NAA, QNAA, was obtained with non-localizing proton MR spectroscopy from 9 subjects (7 women, 2 men) 31.2±5.6 years old. QNAA was converted into absolute millimole amount using phantom-replacement. The WBNAA concentration was derived by dividing QNAA with the brain parenchyma volume, VB, segmented from MRI. Temporal variations were determined with four annual scans of each participant. RESULTS The distribution of WBNAA levels was not different among time points with respect to the mean, 12.1±1.5 mM (p 0.6) nor was its intra-subject change (CV = 8.6%) significant between any two scans (p 0.5). There was a small (0.2 mL), but significant (p=0.05) annual VB decline. CONCLUSION WBNAA is stable over a three year period in healthy adults. It qualifies therefore, as a biomarker for global neuronal loss and dysfunction in diffuse neurological disorders that may be well worth considering as a secondary outcome measure candidate for clinical trials. PMID:21511862

Regulation of brain aromatase activity in rats

International Nuclear Information System (INIS)

Roselli, C.E.; Ellinwood, W.E.; Resko, J.A.

1984-01-01

The distribution and regulation of aromatase activity in the adult rat brain with a sensitive in vitro assay that measures the amount of 3 H 2 O formed during the conversion of [1 beta- 3 H]androstenedione to estrone. The rate of aromatase activity in the hypothalamus-preoptic area (HPOA) was linear with time up to 1 h, and with tissue concentrations up to 5 mgeq/200 microliters incubation mixture. The enzyme demonstrated a pH optimum of 7.4 and an apparent Michaelis-Menten constant (Km) of 0.04 microns. The greatest amount of aromatase activity was found in amygdala and HPOA from intact male rats. The hippocampus, midbrain tegmentum, cerebral cortex, cerebellum, and anterior pituitary all contained negligible enzymatic activity. Castration produced a significant decrease in aromatase activity in the HPOA, but not in the amygdala or cerebral cortex. The HPOAs of male rats contained significantly greater aromatase activity than the HPOAs of female rats. In females, this enzyme activity did not change during the estrous cycle or after ovariectomy. Administration of testosterone to gonadectomized male and female rats significantly enhanced HPOA aromatase activities to levels approximating those found in HPOA from intact males. Therefore, the results suggest that testosterone, or one of its metabolites, is a major steroidal regulator of HPOA aromatase activity in rats

Development of an UPLC-MS/MS method for simultaneous quantitation of 11 d-amino acids in different regions of rat brain: Application to a study on the associations of d-amino acid concentration changes and Alzheimer's disease.

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Li, Zhe; Xing, Yuping; Guo, Xingjie; Cui, Yan

2017-07-15

There are significant differences in d-amino acid concentrations between healthy people and Alzheimer's disease patients. In order to investigate the potential correlation between d-amino acids and Alzheimer's disease, a simple and sensitive ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method has been developed. The method was applied to simultaneous determination of 11 d-amino acids in different regions of rat brain. Rat brain homogenates were firstly pretreated with protein precipitation procedure and then derivatized with (S)-N-(4-nitrophenoxycarbonyl) phenylalanine methoxyethyl ester [(S)-NIFE]. Baseline separation of the derivatives was achieved on an ACQUITY UPLC BEH C 18 column (2.1 mm×50mm, 1.7μm). The mobile phase consisted of acetonitrile and water (containing 8mM ammonium hydrogen carbonate) and the flow rate was 0.6mLmin -1 . The derived analytes were sensitively detected by multiple reaction monitoring in the positive ion mode. The lower limits of quantitation ranged from 0.06 to 10ngmL -1 with excellent linearity (r≥0.9909). The intra- and inter-day RSD were in the range of 3.6-12% and 5.7-12%, respectively. The recovery rate was 82.5%-95.3%. With this UPLC-MS/MS method, the 11 d-amino acids in hippocampus, cerebral cortex, olfactory bulb and cerebellum from Alzheimer's disease rats and age-matched controls could be simultaneously determined. Compared with the normal controls, the concentrations of d-serine, d-alanine, d-leucine, and d-proline in hippocampus and cerebral cortex of Alzheimer's disease rat brain were significantly decreased, while no differences in olfactory bulb and cerebellum of all the d-amino acids were observed. The different amounts and distribution of d-amino acids in brain between the two groups, which regulated by particular pathological changes of Alzheimer's disease, would give new insights into further study in neuropathogenesis and provide novel therapeutic targets of Alzheimer

Effects of ebselen on ischemia/reperfusion injury in rat brain.

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Aras, M; Altaş, M; Meydan, S; Nacar, E; Karcıoğlu, M; Ulutaş, K T; Serarslan, Y

2014-10-01

Interruption of blood flow may result in considerable tissue damage via ischemia/reperfusion (I/R) injury-induced oxidative stress in brain tissues. The aim of the present study was to investigate the effects of Ebselen treatment in short-term global brain I/R injury in rats. The study was carried out on 27 Wistar-albino rats, divided into three groups including Sham group (n = 11), I/R group (n = 8) and I/R+Ebselen group (n = 8). Malondialdehyde (MDA) levels were significantly increased in I/R group in comparison with the Sham group and I/R+Ebselen group (p Ebselen (p Ebselen group when compared with Sham group (p Ebselen group when compared with Sham (p Ebselen showed morphological improvement. Ebselen has neuron-protective effects due to its antioxidant properties as shown by the decrease in MDA overproduction, increase in SOD activity and the histological improvement after administration of Ebselen to I/R in brain tissue.

Volumetric changes in the aging rat brain and its impact on cognitive and locomotor functions.

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Hamezah, Hamizah Shahirah; Durani, Lina Wati; Ibrahim, Nor Faeizah; Yanagisawa, Daijiro; Kato, Tomoko; Shiino, Akihiko; Tanaka, Sachiko; Damanhuri, Hanafi Ahmad; Ngah, Wan Zurinah Wan; Tooyama, Ikuo

2017-12-01

Impairments in cognitive and locomotor functions usually occur with advanced age, as do changes in brain volume. This study was conducted to assess changes in brain volume, cognitive and locomotor functions, and oxidative stress levels in middle- to late-aged rats. Forty-four male Sprague-Dawley rats were divided into four groups: 14, 18, 23, and 27months of age. 1 H magnetic resonance imaging (MRI) was performed using a 7.0-Tesla MR scanner system. The volumes of the lateral ventricles, medial prefrontal cortex (mPFC), hippocampus, striatum, cerebellum, and whole brain were measured. Open field, object recognition, and Morris water maze tests were conducted to assess cognitive and locomotor functions. Blood was taken for measurements of malondialdehyde (MDA), protein carbonyl content, and antioxidant enzyme activity. The lateral ventricle volumes were larger, whereas the mPFC, hippocampus, and striatum volumes were smaller in 27-month-old rats than in 14-month-old rats. In behavioral tasks, the 27-month-old rats showed less exploratory activity and poorer spatial learning and memory than did the 14-month-old rats. Biochemical measurements likewise showed increased MDA and lower glutathione peroxidase (GPx) activity in the 27-month-old rats. In conclusion, age-related increases in oxidative stress, impairment in cognitive and locomotor functions, and changes in brain volume were observed, with the most marked impairments observed in later age. Copyright © 2017. Published by Elsevier Inc.

Repeated exposure of the developing rat brain to magnetic resonance imaging did not affect neurogenesis, cell death or memory function

International Nuclear Information System (INIS)

Zhu, Changlian; Gao, Jianfeng; Li, Qian; Huang, Zhiheng; Zhang, Yu; Li, Hongfu; Kuhn, Hans-Georg; Blomgren, Klas

2011-01-01

Research highlights: → The effect of MRI on the developing brain is a matter of debate. → Repeated exposure to MRI did not affect neurogenesis. → Memory function was not affected by repeated MRI during development. → Neither late gestation nor young postnatal brains were affected by MRI. → Repeated MRI did not cause cell death in the neurogenic region of the hippocampus. -- Abstract: The effect of magnetic fields on the brain is a matter of debate. The objective of this study was to investigate whether repeated exposure to strong magnetic fields, such as during magnetic resonance imaging (MRI), could elicit changes in the developing rat brain. Embryonic day 15 (E15) and postnatal day 14 (P14) rats were exposed to MRI using a 7.05 T MR system. The animals were anesthetized and exposed for 35 min per day for 4 successive days. Control animals were anesthetized but no MRI was performed. Body temperature was maintained at 37 o C. BrdU was injected after each session (50 mg/kg). One month later, cell proliferation, neurogenesis and astrogenesis in the dentate gyrus were evaluated, revealing no effects of MRI, neither in the E15, nor in the P14 group. DNA damage in the dentate gyrus in the P14 group was evaluated on P18, 1 day after the last session, using TUNEL staining. There was no difference in the number of TUNEL-positive cells after MRI compared with controls, neither in mature neurons, nor in newborn progenitors (BrdU/TUNEL double-labeled cells). Novel object recognition was performed to assess memory function 1 month after MRI. There was no difference in the recognition index observed after MRI compared with the control rats, neither for the E15, nor for the P14 group. In conclusion, repeated exposure to MRI did not appear to affect neurogenesis, cell death or memory function in rats, neither in late gestation (E15-E18) nor in young postnatal (P14-P17) rats.

Exogenous agmatine has neuroprotective effects against restraint-induced structural changes in the rat brain

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Zhu, Meng-Yang; Wang, Wei-Ping; Cai, Zheng-Wei; Regunathan, Soundar; Ordway, Gregory

2009-01-01

Agmatine is an endogenous amine derived from decarboxylation of arginine catalysed by arginine decarboxylase. Agmatine is considered a novel neuromodulator and possesses neuroprotective properties in the central nervous system. The present study examined whether agmatine has neuroprotective effects against repeated restraint stress-induced morphological changes in rat medial prefrontal cortex and hippocampus. Sprague-Dawley rats were subjected to 6 h of restraint stress daily for 21 days. Immunohistochemical staining with β-tubulin III showed that repeated restraint stress caused marked morphological alterations in the medial prefrontal cortex and hippocampus. Stress-induced alterations were prevented by simultaneous treatment with agmatine (50 mg/kg/day, i.p.). Interestingly, endogenous agmatine levels, as measured by high-performance liquid chromatography, in the prefrontal cortex and hippocampus as well as in the striatum and hypothalamus of repeated restraint rats were significantly reduced as compared with the controls. Reduced endogenous agmatine levels in repeated restraint animals were accompanied by a significant increase of arginine decarboxylase protein levels in the same regions. Moreover, administration of exogenous agmatine to restrained rats abolished increases of arginine decarboxylase protein levels. Taken together, these results demonstrate that exogenously administered agmatine has neuroprotective effects against repeated restraint-induced structural changes in the medial prefrontal cortex and hippocampus. These findings indicate that stress-induced reductions in endogenous agmatine levels in the rat brain may play a permissive role in neuronal pathology induced by repeated restraint stress. PMID:18364017

Developmental vitamin D deficiency alters multiple neurotransmitter systems in the neonatal rat brain.

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Kesby, James P; Turner, Karly M; Alexander, Suzanne; Eyles, Darryl W; McGrath, John J; Burne, Thomas H J

2017-11-01

Epidemiological evidence suggests that developmental vitamin D (DVD) deficiency is a risk factor for neuropsychiatric disorders, such as schizophrenia. DVD deficiency in rats is associated with altered brain structure and adult behaviours indicating alterations in dopamine and glutamate signalling. Developmental alterations in dopamine neurotransmission have also been observed in DVD-deficient rats but a comprehensive assessment of brain neurochemistry has not been undertaken. Thus, the current study determined the regional concentrations of dopamine, noradrenaline, serotonin, glutamine, glutamate and γ-aminobutyric acid (GABA), and associated metabolites, in DVD-deficient neonates. Sprague-Dawley rats were fed a vitamin D deficient diet or control diet six weeks prior to mating until birth and housed under UVB-free lighting conditions. Neurotransmitter concentration was assessed by high-performance liquid chromatography on post-mortem neonatal brain tissue. Ubiquitous reductions in the levels of glutamine (12-24%) were observed in DVD-deficient neonates compared with control neonates. Similarly, in multiple brain regions DVD-deficient neonates had increased levels of noradrenaline and serine compared with control neonates. In contrast, increased levels of dopamine and decreased levels of serotonin in DVD-deficient neonates were limited to striatal subregions compared with controls. Our results confirm that DVD deficiency leads to changes in multiple neurotransmitter systems in the neonate brain. Importantly, this regionally-based assessment in DVD-deficient neonates identified both widespread neurotransmitter changes (glutamine/noradrenaline) and regionally selective neurotransmitter changes (dopamine/serotonin). Thus, vitamin D may have both general and local actions depending on the neurotransmitter system being investigated. Taken together, these data suggest that DVD deficiency alters neurotransmitter systems relevant to schizophrenia in the developing rat

Housing conditions influence motor functions and exploratory behavior following focal damage of the rat brain.

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Gornicka-Pawlak, Elzbieta; Jabłońska, Anna; Chyliński, Andrzej; Domańska-Janik, Krystyna

2009-01-01

The present study investigated influence of housing conditions on motor functions recovery and exploratory behavior following ouabain focal brain lesion in the rat. During 30 days post-surgery period rats were housed individually in standard cages (IS) or in groups in enriched environment (EE) and behaviorally tested. The EE lesioned rats showed enhanced recovery from motor impairments in walking beam task, comparing with IS animals. Contrarily, in the open field IS rats (both lesioned and control) traveled a longer distance, showed less habituation and spent less time resting at the home base than the EE animals. Unlike the EE lesioned animals, the lesioned IS rats, presented a tendency to hyperactivity in postinjury period. Turning tendency was significantly affected by unilateral brain lesion only in the EE rats. We can conclude that housing conditions distinctly affected the rat's behavior in classical laboratory tests.

Gamma Knife irradiation method based on dosimetric controls to target small areas in rat brains

International Nuclear Information System (INIS)

Constanzo, Julie; Paquette, Benoit; Charest, Gabriel; Masson-Côté, Laurence; Guillot, Mathieu

2015-01-01

Purpose: Targeted and whole-brain irradiation in humans can result in significant side effects causing decreased patient quality of life. To adequately investigate structural and functional alterations after stereotactic radiosurgery, preclinical studies are needed. The purpose of this work is to establish a robust standardized method of targeted irradiation on small regions of the rat brain. Methods: Euthanized male Fischer rats were imaged in a stereotactic bed, by computed tomography (CT), to estimate positioning variations relative to the bregma skull reference point. Using a rat brain atlas and the stereotactic bregma coordinates obtained from CT images, different regions of the brain were delimited and a treatment plan was generated. A single isocenter treatment plan delivering ≥100 Gy in 100% of the target volume was produced by Leksell GammaPlan using the 4 mm diameter collimator of sectors 4, 5, 7, and 8 of the Gamma Knife unit. Impact of positioning deviations of the rat brain on dose deposition was simulated by GammaPlan and validated with dosimetric measurements. Results: The authors’ results showed that 90% of the target volume received 100 ± 8 Gy and the maximum of deposited dose was 125 ± 0.7 Gy, which corresponds to an excellent relative standard deviation of 0.6%. This dose deposition calculated with GammaPlan was validated with dosimetric films resulting in a dose-profile agreement within 5%, both in X- and Z-axes. Conclusions: The authors’ results demonstrate the feasibility of standardizing the irradiation procedure of a small volume in the rat brain using a Gamma Knife

Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats

DEFF Research Database (Denmark)

Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne

2014-01-01

, and aspartate and incorporation of (15)NH4(+) into these amino acids in brain, liver, muscle, kidney, and plasma were similar in sham and BDL rats treated with saline. Methionine sulfoximine reduced glutamine concentrations in liver, kidney, and plasma but not in brain and muscle; MSO reduced incorporation...... of (15)NH4(+) into glutamine in all tissues. It did not affect alanine concentrations in any of the tissues but plasma alanine concentration increased; incorporation of (15)NH4(+) into alanine was increased in brain in sham and BDL rats and in kidney in sham rats. It inhibited GS in all tissues examined...

Dobutamine stress echocardiography in healthy adult male rats

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Couet Jacques

2005-10-01

Full Text Available Abstract Background Dobutamine stress echocardiography is used to investigate a wide variety of heart diseases in humans. Dobutamine stress echocardiography has also been used in animal models of heart disease despite the facts that the normal response of healthy rat hearts to this type of pharmacological stress testing is unknown. This study was performed to assess this normal response. Methods 15 normal adult male Wistar rats were evaluated. Increasing doses of dobutamine were infused intravenously under continuous imaging of the heart by a 12 MHz ultrasound probe. Results Dobutamine stress echocardiography reduced gradually LV diastolic and systolic dimensions. Ejection fraction increased by a mean of +24% vs. baseline. Heart rate increased progressively without reaching a plateau. Changes in LV dimensions and ejection fraction reached a plateau after a mean of 4 minutes at a constant infusion rate. Conclusion DSE can be easily performed in rats. The normal response is an increase in heart rate and ejection fraction and a decrease in LV dimensions. A plateau in echocardiographic measurements is obtained after 4 minutes of a constant infusion rate in most animals.

The Effects of Dietary Iron and Capsaicin on Hemoglobin, Blood Glucose, Insulin Tolerance, Cholesterol, and Triglycerides, in Healthy and Diabetic Wistar Rats.

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Márquez-Ibarra, Adriana; Huerta, Miguel; Villalpando-Hernández, Salvador; Ríos-Silva, Mónica; Díaz-Reval, María I; Cruzblanca, Humberto; Mancilla, Evelyn; Trujillo, Xóchitl

2016-01-01

Our aim was to assess the effects of dietary iron, and the compound capsaicin, on hemoglobin as well as metabolic indicators including blood glucose, cholesterol, triglycerides, insulin, and glucose tolerance. Our animal model was the Wistar rat, fed a chow diet, with or without experimentally induced diabetes. Diabetic males were fed control, low, or high-iron diets, the latter, with or without capsaicin. Healthy rats were fed identical diets, but without the capsaicin supplement. We then measured the parameters listed above, using the Student t-test and ANOVA, to compare groups. Healthy rats fed a low-iron diet exhibited significantly reduced total cholesterol and triglyceride levels, compared with rats fed a control diet. Significantly reduced blood lipid was also provoked by low dietary iron in diabetic rats, compared with those fed a control diet. Insulin, and glucose tolerance was only improved in healthy rats fed the low-iron diet. Significant increases in total cholesterol were found in diabetic rats fed a high-iron diet, compared with healthy rats fed the same diet, although no statistical differences were found for triglycerides. Hemoglobin levels, which were not statistically different in diabetic versus healthy rats fed the high-iron diet, fell when capsaicin was added. Capsaicin also provoked a fall in the level of cholesterol and triglycerides in diabetic animals, versus diabetics fed with the high iron diet alone. In conclusion, low levels of dietary iron reduced levels of serum triglycerides, hemoglobin, and cholesterol, and significantly improved insulin, and glucose tolerance in healthy rats. In contrast, a high-iron diet increased cholesterol significantly, with no significant changes to triglyceride concentrations. The addition of capsaicin to the high-iron diet (for diabetic rats) further reduced levels of hemoglobin, cholesterol, and triglycerides. These results suggest that capsaicin, may be suitable for the treatment of elevated hemoglobin

An improved in vitro blood-brain barrier model: rat brain endothelial cells co-cultured with astrocytes.

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Abbott, N Joan; Dolman, Diana E M; Drndarski, Svetlana; Fredriksson, Sarah M

2012-01-01

In vitro blood-brain barrier (BBB) models using primary cultured brain endothelial cells are important for establishing cellular and molecular mechanisms of BBB function. Co-culturing with BBB-associated cells especially astrocytes to mimic more closely the in vivo condition leads to upregulation of the BBB phenotype in the brain endothelial cells. Rat brain endothelial cells (RBECs) are a valuable tool allowing ready comparison with in vivo studies in rodents; however, it has been difficult to obtain pure brain endothelial cells, and few models achieve a transendothelial electrical resistance (TEER, measure of tight junction efficacy) of >200 Ω cm(2), i.e. the models are still relatively leaky. Here, we describe methods for preparing high purity RBECs and neonatal rat astrocytes, and a co-culture method that generates a robust, stable BBB model that can achieve TEER >600 Ω cm(2). The method is based on >20 years experience with RBEC culture, together with recent improvements to kill contaminating cells and encourage BBB differentiation.Astrocytes are isolated by mechanical dissection and cell straining and are frozen for later co-culture. RBECs are isolated from 3-month-old rat cortices. The brains are cleaned of meninges and white matter and enzymatically and mechanically dissociated. Thereafter, the tissue homogenate is centrifuged in bovine serum albumin to separate vessel fragments from other cells that stick to the myelin plug. The vessel fragments undergo a second enzyme digestion to separate pericytes from vessels and break down vessels into shorter segments, after which a Percoll gradient is used to separate capillaries from venules, arterioles, and single cells. To kill remaining contaminating cells such as pericytes, the capillary fragments are plated in puromycin-containing medium and RBECs grown to 50-60% confluence. They are then passaged onto filters for co-culture with astrocytes grown in the bottom of the wells. The whole procedure takes ∼2

Fingolimod against endotoxin-induced fetal brain injury in a rat model.

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Yavuz, And; Sezik, Mekin; Ozmen, Ozlem; Asci, Halil

2017-11-01

Fingolimod is a sphingosine-1-phosphate receptor modulator used for multiple sclerosis treatment and acts on cellular processes such as apoptosis, endothelial permeability, and inflammation. We hypothesized that fingolimod has a positive effect on alleviating preterm fetal brain injury. Sixteen pregnant rats were divided into four groups of four rats each. On gestational day 17, i.p. endotoxin was injected to induce fetal brain injury, followed by i.p. fingolimod (4 mg/kg maternal weight). Hysterotomy for preterm delivery was performed 6 h after fingolimod. The study groups included (i) vehicle controls (i.p. normal saline only); (ii) positive controls (endotoxin plus saline); (iii) saline plus fingolimod; and (iv) endotoxin plus fingolimod treatment. Brain tissues of the pups were dissected for evaluation of interleukin (IL)-6, caspase-3, and S100β on immunohistochemistry. Maternal fingolimod treatment attenuated endotoxin-related fetal brain injury and led to lower immunoreactions for IL-6, caspase-3, and S100β compared with endotoxin controls (P < 0.0001 for all comparisons). Antenatal maternal fingolimod therapy had fetal neuroprotective effects by alleviating preterm birth-related fetal brain injury with inhibitory effects on inflammation and apoptosis. © 2017 Japan Society of Obstetrics and Gynecology.

Effects of electroconvulsive seizures on depression-related behavior, memory and neurochemical changes in Wistar and Wistar-Kyoto rats.

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Kyeremanteng, C; MacKay, J C; James, J S; Kent, P; Cayer, C; Anisman, H; Merali, Z

2014-10-03

Investigations in healthy outbred rat strains have shown a potential role for brain-derived neurotrophic factor (BDNF) and the hypothalamic-pituitary-adrenal (HPA) axis in the antidepressant and memory side effects of electroconvulsive therapy (ECT, or ECS in animals). The Wistar-Kyoto (WKY) rat strain is used as a genetic model of depression yet no studies to date have directly compared the impact of ECS on the WKY strain to its healthy outbred control (Wistar). The objective of this study is to examine behavioral (antidepressant and retrograde memory) and neurochemical (BDNF and HPA axis) changes immediately (1day) and at a longer delay (7days) after repeated ECS (5 daily administrations) in WKY and Wistar rats. Male Wistar and WKY rats received 5days of repeated ECS or sham treatment and were assessed 1 and 7days later for 1) depression-like behavior and mobility; 2) retrograde memory; and 3) brain BDNF protein, brain corticotropin-releasing factor (CRF) and plasma corticosterone levels. Both strains showed the expected antidepressant response and retrograde memory impairments at 1day following ECS, which were sustained at 7days. In addition, at 1day after ECS, Wistar and WKY rats showed similar elevations in brain BDNF and extra-hypothalamic CRF and no change in plasma corticosterone. At 7days after ECS, Wistar rats showed sustained elevations of brain BDNF and CRF, whereas WKY rats showed a normalization of brain BDNF, despite sustained elevations of brain CRF. The model of 5 daily ECS was effective at eliciting behavioral and neurochemical changes in both strains. A temporal association was observed between brain CRF levels, but not BDNF, and measures of antidepressant effectiveness of ECS and retrograde memory impairments suggesting that extra-hypothalamic CRF may be a potential important contributor to these behavioral effects after repeated ECS/ECT. Copyright © 2014 Elsevier Inc. All rights reserved.

Fast and Accurate Rat Head Motion Tracking With Point Sources for Awake Brain PET.

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Miranda, Alan; Staelens, Steven; Stroobants, Sigrid; Verhaeghe, Jeroen

2017-07-01

To avoid the confounding effects of anesthesia and immobilization stress in rat brain positron emission tomography (PET), motion tracking-based unrestrained awake rat brain imaging is being developed. In this paper, we propose a fast and accurate rat headmotion tracking method based on small PET point sources. PET point sources (3-4) attached to the rat's head are tracked in image space using 15-32-ms time frames. Our point source tracking (PST) method was validated using a manually moved microDerenzo phantom that was simultaneously tracked with an optical tracker (OT) for comparison. The PST method was further validated in three awake [ 18 F]FDG rat brain scans. Compared with the OT, the PST-based correction at the same frame rate (31.2 Hz) reduced the reconstructed FWHM by 0.39-0.66 mm for the different tested rod sizes of the microDerenzo phantom. The FWHM could be further reduced by another 0.07-0.13 mm when increasing the PST frame rate (66.7 Hz). Regional brain [ 18 F]FDG uptake in the motion corrected scan was strongly correlated ( ) with that of the anesthetized reference scan for all three cases ( ). The proposed PST method allowed excellent and reproducible motion correction in awake in vivo experiments. In addition, there is no need of specialized tracking equipment or additional calibrations to be performed, the point sources are practically imperceptible to the rat, and PST is ideally suitable for small bore scanners, where optical tracking might be challenging.

Antioxidant potential properties of mushroom extract (Agaricus bisporus) against aluminum-induced neurotoxicity in rat brain.

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Waly, Mostafa I; Guizani, Nejib

2014-09-01

Aluminum (Al) is an environmental toxin that induces oxidative stress in neuronal cells. Mushroom cultivar extract (MCE) acted as a potent antioxidant agent and protects against cellular oxidative stress in human cultured neuronal cells. This study aimed to investigate the neuroprotective effect of MCE against Al-induced neurotoxicity in rat brain. Forty Sprague-Dawley rats were divided into 4 groups (10 rats per group), control group, MCE-fed group, Al-administered group and MCE/Al-treated group. Animals were continuously fed ad-libitum their specific diets for 4 weeks. At the end of the experiment, all rats were sacrificed and the brain tissues were homogenized and examined for biochemical measurements of neurocellular oxidative stress indices [glutathione (GSH), Total Antioxidant Capacity (TAC), antioxidant enzymes and oxidized dichlorofluorescein (DCF)]. Al-administration caused inhibition of antioxidant enzymes and a significant decrease in GSH and TAC levels, meanwhile it positively increased cellular oxidized DCF level, as well as Al concentration in brain tissues. Feeding animals with MCE had completely offset the Al-induced oxidative stress and significantly restrict the Al accumulation in brain tissues of Al-administered rats. The results obtained suggest that MCE acted as a potent dietary antioxidant and protects against Al-mediated neurotoxicity, by abrogating neuronal oxidative stress.

Posttraining Epinephrine Reverses Memory Deficits Produced by Traumatic Brain Injury in Rats

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Alejandro Lorón-Sánchez

2016-01-01

Full Text Available The aim of this research is to evaluate whether posttraining systemic epinephrine is able to improve object recognition memory in rats with memory deficits produced by traumatic brain injury. Forty-nine two-month-old naïve male Wistar rats were submitted to surgical procedures to induce traumatic brain injury (TBI or were sham-operated. Rats were trained in an object recognition task and, immediately after training, received an intraperitoneal injection of distilled water (Sham-Veh and TBI-Veh group or 0.01 mg/kg epinephrine (TBI-Epi group or no injection (TBI-0 and Sham-0 groups. Retention was tested 3 h and 24 h after acquisition. The results showed that brain injury produced severe memory deficits and that posttraining administration of epinephrine was able to reverse them. Systemic administration of distilled water also had an enhancing effect, but of a lower magnitude. These data indicate that posttraining epinephrine and, to a lesser extent, vehicle injection reduce memory deficits associated with TBI, probably through induction of a low-to-moderate emotional arousal.

Posttraining Epinephrine Reverses Memory Deficits Produced by Traumatic Brain Injury in Rats

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Lorón-Sánchez, Alejandro; Torras-Garcia, Meritxell; Coll-Andreu, Margalida; Costa-Miserachs, David; Portell-Cortés, Isabel

2016-01-01

The aim of this research is to evaluate whether posttraining systemic epinephrine is able to improve object recognition memory in rats with memory deficits produced by traumatic brain injury. Forty-nine two-month-old naïve male Wistar rats were submitted to surgical procedures to induce traumatic brain injury (TBI) or were sham-operated. Rats were trained in an object recognition task and, immediately after training, received an intraperitoneal injection of distilled water (Sham-Veh and TBI-Veh group) or 0.01 mg/kg epinephrine (TBI-Epi group) or no injection (TBI-0 and Sham-0 groups). Retention was tested 3 h and 24 h after acquisition. The results showed that brain injury produced severe memory deficits and that posttraining administration of epinephrine was able to reverse them. Systemic administration of distilled water also had an enhancing effect, but of a lower magnitude. These data indicate that posttraining epinephrine and, to a lesser extent, vehicle injection reduce memory deficits associated with TBI, probably through induction of a low-to-moderate emotional arousal. PMID:27127685

Fetal hypothalamic transplants into brain irradiated rats: Graft morphometry and host behavioral responses

International Nuclear Information System (INIS)

Pearlman, S.H.; Rubin, P.; White, H.C.; Wiegand, S.J.; Gash, D.M.

1990-01-01

This study was designed to test the hypothesis that neural implants can ameliorate or prevent some of the long-term changes associated with CNS irradiation. Using a rat model, the initial study focused on establishing motor, regulatory, and morphological changes associated with brain radiation treatments. Secondly, fetal hypothalamic tissue grafts were placed into the third ventricle of rats which had been previously irradiated. Adult male Long Evans rats received one of three radiation doses (15, 22.5, ampersand 30 Gy) or no radiation. Three days after irradiation, 7 animals in each dose group received an embryonic day 17 hypothalamic graft into the third ventricle while the remaining 8-9 animals in each group received injections of vehicle solution (sham). Few changes were observed in the 15 and 22.5 Gy animals, however rats in the 30 Gy treatment group showed stereotypic and ambulatory behavioral hyperactivity 32 weeks after irradiation. Regulatory changes in the high dose group included decreased growth rate and decreased urine osmolalities, but these measures were extremely variable among animals. Morphological results demonstrated that 30 Gy irradiated animals showed extensive necrosis primarily in the fimbria, which extended into the internal capsule, optic nerve, hippocampus, and thalamus. Hemorrhages were found in the hippocampus, thalamus, and fimbria. Defects in the blood-brain barrier also were evident by entry of intravascularly injected horseradish peroxidase into the parenchyma of the brain. Animals in the 30 Gy grafted group showed fewer behavioral changes and less brain damage than their sham grafted counterparts. Specifically, activity measures were comparable to normal levels, and a dilute urine was not found in the 30 Gy implanted rats. Morphological changes support these behavioral results since only two 30 Gy implanted rats showed necrosis

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.

Acute hyperammonemia and systemic inflammation is associated with increased extracellular brain adenosine in rats

DEFF Research Database (Denmark)

Bjerring, Peter Nissen; Dale, Nicholas; Larsen, Fin Stolze

2015-01-01

) and cerebral blood flow (CBF). We measured the adenosine concentration with biosensors in rat brain slices exposed to ammonia and in a rat model with hyperammonemia and systemic inflammation. Exposure to ammonia in concentrations from 0.15-10 mM led to increases in the cortical adenosine concentration up to 18......Acute liver failure (ALF) can lead to brain edema, cerebral hyperperfusion and intracranial hypertension. These complications are thought to be mediated by hyperammonemia and inflammation leading to altered brain metabolism. As increased levels of adenosine degradation products have been found...... in brain tissue of patients with ALF we investigated whether hyperammonemia could induce adenosine release in brain tissue. Since adenosine is a potent vasodilator and modulator of cerebral metabolism we furthermore studied the effect of adenosine receptor ligands on intracranial pressure (ICP...

An HPLC tracing of the enhancer regulation in selected discrete brain areas of food-deprived rats.

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Miklya, I; Knoll, B; Knoll, J

2003-05-09

The recent discovery of the enhancer regulation in the mammalian brain brought a different perspective to the brain-organized realization of goal-oriented behavior, which is the quintessence of plastic behavioral descriptions such as drive or motivation. According to this new approach, 'drive' means that special endogenous enhancer substances enhance the impulse-propagation-mediated release of transmitters in a proper population of enhancer-sensitive neurons, and keep these neurons in the state of enhanced excitability until the goal is reached. However, to reach any goal needs the participation of the catecholaminergic machinery, the engine of the brain. We developed a method to detect the specific enhancer effect of synthetic enhancer substances [(-)-deprenyl, (-)-PPAP, (-)-BPAP] by measuring the release of transmitters from freshly isolated selected discrete brain areas (striatum, substantia nigra, tuberculum olfactorium, locus coeruleus, raphe) by the aid of HPLC with electrochemical detection. To test the validity of the working hypothesis that in any form of goal-seeking behavior the catecholaminergic and serotonergic neurons work on a higher activity level, we compared the amount of norepinephrine, dopamine, and serotonin released from selected discrete brain areas isolated from the brain of sated and food-deprived rats. Rats were deprived of food for 48 and 72 hours, respectively, and the state of excitability of their catecholaminergic and serotonergic neurons in comparison to that of sated rats was measured. We tested the orienting-searching reflex activity of the rats in a special open field, isolated thereafter selected discrete brain areas and measured the release of norepinephrine, dopamine, and serotonin from the proper tissue samples into the organ bath. The orienting-searching reflex activity of the rats increased proportionally to the time elapsed from the last feed and the amount of dopamine released from the striatum, substantia nigra and

A novel rat genomic simple repeat DNA with RNA-homology shows triplex (H-DNA)-like structure and tissue-specific RNA expression

International Nuclear Information System (INIS)

Dey, Indranil; Rath, Pramod C.

2005-01-01

Mammalian genome contains a wide variety of repetitive DNA sequences of relatively unknown function. We report a novel 227 bp simple repeat DNA (3.3 DNA) with a d {(GA) 7 A (AG) 7 } dinucleotide mirror repeat from the rat (Rattus norvegicus) genome. 3.3 DNA showed 75-85% homology with several eukaryotic mRNAs due to (GA/CU) n dinucleotide repeats by nBlast search and a dispersed distribution in the rat genome by Southern blot hybridization with [ 32 P]3.3 DNA. The d {(GA) 7 A (AG) 7 } mirror repeat formed a triplex (H-DNA)-like structure in vitro. Two large RNAs of 9.1 and 7.5 kb were detected by [ 32 P]3.3 DNA in rat brain by Northern blot hybridization indicating expression of such simple sequence repeats at RNA level in vivo. Further, several cDNAs were isolated from a rat cDNA library by [ 32 P]3.3 DNA probe. Three such cDNAs showed tissue-specific RNA expression in rat. pRT 4.1 cDNA showed strong expression of a 2.39 kb RNA in brain and spleen, pRT 5.5 cDNA showed strong expression of a 2.8 kb RNA in brain and a 3.9 kb RNA in lungs, and pRT 11.4 cDNA showed weak expression of a 2.4 kb RNA in lungs. Thus, genomic simple sequence repeats containing d (GA/CT) n dinucleotides are transcriptionally expressed and regulated in rat tissues. Such d (GA/CT) n dinucleotide repeats may form structural elements (e.g., triplex) which may be sites for functional regulation of genomic coding sequences as well as RNAs. This may be a general function of such transcriptionally active simple sequence repeats widely dispersed in mammalian genome

Impact of prenatal antimicrobial treatment on fetal brain damage due to autogenous fecal peritonitis in Wistar rats: A Histomorphometric Study

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Neylane Gadelha

2017-10-01

Full Text Available Purpose: To investigate brain neuronal density in newborn rats whose mothers were subjected to fecal peritonitis and compare findings between rats born to mothers treated and not treated with antimicrobials. Methods: Peritonitis was induced with a 10% fecal suspension (4mL/kg in 2 pregnant rats. Of these, 1 received antimicrobial treatment 24 hours after peritonitis induction: moxifloxacin and dexamethasone plus 2 mL of the inner bark of the Schinus terebinthifolius raddi extract. One pregnant rat underwent no intervention and served as a control. Results: The newborn brains of rats born to mothers with fecal peritonitis were significantly smaller and of less firm consistency. Brain neuronal density was lower in the untreated group than in the control and treated groups (P<0.01. Conclusions: Untreated peritonitis caused brain damage in the offspring, which was averted by effective early antimicrobial treatment. This approach may provide an early avenue for translation of such therapy in humans. Keywords: peritonitis, brain injuries, rats

Experimental study of Gadofluorine M enhancement in early diagnosis of radiation brain injury by MRI in rats

International Nuclear Information System (INIS)

Bai Shoumin; Liao Chengde; Guo Ruomi; Huang Ying; Liang Biling; Shen Jun; Lu Taixiang

2011-01-01

Objective: To explore the value of Gadofluorine M, a novel MRI enhancement agent,in the diagnosis the early radiation brain injury. Methods: Seventy-two Wistar rats were randomly divided into 5 equal groups. To establish the radiation injury model, the rat's posterior brain was irradiated with 0 (blank controls), 25, 35, 45, 55, and 65 Gy, respectively. After irradiation MR plain scanning and Gadofluorine M enhancement scanning (after the T1WI and T2WI scanning Gf at the dosage of 0.1 mmol/kg was injected intravenously and scanning was performed again 12 h later) were performed once a week for 8 weeks. Another 12 rats were randomly divided into 2 equal groups to exposure to 55 and 65 Gy, respectively, and MR scanning was performed once a week for 8 weeks since the third week after MR. After T1WI and T2WI scanning Gd-DTPA was injected intravenously, MR was conducted again 30 min later, and Gf was injected intravenously (Gd-DTPA enhancement and Gf enhancement contrast). The MR image and the pixel count were compared. Since the third week 2 rats from the Gf enhancement scanning group and 1 rat from the Gd-DTPA enhancement and Gf enhancement contrast were killed after MR with their brains taken out to undergo pathological examination. Results: No abnormal signal changes were found in MRI in 25 and 35 Gy groups within 2 months after irradiation. A high signal in the Gf enhancement T1WI image was found in 45, 55, and 65 Gy groups within the period of 4-6 weeks after radiation. The signal intensity was significantly higher than that of the control, 25, and 35 Gy groups (F=2.15, P<0.05). The emerge time of this signal was negatively correlated with the dose of radiation (r =-0.62, P<0.05). When there was no obvious change was found by Gd-DTPA enhancement, a high signal representing change of injury could be found in Gf enhancement in the same rat. The signal intensity was significantly enhanced in Gf enhancement compared to the Gd-DTPA enhancement (F=2.74, P<0

Effect of aging on phosphate metabolites of rat brain as revealed by the in vivo and in vitro 31P NMR measurements

International Nuclear Information System (INIS)

Liu, Hsiuchih; Chi, Chinwen; Liu, Tsungyun; Liu, Lianghui; Luh, Wenming; Hsieh, Changhuain; Wu, Wenguey

1991-01-01

Changes of phosphate metabolism in brains of neonate, weaning and adult rats were compared using both in vivo and in vitro nuclear magnetic resonance spectra. Ratios of phosphocreatine/nucleoside triphosphate (PCr/NTP) were the same in neonatal brain in both in vivo and in vitro studies, but not in weaning and adult brains. This discrepancy may have resulted from extended cerebral hypoxia due to slowed freezing of the brain by the increased skull thickness and brain mass in the weaning and adult rats. Variations of in vitro extraction condition for this age-related study may lead to systematic errors in the adult rats. Nevertheless, the phosphomonoester/nucleoside triphosphate (PME/NTP) ratios in extracts of brain from neonatal rats were higher than those obtained in vivo. In addition, the glycerophosphorylethanolamine plus glycerophosphorylcholine/nucleoside triphosphate (GPE+GPC/NTP) ratios, which were not measurable in vivo, showed age-dependent increase in extracts of rat brain. Some of the phosphomonoester and phosphodiester molecules in rat brain may be undetectable in in vivo NMR analysis because of their interaction with cellular components. The total in vitro GPE and GPC concentration in brain from neonatal rat was estimated to be 0.34 mmole/g wet tissue

Effect of 60Co-irradiation on normal and low protein diet fed rat brain

International Nuclear Information System (INIS)

Hasan, S.S.; Habibullah, M.

1980-01-01

The effect of whole-body irradiation (Co-60) on the brain tissue in Holtzmann strain adult male rats was studied. Two doses of irradiation (450 R,950 R) were tried on animals which were fed on normal as well as low protein diets over a period of 10 generations. In the normal rats, 450 R initially caused a lowered total protein. DNA and RNA content in the brain. After 7 days a tendency towards normalcy was observed. In the 950 R irradiated normal rats the diminution of protein content appeared irreversible. In malnourished 450 R irradiated rats, the protein content rose less steeply over the 7 days of observation. A higher dose of 950 R enhanced this effect on protein and also lowered the DNA content on day 5. The RNA content in the 950 R group with malnutrition showed a marked increase towards or beyond control perhaps as an expression of uncoupled feedback control. The paper gives evidence that protein deficiency may interfere with cellular regeneration in irradiated brain. (orig.) [de

Melanin-concentrating hormone: unique peptide neuronal systems in the rat brain and pituitary gland

International Nuclear Information System (INIS)

Zamir, N.; Skofitsch, G.; Bannon, M.J.; Jacobowitz, D.M.

1986-01-01

A unique neuronal system was detected in the rat central nervous system by immunohistochemistry and radioimmunoassay with antibodies to salmon melanin-concentrating hormone (MCH). MCH-like immunoreactive (MCH-LI) cell bodies were confined to the hypothalamus. MCH-LI fibers were found throughout the brain but were most prevalent in hypothalamus, mesencephalon, and pons-medulla regions. High concentrations of MCH-LI were measured in the hypothalamic medial forebrain bundle (MFB), posterior hypothalamic nucleus, and nucleus of the diagonal band. Reversed-phase high-performance liquid chromatography of MFB extracts from rat brain indicate that MCH-like peptide from the rat has a different retention time than that of the salmon MCH. An osmotic stimuls (2% NaCl as drinking water for 120 hr) caused a marked increase in MCH-LI concentrations in the lateral hypothalamus and neurointermediate lobe. The present studies establish the presence of MCH-like peptide in the rat brain. The MCH-LI neuronal system is well situated to coordinate complex functions such as regulation of water intake

Structural and functional effects of social isolation on the hippocampus of rats with traumatic brain injury.

Science.gov (United States)

Khodaie, Babak; Lotfinia, Ahmad Ali; Ahmadi, Milad; Lotfinia, Mahmoud; Jafarian, Maryam; Karimzadeh, Fariba; Coulon, Philippe; Gorji, Ali

2015-02-01

Social isolation has significant long-term psychological and physiological consequences. Both social isolation and traumatic brain injury (TBI) alter normal brain function and structure. However, the influence of social isolation on recovery from TBI is unclear. This study aims to evaluate if social isolation exacerbates the anatomical and functional deficits after TBI in young rats. Juvenile male rats were divided into four groups; sham operated control with social contacts, sham control with social isolation, TBI with social contacts, and TBI with social isolation. During four weeks after brain injury in juvenile rats, we evaluated the animal behaviors by T-maze and open-field tests, recorded brain activity with electrocorticograms and assessed structural changes by histological procedures in the hippocampal dentate gyrus, CA1, and CA3 areas. Our findings revealed significant memory impairments and hyperactivity conditions in rats with TBI and social isolation compared to the other groups. Histological assessments showed an increase of the mean number of dark neurons, apoptotic cells, and caspase-3 positive cells in all tested areas of the hippocampus in TBI rats with and without social isolation compared to sham rats. Furthermore, social isolation significantly increased the number of dark cells, apoptotic neurons, and caspase-3 positive cells in the hippocampal CA3 region in rats with TBI. This study indicates the harmful effect of social isolation on anatomical and functional deficits induced by TBI in juvenile rats. Prevention of social isolation may improve the outcome of TBI. Copyright © 2014 Elsevier B.V. All rights reserved.

Characterization of rat brain NCAM mRNA using DNA oligonucleotide probes

DEFF Research Database (Denmark)

Andersson, A M; Gaardsvoll, H; Giladi, E

1990-01-01

A number of different isoforms of the neural cell adhesion molecule (NCAM) have been identified. The difference between these is due to alternative splicing of a single NCAM gene. In rat brain NCAM mRNAs with sizes of 7.4, 6.7, 5.2, 4.3 and 2.9 kb have been reported. We have synthesized six DNA...... oligonucleotides, that hybridize to different exons in the NCAM gene. Furthermore we have constructed three oligonucleotides, that exclusively hybridize to mRNAs lacking certain exons, by letting them consist of sequences adjacent to both sides of the splice sites. By means of these probes we have characterized...... the five NCAM mRNAs in rat brain....

Synapses of the rat end brain in response to flight effects

International Nuclear Information System (INIS)

Antipov, V.V.; Tikhonchuk, V.S.; Ushakov, I.B.; Fedorov, V.P.

1988-01-01

Using electron microscopy, synapses of different structures of the rat end brain related to cognitive and motor acts (sensorimotor cortex, caudate nucleus) as well as memory and behavior (hippocampus) were examined. Rats were exposed to ionizing radiation, superhigh frequency, hypoxia, hyperoxia, vibration and acceleration (applied separately or in combination) which have been traditionally in the focus of space and aviation medicine. Brain internuronal junctions were found to be very sensitive to the above effects, particularly ionizing radiation and hypoxia. Conversely, synapses were shown to be highly resistant to short-term hyperoxia and electromagnetic radiation. When combined effects were used, response of interneuronal junctions depended on the irradiation dose and order of application of radiation and other flight factors

Changes in Rat Brain Tissue Microstructure and Stiffness during the Development of Experimental Obstructive Hydrocephalus

Science.gov (United States)

Jugé, Lauriane; Pong, Alice C.; Bongers, Andre; Sinkus, Ralph; Bilston, Lynne E.; Cheng, Shaokoon

2016-01-01

Understanding neural injury in hydrocephalus and how the brain changes during the course of the disease in-vivo remain unclear. This study describes brain deformation, microstructural and mechanical properties changes during obstructive hydrocephalus development in a rat model using multimodal magnetic resonance (MR) imaging. Hydrocephalus was induced in eight Sprague-Dawley rats (4 weeks old) by injecting a kaolin suspension into the cisterna magna. Six sham-injected rats were used as controls. MR imaging (9.4T, Bruker) was performed 1 day before, and at 3, 7 and 16 days post injection. T2-weighted MR images were collected to quantify brain deformation. MR elastography was used to measure brain stiffness, and diffusion tensor imaging (DTI) was conducted to observe brain tissue microstructure. Results showed that the enlargement of the ventricular system was associated with a decrease in the cortical gray matter thickness and caudate-putamen cross-sectional area (P hydrocephalus development, increased space between the white matter tracts was observed in the CC+PVWM (P hydrocephalus development. PMID:26848844

Effects of tetrahydrocannabinol on glucose uptake in the rat brain.

Science.gov (United States)

Miederer, I; Uebbing, K; Röhrich, J; Maus, S; Bausbacher, N; Krauter, K; Weyer-Elberich, V; Lutz, B; Schreckenberger, M; Urban, R

2017-05-01

Δ 9 -Tetrahydrocannabinol (THC) is the psychoactive component of the plant Cannabis sativa and acts as a partial agonist at cannabinoid type 1 and type 2 receptors in the brain. The goal of this study was to assess the effect of THC on the cerebral glucose uptake in the rat brain. 21 male Sprague Dawley rats (12-13 w) were examined and received five different doses of THC ranging from 0.01 to 1 mg/kg. For data acquisition a Focus 120 small animal PET scanner was used and 24.1-28.0 MBq of [ 18 F]-fluoro-2-deoxy-d-glucose were injected. The data were acquired for 70 min and arterial blood samples were collected throughout the scan. THC, THC-OH and THC-COOH were determined at 55 min p.i. Nine volumes of interest were defined, and the cerebral glucose uptake was calculated for each brain region. Low blood THC levels of glucose uptake (6-30 %), particularly in the hypothalamus (p = 0.007), while blood THC levels > 10 ng/ml (injected dose: ≥ 0.05 mg/kg) coincided with a decreased glucose uptake (-2 to -22 %), especially in the cerebellar cortex (p = 0.008). The effective concentration in this region was estimated 2.4 ng/ml. This glucose PET study showed that stimulation of CB1 receptors by THC affects the glucose uptake in the rat brain, whereby the effect of THC is regionally different and dependent on dose - an effect that may be of relevance in behavioural studies. Copyright © 2017 Elsevier Ltd. All rights reserved.

The different effects of lithium and tamoxifen on memory formation and the levels of neurotrophic factors in the brain of male and female rats.

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Valvassori, Samira S; Borges, Cenita P; Varela, Roger B; Bavaresco, Daniela V; Bianchini, Guilherme; Mariot, Edemilson; Arent, Camila O; Resende, Wilson R; Budni, Josiane; Quevedo, João

2017-09-01

Lithium (Li) is a mood-stabilizing drug used in the treatment of bipolar disorder (BD). Recently, preclinical studies have demonstrated the potential of tamoxifen (TMX) in the treatment of acute episodes of BD. However, the prolonged use of TMX for mood disorders treatment is controversial. In this study, we evaluated the effects of TMX or Li on cognitive behavior, as well as the levels of neurotrophic factors in the brain of male and female rats. Male and female Wistar rats received administrations of water (control group), TMX or Li via gavage for a period of 28days; the rats were then subjected to the open-field test (to evaluate spontaneous locomotion), and the novel object recognition and step-down inhibitory avoidance tests (to evaluate cognition). The levels of NGF, BDNF and GDNF were evaluated in the hippocampus and frontal cortex of the subject rats. No significant differences were observed in the open-field and inhibitory avoidance tests after drug administration in either the male or female rats. The administration of TMX, but not Li, decreased the recognition index of both the male and female rats in the object recognition test. The chronic administration of TMX decreased, whereas Li increased the levels of BDNF in the hippocampus of both the male and female rats. Tamoxifen decreased the levels of NGF in the hippocampus of female rats. In conclusion, it can be suggested that long-term treatments with TMX can lead to significant cognitive impairments by reducing the levels of neurotrophic factors in the brain of rats. Copyright © 2017. Published by Elsevier Inc.

Dietary guanidinoacetic acid does not accumulate in the brain of healthy men

DEFF Research Database (Denmark)

Ostojic, Sergej M.; Ostojic, Jelena

2018-01-01

analyzed for brain GAA and glutamate concentrations using TARQUIN 4.3.10 software. Brain GAA levels remained essentially unchanged at follow-up (an increase of 7.7% from baseline levels; 95% confidence interval, - 24.1% to 39.5%; P = 0.88) when averaged across 12 white and grey matter voxel locations......We conducted a secondary analysis of a previously completed trial to determine the effects of 8-week guanidinoacetic acid (GAA) loading on brain GAA levels in five healthy men. Brain magnetic resonance spectroscopy (1H-MRS) was taken at baseline and post-administration, with spectra additionally....... No significant changes were found for brain glutamate levels during the study (P = 0.64). Supplemental GAA appears to be safe intervention concerning brain GAA deposition, at least with GAA dosages used....

Amphetamine in rat brain after intraperitoneal injection of N-alkylated analogues.

Science.gov (United States)

Nazarali, A J; Baker, G B; Coutts, R T; Pasutto, F M

1983-01-01

Three N-alkylated analogues of amphetamine were administered intraperitoneally to male Sprague-Dawley rats and whole brain levels of amphetamine (AM) and the N-alkyl analogue were determined one hour after injection of the N-alkylated compounds. The drugs administered were the N-2-cyanoethyl-(I) (fenproporex), the N-3-chloropropyl-(II) (mefenorex) and the N-n-propyl-(III) derivatives of AM: the first two of these are used clinically as anorexiants, and the latter has been used extensively to study aspects of metabolism of AM-like compounds. Analysis of AM, I, II and III was performed using electron-capture gas chromatography with a capillary column after reaction of compounds with pentafluorobenzoyl chloride under aqueous conditions. In a second comparative study, equimolar doses (0.05 mMole/kg) of I or AM were administered intraperitoneally to the rats and brain levels determined after one hour. Results indicate extensive N-dealkylation occurs for compounds I, II and III in the rat.

Brain SERT Expression of Male Rats Is Reduced by Aging and Increased by Testosterone Restitution

Directory of Open Access Journals (Sweden)

José Jaime Herrera-Pérez

2013-01-01

Full Text Available In preclinical and clinical studies aging has been associated with a deteriorated response to antidepressant treatment. We hypothesize that such impairment is explained by an age-related decrease in brain serotonin transporter (SERT expression associated with low testosterone (T levels. The objectives of this study were to establish (1 if brain SERT expression is reduced by aging and (2 if the SERT expression in middle-aged rats is increased by T-restitution. Intact young rats (3–5 months and gonad-intact middle-aged rats with or without T-restitution were used. The identification of the brain SERT expression was done by immunofluorescence in prefrontal cortex, lateral septum, hippocampus, and raphe nuclei. An age-dependent reduction of SERT expression was observed in all brain regions examined, while T-restitution recovered the SERT expression only in the dorsal raphe of middle-aged rats. This last action seems relevant since dorsal raphe plays an important role in the antidepressant action of selective serotonin reuptake inhibitors. All data suggest that this mechanism accounts for the T-replacement usefulness to improve the response to antidepressants in the aged population.

Protective effects of edaravone on the radiation response of oligodendrocyte in rats following whole brain irradiation

International Nuclear Information System (INIS)

Chen Yingzhu; Tian Ye; Bao Shiyao; Bao Huan; Zhan Zhilin

2007-01-01

Objective: To investigate the changes of the oligodendrocyte lineage cells in the cortex following whole brain irradiation and the effects of the neotype free radical scavenger, edaravone on radiation response of oligodendrocyte in rats. Methods: 120 male Sprague Dawley rats were randomly divided into sham- irradiation group, irradiation group and edaravone group. The model of whole-brain irradiation was established with exposure of the whole brain of the rats to 4 MeV X-rays with a single-dose of 10 Gy. The rats were injected intraperitoneally with edaravone at 0.3, 1.0 and 3.0 mg/kg. Tissue microarray of irradiation-induced brain injury in rats was constructed. The expression of A2BS, oligodendrocyte market 4(O4) and 2', 3'-cyclic nucleotide 3'- phosphodiesterase (CNPase) in the cortex was examined by tissue microarray technology and immunohistochemistry. The positive cells were counted. Results: Compared with the sham-irradiation group, the number of A2BS-positive cells increased and the number of O4, CNPase-positive cells decreased significantly at certain time in the irradiation group(P<0.05). Compared with irradiation group, A2BS-positive cells decreased significantly after edaravone treatment, while O4-positive cells and CNPase-positive cells increased significantly (P<0.05, or P<0.01). Conclusions: The number of oligodendrocyte precursor cells in the cortex of rats increased reactively following whole brain irradiation and changed with time. Edaravone played a protective role in oligodendrocyte ischemic reaction in a dose-dependent manner. (authors)

Protective effects of edaravone on the radiation response of oligodendrocyte in rats following whole brain irradiation

Energy Technology Data Exchange (ETDEWEB)

Yingzhu, Chen; Ye, Tian; Shiyao, Bao; Huan, Bao; Zhilin, Zhan [The Second Affiliated Hospital of Suzhou Univ., Suzhou (China)

2007-08-15

Objective: To investigate the changes of the oligodendrocyte lineage cells in the cortex following whole brain irradiation and the effects of the neotype free radical scavenger, edaravone on radiation response of oligodendrocyte in rats. Methods: 120 male Sprague Dawley rats were randomly divided into sham- irradiation group, irradiation group and edaravone group. The model of whole-brain irradiation was established with exposure of the whole brain of the rats to 4 MeV X-rays with a single-dose of 10 Gy. The rats were injected intraperitoneally with edaravone at 0.3, 1.0 and 3.0 mg/kg. Tissue microarray of irradiation-induced brain injury in rats was constructed. The expression of A2BS, oligodendrocyte market 4(O4) and 2', 3'-cyclic nucleotide 3'- phosphodiesterase (CNPase) in the cortex was examined by tissue microarray technology and immunohistochemistry. The positive cells were counted. Results: Compared with the sham-irradiation group, the number of A2BS-positive cells increased and the number of O4, CNPase-positive cells decreased significantly at certain time in the irradiation group(P<0.05). Compared with irradiation group, A2BS-positive cells decreased significantly after edaravone treatment, while O4-positive cells and CNPase-positive cells increased significantly (P<0.05, or P<0.01). Conclusions: The number of oligodendrocyte precursor cells in the cortex of rats increased reactively following whole brain irradiation and changed with time. Edaravone played a protective role in oligodendrocyte ischemic reaction in a dose-dependent manner. (authors)

[Measurement of the blood flow in various areas of the rat brain by means of microspheres].

Science.gov (United States)

Deroo, J; Gerber, G B

1976-01-01

A method is described to measure regional blood flow in different structures of the rat brain. Microspheres (15 micron) are injected, the brain is sectioned, stained for myeline, radioautographs are prepared and the microspheres in the different structures are counted. The values obtained for different brain structures are counted. The values obtained for different brain regions (cortex, corpus callosum, thalamus hipocampus, hypothalamic region, colliculi, cerebellum, pons, medulla) compare well with those published by others on larger animals. In rats fed 1% of lead from birth, higher blood flow is found in the cortex and a lower one in the interior part of the brain compared to controls.

Distribution of kappa opioid receptors in the brain of young and old male rats

International Nuclear Information System (INIS)

Maggi, R.; Limonta, P.; Dondi, D.; Martini, L.; Piva, F.

1989-01-01

The experiments to be described have been designed in order to: (a) provide new information on the concentrations of opioid kappa receptors in different regions of the brain of the male rats; and (b) to analyze whether the density of brain kappa receptors might be modified by the process of aging. The concentration of kappa receptors was investigated in the hypothalamus, amygdala, mesencephalon, corpus striatum, hippocampus, thalamus, frontal poles, anterior and posterior cortex collected from male rats of 2 and 19 months of age. 3 H-bremazocine (BRZ) was used as the ligand of kappa receptors, after protection of mu and delta receptors respectively with dihydromorphine and d-ala-d-leu-enkephalin. The results obtained show that: (1) in young male rats, the number of kappa opioid receptors is different in the various brain areas examined. (2) Aging exerts little influence on the number of kappa receptors in the majority of the brain structures considered. However in the amygdala and in the thalamus the number of kappa receptors was increased in old animals

Differences in postmortem stability of sex steroid receptor immunoreactivity in rat brain

NARCIS (Netherlands)

Fodor, Mariann; van Leeuwen, Fred W.; Swaab, Dick F.

2002-01-01

Difficulties in demonstrating sex steroid receptors in the human brain by immunohistochemistry (IHC) may depend on postmortem delay and a long fixation time. The effect of different postmortem times was therefore studied in rat brain kept in the skull at room temperature for 0, 6, or 24 hr after

Morphology of subcortical brain nuclei is associated with autonomic function in healthy humans.

Science.gov (United States)

Ruffle, James K; Coen, Steven J; Giampietro, Vincent; Williams, Steven C R; Apkarian, A Vania; Farmer, Adam D; Aziz, Qasim

2018-01-01

The autonomic nervous system (ANS) is a brain body interface which serves to maintain homeostasis by influencing a plethora of physiological processes, including metabolism, cardiorespiratory regulation and nociception. Accumulating evidence suggests that ANS function is disturbed in numerous prevalent clinical disorders, including irritable bowel syndrome and fibromyalgia. While the brain is a central hub for regulating autonomic function, the association between resting autonomic activity and subcortical morphology has not been comprehensively studied and thus was our aim. In 27 healthy subjects [14 male and 13 female; mean age 30 years (range 22-53 years)], we quantified resting ANS function using validated indices of cardiac sympathetic index (CSI) and parasympathetic cardiac vagal tone (CVT). High resolution structural magnetic resonance imaging scans were acquired, and differences in subcortical nuclei shape, that is, 'deformation', contingent on resting ANS activity were investigated. CSI positively correlated with outward deformation of the brainstem, right nucleus accumbens, right amygdala and bilateral pallidum (all thresholded to corrected P right amygdala and pallidum (all thresholded to corrected P Left and right putamen volume positively correlated with CVT (r = 0.62, P = 0.0047 and r = 0.59, P = 0.008, respectively), as did the brainstem (r = 0.46, P = 0.049). These data provide novel evidence that resting autonomic state is associated with differences in the shape and volume of subcortical nuclei. Thus, subcortical morphological brain differences in various disorders may partly be attributable to perturbation in autonomic function. Further work is warranted to investigate these findings in clinical populations. Hum Brain Mapp 39:381-392, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Identification of a third form of NaK-ATPase catalytic subunit in rat brain by photoaffinity labeling

International Nuclear Information System (INIS)

Lowndes, J.M.; Millan, N.M.; Ruoho, A.E.; Hokin-Neaverson, M.

1987-01-01

Using photoaffinity labeling, they have found a form of the NaK-ATPase catalytic subunit, α(-), in the rat brain that is distinct from the α and α(+) forms. Strong radiolabeling of α(-) was obtained with [ 125 I]azido-iodophenethylamido-succinyl-cymarin (AISC). AISC is a new cardiotonic steroid photolabel which they have synthesized and characterized chemically and biochemically. This compound labels α(-) better than the photolabels that they have previously reported. SDS-PAGE (5%) of photolabeled rat brain microsomes showed that α(-) migrated with faster mobility than the dog kidney α subunit. The α(-) appears to have different specificity for different cardiotonic steroids than either α(+) or α. The radiolabeling of rat brain α(+) and dog kidney α with [ 125 I]AISC was protectable by ouabain; in contrast, 1 mM ouabain did not reduce the [ 125 I]AISC-labeling of α(-), although the labeling was protected with 200 μM cymarin or AISC. The results indicate that the α(-) form of the NaK-ATPase in rat brain binds cymarin and its derivative but has little affinity for ouabain. It is possible that α(-) may be the translation product of the rat brain α(III) mRNA which has recently been described

The neuroprotective effects of intramuscular insulin-like growth factor-I treatment in brain ischemic rats.

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Heng-Chih Chang

Full Text Available Brain ischemia leads to muscle inactivity-induced atrophy and may exacerbate motor function deficits. Intramuscular insulin-like growth factor I (IGF-I injection has been shown to alleviate the brain ischemia-induced muscle atrophy and thus improve the motor function. Motor function is normally gauged by the integrity and coordination of the central nervous system and peripheral muscles. Whether brain ischemic regions are adaptively changed by the intramuscular IGF-I injection is not well understood. In this study, the effect of intramuscular IGF-I injection was examined on the central nervous system of brain ischemic rats. Rats were divided into 4 groups: sham control, brain ischemia control, brain ischemia with IGF-I treatment, and brain ischemia with IGF-I plus IGF-I receptor inhibitor treatment. Brain ischemia was induced by right middle cerebral artery occlusion. IGF-I and an IGF-1 receptor inhibitor were injected into the affected calf and anterior tibialis muscles of the treated rats for 4 times. There was an interval of 2 days between each injection. Motor function was examined and measured at the 24 hours and 7 days following a brain ischemia. The affected hind-limb muscles, sciatic nerve, lumbar spinal cord, and motor cortex were collected for examination after euthanizing the rats. IGF-I expression in the central nervous system and affected muscles were significantly decreased after brain ischemia. Intramuscular IGF-I injection increased the IGF-I expression in the affected muscles, sciatic nerve, lumbar spinal cord, and motor cortex. It also increased the p-Akt expression in the affected motor cortex. Furthermore, intramuscular IGF-I injection decreased the neuronal apoptosis and improved the motor function. However, co-administration of the IGF-I receptor inhibitor eliminated these effects. Intramuscular IGF-I injection after brain ischemia attenuated or reversed the decrease of IGF-I in both central and peripheral tissues, and

Study on developing brain damage of neonatal rats induced by enriched uranium

International Nuclear Information System (INIS)

Gu Guixiong; Zhu Shoupeng; Yang Shuqin

2000-01-01

Objective: The injurious effects of enriched uranium 235 U on developing brain of neonatal Wistar pure bred rats were studied. Methods: The model of irradiation induced brain damage in vivo was settled. The effects of cerebrum exposure by 235 U on somatic growth and neuro-behavior development of neonatal rats were examined by thirteen index determination of multiple parameters. The dynamic retention of autoradiographic tracks of 235 U in cells of developing brain was observed. The changes of NSE, IL-1β, SOD, and ET in cerebral cortex, hippocampus, diencephalon, cerebellum after expose to 235 U were examined with radioimmunoassay. Results: The somatic growth such as increase of body weight and brain weight was lower significantly. The retardation of development was found such as eye opening, sensuous function as auditory startle, movement and coordination function and activity as swimming, physiological reflexes as negative geotaxis, surface righting, grasping reflex suspension and the tendency behavior. The data showed delayed growth and abnormal neuro-behavior. The micro-autoradiographic tracing showed that the tracks of 235 U were mainly accumulated in the nucleus of developing brain. At the same time only few tracks appeared in the cytoplasm and interval between cells. Experimental study showed that when the dose of 235 U irradiation was increased, the level of NSE was decreased and the IL-1β was increased. However, the results indicated that SOD and ET can be elevated by the low dose irradiation of 235 U, and can be inhibited by the high dose. Conclusion: The behavior of internal irradiation from 235 U on the developing brain damage of neonatal rats were of sensibility and compensation in nervous cells

Novel G Protein-Coupled Oestrogen Receptor GPR30 Shows Changes in mRNA Expression in the Rat Brain over the Oestrous Cycle

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Emma J. Spary

2012-02-01

Full Text Available Oestrogen influences autonomic function via actions at classical nuclear oestrogen receptors α and β in the brain, and recent evidence suggests the orphan G protein-coupled receptor GPR30 may also function as a cytoplasmic oestrogen receptor. We investigated the expression of GPR30 in female rat brains throughout the oestrous cycle and after ovariectomy to determine whether GPR30 expression in central autonomic nuclei is correlated with circulating oestrogen levels. In the nucleus of the solitary tract (NTS, ventrolateral medulla (VLM and periaqueductal gray (PAG GPR30 mRNA, quantified by real-time PCR, was increased in proestrus and oestrus. In ovariectomised (OVX rats, expression in NTS and VLM appeared increased compared to metoestrus, but in the hypothalamic paraventricular nucleus and PAG lower mRNA levels were seen in OVX. GPR30-like immunoreactivity (GPR30-LI colocalised with Golgi in neurones in many brain areas associated with autonomic pathways, and analysis of numbers of immunoreactive neurones showed differences consistent with the PCR data. GPR30-LI was found in a variety of transmitter phenotypes, including cholinergic, serotonergic, catecholaminergic and nitrergic neurones in different neuronal groups. These observations support the view that GPR30 could act as a rapid transducer responding to oestrogen levels and thus modulate the activity of central autonomic pathways.

Assessment of social behavior directed toward sick partners and its relation to central cytokine expression in rats.

Science.gov (United States)

Hamasato, Eduardo Kenji; Lovelock, Dennis; Palermo-Neto, João; Deak, Terrence

2017-12-01

Acute illness not only reduces the expression of social behavior by sick rodents, but can also lead to avoidance responses when detected by healthy, would-be social partners. When healthy animals interact with a sick partner, an intriguing question arises: does exposure to a sick conspecific elicit an anticipatory immune response that would facilitate defense against future infection? To address this question, healthy adult male Sprague-Dawley rats (N=64) were given a brief social interaction (30min) with a partner that was either sick (250μg/kg injection with lipopolysaccharide [LPS] 3h prior to test) or healthy (sterile saline injection). During this exposure, social behavior directed toward the healthy or sick conspecific was measured. Additionally, the impact of housing condition was assessed, with rats group- or isolate-housed. Immediately after social interaction, brains were harvested for cytokine assessments within socially-relevant brain structures (olfactory bulb, amygdala, hippocampus and PVN). As expected, behavioral results demonstrated that (i) there was a robust suppression of social interaction directed against sick conspecifics; and (ii) isolate-housing generally increased social behavior. Furthermore, examination of central cytokine expression in healthy experimental subjects revealed a modest increase in TNF-α in rats that interacted with a sick social partner, but only in the olfactory bulb. Among the LPS-injected partners, expected increases in IL-1β, IL-6, and TNF-α expression were observed across all brain sites. Moreover, IL-1β and IL-6 expression was exacerbated in LPS-injected partners that interacted with isolate-housed experimental subjects. Together, these data replicate and extend our prior work showing that healthy rats avoid sick conspecifics, and provide preliminary evidence for an anticipatory cytokine response when rats are exposed to a sick partner. These data also provide new evidence to suggest that recent housing history

Rat brain digital stereotaxic white matter atlas with fine tract delineation in Paxinos space and its automated applications in DTI data analysis.

Science.gov (United States)

Liang, Shengxiang; Wu, Shang; Huang, Qi; Duan, Shaofeng; Liu, Hua; Li, Yuxiao; Zhao, Shujun; Nie, Binbin; Shan, Baoci

2017-11-01

To automatically analyze diffusion tensor images of the rat brain via both voxel-based and ROI-based approaches, we constructed a new white matter atlas of the rat brain with fine tracts delineation in the Paxinos and Watson space. Unlike in previous studies, we constructed a digital atlas image from the latest edition of the Paxinos and Watson. This atlas contains 111 carefully delineated white matter fibers. A white matter network of rat brain based on anatomy was constructed by locating the intersection of all these tracts and recording the nuclei on the pathway of each white matter tract. Moreover, a compatible rat brain template from DTI images was created and standardized into the atlas space. To evaluate the automated application of the atlas in DTI data analysis, a group of rats with right-side middle cerebral artery occlusion (MCAO) and those without were enrolled in this study. The voxel-based analysis result shows that the brain region showing significant declines in signal in the MCAO rats was consistent with the occlusion position. We constructed a stereotaxic white matter atlas of the rat brain with fine tract delineation and a compatible template for the data analysis of DTI images of the rat brain. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of sublethal doses of gamma radiation on the developing rat brain

International Nuclear Information System (INIS)

Cerda, H.; Carlsson, J.; Larsson, B.; Saefwenberg, J.O.

1975-01-01

Newborn rats were irradiated with 60 Co gamma rays. Doses of 0, 80 or 160 rads were given to the whole body. The whole body and brain weights, DNA and RNA contents of the brain and 3 H-thymidine or 3 H-uridine incorporated by the brain were measured at 5, 10 or 15 days after birth. A dose of 160 rads produced clear alterations in the brain but no clear effects could be detected when 80 rads were given. (author)

Characteristics of novel polymer based on pseudo-polyamino acids GluLa-DPG-PEG600: binding of albumin, biocompatibility, biodistribution and potential crossing the blood-brain barrier in rats

Directory of Open Access Journals (Sweden)

B. O. Chekh

2017-08-01

Full Text Available The aim of our work was to study biological properties of the polymer based on pseudo-polyamino acids GluLa-DPG-PEG600, its ability to bind albumin, as well as its localization in rat body and influence on physio­logical and functional state of rat kidneys and liver. We have found the ability of GluLa-DPG-PEG600 to bind bovine serum albumin (BSA using electrophoresis in 5% polyacrylamide gel. Structural and functional state of the liver and kidneys of rats after injections of polymer were investigated by histological analysis of organs and determination the activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, gamma-glutamyltransferase and content of cholesterol and creatinine in blood. Our results showed little toxic effect of GluLa-DPG-PEG600 on rat body. Using fluorescent microscopy we have studied polymer in complex with BSA distribution in rat body: after intravenous injection polymer are localized in kidneys and spleen, and after intramuscular – in liver and brain. It has been shown that polymer passed through the blood-brain barrier and are localized in the immune organ – spleen, indicating GluLa-DPG-PEG600 as a potential drug transporter.

Does brain creatine content rely on exogenous creatine in healthy youth? A proof-of-principle study.

Science.gov (United States)

Merege-Filho, Carlos Alberto Abujabra; Otaduy, Maria Concepción Garcia; de Sá-Pinto, Ana Lúcia; de Oliveira, Maira Okada; de Souza Gonçalves, Lívia; Hayashi, Ana Paula Tanaka; Roschel, Hamilton; Pereira, Rosa Maria Rodrigues; Silva, Clovis Artur; Brucki, Sonia Maria Dozzi; da Costa Leite, Claudia; Gualano, Bruno

2017-02-01

It has been hypothesized that dietary creatine could influence cognitive performance by increasing brain creatine in developing individuals. This double-blind, randomized, placebo-controlled, proof-of-principle study aimed to investigate the effects of creatine supplementation on cognitive function and brain creatine content in healthy youth. The sample comprised 67 healthy participants aged 10 to 12 years. The participants were given creatine or placebo supplementation for 7 days. At baseline and after the intervention, participants undertook a battery of cognitive tests. In a random subsample of participants, brain creatine content was also assessed in the regions of left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe by proton magnetic resonance spectroscopy (1H-MRS) technique. The scores obtained from verbal learning and executive functions tests did not significantly differ between groups at baseline or after the intervention (all p > 0.05). Creatine content was not significantly different between groups in left dorsolateral prefrontal cortex, left hippocampus, and occipital lobe (all p > 0.05). In conclusion, a 7-day creatine supplementation protocol did not elicit improvements in brain creatine content or cognitive performance in healthy youth, suggesting that this population mainly relies on brain creatine synthesis rather than exogenous creatine intake to maintain brain creatine homeostasis.

Localisation of relaxin peptides in the brain: comparative mapping of relaxin-R2 and the novel relaxin-R3 gene expression

International Nuclear Information System (INIS)

Burazin, T.C.D.; Macris, M.; Gundlach, A.L.; Tregear, G.W.

2002-01-01

Full text: Relaxin is a peptide hormone with known actions in the female reproductive tract that has also been identified in brain. Until recently, only one relaxin gene has been described in the rat and mouse. However, we have recently identified a new member of the relaxin gene family, relaxin gene-3, expressed in human, mouse and rat. Using [ 35 S]-labelled oligonucleotide probes and in situ hybridisation histochemistry, the current studies describe the distribution of mRNA encoding rat relaxin gene-1 (R1) and rat relaxin gene-3 (R3) in the adult rat brain. R1 mRNA was detected in several regions including the anterior olfactory nucleus, tenia tecta, orbital, frontal and piriform cortices, and in lower abundance in the hippocampus. In contrast, highly abundant expression of R3 mRNA was more restricted being present in the pars ventromedialis subdivision of the dorsal tegmental nucleus (vmDTg), with some low level expression in the hippocampus. Autoradiographic visualisation of [ 33 P]-labelled human relaxin binding sites revealed the presence of putative relaxin receptors in the DTg centralis and vmDTg, as well as in several forebrain areas previously identified. Studies are currently underway to investigate the activity-dependent regulation and developmental expression of relaxin transcripts, including the possible co-localisation of R3 mRNA with neurotransmitters such as GABA and 5- HT, and other peptides. These studies are consistent with an important role for these novel relaxin peptides in the rat central nervous system. Copyright (2002) Australian Neuroscience Society

A quantitative magnetic resonance histology atlas of postnatal rat brain development with regional estimates of growth and variability.

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Calabrese, Evan; Badea, Alexandra; Watson, Charles; Johnson, G Allan

2013-05-01

There has been growing interest in the role of postnatal brain development in the etiology of several neurologic diseases. The rat has long been recognized as a powerful model system for studying neuropathology and the safety of pharmacologic treatments. However, the complex spatiotemporal changes that occur during rat neurodevelopment remain to be elucidated. This work establishes the first magnetic resonance histology (MRH) atlas of the developing rat brain, with an emphasis on quantitation. The atlas comprises five specimens at each of nine time points, imaged with eight distinct MR contrasts and segmented into 26 developmentally defined brain regions. The atlas was used to establish a timeline of morphometric changes and variability throughout neurodevelopment and represents a quantitative database of rat neurodevelopment for characterizing rat models of human neurologic disease. Published by Elsevier Inc.

Edaravone attenuates neuronal apoptosis in hypoxic-ischemic brain damage rat model via suppression of TRAIL signaling pathway.

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Li, Chunyi; Mo, Zhihuai; Lei, Junjie; Li, Huiqing; Fu, Ruying; Huang, Yanxia; Luo, Shijian; Zhang, Lei

2018-06-01

Edaravone is a new type of oxygen free radical scavenger and able to attenuate various brain damage including hypoxic-ischemic brain damage (HIBD). This study was aimed at investigating the neuroprotective mechanism of edaravone in rat hypoxic-ischemic brain damage model and its correlation with tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) signaling pathway. 75 seven-day-old Sprague-Dawley neonatal rats were equally divided into three groups: sham-operated group (sham), HIBD group and HIBD rats injected with edaravone (HIBD + EDA) group. Neurological severity and space cognitive ability of rats in each group were evaluated using Longa neurological severity score and Morris water maze testing. TUNEL assay and flow cytometry were used to determine brain cell apoptosis. Western blot was used to estimate the expression level of death receptor-5 (DR5), Fas-associated protein with death domain (FADD), caspase 8, B-cell lymphoma-2 (Bcl-2) and Bcl-2 associated X protein (Bax). In addition, immunofluorescence was performed to detect caspase 3. Edaravone reduced neurofunctional damage caused by HIBD and improved the cognitive capability of rats. The above experiment results suggested that edaravone could down-regulate the expression of active caspase 3 protein, thereby relieving neuronal apoptosis. Taken together, edaravone could attenuate neuronal apoptosis in rat hypoxic-ischemic brain damage model via suppression of TRAIL signaling pathway, which also suggested that edaravone might be an effective therapeutic strategy for HIBD clinical treatment. Copyright © 2018 Elsevier Ltd. All rights reserved.

Dynamic Multi-Coil Technique (DYNAMITE) Shimming of the Rat Brain at 11.7 Tesla

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Juchem, Christoph; Herman, Peter; Sanganahalli, Basavaraju G.; Brown, Peter B.; McIntyre, Scott; Nixon, Terence W.; Green, Dan; Hyder, Fahmeed; de Graaf, Robin A.

2014-01-01

The in vivo rat model is a workhorse in neuroscience research, preclinical studies and drug development. A repertoire of MR tools has been developed for its investigation, however, high levels of B0 magnetic field homogeneity are required for meaningful results. The homogenization of magnetic fields in the rat brain, i.e. shimming, is a difficult task due to a multitude of complex, susceptibility-induced field distortions. Conventional shimming with spherical harmonic (SH) functions is capable of compensating shallow field distortions in limited areas, e.g. in the cortex, but performs poorly in difficult-to-shim subcortical structures or for the entire brain. Based on the recently introduced multi-coil approach for magnetic field modeling, the DYNAmic Multi-coIl TEchnique (DYNAMITE) is introduced for magnetic field shimming of the in vivo rat brain and its benefits for gradient-echo echo-planar imaging (EPI) are demonstrated. An integrated multi-coil/radio-frequency (MC/RF) system comprising 48 individual localized DC coils for B0 shimming and a surface transceive RF coil has been developed that allows MR investigations of the anesthetized rat brain in vivo. DYNAMITE shimming with this MC/RF setup is shown to reduce the B0 standard deviation to a third of that achieved with current shim technology employing static first through third order SH shapes. The EPI signal over the rat brain increased by 31% and a 24% gain in usable EPI voxels could be realized. DYNAMITE shimming is expected to critically benefit a wide range of preclinical and neuroscientific MR research. Improved magnetic field homogeneity, along with the achievable large brain coverage of this method will be crucial when signal pathways, cortical circuitry or the brain’s default network are studied. Along with the efficiency gains of MC-based shimming compared to SH approaches demonstrated recently, DYNAMITE shimming has the potential to replace conventional SH shim systems in small bore animal

Protective role of Cynodon dactylon in ameliorating the aluminium-induced neurotoxicity in rat brain regions.

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Sumathi, Thangarajan; Shobana, Chandrasekar; Kumari, Balasubramanian Rathina; Nandhini, Devarajulu Nisha

2011-12-01

Cynodon dactylon (Poaceae) is a creeping grass used as a traditional ayurvedic medicine in India. Aluminium-induced neurotoxicity is well known and different salts of aluminium have been reported to accelerate damage to biomolecules like lipids, proteins and nucleic acids. The objective of the present study was to investigate whether the aqueous extract of C. dactylon (AECD) could potentially prevent aluminium-induced neurotoxicity in the cerebral cortex, hippocampus and cerebellum of the rat brain. Male albino rats were administered with AlCl(3) at a dose of 4.2 mg/kg/day i.p. for 4 weeks. Experimental rats were given C. dactylon extract in two different doses of 300 mg and 750 mg/keg/day orally 1 h prior to the AlCl(3) administration for 4 weeks. At the end of the experiments, antioxidant status and activities of ATPases in cerebral cortex, hippocampus and cerebellum of rat brain were measured. Aluminium administration significantly decreased the level of GSH and the activities of SOD, GPx, GST, Na(+)/K(+) ATPase, and Mg(2+) ATPase and increased the level of lipid peroxidation (LPO) in all the brain regions when compared with control rats. Pre-treatment with AECD at a dose of 750 mg/kg b.w increased the antioxidant status and activities of membrane-bound enzymes (Na(+)/K(+) ATPase and Mg(2+) ATPase) and also decreased the level of LPO significantly, when compared with aluminium-induced rats. The results of this study indicated that AECD has potential to protect the various brain regions from aluminium-induced neurotoxicity.

{sup 11}C-ORM-13070, a novel PET ligand for brain α{sub 2C}-adrenoceptors: radiometabolism, plasma pharmacokinetics, whole-body distribution and radiation dosimetry in healthy men

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Luoto, Pauliina; Oikonen, Vesa; Arponen, Eveliina; Helin, Semi; Virta, Jere; Virtanen, Kirsi; Roivainen, Anne [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Suilamo, Sami [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); Turku University Hospital, Department of Oncology and Radiotherapy, Turku (Finland); Herttuainen, Jukka; Hietamaeki, Johanna; Holopainen, Aila; Rouru, Juha; Sallinen, Jukka [Orion Pharma, Espoo and Turku (Finland); Kailajaervi, Marita [GE Healthcare, Turku Imanet, Turku (Finland); Peltonen, Juha M.; Scheinin, Mika; Volanen, Iina [University of Turku, CRST, Turku (Finland); Rinne, Juha O. [University of Turku and Turku University Hospital, Turku PET Centre, Turku (Finland); University of Turku, CRST, Turku (Finland); TYKSLAB, Unit of Clinical Pharmacology, Turku (Finland); University of Turku and Turku University Hospital, Division of Clinical Neurosciences, Turku (Finland)

2014-10-15

{sup 11}C-labelled 1-[(S)-1-(2,3-dihydrobenzo[1,2]dioxin-2-yl)methyl] -4-(3-methoxy-methylpyridin-2- yl)-piperazine ({sup 11}C-ORM-13070) is a novel PET tracer for imaging of α{sub 2C}-adrenoceptors in the human brain. Brain α{sub 2C}-adrenoceptors may be therapeutic targets in several neuropsychiatric disorders, including depression, schizophrenia and Alzheimer's disease. To validate the use of {sup 11}C-ORM-13070 in humans, we investigated its radiometabolism, pharmacokinetics, whole-body distribution and radiation dose. Radiometabolism was studied in a test-retest setting in six healthy men. After intravenous injection of {sup 11}C-ORM-13070, blood samples were drawn over 60 min. Plasma samples were analysed by radio-HPLC for intact tracer and its radioactive metabolites. Metabolite-corrected plasma time-activity curves were used for calculation of pharmacokinetics. In a separate group of 12 healthy men, the whole-body distribution of {sup 11}C-ORM-13070 and radiation exposure were investigated by dynamic PET/CT imaging without blood sampling. Two radioactive metabolites of {sup 11}C-ORM-13070 were detected in human arterial plasma. The proportion of unchanged {sup 11}C-ORM-13070 decreased from 81 ± 4 % of total radioactivity at 4 min after tracer injection to 23 ± 4 % at 60 min. At least one of the radioactive metabolites penetrated into red blood cells, while the parent tracer remained in plasma. The apparent elimination rate constant and corresponding half-life of unchanged {sup 11}C-ORM-13070 in arterial plasma were 0.0117 ± 0.0056 min{sup -1} and 73.6 ± 35.8 min, respectively. The organs with the highest absorbed doses were the liver (12 μSv/MBq), gallbladder wall (12 μSv/MBq) and pancreas (9.1 μSv/MBq). The mean effective dose was 3.9 μSv/MBq, with a range of 3.6 - 4.2 μSv/MBq. {sup 11}C-ORM-13070 was rapidly metabolized in human subjects after intravenous injection. The effective radiation dose of {sup 11}C-ORM-13070 was in the same range

Correlation among body height, intelligence, and brain gray matter volume in healthy children.

Science.gov (United States)

Taki, Yasuyuki; Hashizume, Hiroshi; Sassa, Yuko; Takeuchi, Hikaru; Asano, Michiko; Asano, Kohei; Kotozaki, Yuka; Nouchi, Rui; Wu, Kai; Fukuda, Hiroshi; Kawashima, Ryuta

2012-01-16

A significant positive correlation between height and intelligence has been demonstrated in children. Additionally, intelligence has been associated with the volume of gray matter in the brains of children. Based on these correlations, we analyzed the correlation among height, full-scale intelligence quotient (IQ) and gray matter volume applying voxel-based morphometry using data from the brain magnetic resonance images of 160 healthy children aged 5-18 years of age. As a result, body height was significantly positively correlated with brain gray matter volume. Additionally, the regional gray matter volume of several regions such as the bilateral prefrontal cortices, temporoparietal region, and cerebellum was significantly positively correlated with body height and that the gray matter volume of several of these regions was also significantly positively correlated with full-scale intelligence quotient (IQ) scores after adjusting for age, sex, and socioeconomic status. Our results demonstrate that gray and white matter volume may mediate the correlation between body height and intelligence in healthy children. Additionally, the correlations among gray and white matter volume, height, and intelligence may be at least partially explained by the effect of insulin-like growth factor-1 and growth hormones. Given the importance of the effect of environmental factors, especially nutrition, on height, IQ, and gray matter volume, the present results stress the importance of nutrition during childhood for the healthy maturation of body and brain. Copyright © 2011 Elsevier Inc. All rights reserved.

Prolactin prevents acute stress-induced hypocalcemia and ulcerogenesis by acting in the brain of rat.

Science.gov (United States)

Fujikawa, Takahiko; Soya, Hideaki; Tamashiro, Kellie L K; Sakai, Randall R; McEwen, Bruce S; Nakai, Naoya; Ogata, Masato; Suzuki, Ikukatsu; Nakashima, Kunio

2004-04-01

Stress causes hypocalcemia and ulcerogenesis in rats. In rats under stressful conditions, a rapid and transient increase in circulating prolactin (PRL) is observed, and this enhanced PRL induces PRL receptors (PRLR) in the choroid plexus of rat brain. In this study we used restraint stress in water to elucidate the mechanism by which PRLR in the rat brain mediate the protective effect of PRL against stress-induced hypocalcemia and ulcerogenesis. We show that rat PRL acts through the long form of PRLR in the hypothalamus. This is followed by an increase in the long form of PRLR mRNA expression in the choroid plexus of the brain, which provides protection against restraint stress in water-induced hypocalcemia and gastric erosions. We also show that PRL induces the expression of PRLR protein and corticotropin-releasing factor mRNA in the paraventricular nucleus. These results suggest that the PRL levels increase in response to stress, and it moves from the circulation to the cerebrospinal fluid to act on the central nervous system and thereby plays an important role in helping to protect against acute stress-induced hypocalcemia and gastric erosions.

Increased transfer of 45Ca into brain and cerebrospinal fluid from plasma during chronic hypocalcemia in rats.

Science.gov (United States)

Murphy, V A; Rapoport, S I

1988-06-28

Recent studies have shown regulation of central nervous system [Ca] after chronic hypo- and hypercalcemia. To investigate the mechanism of this regulation, 3-week-old rats were fed diets for 8 weeks that contained low or normal levels of Ca. Plasma [Ca] was 40% less in rats fed the low Ca diet than in animals fed normal diet. Unidirectional transfer coefficients for Ca (KCa) and Cl (KCl) into cerebrospinal fluid (CSF) and brain were determined from the 10 min uptake of intravenously injected 45Ca and 36Cl in awake animals. KCa for CSF was 68% greater in low-Ca rats than in normal rats. Likewise, the values of KCa for brain regions with areas adjacent to the ventricles like the hippocampus and pons-medulla were 50% higher than in normal animals. On the other hand, KCas for parietal cortex, a brain region distant from the choroid plexus and not expected to be influenced by Ca entry into CSF, were similar between the groups. Comparison of the regional ratios of KCa/KCl revealed that a selective increase of Ca transport occurred into CSF and all brain regions except the parietal cortex in Ca-deficient rats. The results suggest that Ca homeostasis of CSF and brain [Ca] during chronic hypocalcemia is due to increased transfer of Ca from blood to brain, and that the regulation occurs via the CSF, possibly at the choroid plexus, but not via the cerebral capillaries.

Protective effect of Kombucha tea on brain damage induced by transient cerebral ischemia and reperfusion in rat

OpenAIRE

Najmeh Kabiri; Mahbubeh Setorki

2016-01-01

The aim of study was to investigate the potential neuroprotective effects of Kombucha on cerebral damage induced by ischemia in rats (n=99). Cerebral infarct volume in the ischemic rats received Kombucha solution showed no significance alteration. However, the permeability of blood-brain barrier significantly decreased in both ischemic rats received 15 mg/kg Kombucha tea and Sham group. In addition, brain water content in the ischemic groups treated with Kombucha solution was significantly hi...

Antidiabetic and Neuroprotective Effects of Trigonella Foenum-graecum Seed Powder in Diabetic Rat Brain

Directory of Open Access Journals (Sweden)

P. Kumar

2012-01-01

Full Text Available Trigonella foenum-graecum seed powder (TSP has been reported to have hypoglycemic and hyperinsulinemic action. The objective of the study was to examine the antidiabetic and neuroprotective role of TSP in hyperglycemiainduced alterations in blood glucose, insulin levels and activities of membrane linked enzymes (Na+K+ATPase, Ca2+ATPase, antioxidant enzymes (superoxide dismutase, glutathione S-transferase, calcium (Ca2+ levels, lipid peroxidation, membrane fluidity and neurolipofuscin accumulation in the diabetic rat brain. Female Wistar rats weighing between 180 and 220 g were made diabetic by a single injection of alloxan monohydrate (15 mg/100 g body weight, diabetic rats were given 2 IU insulin, per day with 5% TSP in the diet for three weeks. A significant increase in lipid peroxidation was observed in diabetic brain. The increased lipid peroxidation following chronic hyperglycemia was accompanied with a significant increase in the neurolipofuscin deposition and Ca2+ levels with decreased activities of membrane linked ATPases and antioxidant enzymes in diabetic brain. A decrease in synaptosomal membrane fluidity may influence the activity of membrane linked enzymes in diabetes. The present study showed that TSP treatment can reverse the hyperglycemia induced changes to normal levels in diabetic rat brain. TSP administration amended effect of hyperglycemia on alterations in lipid peroxidation, restoring membrane fluidity, activities of membrane bound and antioxidant enzymes, thereby ameliorating the diabetic complications.

Ketamine coadministration attenuates morphine tolerance and leads to increased brain concentrations of both drugs in the rat

Science.gov (United States)

Lilius, T O; Jokinen, V; Neuvonen, M S; Niemi, M; Kalso, E A; Rauhala, P V

2015-01-01

Background and Purpose The effects of ketamine in attenuating morphine tolerance have been suggested to result from a pharmacodynamic interaction. We studied whether ketamine might increase brain morphine concentrations in acute coadministration, in morphine tolerance and morphine withdrawal. Experimental Approach Morphine minipumps (6 mg·day–1) induced tolerance during 5 days in Sprague–Dawley rats, after which s.c. ketamine (10 mg·kg–1) was administered. Tail flick, hot plate and rotarod tests were used for behavioural testing. Serum levels and whole tissue brain and liver concentrations of morphine, morphine-3-glucuronide, ketamine and norketamine were measured using HPLC-tandem mass spectrometry. Key Results In morphine-naïve rats, ketamine caused no antinociception whereas in morphine-tolerant rats there was significant antinociception (57% maximum possible effect in the tail flick test 90 min after administration) lasting up to 150 min. In the brain of morphine-tolerant ketamine-treated rats, the morphine, ketamine and norketamine concentrations were 2.1-, 1.4- and 3.4-fold, respectively, compared with the rats treated with morphine or ketamine only. In the liver of morphine-tolerant ketamine-treated rats, ketamine concentration was sixfold compared with morphine-naïve rats. After a 2 day morphine withdrawal period, smaller but parallel concentration changes were observed. In acute coadministration, ketamine increased the brain morphine concentration by 20%, but no increase in ketamine concentrations or increased antinociception was observed. Conclusions and Implications The ability of ketamine to induce antinociception in rats made tolerant to morphine may also be due to increased brain concentrations of morphine, ketamine and norketamine. The relevance of these findings needs to be assessed in humans. PMID:25297798

An onion byproduct affects plasma lipids in healthy rats.

Science.gov (United States)

Roldán-Marín, Eduvigis; Jensen, Runa I; Krath, Britta N; Kristensen, Mette; Poulsen, Morten; Cano, M Pilar; Sánchez-Moreno, Concepción; Dragsted, Lars O

2010-05-12

Onion may contribute to the health effects associated with high fruit and vegetable consumption. A considerable amount of onion production ends up as waste that might find use in foods. Onion byproduct has not yet been explored for potential health benefits. The aim of this study is to elucidate the safety and potential role of onion byproducts in affecting risk markers of cardiovascular disease (CVD). For that purpose, the effects of an onion byproduct, Allium cepa L. cepa 'Recas' (OBP), and its two derived fractions, an ethanolic extract (OE) and a residue (OR), on the distribution of plasma lipids and on factors affecting cholesterol metabolism in healthy rats have been investigated. The OBP or its fractions did not significantly reduce cholesterol or down-regulate hepatic 3-hydroxy-3-methylglutaryl-coenzyme A reductase (Hmgcr) gene expression. The OR even had the effect of increasing plasma triacylglycerides (TAG) and cholesterol in the very low density lipoprotein (VLDL-C) fraction. Neither total bile acids nor total primary or secondary bile acids were significantly affected by feeding rats the OBP or its fractions. Principal component analysis combining all markers revealed that the controls could be completely separated from OBP, OE, and OR groups in the scores plot and also that OE and OR groups were separated. Plasma lipids and bile acid excretion were the discriminating loading factors for separating OE and OR but also contributed to the separation of onion-fed animals and controls. It was concluded that the onion byproduct did not present significant beneficial effects on individual markers related to plasma lipid transport in this healthy rat model but that onion byproduct contains factors with the ability to modulate plasma lipids and lipoprotein levels.

Evaluating Community-Academic Partnerships of the South Carolina Healthy Brain Research Network.

Science.gov (United States)

Soltani, Suzan Neda; Kannaley, Kristie; Tang, Weizhou; Gibson, Andrea; Olscamp, Kate; Friedman, Daniela B; Khan, Samira; Houston, Julie; Wilcox, Sara; Levkoff, Sue E; Hunter, Rebecca H

2017-07-01

Community-academic partnerships have a long history of support from public health researchers and practitioners as an effective way to advance research and solutions to issues that are of concern to communities and their citizens. Data on the development and evaluation of partnerships focused on healthy aging and cognitive health were limited. The purpose of this article is to examine how community partners view the benefits and barriers of a community-academic partner group established to support activities of the South Carolina Healthy Brain Research Network (SC-HBRN). The SC-HBRN is part of the national Healthy Brain Research Network, a thematic research network funded by the Centers for Disease Control and Prevention (CDC). It is focused on improving the scientific and research translation agenda on cognitive health and healthy aging. Semistructured interviews, conducted at end of Year 2 of the 5-year partnership, were used to collect data from partners of the SC-HBRN. Reported benefits of the partnership were information sharing and networking, reaching a broader audience, and humanizing research. When asked to describe what they perceived as barriers to the collaborative, partners described some lack of clarity regarding goals of the network and opportunities to contribute to the partnership. Study results can guide and strengthen other public health-focused partnerships.

Acute effects of organotins on brain, liver and kidney in rats

Energy Technology Data Exchange (ETDEWEB)

Dwivedi, R.S.; Kaur, G.; Srivastava, R.C.; Srivastava, T.N.

1985-01-01

Effects of dioctyltin oxide (DOTO) tricyclohexyltin hydroxide (TCHTOH) and tributyltin oxide (TBTO) were examined on some enzymic activities in liver and kidney and biogenic amines level in brain of rats at 24 hours after single subcutaneous administration (25 ..mu..mole/100 g B. Wt.). All the organotin compounds produced a significant increase in the activity of alkaline phosphatase and adenosin triphosphatase and decrease in monoamine oxidase in both liver and kidney. DOTO and TCHTOH were more effective in impairing the activity of succinate dehydrogenase in liver. Concentrations of ..gamma..-aminobutyric acid (GABA) and dopamine were found to be significantly decreased in brain however, acetylcholine concentration remained unaltered. These results suggest that organotin compounds DOTO and TCHTOH are more toxic to rats than TBTO. 30 references, 3 tables.

Effect of Piper betle leaf extract on alcoholic toxicity in the rat brain.

Science.gov (United States)

Saravanan, R; Rajendra Prasad, N; Pugalendi, K V

2003-01-01

The protective effect of Piper betle, a commonly used masticatory, has been examined in the brain of ethanol-administered Wistar rats. Brain of ethanol-treated rats exhibited increased levels of lipids, lipid peroxidation, and disturbances in antioxidant defense. Subsequent to the experimental induction of toxicity (i.e., the initial period of 30 days), aqueous P. betle extract was simultaneously administered in three different doses (100, 200, and 300 mg kg(-1)) for 30 days along with the daily dose of alcohol. P. betle coadministration resulted in significant reduction of lipid levels (free fatty acids, cholesterol, and phospholipids) and lipid peroxidation markers such as thiobarbituric acid reactive substances and hydroperoxides. Further, antioxidants, like reduced glutathione, vitamin C, vitamin E, superoxide dismutase, catalase, and glutathione peroxidase, were increased in P. betle-coadministered rats. The higher dose of extract (300 mg kg(-1)) was more effective, and these results indicate the neuroprotective effect of P. betle in ethanol-treated rats.

Effects of acrylamide and acrylic acid on creatine kinase activity in the rat brain

International Nuclear Information System (INIS)

Kohriyama, Kazuaki; Matsuoka, Masato; Igisu, Hideki

1994-01-01

In vitro, both acrylamide and acrylic acid inhibited creatine kinase (CK) activity in rat brain homogenates, and acrylic acid was more potent than acrylamide. In vivo, however, when given i.p. 50 mg/kg per day for 8 days to rats, only acrylamide inhibited CK activity in the brain and caused apparent neurological signs. 14 C in the brain 24 h after the injection of 14 C-labelled chemicals was more than 7 times greater with acrylamide than with acrylic acid. The inhibition of CK activity by acrylamide varied in eight regions of the brain; from 54% in hypothalamus to 27% in cerebellar vermis. The regional difference of CK inhibition, however, did not agree well with either 14 C distribution or with the distribution in regions which appear clinically or pathologically vulnerable to acrylamide. (orig.)

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...

Preparation and biocompatibility study of in situ forming polymer implants in rat brains.

Science.gov (United States)

Nasongkla, Norased; Boongird, Atthaporn; Hongeng, Suradej; Manaspon, Chawan; Larbcharoensub, Noppadol

2012-02-01

We describe the development of polymer implants that were designed to solidify once injected into rat brains. These implants comprised of glycofurol and copolymers of D: ,L: -lactide (LA), ε-caprolactone and poly(ethylene glycol) (PLECs). Scanning electron microscopy (SEM) and gel permeation chromatography (GPC) showed that the extent of implant degradation was increased with LA: content in copolymers. SEM analysis revealed the formation of porosity on implant surface as the degradation proceeds. PLEC with 19.3% mole of LA: was chosen to inject in rat brains at the volume of 10, 25 and 40 μl. Body weights, hematological and histopathological data of rats treated with implants were evaluated on day 3, 6, 14, 30 and 45 after the injection. Polymer solution at the injection volume of 10 μl were tolerated relatively well compared to those of 25 and 40 μl as confirmed by higher body weight and healing action (fibrosis tissue) 30 days after treatment. The results from this study suggest a possible application as drug delivery systems that can bypass the blood brain barrier.

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

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Yanier Núñez Figueredo

2016-08-01

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

Development and evaluation of novel biodegradable chitosan based metformin intrapocket dental film for the management of periodontitis and alveolar bone loss in a rat model.

Science.gov (United States)

Khajuria, Deepak Kumar; Patil, Omprakash Nandikamba; Karasik, David; Razdan, Rema

2018-01-01

The aim of this study was to develop a chitosan-metformin based intrapocket dental film (CMIDF) for applications in the treatment of periodontitis and alveolar bone loss in an rat model of periodontitis. CMIDF inserts were fabricated by the solvent casting technique. The fabricated inserts were evaluated for physical characteristics such as folding endurance, surface pH, mucoadhesive strength, metformin content uniformity, and release. X-ray diffraction analysis indicates no crystallinity of metformin in presence of chitosan which confirmed successful entrapment of metformin into the CMIDF. Fourier-transform infrared spectroscopy revealed stability of CMIDF and compatibility between metformin and chitosan. Periodontitis was induced by a combination of Porphyromonas gingivalis- lipopolysaccharide injections in combinations with ligatures around the mandibular first molar. We divided rats into 5 groups (8 rats/group): healthy, untreated periodontitis; periodontitis plus CMIDF-A (1.99±0.09mg metformin; total mass-4.01±0.05mg), periodontitis plus CMIDF-B (2.07±0.06mg metformin; total mass-7.56±0.09mg), and periodontitis plus chitosan film (7.61±0.08mg). After four weeks, mandibles were extracted to evaluate alveolar bone loss by micro-computerized tomography and histological techniques. Alveolar bone was intact in the healthy group. Local administration of CMIDF resulted in significant improvements in the alveolar bone properties when compared to the untreated periodontitis group. The study reported here demonstrates that novel CMIDF showed good antibacterial activity and effectively reduced alveolar bone destruction in a rat model of experimental periodontitis. Novel CMIDF showed good antibacterial activity and improved alveolar bone properties in a rat model. Copyright © 2017 Elsevier Ltd. All rights reserved.

Impact of aspartame consumption on neurotransmitters in rat brain ...

African Journals Online (AJOL)

Background: Aspartame (APM), a common artificial sweetener, has been used for diabetic subjects and body weight control for a long time. The goal of the present study was to evaluate the impact of APM consumption on neurotransmitters and oxidative stress in rat's brain. Materials and Methods: Four groups of male ...

Glutamate decarboxylase activity in rat brain during experimental epileptic seizures induced by pilocarpine

Energy Technology Data Exchange (ETDEWEB)

Netopilova, M; Drsata, J [Department of Biochemical Sciences, Faculty of Pharmacy, Charles University, 50005 Hradec Kralove (Czech Republic); Haugvicova, R; Kubova, H; Mares, P [Institute of Physiology, Czech Academy of Sciences, 14220 Prague (Czech Republic)

1998-07-01

Glutamate decarboxylase (GAD) activity was studied rat brain parts in a pilocarpine model of epileptic seizures. An increased enzyme activity was found in hippocampus a cerebellum during the acute phase of seizures, while the cortex and cerebellum showed increased GAD activity in the chronic phase of the process. Systematic administration of pilocarpine to rats induces status epilepticus. The aim of this research was to find out if seizures induced by pilocarpine are connected changes in glutamate decarboxylase activity, the enzyme that catalyzes synthesis of inhibitory neurotransmitter GABA. GAD was assayed by means of radiometric method using {sup 14}C-carboxyl-labelled glutamate and measurement of {sup 14}CO{sub 2} radioactivity. Obtained results suggest that pilocarpine seizures are connected with changes of GAD activity in individual parts of rat brain. (authors)

Glutamate decarboxylase activity in rat brain during experimental epileptic seizures induced by pilocarpine

International Nuclear Information System (INIS)

Netopilova, M.; Drsata, J.; Haugvicova, R.; Kubova, H.; Mares, P.

1998-01-01

Glutamate decarboxylase (GAD) activity was studied rat brain parts in a pilocarpine model of epileptic seizures. An increased enzyme activity was found in hippocampus a cerebellum during the acute phase of seizures, while the cortex and cerebellum showed increased GAD activity in the chronic phase of the process. Systematic administration of pilocarpine to rats induces status epilepticus. The aim of this research was to find out if seizures induced by pilocarpine are connected changes in glutamate decarboxylase activity, the enzyme that catalyzes synthesis of inhibitory neurotransmitter GABA. GAD was assayed by means of radiometric method using 14 C-carboxyl-labelled glutamate and measurement of 14 CO 2 radioactivity. Obtained results suggest that pilocarpine seizures are connected with changes of GAD activity in individual parts of rat brain. (authors)

A novel multi-tissue RNA diagnostic of healthy ageing relates to cognitive health status.

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Sood, Sanjana; Gallagher, Iain J; Lunnon, Katie; Rullman, Eric; Keohane, Aoife; Crossland, Hannah; Phillips, Bethan E; Cederholm, Tommy; Jensen, Thomas; van Loon, Luc J C; Lannfelt, Lars; Kraus, William E; Atherton, Philip J; Howard, Robert; Gustafsson, Thomas; Hodges, Angela; Timmons, James A

2015-09-07

Diagnostics of the human ageing process may help predict future healthcare needs or guide preventative measures for tackling diseases of older age. We take a transcriptomics approach to build the first reproducible multi-tissue RNA expression signature by gene-chip profiling tissue from sedentary normal subjects who reached 65 years of age in good health. One hundred and fifty probe-sets form an accurate classifier of young versus older muscle tissue and this healthy ageing RNA classifier performed consistently in independent cohorts of human muscle, skin and brain tissue (n = 594, AUC = 0.83-0.96) and thus represents a biomarker for biological age. Using the Uppsala Longitudinal Study of Adult Men birth-cohort (n = 108) we demonstrate that the RNA classifier is insensitive to confounding lifestyle biomarkers, while greater gene score at age 70 years is independently associated with better renal function at age 82 years and longevity. The gene score is 'up-regulated' in healthy human hippocampus with age, and when applied to blood RNA profiles from two large independent age-matched dementia case-control data sets (n = 717) the healthy controls have significantly greater gene scores than those with cognitive impairment. Alone, or when combined with our previously described prototype Alzheimer disease (AD) RNA 'disease signature', the healthy ageing RNA classifier is diagnostic for AD. We identify a novel and statistically robust multi-tissue RNA signature of human healthy ageing that can act as a diagnostic of future health, using only a peripheral blood sample. This RNA signature has great potential to assist research aimed at finding treatments for and/or management of AD and other ageing-related conditions.

Glucocorticoids Protect Neonatal Rat Brain in Model of Hypoxic-Ischemic Encephalopathy (HIE

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Benjamin Harding

2016-12-01

Full Text Available Hypoxic-ischemic encephalopathy (HIE resulting from asphyxia in the peripartum period is the most common cause of neonatal brain damage and can result in significant neurologic sequelae, including cerebral palsy. Currently therapeutic hypothermia is the only accepted treatment in addition to supportive care for infants with HIE, however, many additional neuroprotective therapies have been investigated. Of these, glucocorticoids have previously been shown to have neuroprotective effects. HIE is also frequently compounded by infectious inflammatory processes (sepsis and as such, the infants may be more amenable to treatment with an anti-inflammatory agent. Thus, the present study investigated dexamethasone and hydrocortisone treatment given after hypoxic-ischemic (HI insult in neonatal rats via intracerebroventricular (ICV injection and intranasal administration. In addition, we examined the effects of hydrocortisone treatment in HIE after lipopolysaccharide (LPS sensitization in a model of HIE and sepsis. We found that dexamethasone significantly reduced rat brain infarction size when given after HI treatment via ICV injection; however it did not demonstrate any neuroprotective effects when given intranasally. Hydrocortisone after HI insult also significantly reduced brain infarction size when given via ICV injection; and the intranasal administration showed to be protective of brain injury in male rats at a dose of 300 µg. LPS sensitization did significantly increase the brain infarction size compared to controls, and hydrocortisone treatment after LPS sensitization showed a significant decrease in brain infarction size when given via ICV injection, as well as intranasal administration in both genders at a dose of 300 µg. To conclude, these results show that glucocorticoids have significant neuroprotective effects when given after HI injury and that these effects may be even more pronounced when given in circumstances of additional

Immunochemical method for quantitative evaluation of vasogenic brain edema following cold injury of rat brain

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Bodsch, W; Huerter, T; Hossmann, K A [Max-Planck-Institut fuer Hirnforschung, Koeln (Germany, F.R.). Forschungsstelle fuer Hirnkreislauf-Forschung

1982-10-07

An immunochemical method is described for quantitative assessment of serum proteins and hemoglobin content in brain tissue homogenates. Using a combination of affinity chromatography and radioimmunoassay, the sensitivity of the method is 50 ng hemoglobin and 100 ng serum protein per assay, respectively. The method was used to measure cerebral hematocrit, blood volume and serum protein extravasation in rat brain at various times following cold injury. In control rats cerebral blood volume was 6.88 +- 0.15 ml/100 g and cerebral hematocrit 26.4 +- 0.86% (means +- S.E.). Following cold injury blood volume did not significantly change, but there was a gradual increase of extravasated serum proteins, reaching a maximum of 21.54 +- 2.76 mg/g d.w. after 8 hours. Thereafter protein content gradually declined, but even after 64 h it was distinctly increased. Protein extravasation was partly dissociated from the increase of brain water and sodium which reached a maximum already after 2 h and which normalized within 32 and 64 h, respectively. It is concluded that edema fluid associated with cold injury is not simply an ultrafiltrate of blood serum but consists of cytotoxic and vasogenic components which follow a different time course both during formation and resolution of edema.

Immunochemical method for quantitative evaluation of vasogenic brain edema following cold injury of rat brain

International Nuclear Information System (INIS)

Bodsch, W.; Huerter, T.; Hossmann, K.-A.

1982-01-01

An immunochemical method is described for quantitative assessment of serum proteins and hemoglobin content in brain tissue homogenates. Using a combination of affinity chromatography and radioimmunoassay, the sensitivity of the method is 50 ng hemoglobin and 100 ng serum protein per assay, respectively. The method was used to measure cerebral hematocrit, blood volume and serum protein extravasation in rat brain at various times following cold injury. In control rats cerebral blood volume was 6.88 +- 0.15 ml/100 g and cerebral hematocrit 26.4 +- 0.86% (means +- S.E.). Following cold injury blood volume did not significantly change, but there was a gradual increase of extravasated serum proteins, reaching a maximum of 21.54 +- 2.76 mg/g d.w. after 8 hours. Thereafter protein content gradually declined, but even after 64 h it was distinctly increased. Protein extravasation was partly dissociated from the increase of brain water and sodium which reached a maximum already after 2 h and which normalized within 32 and 64 h, respectively. It is concluded that edema fluid associated with cold injury is not simply an ultrafiltrate of blood serum but consists of cytotoxic and vasogenic components which follow a different time course both during formation and resolution of edema. (Auth.)

The effects of voluntary, involuntary, and forced exercises on brain-derived neurotrophic factor and motor function recovery: a rat brain ischemia model.

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Zheng Ke

Full Text Available BACKGROUND: Stroke rehabilitation with different exercise paradigms has been investigated, but which one is more effective in facilitating motor recovery and up-regulating brain neurotrophic factor (BDNF after brain ischemia would be interesting to clinicians and patients. Voluntary exercise, forced exercise, and involuntary muscle movement caused by functional electrical stimulation (FES have been individually demonstrated effective as stroke rehabilitation intervention. The aim of this study was to investigate the effects of these three common interventions on brain BDNF changes and motor recovery levels using a rat ischemic stroke model. METHODOLOGY/PRINCIPAL FINDINGS: One hundred and seventeen Sprague-Dawley rats were randomly distributed into four groups: Control (Con, Voluntary exercise of wheel running (V-Ex, Forced exercise of treadmill running (F-Ex, and Involuntary exercise of FES (I-Ex with implanted electrodes placed in two hind limb muscles on the affected side to mimic gait-like walking pattern during stimulation. Ischemic stroke was induced in all rats with the middle cerebral artery occlusion/reperfusion model and fifty-seven rats had motor deficits after stroke. Twenty-four hours after reperfusion, rats were arranged to their intervention programs. De Ryck's behavioral test was conducted daily during the 7-day intervention as an evaluation tool of motor recovery. Serum corticosterone concentration and BDNF levels in the hippocampus, striatum, and cortex were measured after the rats were sacrificed. V-Ex had significantly better motor recovery in the behavioral test. V-Ex also had significantly higher hippocampal BDNF concentration than F-Ex and Con. F-Ex had significantly higher serum corticosterone level than other groups. CONCLUSION/SIGNIFICANCE: Voluntary exercise is the most effective intervention in upregulating the hippocampal BDNF level, and facilitating motor recovery. Rats that exercised voluntarily also showed less

Combined treatment with progesterone and magnesium sulfate positively affects traumatic brain injury in immature rats.

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Uysal, Nazan; Baykara, Basak; Kiray, Muge; Cetin, Ferihan; Aksu, Ilkay; Dayi, Ayfer; Gurpinar, Tugba; Ozdemir, Durgul; Arda, M Nuri

2013-01-01

It is well known that head trauma results in damage in hippocampal and cortical areas of the brain and impairs cognitive functions. The aim of this study is to explore the neuroprotective effect of combination therapy with magnesium sulphate (MgSO4) and progesterone in the 7-days-old rat pups subjected to contusion injury. Progesterone (8 mg/kg) and MgSO4 (150 mg/kg) were injected intraperitoneally immediately after induction of traumatic brain injury. Half of groups were evaluated 24 hours later, the remaining animals 3 weeks after trauma or sham surgery. Anxiety levels were assessed with open field activity and elevated plus maze; learning and memory performance were evaluated with Morris Water maze in postnatal 27 days. Combined therapy with progesterone and magnesium sulfate significantly attenuated trauma-induced neuronal death, increased brain VEGF levels and improved spatial memory deficits that appear later in life. Brain VEGF levels were higher in rats that received combined therapy compared to rats that received either medication alone. Moreover, rats that received combined therapy had reduced hipocampus and prefrontal cortex apoptosis in the acute period. These results demonstrate that combination of drugs with different mechanisms of action may be preferred in the treatment of head trauma.

AQP4 expression and its relationship with brain edema after gamma kife radiosurgery in rats

International Nuclear Information System (INIS)

Shen Guangjian; Xu Minhui; Zou Yongwen; Gen Mingying; Li Feipeng; Tang Wenyuan; Sun Shanquan

2007-01-01

Objective: To explore AQP4 expression and its relationship with brain edema after gamma knife radiosurgery (GKRS) in rats. Methods: Wistar rats were divided into two groups-the control group and experimental group. The experimental group model was established by radiating rat left rotral caudate nucleus with GKRS (100 Gy, 4 mm), and was examinded at interval times of 1 d, 3 d, 7 d, 15 d, 30 d and 45 d. Brain water content (BWC) was determined by wet-dry weighing method. AQP4 expression on mRNA and protein were measured by immunohistochemistry (ICH) and in situ hybridization (ISH). Results: In control group, AQP4 protein and its mRNA were expressed in subpial astrocytes, choroid plexus, ependyma and perivascular astrocytes. After GKRS, AQP4 protein and its mRNA in these sites were enhanced, and became most remarkable at 30 d. The positive corrlationship was showed between AQP4 and its mRNA, and AQP4 and BWC. Conclusions: AQP4 protein and its mRNA can be induced in some brain zone after irradiating rat left rotral caudate nucleus with GKRS. The increased expression of AQP4 and its mRNA may play a role in the ocurrence or development of brain edema after GKRS. (authors)

Effect of chronic exposure to aspartame on oxidative stress in the brain of albino rats.

Science.gov (United States)

Iyyaswamy, Ashok; Rathinasamy, Sheeladevi

2012-09-01

This study was aimed at investigating the chronic effect of the artificial sweetener aspartame on oxidative stress in brain regions of Wistar strain albino rats. Many controversial reports are available on the use of aspartame as it releases methanol as one of its metabolite during metabolism. The present study proposed to investigate whether chronic aspartame (75 mg/kg) administration could release methanol and induce oxidative stress in the rat brain. To mimic the human methanol metabolism, methotrexate (MTX)-treated rats were included to study the aspartame effects. Wistar strain male albino rats were administered with aspartame orally and studied along with controls and MTX-treated controls. The blood methanol level was estimated, the animal was sacrificed and the free radical changes were observed in brain discrete regions by assessing the scavenging enzymes, reduced glutathione, lipid peroxidation (LPO) and protein thiol levels. It was observed that there was a significant increase in LPO levels, superoxide dismutase (SOD) activity, GPx levels and CAT activity with a significant decrease in GSH and protein thiol. Moreover, the increases in some of these enzymes were region specific. Chronic exposure of aspartame resulted in detectable methanol in blood. Methanol per se and its metabolites may be responsible for the generation of oxidative stress in brain regions.

Influence of histidine on zinc transport into rat brain

International Nuclear Information System (INIS)

Takeda, Atsushi; Suzuki, Mai; Okada, Shoji; Oku, Naoto

2000-01-01

The brain of rats injected intravenously with 65 Zn-His or 65 ZnCl 2 was subjected to autoradiography to study the role of histidine on zinc transport into the brain. One hour after injection, the radioactivity from 65 Zn-His was largely concentrated in the choroid plexus in the ventricles. Six days after injection, the radioactivity from 65 Zn-His was relatively concentrated in the hippocampal CA3 and dentate gyrus and the amygdala. The relative distribution of 65 Zn-His in the brain was similar to that of 65 ZnCl 2 group at both 1 h and 6 days, suggesting that histidine may participate in zinc uptake in the brain. On the other hand, the clearance of the 65 Zn-His group from the blood was higher than that of the 65 ZnCl 2 group. Brain uptake of the former was lower than that of the latter both 1 h and 6 days after injection. These results suggest that zinc uptake in the brain is influenced by histidine levels in the bloodstream. (author)

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

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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.

Middle age onset short-term intermittent fasting dietary restriction prevents brain function impairments in male Wistar rats.

Science.gov (United States)

Singh, Rumani; Manchanda, Shaffi; Kaur, Taranjeet; Kumar, Sushil; Lakhanpal, Dinesh; Lakhman, Sukhwinder S; Kaur, Gurcharan

2015-12-01

Intermittent fasting dietary restriction (IF-DR) is recently reported to be an effective intervention to retard age associated disease load and to promote healthy aging. Since sustaining long term caloric restriction regimen is not practically feasible in humans, so use of alternate approach such as late onset short term IF-DR regimen which is reported to trigger similar biological pathways is gaining scientific interest. The current study was designed to investigate the effect of IF-DR regimen implemented for 12 weeks in middle age rats on their motor coordination skills and protein and DNA damage in different brain regions. Further, the effect of IF-DR regimen was also studied on expression of energy regulators, cell survival pathways and synaptic plasticity marker proteins. Our data demonstrate that there was an improvement in motor coordination and learning response with decline in protein oxidative damage and recovery in expression of energy regulating neuropeptides. We further observed significant downregulation in nuclear factor kappa B (NF-κB) and cytochrome c (Cyt c) levels and moderate upregulation of mortalin and synaptophysin expression. The present data may provide an insight on how a modest level of short term IF-DR, imposed in middle age, can slow down or prevent the age-associated impairment of brain functions and promote healthy aging by involving multiple regulatory pathways aimed at maintaining energy homeostasis.

Peony glycosides reverse the effects of corticosterone on behavior and brain BDNF expression in rats.

Science.gov (United States)

Mao, Qing-Qiu; Huang, Zhen; Ip, Siu-Po; Xian, Yan-Fang; Che, Chun-Tao

2012-02-01

Repeated injections of corticosterone (CORT) induce the dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in depressive-like behavior. This study aimed to examine the antidepressant-like effect and the possible mechanisms of total glycosides of peony (TGP) in the CORT-induced depression model in rats. The results showed that the 3-week CORT injections induced the significant increase in serum CORT levels in rats. Repeated CORT injections also caused depression-like behavior in rats, as indicated by the significant decrease in sucrose consumption and increase in immobility time in the forced swim test. Moreover, it was found that brain-derived neurotrophic factor (BDNF) protein levels in the hippocampus and frontal cortex were significantly decreased in CORT-treated rats. Treatment of the rats with TGP significantly suppressed the depression-like behavior and increased brain BDNF levels in CORT-treated rats. The results suggest that TGP produces an antidepressant-like effect in CORT-treated rats, which is possibly mediated by increasing BDNF expression in the hippocampus and frontal cortex. Copyright © 2011 Elsevier B.V. All rights reserved.

DNA microarray unravels rapid changes in transcriptome of MK-801 treated rat brain

Science.gov (United States)

Kobayashi, Yuka; Kulikova, Sofya P; Shibato, Junko; Rakwal, Randeep; Satoh, Hiroyuki; Pinault, Didier; Masuo, Yoshinori

2015-01-01

AIM: To investigate the impact of MK-801 on gene expression patterns genome wide in rat brain regions. METHODS: Rats were treated with an intraperitoneal injection of MK-801 [0.08 (low-dose) and 0.16 (high-dose) mg/kg] or NaCl (vehicle control). In a first series of experiment, the frontoparietal electrocorticogram was recorded 15 min before and 60 min after injection. In a second series of experiments, the whole brain of each animal was rapidly removed at 40 min post-injection, and different regions were separated: amygdala, cerebral cortex, hippocampus, hypothalamus, midbrain and ventral striatum on ice followed by DNA microarray (4 × 44 K whole rat genome chip) analysis. RESULTS: Spectral analysis revealed that a single systemic injection of MK-801 significantly and selectively augmented the power of baseline gamma frequency (30-80 Hz) oscillations in the frontoparietal electroencephalogram. DNA microarray analysis showed the largest number (up- and down- regulations) of gene expressions in the cerebral cortex (378), midbrain (376), hippocampus (375), ventral striatum (353), amygdala (301), and hypothalamus (201) under low-dose (0.08 mg/kg) of MK-801. Under high-dose (0.16 mg/kg), ventral striatum (811) showed the largest number of gene expression changes. Gene expression changes were functionally categorized to reveal expression of genes and function varies with each brain region. CONCLUSION: Acute MK-801 treatment increases synchrony of baseline gamma oscillations, and causes very early changes in gene expressions in six individual rat brain regions, a first report. PMID:26629322

Epileptic rat brain tissue analyzed by 2D correlation Raman spectroscopy

Science.gov (United States)

Sacharz, Julia; Wesełucha-Birczyńska, Aleksandra; Zięba-Palus, Janina; Lewandowski, Marian H.; Kowalski, Rafał; Palus, Katarzyna; Chrobok, Łukasz; Moskal, Paulina; Birczyńska, Malwina; Sozańska, Agnieszka

2018-01-01

Absence epilepsy is the neurological disorder characterized by the pathological spike-and wave discharges present in the electroencephalogram, accompanying a sudden loss of consciousness. Experiments were performed on brain slices obtained from young male WAG/Rij rats (2-3 weeks old), so that they were sampled before the appearance of brain-damaging seizures symptoms. Two differing brain areas of the rats' brain tissue were studied: the somatosensory cortex (Sc) and the dorsal lateral geniculate nucleus of the thalamus (DLG). The Raman spectra of the fresh brain scraps, kept during measurements in artificial cerebrospinal fluid, were collected using as an excitation source 442 nm, 514.5 nm, 785 nm and 1064 nm laser line. The average spectra were analyzed by 2D correlation method regarding laser line as an external perturbation. In 2D synchronous spectra positive auto-peaks corresponding to the Cdbnd C stretching and amide I band vibrations show maxima at 1660 cm- 1 and 1662 cm- 1 for Sc and DLG, respectively. The prominent auto-peak at 2937 cm- 1, originated from the CH3 mode in DLG brain area, seems to indicate the importance of methylation, considered to be significant in epileptogenesis. Synchronous and asynchronous correlations peaks, glutamic acid and gamma-aminobutyric acid (GABA), appear in Sc and DLG, respectively. In the 1730-1600 cm- 1 range occur cross-peaks which appearance might be triggered by glial fibrillary acidic protein (GFAP) activation.

Evidence of Neurobiological Changes in the Presymptomatic PINK1 Knockout Rat.

Science.gov (United States)

Ferris, Craig F; Morrison, Thomas R; Iriah, Sade; Malmberg, Samantha; Kulkarni, Praveen; Hartner, Jochen C; Trivedi, Malav

2018-01-01

Genetic models of Parkinson's disease (PD) coupled with advanced imaging techniques can elucidate neurobiological disease progression, and can help identify early biomarkers before clinical signs emerge. PTEN-induced putative kinase 1 (PINK1) helps protect neurons from mitochondrial dysfunction, and a mutation in the associated gene is a risk factor for recessive familial PD. The PINK1 knockout (KO) rat is a novel model for familial PD that has not been neuroradiologically characterized for alterations in brain structure/function, alongside behavior, prior to 4 months of age. To identify biomarkers of presymptomatic PD in the PINK1 -/- rat at 3 months using magnetic resonance imaging techniques. At postnatal weeks 12-13; one month earlier than previously reported signs of motor and cognitive dysfunction, this study combined imaging modalities, including assessment of quantitative anisotropy across 171 individual brain areas using an annotated MRI rat brain atlas to identify sites of gray matter alteration between wild-type and PINK1 -/- rats. The olfactory system, hypothalamus, thalamus, nucleus accumbens, and cerebellum showed differences in anisotropy between experimental groups. Molecular analyses revealed reduced levels of glutathione, ATP, and elevated oxidative stress in the substantia nigra, striatum and deep cerebellar nuclei. Mitochondrial genes encoding proteins in Complex IV, along with mRNA levels associated with mitochondrial function and genes involved in glutathione synthesis were reduced. Differences in brain structure did not align with any cognitive or motor impairment. These data reveal early markers, and highlight novel brain regions involved in the pathology of PD in the PINK1 -/- rat before behavioral dysfunction occurs.

Effects of Junk Foods on Brain Neurotransmitters (Dopamine and Serotonin) and some Biochemical Parameters in Albino Rats

International Nuclear Information System (INIS)

Abd Elmonem, H.A.; Ali, E.A.

2011-01-01

Nutritional Habits have changed significantly and junk foods have become widely popular, in recent years. The present study aimed to shed the light on the effect of potato chips and / or ketchup consumption on some biochemical parameters. Sixty four male and female albino rats were used in the study. Animals were maintained on 0.25 g potato chips/ rat and / or 0.125 g ketchup / rat, 5 days a week for 4 weeks. Potato chips showed the lowest body wt gain in the male rats after 4 weeks but, ketchup modulated this negative effect of the potato chips in the group of male animals fed on potato chips plus ketchup. Potato chips significantly decreased brain serotonin, liver glutathione (GSH) and catalase (CAT) in both sexes; brain dopamine, serum total proteins, albumin, total globulins, α 2 - and β 1 -globulins in the females and serum thyroxine (T 4 ) in the male rats. Ketchup apparently affected serum T 4 and A / G ratio in both sexes, brain dopamine and liver GSH in the males in addition to brain serotonin, serum total globulins and ?1-globulin in the female rats. Potato chips plus ketchup significantly changed T 4 , dopamine, GSH, CAT, α 1 and α 2 -globulins in both sexes; serotonin and β 1 -globulin in the male rats, total proteins and albumin in the females. It could be concluded that potato chips consumption might induce numerous adverse effects in various body organs

Anti-ischemic effect of curcumin in rat brain.

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Shukla, Pradeep K; Khanna, Vinay K; Ali, Mohd M; Khan, Mohd Y; Srimal, Rikhab C

2008-06-01

Turmeric has been in use since ancient times as a condiment and due to its medicinal properties. Curcumin, the yellow colouring principle in turmeric, is polyphenolic and major active constituent. Besides anti-inflammatory, thrombolytic and anticarcinogenic activities, curcumin also possesses strong antioxidant property. In view of the novel combination of properties, neuroprotective efficacy of curcumin was studied in rat middle cerebral artery occlusion (MCAO) model. Rats were subjected to 2 h of focal ischemia followed by 72 h of reperfusion. They were pre-treated with curcumin (100 mg/kg, po) for 5 days prior to MCAO and for another 3 days after MCAO. The parameters studied were behavioural, biochemical and histological. Treatment with curcumin could significantly improve neurobehavioral performance compared to untreated ischemic rats as judged by its effect on rota-rod performance and grid walking. A significant inhibition in lipid peroxidation and an increase in superoxide dismutase (SOD) activity in corpus striatum and cerebral cortex was observed following treatment with curcumin in MCAO rats as compared to MCAO group. Intracellular calcium levels were decreased following treatment with curcumin in MCAO rats. Histologically, a reduction in the infarct area from 33% to 24% was observed in MCAO rats treated with curcumin. The study demonstrates the protective efficacy of curcumin in rat MCAO model.

Brain substrates of unhealthy versus healthy food choices: influence of homeostatic status and body mass index.

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Harding, I H; Andrews, Z B; Mata, F; Orlandea, S; Martínez-Zalacaín, I; Soriano-Mas, C; Stice, E; Verdejo-Garcia, A

2018-03-01

Unhealthy dietary choices are a major contributor to harmful weight gain and obesity. This study interrogated the brain substrates of unhealthy versus healthy food choices in vivo, and evaluated the influence of hunger state and body mass index (BMI) on brain activation and connectivity. Thirty adults (BMI: 18-38 kg m -2 ) performed a food-choice task involving preference-based selection between beverage pairs consisting of high-calorie (unhealthy) or low-calorie (healthy) options, concurrent with functional magnetic resonance imaging (fMRI). Selected food stimuli were delivered to participants using an MRI-compatible gustometer. fMRI scans were performed both after 10-h fasting and when sated. Brain activation and hypothalamic functional connectivity were assessed when selecting between unhealthy-healthy beverage pairings, relative to unhealthy-unhealthy and healthy-healthy options. Results were considered significant at cluster-based family-wise error corrected Pfoods elicited significant activation in the hypothalamus, the medial and dorsolateral prefrontal cortices, the anterior insula and the posterior cingulate. Hunger was associated with higher activation within the ventromedial and dorsolateral prefrontal cortices, as well as lower connectivity between the hypothalamus and both the ventromedial prefrontal cortex and dorsal striatum. Critically, people with higher BMI showed lower activation of the hypothalamus-regardless of hunger state-and higher activation of the ventromedial prefrontal cortex when hungry. People who are overweight and obese have weaker activation of brain regions involved in energy regulation and greater activation of reward valuation regions while making choices between unhealthy and healthy foods. These results provide evidence for a shift towards hedonic-based, and away from energy-based, food selection in obesity.

Brain maps 4.0-Structure of the rat brain: An open access atlas with global nervous system nomenclature ontology and flatmaps.

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Swanson, Larry W

2018-04-15

The fourth edition (following editions in 1992, 1998, 2004) of Brain maps: structure of the rat brain is presented here as an open access internet resource for the neuroscience community. One new feature is a set of 10 hierarchical nomenclature tables that define and describe all parts of the rat nervous system within the framework of a strictly topographic system devised previously for the human nervous system. These tables constitute a global ontology for knowledge management systems dealing with neural circuitry. A second new feature is an aligned atlas of bilateral flatmaps illustrating rat nervous system development from the neural plate stage to the adult stage, where most gray matter regions, white matter tracts, ganglia, and nerves listed in the nomenclature tables are illustrated schematically. These flatmaps are convenient for future development of online applications analogous to "Google Maps" for systems neuroscience. The third new feature is a completely revised Atlas of the rat brain in spatially aligned transverse sections that can serve as a framework for 3-D modeling. Atlas parcellation is little changed from the preceding edition, but the nomenclature for rat is now aligned with an emerging panmammalian neuroanatomical nomenclature. All figures are presented in Adobe Illustrator vector graphics format that can be manipulated, modified, and resized as desired, and freely used with a Creative Commons license. © 2018 The Authors The Journal of Comparative Neurology Published by Wiley Periodicals, Inc.

Effect of /sup 60/Co-irradiation on normal and low protein diet fed rat brain

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Hasan, S S [Garhwal Univ., Srinagar, Uttar Pradesh (India). Dept. of Zoology; Habibullah, M [Jawaharlal Nehru Univ., New Delhi (India). Neurobiology Lab.

1980-06-01

The effect of whole-body irradiation (Co-60) on the brain tissue in Holtzmann strain adult male rats was studied. Two doses of irradiation (450 R,950 R) were tried on animals which were fed on normal as well as low protein diets over a period of 10 generations. In the normal rats, 450 R initially caused a lowered total protein. DNA and RNA content in the brain. After 7 days a tendency towards normalcy was observed. In the 950 R irradiated normal rats the diminution of protein content appeared irreversible. In malnourished 450 R irradiated rats, the protein content rose less steeply over the 7 days of observation. A higher dose of 950 R enhanced this effect on protein and also lowered the DNA content on day 5. The RNA content in the 950 R group with malnutrition showed a marked increase towards or beyond control perhaps as an expression of uncoupled feedback control. The paper gives evidence that protein deficiency may interfere with cellular regeneration in irradiated brain.

Brain maps 4.0—Structure of the rat brain: An open access atlas with global nervous system nomenclature ontology and flatmaps

Science.gov (United States)

2018-01-01

Abstract The fourth edition (following editions in 1992, 1998, 2004) of Brain maps: structure of the rat brain is presented here as an open access internet resource for the neuroscience community. One new feature is a set of 10 hierarchical nomenclature tables that define and describe all parts of the rat nervous system within the framework of a strictly topographic system devised previously for the human nervous system. These tables constitute a global ontology for knowledge management systems dealing with neural circuitry. A second new feature is an aligned atlas of bilateral flatmaps illustrating rat nervous system development from the neural plate stage to the adult stage, where most gray matter regions, white matter tracts, ganglia, and nerves listed in the nomenclature tables are illustrated schematically. These flatmaps are convenient for future development of online applications analogous to “Google Maps” for systems neuroscience. The third new feature is a completely revised Atlas of the rat brain in spatially aligned transverse sections that can serve as a framework for 3‐D modeling. Atlas parcellation is little changed from the preceding edition, but the nomenclature for rat is now aligned with an emerging panmammalian neuroanatomical nomenclature. All figures are presented in Adobe Illustrator vector graphics format that can be manipulated, modified, and resized as desired, and freely used with a Creative Commons license. PMID:29277900

Valnoctamide, which reduces rat brain arachidonic acid turnover, is a potential non-teratogenic valproate substitute to treat bipolar disorder.

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Modi, Hiren R; Ma, Kaizong; Chang, Lisa; Chen, Mei; Rapoport, Stanley I

2017-08-01

Valproic acid (VPA), used for treating bipolar disorder (BD), is teratogenic by inhibiting histone deacetylase. In unanaesthetized rats, chronic VPA, like other mood stabilizers, reduces arachidonic acid (AA) turnover in brain phospholipids, and inhibits AA activation to AA-CoA by recombinant acyl-CoA synthetase-4 (Acsl-4) in vitro. Valnoctamide (VCD), a non-teratogenic constitutional isomer of VPA amide, reported effective in BD, also inhibits recombinant Acsl-4 in vitro. VCD like VPA will reduce brain AA turnover in unanaesthetized rats. A therapeutically relevant (50mg/kg i.p.) dose of VCD or vehicle was administered daily for 30 days to male rats. AA turnover and related parameters were determined using our kinetic model, following intravenous [1- 14 C]AA in unanaesthetized rats for 10min, and measuring labeled and unlabeled lipids in plasma and high-energy microwaved brain. VCD, compared with vehicle, increased λ, the ratio of brain AA-CoA to unesterified plasma AA specific activities; and decreased turnover of AA in individual and total brain phospholipids. VCD's ability like VPA to reduce rat brain AA turnover and inhibit recombinant Acsl-4, and its efficacy in BD, suggest that VCD be further considered as a non-teratogenic VPA substitute for treating BD. Published by Elsevier B.V.

The effects of raloxifene treatment on oxidative status in brain tissues and learning process of ovariectomized rats

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Süreyya Osmanova

2011-01-01

Full Text Available Background: The effects of estrogene on central nervous system are still controversial. Objective: We aimed to investigate the effects of raloxifene on the antioxidant enzyme [superoxide dismutase (SOD and catalase (CAT] activities and malondialdehyde (MDA levels in brain homogenates of ovariectomized female rats and its effect on cognitive process of learning.Materials and Methods: Female Sprague Dawley rats (n=24 were divided into three groups. Three weeks after ovariectomy; nonovariectomized group (control group (n=8 was given physiological saline (SP as placebo. First ovariectomized group (n=8 received raloxifene 1mg/kg dissolved in a 1% solution of carboxymethylcellulose (CMC subcutaneusly (sc and second group of ovariectomized rats were given 1 % CMC 1mg/kg (sc every day for 14 days. Learning behaviors of rats were evaluated in active avoidence cage with using sound and electrical stimulation. The levels of oxidative stress (MDA and antioxidant enzymes (SOD, CAT in different regions of the brain homogenates were compared between three groups of decapitated rats.Results: Raloxifene had a significant attenuating effect on the levels of MDA in brain tissues suggesting raloxifene’s effect against lipid peroxidation at the end of training days. With the comparison of brain regions, cortex showed the highest average activity of SOD and CAT and cerebellum had the lowest average levels for both. Its effects on learning and cognitive process with active avoidence task were considered insignificant.Conclusion: Raloxifene treatment may have preventive effects for the brain against oxidative stress and lipid peroxidation in rats

Analysis of Biotinylated Generation 4 Poly(amidoamine (PAMAM Dendrimer Distribution in the Rat Brain and Toxicity in a Cellular Model of the Blood-Brain Barrier

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Heather A. Bullen

2013-09-01

Full Text Available Dendrimers are highly customizable nanopolymers with qualities that make them ideal for drug delivery. The high binding affinity of biotin/avidin provides a useful approach to fluorescently label synthesized dendrimer-conjugates in cells and tissues. In addition, biotin may facilitate delivery of dendrimers through the blood-brain barrier (BBB via carrier-mediated endocytosis. The purpose of this research was to: (1 measure toxicity using lactate dehydrogenase (LDH assays of generation (G4 biotinylated and non-biotinylated poly(amidoamine (PAMAM dendrimers in a co-culture model of the BBB, (2 determine distribution of dendrimers in the rat brain, kidney, and liver following systemic administration of dendrimers, and (3 conduct atomic force microscopy (AFM on rat brain sections following systemic administration of dendrimers. LDH measurements showed that biotinylated dendrimers were toxic to cell co-culture after 48 h of treatment. Distribution studies showed evidence of biotinylated and non-biotinylated PAMAM dendrimers in brain. AFM studies showed evidence of dendrimers only in brain tissue of treated rats. These results indicate that biotinylation does not decrease toxicity associated with PAMAM dendrimers and that biotinylated PAMAM dendrimers distribute in the brain. Furthermore, this article provides evidence of nanoparticles in brain tissue following systemic administration of nanoparticles supported by both fluorescence microscopy and AFM.

The diffusion permeability to water of the rat blood-brain barrier

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Bolwig, T G; Lassen, N A

1975-01-01

The diffusion permeability to water of the rat blood-brain-barrier (BBB) was studied. Preliminary data obtained with the Oldendorf tissue uptake method (Oldendorf 1970) in seizure experiments suggested that the transfer from blood to brain of labelled water is diffusion-limited. More definite...... passage increased from 0.26 to 0.67 when the arterial carbon dioxide tension was changed from 15 to 85 mm Hg, a change increasing the cerebral blood flow about sixfold. This finding suggests that water does not pass the blood-brain barrier as freely as lipophilic gases....

Blood-brain barrier leakage after status epilepticus in rapamycin-treated rats I: Magnetic resonance imaging.

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van Vliet, Erwin A; Otte, Willem M; Wadman, Wytse J; Aronica, Eleonora; Kooij, Gijs; de Vries, Helga E; Dijkhuizen, Rick M; Gorter, Jan A

2016-01-01

The mammalian target of rapamycin (mTOR) pathway has received increasing attention as a potential antiepileptogenic target. Treatment with the mTOR inhibitor rapamycin after status epilepticus reduces the development of epilepsy in a rat model. To study whether rapamycin mediates this effect via restoration of blood-brain barrier (BBB) dysfunction, contrast-enhanced magnetic resonance imaging (CE-MRI) was used to determine BBB permeability throughout epileptogenesis. Imaging was repeatedly performed until 6 weeks after kainic acid-induced status epilepticus in rapamycin (6 mg/kg for 6 weeks starting 4 h after SE) and vehicle-treated rats, using gadobutrol as contrast agent. Seizures were detected using video monitoring in the week following the last imaging session. Gadobutrol leakage was widespread and extensive in both rapamycin and vehicle-treated epileptic rats during the acute phase, with the piriform cortex and amygdala as the most affected regions. Gadobutrol leakage was higher in rapamycin-treated rats 4 and 8 days after status epilepticus compared to vehicle-treated rats. However, during the chronic epileptic phase, gadobutrol leakage was lower in rapamycin-treated epileptic rats along with a decreased seizure frequency. This was confirmed by local fluorescein staining in the brains of the same rats. Total brain volume was reduced by this rapamycin treatment regimen. The initial slow recovery of BBB function in rapamycin-treated epileptic rats indicates that rapamycin does not reduce seizure activity by a gradual recovery of BBB integrity. The reduced BBB leakage during the chronic phase, however, could contribute to the decreased seizure frequency in post-status epilepticus rats treated with rapamycin. Furthermore, the data show that CE-MRI (using step-down infusion with gadobutrol) can be used as biomarker for monitoring the effect of drug therapy in rats. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Proteomic Analysis of Parkin Isoforms Expression in Different Rat Brain Areas.

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D'Amico, Agata Grazia; Maugeri, Grazia; Reitano, Rita; Cavallaro, Sebastiano; D'Agata, Velia

2016-10-01

PARK2 gene's mutations are related to the familial form of juvenile Parkinsonism, also known as the autosomic recessive juvenile Parkinsonism. This gene encodes for parkin, a 465-amino acid protein. To date, a large number of parkin isoforms, generated by an alternative splicing mechanism, have been described. Currently, Gene Bank lists 27 rat PARK2 transcripts, which matches to 20 exclusive parkin alternative splice variants. Despite the existence of these isoforms, most of the studies carried out so far, have been focused only on the originally cloned parkin. In this work we have analyzed the expression profile of parkin isoforms in some rat brain areas including prefrontal cortex, hippocampus, substantia nigra and cerebellum. To discriminate among these isoforms, we detected their localization through the use of two antibodies that are able to identify different domains of the parkin canonical sequence. Our analysis has revealed that at least fourteen parkin isoforms are expressed in rat brain with a various distribution in the regions analyzed. Our study might help to elucidate the pathophysiological role of these proteins in the central nervous system.

Effect of a water-maze procedure on the redox mechanisms in brain parts of aged rats

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Natalia Andreevna Krivova

2015-03-01

Full Text Available The Morris water maze (MWM is a tool for assessment of age-related cognitive deficits. In our work, MWM was used for appraisal of cognitive deficits in 11-month-old rats and investigation of the effect exerted by training in the Morris water maze on the redox mechanisms in rat brain parts. Young adult (3-month-old and aged (11-month-old male rats were trained in the water maze. Intact animals of the corresponding age were used as the reference groups. The level of pro- and antioxidant capacity in brain tissue homogenates was assessed using the chemiluminescence method.Cognitive deficits were found in 11-month-old rats: at the first day of training they showed only 30% of successful MWM trials. However, at the last training day the percentage of successful trials was equal for young adult and aged animals. This indicates that cognitive deficits in aged rats can be reversed by MWM training. Therewith, the MWM spatial learning procedure itself produces changes in different processes of redox homeostasis in 11-month-old and 3-month-old rats as compared to intact animals. Young adult rats showed a decrease in prooxidant capacity in all brain parts, while 11-month-old rats demonstrated an increase in antioxidant capacity in the olfactory bulb, pons + medulla oblongata and frontal lobe cortex. Hence, the MWM procedure activates the mechanisms that restrict the oxidative stress in brain parts. The obtained results may be an argument for further development of the animal training procedures aimed to activate the mechanisms responsible for age-related cognitive deficits. This may be useful not only for the development of training procedures applicable to human patients with age-related cognitive impairments, but also for their rehabilitation.

Protective effect of Xingnaojia formulation on rats with brain and liver damage caused by chronic alcoholism.

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Li, Shuang; Wang, S U; Guo, Zhi-Gang; Huang, Ning; Zhao, Fan-Rong; Zhu, Mo-Li; Ma, Li-Juan; Liang, Jin-Ying; Zhang, Yu-Lin; Huang, Zhong-Lin; Wan, Guang-Rui

2015-11-01

The aim of this study was to observe the effect of a formulation of traditional Chinese medicine extracts known as Xingnaojia (XNJ) on the liver function, learning ability and memory of rats with chronic alcoholism and to verify the mechanism by which it protects the brain and liver. A rat model of chronic alcoholism was used in the study. The spatial learning ability and memory of the rats were tested. The rats were then sacrificed and their brains and hepatic tissues were isolated. The activity of superoxide dismutase (SOD) and levels of glutamate (Glu), N-methyl D-aspartate receptor subtype 2B (NR2B), cyclin-dependent kinase 5 (CDK5) and cannabinoid receptor 1 (CB1) in the hippocampus were analyzed. The ultrastructure of the hepatic tissue was observed by electron microscopy. In addition, the activities of alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) in serum were tested and the levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), triglycerides (TG) and total cholesterol (TCHOL) were analyzed. XNJ enhanced the learning and memory of rats with chronic alcoholism. Treatment with XNJ increased the activity of SOD, and decreased the expression levels of NR2B mRNA and NR2B, CB1 and CDK5 proteins in the brain tissues compared with those in the model rats. It also increased the activity of ALDH in the serum and liver, decreased the serum levels of LDL, TG and TCHOL and increased the serum level of HDL. These results indicate that XNJ exhibited a protective effect against brain and liver damage in rats with chronic alcoholism.

Intranasal administration of vitamin D attenuates blood-brain barrier disruption through endogenous upregulation of osteopontin and activation of CD44/P-gp glycosylation signaling after subarachnoid hemorrhage in rats.

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Enkhjargal, Budbazar; McBride, Devin W; Manaenko, Anatol; Reis, Cesar; Sakai, Yasushi; Tang, Jiping; Zhang, John H

2017-07-01

In this study, we investigated the role of vitamin D3 (VitD3) on endogenous osteopontin (OPN), a neuroprotective glycoprotein, after subarachnoid hemorrhage (SAH). The endovascular perforation SAH model in Sprague-Dawley rats was used to study the effect of intranasal VitD3 (30 ng/kg) before (Pre-SAH + VitD3) and after (Post-SAH + VitD3) subarachnoid hemorrhage. Vitamin D3 (30, 60, 120 ng/kg/day) increased more than one fold endogenous OPN expression in astrocytes and endothelial cells of rat brain. Vitamin D3 significantly decreased brain edema and Evans blue extravasation. In addition, neurobehavioral scores were significantly higher in Pre-SAH + VitD3, but partly higher in Post-SAH + VitD3, group compared with SAH group. These protective effects of vitamin D3 were completely attenuated by intracerebroventricular injection of transcription inhibitor Actinomycin D and significantly inhibited by small interfering ribonucleic acid (siRNA) for vitamin D receptor and OPN in Pre-SAH + VitD3 rats. OPN expression was significantly higher in Pre-SAH + VitD3 rats, specifically A and C, but not B, isomers were upregulated in the astrocytes, leading to CD44 splicing, and P-gp glycosylation in brain endothelial cells. The results show that intranasal vitamin D3 attenuates blood-brain barrier (BBB) disruption through endogenous upregulation of OPN and subsequent CD44 and P-gp glycosylation signals in brain endothelial cells. Furthermore, this study identifies a novel strategy for the cost-effective management of subarachnoid hemorrhage.

Fecal microbiota variation across the lifespan of the healthy laboratory rat.

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Flemer, Burkhardt; Gaci, Nadia; Borrel, Guillaume; Sanderson, Ian R; Chaudhary, Prem P; Tottey, William; O'Toole, Paul W; Brugère, Jean-François

2017-09-03

Laboratory rats are commonly used in life science research as a model for human biology and disease, but the composition and development of their gut microbiota during life is poorly understood. We determined the fecal microbiota composition of healthy Sprague Dawley laboratory rats from 3 weeks to 2 y of age, kept under controlled environmental and dietary conditions. Additionally, we determined fecal short-chain fatty acid profiles, and we compared the rat fecal microbiota with that of mice and humans. Gut microbiota and to a lesser extent SCFAs profiles separated rats into 3 different clusters according to age: before weaning, first year of life (12- to 26-week-old animals) and second year of life (52- to 104-week-old). A core of 46 bacterial species was present in all rats but its members' relative abundance progressively decreased with age. This was accompanied by an increase of microbiota α-diversity, likely due to the acquisition of environmental microorganisms during the lifespan. Contrastingly, the functional profile of the microbiota across animal species became more similar upon aging. Lastly, the microbiota of rats and mice were most similar to each other but at the same time the microbiota profile of rats was more similar to that of humans than was the microbiota profile of mice. These data offer an explanation as to why germ-free rats are more efficient recipients and retainers of human microbiota than mice. Furthermore, experimental design should take into account dynamic changes in the microbiota of model animals considering that their changing gut microbiota interacts with their physiology.

Obesity and type 2 diabetes in rats are associated with altered brain glycogen and amino-acid homeostasis

DEFF Research Database (Denmark)

Sickmann, Helle M; Waagepetersen, Helle S; Schousboe, Arne

2010-01-01

Obesity and type 2 diabetes have reached epidemic proportions; however, scarce information about how these metabolic syndromes influence brain energy and neurotransmitter homeostasis exist. The objective of this study was to elucidate how brain glycogen and neurotransmitter homeostasis are affected...... by these conditions. [1-(13)C]glucose was administered to Zucker obese (ZO) and Zucker diabetic fatty (ZDF) rats. Sprague-Dawley (SprD), Zucker lean (ZL), and ZDF lean rats were used as controls. Several brain regions were analyzed for glycogen levels along with (13)C-labeling and content of glutamate, glutamine...... of glutamine and glutamate were decreased in the cerebellum of the ZO and the ZDF rats. Glycogen levels were also lower in this region. These results suggest that the obese and type 2 diabetic models were associated with lower brain glucose metabolism. Glucose metabolism through the TCA cycle was more...

Extended Erythropoietin Treatment Prevents Chronic Executive Functional and Microstructural Deficits Following Early Severe Traumatic Brain Injury in Rats

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Shenandoah Robinson

2018-06-01

Full Text Available Survivors of infant traumatic brain injury (TBI are prone to chronic neurological deficits that impose lifelong individual and societal burdens. Translation of novel interventions to clinical trials is hampered in part by the lack of truly representative preclinical tests of cognition and corresponding biomarkers of functional outcomes. To address this gap, the ability of a high-dose, extended, post-injury regimen of erythropoietin (EPO, 3000U/kg/dose × 6d to prevent chronic cognitive and imaging deficits was tested in a postnatal day 12 (P12 controlled-cortical impact (CCI model in rats, using touchscreen operant chambers and regional analysis of diffusion tensor imaging (DTI. Results indicate that EPO prevents functional injury and MRI injury after infant TBI. Specifically, subacute DTI at P30 revealed widespread microstructural damage that is prevented by EPO. Assessment of visual discrimination on a touchscreen operant chamber platform demonstrated that all groups can perform visual discrimination. However, CCI rats treated with vehicle failed to pass reversal learning, and perseverated, in contrast to sham and CCI-EPO rats. Chronic DTI at P90 showed EPO treatment prevented contralateral white matter and ipsilateral lateral prefrontal cortex damage. This DTI improvement correlated with cognitive performance. Taken together, extended EPO treatment restores executive function and prevents microstructural brain abnormalities in adult rats with cognitive deficits in a translational preclinical model of infant TBI. Sophisticated testing with touchscreen operant chambers and regional DTI analyses may expedite translation and effective yield of interventions from preclinical studies to clinical trials. Collectively, these data support the use of EPO in clinical trials for human infants with TBI.

Whole body synthesis rates of DHA from α-linolenic acid are greater than brain DHA accretion and uptake rates in adult rats.

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Domenichiello, Anthony F; Chen, Chuck T; Trepanier, Marc-Olivier; Stavro, P Mark; Bazinet, Richard P

2014-01-01

Docosahexaenoic acid (DHA) is important for brain function, however, the exact amount required for the brain is not agreed upon. While it is believed that the synthesis rate of DHA from α-linolenic acid (ALA) is low, how this synthesis rate compares with the amount of DHA required to maintain brain DHA levels is unknown. The objective of this work was to assess whether DHA synthesis from ALA is sufficient for the brain. To test this, rats consumed a diet low in n-3 PUFAs, or a diet containing ALA or DHA for 15 weeks. Over the 15 weeks, whole body and brain DHA accretion was measured, while at the end of the study, whole body DHA synthesis rates, brain gene expression, and DHA uptake rates were measured. Despite large differences in body DHA accretion, there was no difference in brain DHA accretion between rats fed ALA and DHA. In rats fed ALA, DHA synthesis and accretion was 100-fold higher than brain DHA accretion of rats fed DHA. Also, ALA-fed rats synthesized approximately 3-fold more DHA than the DHA uptake rate into the brain. This work indicates that DHA synthesis from ALA may be sufficient to supply the brain.

Brain-wide map of efferent projections from rat barrel cortex

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Izabela M. Zakiewicz

2014-02-01

Full Text Available The somatotopically organized whisker barrel field of the rat primary somatosensory (S1 cortex is a commonly used model system for anatomical and physiological investigations of sensory processing. The neural connections of the barrel cortex have been extensively mapped. But most investigations have focused on connections to limited regions of the brain, and overviews in the literature of the connections across the brain thus build on a range of material from different laboratories, presented in numerous publications. Furthermore, given the limitations of the conventional journal article format, analyses and interpretations are hampered by lack of access to the underlying experimental data. New opportunities for analyses have emerged with the recent release of an online resource of experimental data consisting of collections of high-resolution images from 6 experiments in which anterograde tracers were injected in S1 whisker or forelimb representations. Building on this material, we have conducted a detailed analysis of the brain wide distribution of the efferent projections of the rat barrel cortex. We compare our findings with the available literature and reports accumulated in the Brain Architecture Management System (BAMS2 database. We report well-known and less known intracortical and subcortical projections of the barrel cortex, as well as distinct differences between S1 whisker and forelimb related projections. Our results correspond well with recently published overviews, but provide additional information about relative differences among S1 projection targets. Our approach demonstrates how collections of shared experimental image data are suitable for brain-wide analysis and interpretation of connectivity mapping data.

Rat brain sagittal organotypic slice cultures as an ex vivo dopamine cell loss system.

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McCaughey-Chapman, Amy; Connor, Bronwen

2017-02-01

Organotypic brain slice cultures are a useful tool to study neurological function as they provide a more complex, 3-dimensional system than standard 2-dimensional in vitro cell cultures. Building on a previously developed mouse brain slice culture protocol, we have developed a rat sagittal brain slice culture system as an ex vivo model of dopamine cell loss. We show that rat brain organotypic slice cultures remain viable for up to 6 weeks in culture. Using Fluoro-Gold axonal tracing, we demonstrate that the slice 3-dimensional cytoarchitecture is maintained over a 4 week culturing period, with particular focus on the nigrostriatal pathway. Treatment of the cultures with 6-hydroxydopamine and desipramine induces a progressive loss of Fluoro-Gold-positive nigral cells with a sustained loss of tyrosine hydroxylase-positive nigral cells. This recapitulates the pattern of dopaminergic degeneration observed in the rat partial 6-hydroxydopamine lesion model and, most importantly, the progressive pathology of Parkinson's disease. Our slice culture platform provides an advance over other systems, as we demonstrate for the first time 3-dimensional cytoarchitecture maintenance of rat nigrostriatal sagittal slices for up to 6 weeks. Our ex vivo organotypic slice culture system provides a long term cellular platform to model Parkinson's disease, allowing for the elucidation of mechanisms involved in dopaminergic neuron degeneration and the capability to study cellular integration and plasticity ex vivo. Copyright © 2017 Elsevier B.V. All rights reserved.

Effect of hyperbaric oxygen on lipid peroxidation and visual development in neonatal rats with hypoxia-ischemia brain damage.

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Chen, Jing; Chen, Yan-Hui; Lv, Hong-Yan; Chen, Li-Ting

2016-07-01

The aim of the present study was to investigate the effect of hyperbaric oxygen (HBO) on lipid peroxidation and visual development in a neonatal rat model of hypoxic-ischemic brain damage (HIBD). The rat models of HIBD were established by delayed uterus dissection and were divided randomly into two groups (10 rats each): HIBD and HBO-treated HIBD (HIBD+HBO) group. Another 20 rats that underwent sham-surgery were also divided randomly into the HBO-treated and control groups. The rats that underwent HBO treatment received HBO (0.02 MPa, 1 h/day) 24 h after the surgery and this continued for 14 days. When rats were 4 weeks old, their flash visual evoked potentials (F-VEPs) were monitored and the ultrastructures of the hippocampus were observed under transmission electron microscope. The levels of superoxide dismutase (SOD) and malonyldialdehyde (MDA) in the brain tissue homogenate were detected by xanthine oxidase and the thiobarbituric acid colorimetric method. Compared with the control group, the ultrastructures of the pyramidal neurons in the hippocampal CA3 area were distorted, the latencies of F-VEPs were prolonged (P0.05). HBO enhances antioxidant capacity and reduces the ultrastructural damage induced by hypoxic-ischemia, which may improve synaptic reconstruction and alleviate immature brain damage to promote the habilitation of brain function.

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

Primary microglia isolation from mixed glial cell cultures of neonatal rat brain tissue.

Science.gov (United States)

Tamashiro, Tami T; Dalgard, Clifton Lee; Byrnes, Kimberly R

2012-08-15

Microglia account for approximately 12% of the total cellular population in the mammalian brain. While neurons and astrocytes are considered the major cell types of the nervous system, microglia play a significant role in normal brain physiology by monitoring tissue for debris and pathogens and maintaining homeostasis in the parenchyma via phagocytic activity. Microglia are activated during a number of injury and disease conditions, including neurodegenerative disease, traumatic brain injury, and nervous system infection. Under these activating conditions, microglia increase their phagocytic activity, undergo morpohological and proliferative change, and actively secrete reactive oxygen and nitrogen species, pro-inflammatory chemokines and cytokines, often activating a paracrine or autocrine loop. As these microglial responses contribute to disease pathogenesis in neurological conditions, research focused on microglia is warranted. Due to the cellular heterogeneity of the brain, it is technically difficult to obtain sufficient microglial sample material with high purity during in vivo experiments. Current research on the neuroprotective and neurotoxic functions of microglia require a routine technical method to consistently generate pure and healthy microglia with sufficient yield for study. We present, in text and video, a protocol to isolate pure primary microglia from mixed glia cultures for a variety of downstream applications. Briefly, this technique utilizes dissociated brain tissue from neonatal rat pups to produce mixed glial cell cultures. After the mixed glial cultures reach confluency, primary microglia are mechanically isolated from the culture by a brief duration of shaking. The microglia are then plated at high purity for experimental study. The principle and protocol of this methodology have been described in the literature. Additionally, alternate methodologies to isolate primary microglia are well described. Homogenized brain tissue may be separated

Distribution of [3H]diadenosine tetraphosphate binding sites in rat brain

International Nuclear Information System (INIS)

Miras-Portugal, M.T.; Palacios, J.M.; Torres, M.; Cortes, R.; Rodriguez-Pascual, F.

1997-01-01

The distribution of the diadenosine tetraphosphate high-affinity binding sites has been studied in rat brain by an autoradiographic method using [ 3 H]diadenosine tetraphosphate as the ligand. The binding characteristics are comparable to those described in studies performed on rat brain synaptosomes. White matter is devoid of specific binding. The range of binding site densities in gray matter varies from 3 to 15 fmol/mg of tissue, exhibiting a widespread but heterogeneous distribution. The highest densities correspond to the seventh cranial nerve, medial superior olive, pontine nuclei, glomerular and external plexiform layers of the olfactory bulb, and the granule cell layer of the cerebellar cortex. Intermediate density levels of binding correspond to different cortical areas, several nuclei of the amygdala, and the oriens and pyramidal layers of the hippocampal formation.The localization of diadenosine tetraphosphate binding sites in the brain may provide information on the places where diadenosine polyphosphate compounds can be expected to function in the central nervous system. (Copyright (c) 1997 Elsevier Science B.V., Amsterdam. All rights reserved.)

Dynamics of pathomorphological changes in rat brain as a function of γ-radiation dose

International Nuclear Information System (INIS)

Fedorov, V.P.

1990-01-01

Neurohistological, histochemical, electron-microscopic and biometric techniques were used to study the response of rat brain to irradiation within a wide range of doses. Nerve cells were shown to be highly radioresistant. At the same time, synapses and blood-brain barrier structures were highly radiosensitive. The pathomorphologic changes in different brain areas followed a dose-time function