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

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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

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)

Differential numbers of foci of lymphocytes within the brains of Lewis rats exposed to weak complex nocturnal magnetic fields during development of experimental allergic encephalomyelitis.

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Persinger, Michael A

2009-01-01

To discern if specific structures of the rat brain contained more foci of lymphocytes following induction of experimental allergic encephalomyelitis and exposures to weak, amplitude-modulated magnetic fields for 6 min once per hour during the scotophase, the residuals between the observed and predicted values for the numbers of foci for 320 structures were obtained. Compared to the brains of sham-field exposed rats, the brains of rats exposed to 7-Hz 50 nT (0.5 mG) amplitude-modulated fields showed more foci within hippocampal structures and the dorsal central grey of the midbrain while those exposed to 7-Hz 500 nT (5 mG) fields showed greater densities within the hypothalamus and optic chiasm. The brains of rats exposed to either the 50 nT or 500 nT amplitude-modulated 40-Hz fields displayed greater densities of foci within the midbrain structures related to rapid eye movement. Most of the enhancements of infiltrations within the magnetic field-exposed rats occurred in structures within periventricular or periaqueductal regions and were both frequency- and intensity-dependent. The specificity and complexity of the configurations of the residuals of the numbers of infiltrated foci following exposures to the different fields suggest that the brain itself may be a "sensory organ" for the detection of these stimuli.

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

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

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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

Impact of experimental hypothyroidism on monoamines level in discrete brain regions and other peripheral tissues of young and adult male rats.

Science.gov (United States)

Hassan, Wafaa A; Aly, Mona S; Rahman, Taghride Abdel; Shahat, Asmaa S

2013-06-01

The levels of dopamine (DA), norepinephrine (NE) and serotonin (5-HT) in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats were measured following experimentally induced hypothyroidism. Hypothyroidism induced by daily oral administration of propylthiouracil (PTU, 5mg/kg body wt) caused a significant reduction in DA levels in most of the tissues examined of both young and adult rats after 21 and 28 days, in NE levels after all the time intervals studied in young rats, and after 21 and 28 days in adult rats. 5-HT exhibited a significant reduction in the selected brain regions and blood plasma after 21 and 28 days and in cardiac muscle after all the time intervals in the two age groups of animals. It may be suggested that the changes in monoamine levels induced by hypothyroidism may be due to disturbance in the synthesis and release of these amines through the neurons impairment or may be due to an alteration pattern of their synthesizing and/or degradative enzymes. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

Functional Magnetic Resonance Imaging of Rats with Experimental Autoimmune Encephalomyelitis Reveals Brain Cortex Remodeling

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Tambalo, Stefano; Peruzzotti-Jametti, Luca; Rigolio, Roberta; Fiorini, Silvia; Bontempi, Pietro; Mallucci, Giulia; Balzarotti, Beatrice; Marmiroli, Paola; Sbarbati, Andrea; Cavaletti, Guido

2015-01-01

Cortical reorganization occurring in multiple sclerosis (MS) patients is thought to play a key role in limiting the effect of structural tissue damage. Conversely, its exhaustion may contribute to the irreversible disability that accumulates with disease progression. Several aspects of MS-related cortical reorganization, including the overall functional effect and likely modulation by therapies, still remain to be elucidated. The aim of this work was to assess the extent of functional cortical reorganization and its brain structural/pathological correlates in Dark Agouti rats with experimental autoimmune encephalomyelitis (EAE), a widely accepted preclinical model of chronic MS. Morphological and functional MRI (fMRI) were performed before disease induction and during the relapsing and chronic phases of EAE. During somatosensory stimulation of the right forepaw, fMRI demonstrated that cortical reorganization occurs in both relapsing and chronic phases of EAE with increased activated volume and decreased laterality index versus baseline values. Voxel-based morphometry demonstrated gray matter (GM) atrophy in the cerebral cortex, and both GM and white matter atrophy were assessed by ex vivo pathology of the sensorimotor cortex and corpus callosum. Neuroinflammation persisted in the relapsing and chronic phases, with dendritic spine density in the layer IV sensory neurons inversely correlating with the number of cluster of differentiation 45-positive inflammatory lesions. Our work provides an innovative experimental platform that may be pivotal for the comprehension of key mechanisms responsible for the accumulation of irreversible brain damage and for the development of innovative therapies to reduce disability in EAE/MS. SIGNIFICANCE STATEMENT Since the early 2000s, functional MRI (fMRI) has demonstrated profound modifications in the recruitment of cortical areas during motor, cognitive, and sensory tasks in multiple sclerosis (MS) patients. Experimental autoimmune

Significance of the expression of matrix metalloproteinase-9 (MMP-9) in brain tissue of rat models of experimental intracerebral haemorrhage (ICH)

International Nuclear Information System (INIS)

Wu Jiami; Liu Shengda

2005-01-01

Objective: To study the relationship between the brain tissue expression of MMP-9 and brain water content in rat models of experimental ICH. Methods: Rat models of ICH were prepared with intracerebral (caudate nuclei) injection of autologous noncoagulated blood (50 μl). Animals were sacrificed at 6h, 12h, 24h, 48h, 72h, 120h, lw, 2w and the MMP-9 expressions at the periphery of intracerebral hematoma were examined with immunohisto chemistry. The brain water content was also determined at the same time. Control models were prepared with intracerebral sham injection of normal saline. Results: (1) In the ICH models, the number of MMP-9 positive capillaries at the periphery of hematoma began to rise at 6h (vs that of sham group, P < 0.01 ) with peak at 48h, then gradually dropped. At lwk, the number was still significantly higher than that in the sham group (P <0.01 ). However, there were no expression at 2wk. (2) The brain water content in the ICH group was significantly increased at 12h (vs sham group, P < 0.05) with peak at 72h. At lwk, the brain water content was still significantly higher in the ICH group (P <0.01 ) but at 2wk, the brain water content was about the same in both groups. (3) Animals injected with different amounts of blood (30 μl, 50 μl, 100 μl) showed increased expression of MMP-9 along with the increase of dose (P<0.01). (4) The MMP-9 expression was positively correlated with the brain water content (r=0.8291, P<0.05). Conclusion: In the rat models, MMP-9 expression was activated after ICH. The increase paralleled that of the amount of haemorrhage and brain water content. It was postulated that MMP-9 enhanced development of brain edema through degrading of the blood brain barrier component substances. (authors)

Aluminum neurotoxicity in the rat brain

International Nuclear Information System (INIS)

Yumoto, S.; Ohashi, H.; Nagai, H.; Kakimi, S.; Ogawa, Y.; Iwata, Y.; Ishii, K.

1992-01-01

To investigate the etiology of Alzheimer's disease, we administered aluminum to healthy rats and examined the aluminum uptake in the brain and isolated brain cell nuclei by particle-induced X-ray emission (PIXE) analysis. Ten days after the last injection, Al was detected in the rat brain and in isolated brain cell nuclei by PIXE analysis. Al was also demonstrated in the brain after 15 months of oral aluminum administration. Moreover, Al was detected in the brain and isolated brain cell nuclei from the patients with Alzheimer's disease. Silver impregnation studies revealed that spines attached to the dendritic processes of cortical nerve cells decreased remarkably after aluminum administration. Electron microscopy revealed characteristic inclusion bodies in the hippocampal nerve cells 75 days after the injection. These morphological changes in the rat brain after the aluminum administration were similar to those reportedly observed in the brain of Alzheimer's disease patients. Our results indicate that Alzheimer's disease is caused by irreversible accumulation of aluminum in the brain, as well as in the nuclei of brain cells. (author)

Aluminum neurotoxicity in the rat brain

Energy Technology Data Exchange (ETDEWEB)

Yumoto, S [Tokyo Univ. (Japan). Faculty of Medicine; Ohashi, H; Nagai, H; Kakimi, S; Ogawa, Y; Iwata, Y; Ishii, K

1993-12-31

To investigate the etiology of Alzheimer`s disease, we administered aluminum to healthy rats and examined the aluminum uptake in the brain and isolated brain cell nuclei by particle-induced X-ray emission (PIXE) analysis. Ten days after the last injection, Al was detected in the rat brain and in isolated brain cell nuclei by PIXE analysis. Al was also demonstrated in the brain after 15 months of oral aluminum administration. Moreover, Al was detected in the brain and isolated brain cell nuclei from the patients with Alzheimer`s disease. Silver impregnation studies revealed that spines attached to the dendritic processes of cortical nerve cells decreased remarkably after aluminum administration. Electron microscopy revealed characteristic inclusion bodies in the hippocampal nerve cells 75 days after the injection. These morphological changes in the rat brain after the aluminum administration were similar to those reportedly observed in the brain of Alzheimer`s disease patients. Our results indicate that Alzheimer`s disease is caused by irreversible accumulation of aluminum in the brain, as well as in the nuclei of brain cells. (author).

Brain protection by methylprednisolone in rats with spinal cord injury.

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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.

Complement mRNA in the mammalian brain: responses to Alzheimer's disease and experimental brain lesioning.

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Johnson, S A; Lampert-Etchells, M; Pasinetti, G M; Rozovsky, I; Finch, C E

1992-01-01

This study describes evidence in the adult human and rat brain for mRNAs that encode two complement (C) proteins, C1qB and C4. C proteins are important effectors of humoral immunity and inflammation in peripheral tissues but have not been considered as normally present in brain. Previous immunocytochemical studies showed that C proteins are associated with plaques, tangles, and dystrophic neurites in Alzheimer's disease (AD), but their source is unknown. Combined immunocytochemistry and in situ hybridization techniques show C4 mRNA in pyramidal neurons and C1qB mRNA in microglia. Primary rat neuron cultures also show C1qB mRNA. In the cortex from AD brains, there were two- to threefold increases of C1qB mRNA and C4 mRNA, and increased C1qB mRNA prevalence was in part associated with microglia. As a model for AD, we examined entorhinal cortex perforant path transection in the rat brain, which caused rapid increases of C1qB mRNA in the ipsilateral, but not contralateral, hippocampus and entorhinal cortex. The role of brain-derived acute and chronic C induction during AD and experimental lesions can now be considered in relation to functions of C proteins that pertain to cell degeneration and/or cell preservation and synaptic plasticity.

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.

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

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.

Effect of MgSO4 on expression of NSE and S-100 in rats brain tissue irradiated by 6 MeV electron beam

International Nuclear Information System (INIS)

Zhou Juying; Wang Lili; Yu Zhiying; Qin Songbing; Xu Xiaoting; Li Li; Tu Yu

2007-01-01

Objective: To explore the protection of magnesium sulfate (MgSO 4 ) on radiation-induced acute brain injuries. Methods: Thirty six mature Sprague-Dawley rats were randomly divided into 3 groups: blank control group, experimental control group and experimental administered group. The whole brain of SD rats of experimental control group and experimental-therapeutic group were irradiated with a dose of 20 Gy using 6 MeV electron beam. Magnesium sulfate was injected intraperitoneally into the rats of experimental-therapeutic group before and after irradiation for five times. The brain tissue were taken on days 1, 7, 14 and 30 after irradiation. Immunohistochemical method was used to detect the expressions of NSE and S-100 in brain tissue. All data were processed statistically with One-ANOVA analysis. Results: The expressions of NSE and S-100 after whole brain irradiation were time-dependent. Compared with blank control group, the expression of NSE in brains of experimental control group decreased significantly (P 4 can inhibit the expression of S-100, but induce the expression of NSE on radiation-induced acute brain injury. MgSO 4 has a protective effect on radiation-induced acute brain injury. (authors)

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

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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.).

Alterations in monoamines level in discrete brain regions and other peripheral tissues in young and adult male rats during experimental hyperthyroidism.

Science.gov (United States)

Hassan, Wafaa A; Rahman, Taghride Abdel; Aly, Mona S; Shahat, Asmaa S

2013-08-01

The present study was conducted to investigate the effect of experimentally-induced hyperthyroidism on dopamine (DA), norepinephrine (NE) and serotonin (5-HT) levels in different brain regions as well as in blood plasma, cardiac muscle and adrenal gland of young and adult male albino rats (60 rats of each age). Hyperthyroidism was induced by daily s.c. injection of L-thyroxine (L-T4, 500 μg/kg body wt.) for 21 consecutive days. Induction of hyperthyroidism caused a significant elevation in DA and 5-HT levels in most of the tissues studied of both young and adult animals after 7, 14, and 21 days. NE content significantly decreased after 21 days in most of the brain regions examined and after 14 and 21 days in blood plasma of young rats following hyperthyroidism. In adult rats, NE content decreased after 14 and 21 days in cardiac muscle and after 21 days only in adrenal gland. It may be suggested that the changes in monoamines level induced by hyperthyroidism may be due to disturbance in the synthesis, turnover and release of these amines through the neurons impairment or may attributed to an alteration pattern of their synthesis and/or degradative enzymes or changes in the sensitivity of their receptors. Copyright © 2013 ISDN. Published by Elsevier Ltd. All rights reserved.

An experimental study on the mechanical properties of rat brain tissue using different stress-strain definitions.

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Karimi, Alireza; Navidbakhsh, Mahdi

2014-07-01

There are different stress-strain definitions to measure the mechanical properties of the brain tissue. However, there is no agreement as to which stress-strain definition should be employed to measure the mechanical properties of the brain tissue at both the longitudinal and circumferential directions. It is worth knowing that an optimize stress-strain definition of the brain tissue at different loading directions may have implications for neuronavigation and surgery simulation through haptic devices. This study is aimed to conduct a comparative study on different results are given by the various definitions of stress-strain and to recommend a specific definition when testing brain tissues. Prepared cylindrical samples are excised from the parietal lobes of rats' brains and experimentally tested by applying load on both the longitudinal and circumferential directions. Three stress definitions (second Piola-Kichhoff stress, engineering stress, and true stress) and four strain definitions (Almansi-Hamel strain, Green-St. Venant strain, engineering strain, and true strain) are used to determine the elastic modulus, maximum stress and strain. The highest non-linear stress-strain relation is observed for the Almansi-Hamel strain definition and it may overestimate the elastic modulus at different stress definitions at both the longitudinal and circumferential directions. The Green-St. Venant strain definition fails to address the non-linear stress-strain relation using different definitions of stress and triggers an underestimation of the elastic modulus. The results suggest the application of the true stress-true strain definition for characterization of the brain tissues mechanics since it gives more accurate measurements of the tissue's response using the instantaneous values.

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.

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)

Caspase Activation in Fetal Rat Brain Following Experimental Intrauterine Inflammation

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Sharangpani, Aditi; Takanohashi, Asako; Bell, Michael J.

2009-01-01

Intrauterine inflammation has been implicated in developmental brain injuries, including the development of periventricular leukomalacia (PVL) and cerebral palsy (CP). Previous studies in our rat model of intrauterine inflammation demonstrated apoptotic cell death in fetal brains within the first 5 days after lipopolysaccharide (LPS) administration to mothers and eventual dysmyelination. Cysteine-containing, aspartate-specific proteases, or caspases, are proteins involved with apoptosis through both intracellular (intrinsic pathway) and extracellular (extrinsic pathway) mechanisms. We hypothesized that cell death in our model would occur mainly via activation of the extrinsic pathway. We further hypothesized that Fas, a member of the tumor necrosis factor receptor (TNFR) superfamily, would be increased and the death inducing signaling complex (DISC) would be detectable. Pregnant rats were injected intracervically with LPS at E15 and immunoblotting, immunohistochemical and immunoprecipitation analyses were performed. The presence of the activated form of the effector caspase (caspase-3) was observed 24 h after LPS administration. Caspase activity assays demonstrated rapid increases in (i) caspases-9 and -10 within 1 h, (ii) caspase-8 at 2 h and (iii) caspase-3 at 4 h. At 24 h after LPS, activated caspase-3+/Fas+ cells were observed within the developing white matter. Lastly, the DISC complex (caspase-8, Fas and Fas-associated Death Domain (FADD)) was observed within 30 min by immunoprecipitation. Apoptosis in our model occurs via both extrinsic and intrinsic pathways, and activation of Fas may play a role. Understanding the mechanisms of cell death in models of intrauterine inflammation may affect development of future strategies to mitigate these injuries in children. PMID:18289516

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.

Content of NCAM in the brain and pancreas of rats in response to endointoxication under conditions of experimental chronic pancreatitis

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V. A. Makarchuk

2014-08-01

Full Text Available The study was undertaken to examine the influence of chronic pancreatitis on the distribution of neuronal cell adhesion molecule (NCAM in the pancreas and various brain regions of rats under the conditions of endogenous intoxication. The study was conducted using 36 white nonlinear male rats (6 months old, 190–220 g. To develop the state of chronic pancreatitis, animals were subjected tolaparotomy under general anesthesia and prolonged occlusion of the pancreatic duct. The morphological examination of pancreatic tissue hasbeen performed to confirm the chronic pancreatitis development in animals. Biochemical evaluation of the pancreatic fibrosis has been performed by measuring plasma levels of hyaluronic acid, hydroxyproline and protein-free hydroxyproline. The intensity of free radical oxidation has been assessed by the change in the concentration of TBA-active products in plasma. The level of endotoxemia has been determinedby the content of average weight molecules in plasma. Protein fractions were extracted from the pancreas and various parts of the rat brain and the levels of soluble (sNCAM and membrane (mNCAM proteins were studied with the use of the competitive ELISA. Total protein in the obtained fractions was measured by the Bradford assay. Occlusion of the pancreatic duct resultedin significant atrophy of acinar tissue, fibrosis and disfunction of the pancreas along with the decreasing in the antioxidant defense of animals. The present study shows developing of endointoxication in experimentalrats, signified by considerable increase of molecules with average weight in plasma due to the activation of lipid peroxidation. It was established that, as a result of the experimental pancreas dysfunction, significant redistribution of soluble and membrane forms of NCAM took place, more especially in the cerebellum and thalamus of rats; it caused changing of cell-cell adhesion in these brain regions. Multidirectional NCAM distribution in the

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

Possible antidepressant effects of vanillin against experimentally induced chronic mild stress in rats

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Amira M. Abo-youssef

2016-06-01

Full Text Available Vanillin is a flavoring agent widely used in food and beverages such as chocolates and dairy products and it is also used to mask unpleasant tastes in medicine. It has been reported to have antioxidant, anti-inflammatory and antiapoptotic properties. The current study was designed to investigate the protective effects of vanillin against experimentally induced stress in rats. Briefly rats were subdivided into four groups. Three groups were subjected to chronic mild stress and the fourth group served as normal control group. One week before induction of stress drugs or saline was administered daily and continued for another nine weeks. At the end of the experimental period behavioral tests including sucrose preference test, forced swim test and elevated plus maze test were assessed. In addition, brain biochemical parameters including MDA, GSH, NO and serotonin were determined. Vanillin succeeded to restore the behavioral and biochemical changes associated with stress. It significantly increased sucrose consumption in sucrose preference test and time spent in open arm in elevated plus maze test as compared to stress control group. It also reduced immobility time in forced swim test and time spent in closed arm in elevated plus maze test. Additionally, it significantly decreased brain MDA and NO levels and significantly increased brain GSH and Serotonin levels compared to stress control group. It could be concluded that vanillin showed beneficial protective effects against experimentally induced stress in rats.

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

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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.

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.

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 ...

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.

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.

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

Comparative study of the effects of experimentally induced hypothyroidism and hyperthyroidism in some brain regions in albino rats.

Science.gov (United States)

El-Bakry, A M; El-Gareib, A W; Ahmed, R G

2010-08-01

Thyroid hormones (THs) play a crucial role in the development and physiological functioning of different body organs especially the brain. Therefore, the objective of this study was to show the histopathological effects of the different thyroid states on some brain regions (cerebrum and cerebellum) and the skeletal features of their newborns during the postnatal development from the 1st to 3rd week. The female white albino rats were allocated into 3 groups as follows: the experimental hypothyroidism group is induced by 0.02% methimazole (MMI) (w/v) in drinking water, while the experimental hyperthyroidism group is performed by exogenous T4 [from 50 to 200microg/kg body weight intragastric administration beside adding 0.002% T4 (w/v) to the drinking water] from the gestation day 1 to lactation day 21 and control group which received tap water. As well, both maternal hypo- and hyperthyroidism caused some malformation and developmental defects in the cerebellar and cerebral cortex of their newborns along the duration of the experiment. These degenerative symptoms became more prominent and widely spread at the 3rd postnatal week. Concomitantly, there were some degeneration, deformation and severe growth retardation in neurons of these regions in both treated groups throughout the experimental period. Moreover, the skeletal features of these newborns were accelerated in hyperthyroid group while these maturations were delayed partially in hypothyroid ones during the examined periods. These alterations, on both treated groups, were age and dose dependent. Thus, further studies need to be done to emphasize this concept. Published by Elsevier Ltd.

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

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Julie Y H Chan

2011-03-01

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

[Liposome-mediated glial growth factor 2 gene therapy in brain injury: an experimental study with rats].

Science.gov (United States)

Xue, Ya-jun; Dong, Yan; Han, Xi; Wei, Mei-yang; Ge, Jun-hui; Cai, Ru-jue; Hu, Guo-han; Luo, Chun; Zhu, Cheng; Lu, Yi-cheng

2006-09-05

To explore the protective effect of glial growth factor-2 (GGF2) on brain injury. Thirty-four SD rats underwent lateral fluid percussion to establish brain injury models and then were randomly divided into 4 groups: treatment group (n = 10, the plasmid pEGFP-N1-GGF2 mixed with liposome was injected into the brain tissue directly), vector control group (n = 10, the vector pEGFP-N1 mixed with liposome was injected into the brain tissue directly), liposome control group (n = 10, liposome was injected), and sham operation group (n = 4). Three assessment tasks were performed for neurobehavioral evaluation: Clivas Test, Beam Balance Test and Beam Walking Test. 10 days after brain injury, the rats were sacrificed and their brains were embedded in paraffin for HE staining, Nissle staining and immunohistochemical examination of MBP, NSE, and GFAP. The Clivas test score of the treatment group was 66.25 +/- 3.54, significantly higher than those of the vector control group and. liposome control group (58.31 +/- 3.72 and 57.21 +/- 3.93 respectively, both P beam test score of the treatment group was 2.59 +/- 0.21, significantly lower than those the vector control group and liposome control group (3.41 +/- 0.25 and 3.24 +/- 0.22 respectively, both P walking test score of the treatment group was 20.15 +/- 2.59, significantly lower than those of control group and liposome control group (27.00 +/- 3.47 and 27.80 +/- 3.00 respectively, both P beam walking test was the greatest. The neuron number in the external granular layer and external pyramidal layer in cortex of the treatment group was 98 +/- 10, significantly more than those of the vector control group and liposome group (75 +/- 7 and 67 +/- 8, both P < 0.05). The neuron number in the internal pyramidal layer in cortex of the treatment group was 37 +/- 4, significantly more than those of the vector control group and liposome group (19 +/- 3 and 23 +/- 4 respectively, both P < 0.05). The neuron number in the CA1 region in

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

Effects Of Amitryptilin Administration on Rat Sera and Brain Beta-endorphins

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Radivoj Jadrić

2006-11-01

Full Text Available The aim of our study was to establish the influence of antidepressive drugs on serum and brain beta-endorphins in experimental animals. Experiment was performed on albino Wistar rats. Antidepressant amitryptiline was used, and for quantification of sera and brain beta-endorphins RIA technique. Our results showed difference between sera and brain beta-endorphins concentration in amitryptiline pretreated animals, vs. those in serum and brain of control group treated with 0.95% NaCl. This study shows that use of psychoactive drugs have influence on sera and brain beta-endorphins concentration. Beta-endorphins could be of great importance, used as markers for evaluation of antidepressant drug effects.

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.

Early intervention with human albumin to reduce the tissue plasminogen activator-mediated blood-brain barrier permeability damaged by delayed reperfusion: an experimental study in rats

International Nuclear Information System (INIS)

Lu Haitao; Zhao Jungong; Li Minghua; Li Yongdong; Zhang Peilei

2011-01-01

albumin+rt-PA group. Evans blue leakage at the corresponding reperfusion time points in albumin group and albumin+rt-PA group was significantly decreased when compared with that in the control group (P<0.05). Compared with the control group, the expression of MMP-9 at the infarct margin was significantly decreased in the albumin group and albumin+rt-PA group. Conclusion: The results of this study indicate that early use of high-dose human albumin can reduce can reduce the permeability of the blood-brain barrier damaged by delayed thrombolysis and can reduce the infarct volume as well in the experimental rats. (authors)

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

Autoradiographic analysis of iodoamphetamine redistribution in experimental brain ischemia

International Nuclear Information System (INIS)

Matsuda, H.; Tsuji, S.; Oba, H.; Shiba, K.; Terada, H.; Kinuya, K.; Mori, H.; Sumiya, H.; Hisada, K.

1990-01-01

The pathophysiologic significance of iodoamphetamine (IMP) redistribution was analyzed using a double radionuclide autoradiography technique in experimental brain ischemia in the rat. Within 4 hr after unilateral arterial occlusion, IMP almost completely redistributed at 150 min postinjection in the affected areas. At 2 min postinjection, both a remarkable decrease of IMP accumulation and histopathologic change of diminished staining were observed in these areas. The redistribution amplitude was higher in the affected hemisphere, especially in the regions surrounding the ischemic core than in the unaffected hemisphere. These findings were consistent with computer simulation studies of the time course of brain activity based on the standard diffusible tracer model. The results suggest that IMP redistribution in the ischemic area is due to differences of the temporal changes of the brain activity between the unaffected and affected areas and that it is a physical phenomenon (only flow related) rather than a biologic one

Incorporation of DL-methionine /sup 3/H into the rat brain in the course of triethyl tin sulphate intoxication

Energy Technology Data Exchange (ETDEWEB)

Kozik, M B; Ozarzewska, E; Piechowski, A [Akademia Medyczna, Poznan (Poland)

1976-01-01

The incorporation of DL-methionine /sup 3/H into the rat brain in the course of acute edema caused by the triethyl tin sulphate (TET) was investigated by autoradiography. The results indicate that TET intoxication effects in lower incorporation of methionine into the experimental rat brain in comparison to that in normal animals. The changes in dynamics of DL-methionine /sup 3/H incorporation after TET intoxication are presented. The possible pathogenetic mechanism of the observed changes is discussed.

Genetically engineered rat gliomas: PDGF-driven tumor initiation and progression in tv-a transgenic rats recreate key features of human brain cancer.

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Nina P Connolly

Full Text Available Previously rodent preclinical research in gliomas frequently involved implantation of cell lines such as C6 and 9L into the rat brain. More recently, mouse models have taken over, the genetic manipulability of the mouse allowing the creation of genetically accurate models outweighed the disadvantage of its smaller brain size that limited time allowed for tumor progression. Here we illustrate a method that allows glioma formation in the rat using the replication competent avian-like sarcoma (RCAS virus / tumor virus receptor-A (tv-a transgenic system of post-natal cell type-specific gene transfer. The RCAS/tv-a model has emerged as a particularly versatile and accurate modeling technology by enabling spatial, temporal, and cell type-specific control of individual gene transformations and providing de novo formed glial tumors with distinct molecular subtypes mirroring human GBM. Nestin promoter-driven tv-a (Ntv-a transgenic Sprague-Dawley rat founder lines were created and RCAS PDGFA and p53 shRNA constructs were used to initiate intracranial brain tumor formation. Tumor formation and progression were confirmed and visualized by magnetic resonance imaging (MRI and spectroscopy. The tumors were analyzed using histopathological and immunofluorescent techniques. All experimental animals developed large, heterogeneous brain tumors that closely resembled human GBM. Median survival was 92 days from tumor initiation and 62 days from the first point of tumor visualization on MRI. Each tumor-bearing animal showed time dependent evidence of malignant progression to high-grade glioma by MRI and neurological examination. Post-mortem tumor analysis demonstrated the presence of several key characteristics of human GBM, including high levels of tumor cell proliferation, pseudopalisading necrosis, microvascular proliferation, invasion of tumor cells into surrounding tissues, peri-tumoral reactive astrogliosis, lymphocyte infiltration, presence of numerous tumor

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

Science.gov (United States)

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.

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

Ameliorative effects of oleanolic acid on fluoride induced metabolic and oxidative dysfunctions in rat brain: Experimental and biochemical studies.

Science.gov (United States)

Sarkar, Chaitali; Pal, Sudipta; Das, Niranjan; Dinda, Biswanath

2014-04-01

Beneficial effects of oleanolic acid on fluoride-induced oxidative stress and certain metabolic dysfunctions were studied in four regions of rat brain. Male Wistar rats were treated with sodium fluoride at a dose of 20 mg/kg b.w./day (orally) for 30 days. Results indicate marked reduction in acidic, basic and neutral protein contents due to fluoride toxicity in cerebrum, cerebellum, pons and medulla. DNA, RNA contents significantly decreased in those regions after fluoride exposure. Activities of proteolytic enzymes (such as cathepsin, trypsin and pronase) were inhibited by fluoride, whereas transaminase enzyme (GOT and GPT) activities increased significantly in brain tissue. Fluoride appreciably elevated brain malondialdehyde level, free amino acid nitrogen, NO content and free OH radical generation. Additionally, fluoride perturbed GSH content and markedly reduced SOD, GPx, GR and CAT activities in brain tissues. Oral supplementation of oleanolic acid (a plant triterpenoid), at a dose of 5mg/kgb.w./day for last 14 days of fluoride treatment appreciably ameliorated fluoride-induced alteration of brain metabolic functions. Appreciable counteractive effects of oleanolic acid against fluoride-induced changes in protein and nucleic acid contents, proteolytic enzyme activities and other oxidative stress parameters indicate that oleanolic acid has potential antioxidative effects against fluoride-induced oxidative brain damage. Copyright © 2014 Elsevier Ltd. All rights reserved.

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

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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

Brain glucose content in fetuses of ethanol-fed rats

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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.

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

Experimental increase in brain HIPDM uptake by hypercapnia

International Nuclear Information System (INIS)

Karatzas, N.D.; Sfakianakis, G.N.; Pappas, D.; Duncan, R.; Heal, A.; Serafini, A.; Kung, H.F.

1988-01-01

The 30-min brain uptake of [ 125 I]HIPDM was measured in conscious rats--normocapnic (n = 8), hypercapnic (n = 12), and hyperoxic (n = 6). A mean 41.2% higher uptake was found in the brains of hypercapnic animals (p less than 0.01). In the three groups of rats, brain HIPDM uptake had a negative correlation with body weight (p less than 0.001) and a positive correlation with arterial pCO 2 (p less than 0.01), when adjusted for body weight. These results indicate that HIPDM uptake with hypercapnia may be used as a provocative test to measure cerebral blood flow reserves

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

Effects of traumatic brain injury on regional cerebral blood flow in rats as measured with radiolabeled microspheres

International Nuclear Information System (INIS)

Yamakami, I.; McIntosh, T.K.

1989-01-01

To clarify the effect of experimental brain injury on regional CBF (rCBF), repeated rCBF measurements were performed using radiolabeled microspheres in rats subjected to fluid-percussion traumatic brain injury. Three consecutive microsphere injections in six uninjured control rats substantiated that the procedure induces no significant changes in hemodynamic variables or rCBF. Animals were subjected to left parietal fluid-percussion brain injury of moderate severity (2.1-2.4 atm) and rCBF values were determined (a) prior to injury and 15 min and 1 h following injury (n = 7); and (b) prior to injury and 30 min and 2 h following injury (n = 7). At 15 min post injury, there was a profound reduction of rCBF in all brain regions studied (p less than 0.01). Although rCBF in the hindbrain had recovered to near-normal by 30 min post injury, rCBF in both injured and contralateral (uninjured) forebrain areas remained significantly suppressed up to 1 h post injury. At 2 h post injury, recovery of rCBF to near-normal values was observed in all brain regions except the focal area of injury (left parietal cortex) where rCBF remained significantly depressed (p less than 0.01). This prolonged focal oligemia at the injury site was associated with the development of reproducible cystic necrosis in the left parietotemporal cortex at 4 weeks post injury. Our results demonstrate that acute changes in rCBF occur following experimental traumatic brain injury in rats and that rCBF remains significantly depressed up to 2 h post injury in the area circumscribing the trauma site

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

Experimental gastritis leads to anxiety- and depression-like behaviors in female but not male rats

Science.gov (United States)

2013-01-01

Human and animals studies support the idea that there is a gender-related co-morbidity of pain-related and inflammatory gastrointestinal (GI) diseases with psychological disorders. This co-morbidity is the evidence for the existence of GI-brain axis which consists of immune (cytokines), neural (vagus nerve) and neuroendocrine (HPA axis) pathways. Psychological stress causes disturbances in GI physiology, such as altered GI barrier function, changes in motility and secretion, development of visceral hypersensitivity, and dysfunction of inflammatory responses. Whether GI inflammation would exert impact on psychological behavior is not well established. We examined the effect of experimental gastritis on anxiety- and depression-like behaviors in male and female Sprague–Dawley rats, and evaluated potential mechanisms of action. Gastritis was induced by adding 0.1% (w/v) iodoacetamide (IAA) to the sterile drinking water for 7 days. Sucrose preference test assessed the depression-like behavior, open field test and elevated plus maze evaluated the anxiety-like behavior. IAA treatment induced gastric inflammation in rats of either gender. No behavioral abnormality or dysfunction of GI-brain axis was observed in male rats with IAA-induced gastritis. Anxiety- and depression-like behaviors were apparent and the HPA axis was hyperactive in female rats with IAA-induced gastritis. Our results show that gastric inflammation leads to anxiety- and depression-like behaviors in female but not male rats via the neuroendocrine (HPA axis) pathway, suggesting that the GI inflammation can impair normal brain function and induce changes in psychological behavior in a gender-related manner through the GI-to-brain signaling. PMID:24345032

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

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

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)

Whole-brain blood flow and oxygen metabolism in the rat after halothane anesthesia

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Gjedde, A; Hindfeldt, B [Cerebrovascular Research Center, Department of Neurology, The New York Hospital-Cornell Medical Center, New York, U.S.A.; Department of Neurology, University Hospital, Lund, Sweden)

1975-01-01

A recent modification of the Kety-Schmidt wash-out technique for /sup 133/xenon was used to measure whole-brain flow (CBF) and oxygen consumption (CMRsub(o2)) 1 to 4 hours after termination of halothane anesthesia in 15 Wistar rats. In this 3-hour experimental period, mean CBF and CMRsub(o2) were reduced to 29 and 43 percent of control values, respectively. CBF and CMRsub(o2) determined at the beginning and end of the experimental period were not significantly different from each other. Cerebral venous O/sub 2/ tension was significantly higher than in the control group, supporting recent suggestions of a primary, intrinsic effect of halothane on the homeostatic control of this variable. It is concluded that halothane is not useful for cerebral metabolic studies in the rat.

Minocycline attenuates brain injury and iron overload after intracerebral hemorrhage in aged female rats.

Science.gov (United States)

Dai, Shuhui; Hua, Ya; Keep, Richard F; Novakovic, Nemanja; Fei, Zhou; Xi, Guohua

2018-06-05

Brain iron overload is involved in brain injury after intracerebral hemorrhage (ICH). There is evidence that systemic administration of minocycline reduces brain iron level and improves neurological outcome in experimental models of hemorrhagic and ischemic stroke. However, there is evidence in cerebral ischemia that minocycline is not protective in aged female animals. Since most ICH research has used male models, this study was designed to provide an overall view of ICH-induced iron deposits at different time points (1 to 28 days) in aged (18-month old) female Fischer 344 rat ICH model and to investigate the neuroprotective effects of minocycline in those rats. According to our previous studies, we used the following dosing regimen (20 mg/kg, i.p. at 2 and 12 h after ICH onset followed by 10 mg/kg, i.p., twice a day up to 7 days). T2-, T2 ⁎ -weighted and T2 ⁎ array MRI was performed at 1, 3, 7 and 28 days to measure brain iron content, ventricle volume, lesion volume and brain swelling. Immunohistochemistry was used to examine changes in iron handling proteins, neuronal loss and microglial activation. Behavioral testing was used to assess neurological deficits. In aged female rats, ICH induced long-term perihematomal iron overload with upregulated iron handling proteins, neuroinflammation, brain atrophy, neuronal loss and neurological deficits. Minocycline significantly reduced ICH-induced perihematomal iron overload and iron handling proteins. It further reduced brain swelling, neuroinflammation, neuronal loss, delayed brain atrophy and neurological deficits. These effects may be linked to the role of minocycline as an iron chelator as well as an inhibitor of neuroinflammation. Copyright © 2018 Elsevier Inc. All rights reserved.

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).

Peculiarities of reaction of HIF-1α protein of the hippocampus neurons in rats with experimental diabetes mellitus in the dynamics of ischemic-reperfusion damage of the brain

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T. M. Boychuk

2016-12-01

Higher State Educational Establishment of Ukraine “Bukovinian State medical University”, Chernivtsi, Ukraine   Abstract Introduction. The role of the transcriptional factor Hif-1α in pathogenesis of hypoxic damages and diabetes mellitus (DM is proved, although molecular mechanisms underlying the basis of this factor dysfunction in association with DM with ischemic-reperfusion damage of the brain remain unknown. Objective. The objective of this investigation was to study the content of Hif-1α protein in the hippocampus neurons of rats with experimental DM in the dynamics of ischemic-reperfusion damage of the brain. Results. In rats without DM 20 minute ischemia with one hour reperfusion increases the content of Hif-1α protein in all the fields of the hippocampus. On the 12th day of ischemic-reperfusion period in the hippocampus CA2-CA4 fields the values of certain examined indices of the activity of Hif-1α transcriptional factor continue to increase, and in СА1field they normalize or approach to the values of animals in the control group.  In rats with DM during early post-ischemic period there are no changes of Hif-1α protein content in CA1 field, in CA2 field there are signs of its reduced activity, in CA3 field they are limited by the reaction of one index, in CA4 field they are of a similar character with those of the control rats under experimental conditions.  On the 12th day of ischemic-reperfusion period in CA1 field all the indices of activity of Hif-1α transcriptional factor increase exceeding corresponding indices by absolute values in animals of the control group under the same experimental conditions, in СА2 and СА3 fields changes of the examined parameters are limited as compared to the same ones in animals from the control group, in CA4 field values that were increased in the control group decrease. Conclusions. Diabetes mellitus restricts reaction of Hif-1α protein on ischemia-reperfusion inn the neurons of СА1-СА3 fields in

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

The neuro-radiological anatomy of the normal and abnormal rat brain

International Nuclear Information System (INIS)

Schumacher, M.; Doller, P.; Voigt, K.

1979-01-01

In vivo and post mortem techniques for the radiological examination of normal brains have been developed, using 66 white adult rats. Aortic arch injections for survey angiograms (10 animals), selective catheterisation of the internal carotid artery (16 animals) and ventriculography by percutaneous needle puncture (20 animals) were performed in vivo; the animals survived and the examinations could be repeated. The techniques proved useful and accurate methods for the radiological demonstration of the topography and morphology of cerebral vessels and chambers; they also provided information on the function of the cerebral circulation and C.S.F. dynamics. The findings were checked and correlated by post mortem studies (20 animals) using contact radiography, micro-angiography and casts of the ventricles. As a result, extensive topographic and anatomic information concerning the cerebral vessels in the rat was obtained, including some microscopic-radiological findings. The combined use of these methods provided a basis for studying the growth of experimentally induced brain tumours and the effect of various types of treatment. (orig.) [de

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

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

Science.gov (United States)

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.

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

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

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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.

Neuroprotective effect of Quince leaf hydroalcoholic extract on intracerebroventricular streptozotocin-induced oxidative stress in cortical tissue of rat brain

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A Hajizadeh Moghaddam

2015-12-01

Full Text Available Background & aim: Oxidative stress is a result of the imbalance between free radicals and the antioxidant system of the body. Increased oxidative stress in brain causes dysfunction of brain activities, destruction of neurons, and disease such as Alzheimer. Antioxidants, for example vitamins, phenolic compounds and flavonoids have been extensively investigated as potential therapeutic agents in vitro and in vivo for prevention of neurodegenerative diseases. In the present experimental study, the neuro-protective effect of quince leaf hydroalcoholic extract (QLHE on intracerebroventricular streptozotocin (icv-STZ-induced oxidative stress in cortical tissue of rat brain was examined. Methods: In the present experimental research, forty-two Wistar rats were randomly divided into control, sham, icv-STZ and icv-STZ treated with QLHE groups. The ICV-STZ group rats were injected unilaterally with ICV-STZ (3 mg/kg using a stereotactic device and QLHE (50, 100 and 150 mg/kg/day were administered for 6 weeks starting from 3 weeks before of ICV-STZ injection. The rats were killed at the end of the study and their brain cortical tissue superoxide dismutase and catalase activity were measured. The assay of catalase and superoxide dismutase was performed by following the Genet method. The amount of protein was determined according to the Bradford method.The statistical analysis was performed using one way ANOVA. Data were expressed as mean±SD and  P<0.05 was considered significant. Results: The present study indicated that in the ICV-STZ group showed significant decrease (P<0.001 in enzymatic antioxidants superoxide dismutase and catalase in the cortical tissue of the brain. Treatment of different doses of QLHE significantly increased superoxide dismutase and catalase activity compared to icv-STZ group (P<0.001 in cortical tissue of the brain. Conclusion: The study demonstrated the effectiveness of quince leaf hydroalcoholic extract as a powerful antioxidant

Effect of Transient Maternal Hypotension on Apoptotic Cell Death in Foetal Rat Brain

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Hamit Özyürek

2014-03-01

Full Text Available Background: Intrauterine perfusion insufficiency induced by transient maternal hypotension has been reported to be associated with foetal brain malformations. However, the effects of maternal hypotension on apoptotic processes in the foetal brain have not been investigated experimentally during the intrauterine period. Aims: The aim of this study was to investigate the effects of transient maternal hypotension on apoptotic cell death in the intrauterine foetal brain. Study Design: Animal experimentation. Methods: Three-month-old female Wistar albino rats were allocated into four groups (n=5 each. The impact of hypoxic/ischemic injury induced by transient maternal hypotension on the 15th day of pregnancy (late gestation in rats was investigated at 48 (H17 group or 96 hours (H19 group after the insult. Control groups underwent the same procedure except for induction of hypotension (C17 and H17 groups. Brain sections of one randomly selected foetus from each pregnant rat were histopathologically evaluated for hypoxic/ischemic injury in the metencephalon, diencephalon, and telencephalon by terminal transferase-mediated dUTP nick end labelling and active cysteine-dependent aspartate-directed protease-3 (caspase-3 positivity for cell death. Results: The number of terminal transferase-mediated dUTP nick end labelling (+ cells in all the areas examined was comparable in both hypotension and control groups. The H17 group had active caspase-3 (+ cells in the metencephalon and telencephalon, sparing diencephalon, whereas the C19 and H19 groups had active caspase-3 (+ cells in all three regions. The number of active caspase-3 (+ cells in the telencephalon in the H19 group was higher compared with the metencephalon and diencephalon and compared with H17 group (p<0.05. Conclusion: Our results suggest that prenatal hypoxic/ischemic injury triggers apoptotic mechanisms. Therefore, blockade of apoptotic pathways, considering the time pattern of the insult, may

Mobilization of stem cell with granulocyte-colony stimulating factor promotes recovery after traumatic brain injury in rat

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Mohsen Marzban

2010-01-01

Full Text Available Introduction: This study was designed to investigate the effects of granulocyte colony-stimulating factor (G-CSF administration in rats for 6 weeks after traumatic brain injury (TBI. Methods: Adult male Wistar rats (n = 30 were injured with controlled cortical impact device and divided into four groups. The treatment groups (n = 10 each were injected subcutaneously with recombinant human G-CSF. Vehicle group (n=10 received phosphate buffered saline (PBS and only Brdu intraperitoneally. Bromodeoxyuridine (BrdU was used for mitotic labeling. Experimental rats were injected intraperitoneally with BrdU. Rats were killed at 6th week after traumatic brain injury. Neurological functional evaluation of animals was performed before and after injury using neurological severity scores (NSS. Animals were sacrificed 42 days after TBI and brain sections were stained using Brdu immunohistochemistry. Results: Statistically significant improvement in functional outcome was observed in treatment groups when compared with control (p<0.01. This benefit was visible 7 days after TBI and persisted until 42 days (end of trial. Histological analysis showed that Brdu cell positive was more in the lesion boundary zone at treatment animal group than all injected animals. Discussion: We believe that G-CSF therapeutic protocol reported here represents an attractive strategy for the development of a clinically significant noninvasive traumatic brain injury therapy.

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

Effects of Biotin Deficiency on Biotinylated Proteins and Biotin-Related Genes in the Rat Brain.

Science.gov (United States)

Yuasa, Masahiro; Aoyama, Yuki; Shimada, Ryoko; Sawamura, Hiromi; Ebara, Shuhei; Negoro, Munetaka; Fukui, Toru; Watanabe, Toshiaki

2016-01-01

Biotin is a water-soluble vitamin that functions as a cofactor for biotin-dependent carboxylases. The biochemical and physiological roles of biotin in brain regions have not yet been investigated sufficiently in vivo. Thus, in order to clarify the function of biotin in the brain, we herein examined biotin contents, biotinylated protein expression (e.g. holocarboxylases), and biotin-related gene expression in the brain of biotin-deficient rats. Three-week-old male Wistar rats were divided into a control group, biotin-deficient group, and pair-fed group. Rats were fed experimental diets from 3 wk old for 8 wk, and the cortex, hippocampus, striatum, hypothalamus, and cerebellum were then collected. In the biotin-deficient group, the maintenance of total biotin and holocarboxylases, increases in the bound form of biotin and biotinidase activity, and the expression of an unknown biotinylated protein were observed in the cortex. In other regions, total and free biotin contents decreased, holocarboxylase expression was maintained, and bound biotin and biotinidase activity remained unchanged. Biotin-related gene (pyruvate carboxylase, sodium-dependent multivitamin transporter, holocarboxylase synthetase, and biotinidase) expression in the cortex and hippocampus also remained unchanged among the dietary groups. These results suggest that biotin may be related to cortex functions by binding protein, and the effects of a biotin deficiency and the importance of biotin differ among the different brain regions.

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.

The effect of steroids on experimental brain edema induced by irradiation

Energy Technology Data Exchange (ETDEWEB)

Yamaguchi, M [Kobe Univ. (Japan). School of Medicine; Kakei, M

1975-04-01

In order to study the effect of steroids on brain edema, complicated by radiotherapy to brain tumors, an experiment was carried out in rats. Five thousand rads of cobalt-60 were irradiated to the head only of a rat, and 20 mg/kg of water-soluble prednine was given intraperitoneally. A single administration of the whole dose increased the amount of brain fluid to 79.35 +- 0.30 g/ 100 g wet wt.. This value was not significantly different from that of the rat which had received only the 5,000 rad irradiation. In a rat which received prednine in 6 divided doses at intervals of 4 hours, the fluid amount reached 78.33 +- 0.52 g/ 100 g wet wt. and was clearly lower than that of the rat which had been irradiated only, 79.51 +- 0.23 g/ 100 g wet wt. neither was the value significantly different from that of a normal rat which had not been exposed 78.72 +- 0.82 g/ 100 g wet wt.. Therefore, fractional administration of prednine was demonstrated to be effective.

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

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 effect of ingested sulfite on visual evoked potentials, lipid peroxidation, and antioxidant status of brain in normal and sulfite oxidase-deficient aged rats.

Science.gov (United States)

Ozsoy, Ozlem; Aras, Sinem; Ozkan, Ayse; Parlak, Hande; Aslan, Mutay; Yargicoglu, Piraye; Agar, Aysel

2016-07-01

Sulfite, commonly used as a preservative in foods, beverages, and pharmaceuticals, is a very reactive and potentially toxic molecule which is detoxified by sulfite oxidase (SOX). Changes induced by aging may be exacerbated by exogenous chemicals like sulfite. The aim of this study was to investigate the effects of ingested sulfite on visual evoked potentials (VEPs) and brain antioxidant statuses by measuring superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) activities. Brain lipid oxidation status was also determined via thiobarbituric acid reactive substances (TBARS) in normal- and SOX-deficient aged rats. Rats do not mimic the sulfite responses seen in humans because of their relatively high SOX activity level. Therefore this study used SOX-deficient rats since they are more appropriate models for studying sulfite toxicity. Forty male Wistar rats aged 24 months were randomly assigned to four groups: control (C), sulfite (S), SOX-deficient (D) and SOX-deficient + sulfite (DS). SOX deficiency was established by feeding rats with low molybdenum (Mo) diet and adding 200 ppm tungsten (W) to their drinking water. Sulfite in the form of sodium metabisulfite (25 mg kg(-1) day(-1)) was given by gavage. Treatment continued for 6 weeks. At the end of the experimental period, flash VEPs were recorded. Hepatic SOX activity was measured to confirm SOX deficiency. SOX-deficient rats had an approximately 10-fold decrease in hepatic SOX activity compared with the normal rats. The activity of SOX in deficient rats was thus in the range of humans. There was no significant difference between control and treated groups in either latence or amplitude of VEP components. Brain SOD, CAT, and GPx activities and brain TBARS levels were similar in all experimental groups compared with the control group. Our results indicate that exogenous administration of sulfite does not affect VEP components and the antioxidant/oxidant status of aged rat brains. © The Author

Behavior outcome after ischemic and hemorrhagic stroke, with similar brain damage, in rats.

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Mestriner, Régis Gemerasca; Miguel, Patrícia Maidana; Bagatini, Pamela Brambilla; Saur, Lisiani; Boisserand, Lígia Simões Braga; Baptista, Pedro Porto Alegre; Xavier, Léder Leal; Netto, Carlos Alexandre

2013-05-01

Stroke causes disability and mortality worldwide and is divided into ischemic and hemorrhagic subtypes. Although clinical trials suggest distinct recovery profiles for ischemic and hemorrhagic events, this is not conclusive due to stroke heterogeneity. The aim of this study was to produce similar brain damage, using experimental models of ischemic (IS) and hemorrhagic (HS) stroke and evaluate the motor spontaneous recovery profile. We used 31 Wistar rats divided into the following groups: Sham (n=7), ischemic (IS) (n=12) or hemorrhagic (HS) (n=12). Brain ischemia or hemorrhage was induced by endotelin-1 (ET-1) and collagenase type IV-S (collagenase) microinjections, respectively. All groups were evaluated in the open field, cylinder and ladder walk behavioral tests at distinct time points as from baseline to 30 days post-surgery (30 PS). Histological and morphometric analyses were used to assess the volume of lost tissue and lesion length. Present results reveal that both forms of experimental stroke had a comparable long-term pattern of damage, since no differences were found in volume of tissue lost or lesion size 30 days after surgery. However, behavioral data showed that hemorrhagic rats were less impaired at skilled walking than ischemic ones at 15 and 30 days post-surgery. We suggest that experimentally comparable stroke design is useful because it reduces heterogeneity and facilitates the assessment of neurobiological differences related to stroke subtypes; and that spontaneous skilled walking recovery differs between experimental ischemic and hemorrhagic insults. Copyright © 2013 Elsevier B.V. All rights reserved.

Inhibitory effect of MgSO4 on calcium overload after radiation-induced brain injuries

International Nuclear Information System (INIS)

Tu Yu; Zhou Yuying; Wang Lili

2005-01-01

Objective: To explore the neuroprotective effect of magnesium sulfate (MgSO 4 ) on radiation-induced acute brain injuries. Methods: A total of 60 mature Sprague-Dawley rats were randomly divided into 3 groups: blank control group, experimental control group and experimental therapy group. The whole brain of SD rats of experimental control group and experimental therapy group was irradiated to a dose of 20 Gy using 6 MeV electrons. Magnesium sulfate was injected intraperitoneally into the rats of experimental therapy group before and after irradiation for five times. At different time points (24 h, 7 days, 14 days, 30 days after irradiation), the brain tissue was taken. Plasma direct reading spectrography was used to measure the contents of Ca 2+ , Mg 2+ in brain tissue, and the percentage of brain water content was calculated with the wet-dry weight formula. Results: Compared with the blank control group, the percentage of brain water and content of Ca 2+ in brain of the experimental control group increased markedly (P 2+ decreased significantly (P 2+ in brain of the experimental therapy group were significantly lower than those of the experimental control group (P<0.05). Conclusion: Magnesium sulfate used in the early stage after irradiation can inhibit the calcium overload in rat brain , and attenuate brain edema and injuries. (authors)

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

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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

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.

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

International Nuclear Information System (INIS)

Ye Tian; Shiyao Bao; Weibo Yin; Chunfeng Liu; Zhilin Zhang

2000-01-01

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

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

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

2000-05-01

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

Neuroprotective actions of taurine on hypoxic-ischemic brain damage in neonatal rats.

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Zhu, Xiao-Yun; Ma, Peng-Sheng; Wu, Wei; Zhou, Ru; Hao, Yin-Ju; Niu, Yang; Sun, Tao; Li, Yu-Xiang; Yu, Jian-Qiang

2016-06-01

Taurine is an abundant amino acid in the nervous system, which has been proved to possess antioxidation, osmoregulation and membrane stabilization. Previously it has been demonstrated that taurine exerts ischemic brain injury protective effect. This study was designed to investigate whether the protective effect of taurine has the possibility to be applied to treat neonatal hypoxic-ischemic brain damage. Seven-day-old Sprague-Dawley rats were treated with left carotid artery ligation followed by exposure to 8% oxygen to generate the experimental group. The cerebral damage area was measured after taurine post-treatment with 2,3,5-triphenyltetrazolium chloride (TTC) staining, Hematoxyline-Eosin (HE) staining and Nissl staining. The activities of superoxide dismutase (SOD), malondialdehyde (MDA), glutathione peroxidase (GSH-Px), total antioxidant capacity (T-AOC), myeloperoxtidase (MPO), ATP and Lactic Acid productions were assayed with ipsilateral hemisphere homogenates. Western-blot and immunofluorescence assay were processed to detect the expressions of AIF, Cyt C, Bax, Bcl-2 in brain. We found that taurine significantly reduced brain infarct volume and ameliorated morphological injury obviously reversed the changes of SOD, MDA, GSH-Px, T-AOC, ATP, MPO, and Lactic Acid levels. Compared with hypoxic-ischemic group, it showed marked reduction of AIF, Cyt C and Bax expressions and increase of Bcl-2 after post-treatment. We conclude that taurine possesses an efficacious neuroprotective effect after cerebral hypoxic-ischemic damage in neonatal rats. Copyright © 2016 Elsevier Inc. All rights reserved.

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

DEFF Research Database (Denmark)

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

2011-01-01

Stroke leads to brain damage with subsequent slow and incomplete recovery of lost brain functions. Enriched housing of stroke-injured rats provides multi-modal sensorimotor stimulation, which improves recovery, although the specific mechanisms involved have not been identified. In rats housed in ...... of biomolecules required for brain repair, thereby stimulating brain plasticity. Pharmacological targeting of the sigma-1 receptor provides new opportunities for stroke treatment beyond the therapeutic window of neuroprotection....

Glucagon-Like Peptide-1 Analog, Liraglutide, Delays Onset of Experimental Autoimmune Encephalitis in Lewis Rats

DEFF Research Database (Denmark)

DellaValle, Brian; Brix, Gitte S; Brock, Birgitte

2016-01-01

(GLP-1) family, is also anti-diabetic and weight-reducing and is, moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing...... the experimental model, experimental autoimmune encephalitis (EAE). Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 μg/kg s.c.) or saline. Healthy controls were included (saline, n = 6, liraglutide, n = 7). Clinical score and weight were assessed daily...... treatment delayed disease onset (group clinical score significantly >0) by 2 days and markedly reduced disease severity (median clinical score 2 vs. 5; p = 0.0003). Fourteen of 15 (93%) of vehicle-treated rats reached the humane endpoint (clinical score ≥4) by day 11 compared to 5 of 15 (33%) of liraglutide...

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

The effect of irradiation and cis-diamminedichloroplatinum(II) in the rat brain : analysis of histopathology at 3 and 6 months after treatment

International Nuclear Information System (INIS)

Lee, Kyung Ja; Chang, Seung Hee; Koo, Hea Soo

1998-01-01

To evalute the late effect(3 and 6 months) of cis-diamminedichloroplatinum(II)(cisplatin) on the radiation brain damage when the cisplatin was intraperitoneally infused immediately after whole brain irradiation in the rats. The histolopathological findings of the brain were examined in rat brains at 3 and 6 months after the treatment. The rats were irradiated(20 or 22.5 Gy, RT) or cisplatin was injected intraperitoneally(2, 4, or 8mg/kg, CT) and in combined treatment group, cisplatin(2mg/kg) was injected immediately after irradiation (20 or 22.5 Gy). Histopathological examination was done mostly in irradiation or cisplatin alone groups, because the rats in combined group died during experimental period except 2 rats. The rats treated with cisplatin showed marked epithelial vacuolation with perivascular edema and vascular dilatation in choroid plexus at 3 months as well as multifocal necrosis involving fimbria and cerebellar hemispheres at 3 and 6 months. The changes were more prominent in rats with 2mg/kg injection compared to rats with 8mg/kg injection. The rats with RT and combined CT and RT showed characteristic delayed irradiation effects such as focal coagulation necrosis and vascular changes, which were more marked than previous reports. Prominent perivascular and leptomeningeal astrocytic proliferation was well documented by anti-GFAP antibody. Cisplatin treatment did not enhance the effect of radiation -induced changes of blood vessels and astrocytic proliferation. The focal necrosis was the most consistently noted finding in this study, it suggested the possibility to use this as an evaluation factor for combined effects of RT and cisplatin

Inhibitory effect of magnesium sulfate on reaction of lipid hyperoxidation after radiation-induced acute brain injuries

International Nuclear Information System (INIS)

Wang Lili; Zhou Juying; Yu Zhiying; Qin Songbing; Xu Xiaoting; Li Li; Tu Yu

2007-01-01

Objective: To explore the protection of magnesium sulfate (MgSO 4 ) on radiation-induced acute brain injuries. Methods: 60 maturity Sprague-Dawley (SD) rats were randomly divided into 3 groups: blank control group, experimental control group and experimental-therapeutic group. The whole brain of SD rats of experimental control group and experimental-therapeutic group was irradiated to a dose of 20 Gy using 6 MeV electron. MgSO 4 was injected intraperitoneally into the rats of experimental-therapeutic group before and after irradiation for five times. At different time points ranging from the 1 d, 7 d, 14 d, 30 d after irradiation, the brain tissue were taken. The xanthine oxidase and colorimetric examination were used to measure the superoxide dismutase (SOD) and malonyldialdehyde (MDA) respectively in the rat brain respectively. Results: Compared with blank control group, the SOD in brain of experimental control group decreased significantly (P 4 used in early stage can inhibit the lipid peroxidation after radiation-induced acute brain injuries and alleviate the damage induced by free radicals to brain tissue. (authors)

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

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Firas H Kobeissy

2016-11-01

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

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

Science.gov (United States)

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.

Whey protein concentrate supplementation protects rat brain against aging-induced oxidative stress and neurodegeneration.

Science.gov (United States)

Garg, Geetika; Singh, Sandeep; Singh, Abhishek Kumar; Rizvi, Syed Ibrahim

2018-05-01

Whey protein concentrate (WPC) is a rich source of sulfur-containing amino acids and is consumed as a functional food, incorporating a wide range of nutritional attributes. The purpose of this study is to evaluate the neuroprotective effect of WPC on rat brain during aging. Young (4 months) and old (24 months) male Wistar rats were supplemented with WPC (300 mg/kg body weight) for 28 days. Biomarkers of oxidative stress and antioxidant capacity in terms of ferric reducing antioxidant potential (FRAP), lipid hydroperoxide (LHP), total thiol (T-SH), protein carbonyl (PC), reactive oxygen species (ROS), nitric oxide (NO), and acetylcholinesterase (AChE) activity were measured in brain of control and experimental (WPC supplemented) groups. In addition, gene expression and histopathological studies were also performed. The results indicate that WPC augmented the level of FRAP, T-SH, and AChE in old rats as compared with the old control. Furthermore, WPC-treated groups exhibited significant reduction in LHP, PC, ROS, and NO levels in aged rats. WPC supplementation also downregulated the expression of inflammatory markers (tumor necrosis factor alpha, interleukin (IL)-1β, IL-6), and upregulated the expression of marker genes associated with autophagy (Atg3, Beclin-1, LC3B) and neurodegeneration (neuron specific enolase, Synapsin-I, MBP-2). The findings suggested WPC to be a potential functional nutritional food supplement that prevents the progression of age-related oxidative damage in Wistar rats.

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

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Klaus Kraitsy

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

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

SIRT3 Expression Decreases with Reactive Oxygen Species Generation in Rat Cortical Neurons during Early Brain Injury Induced by Experimental Subarachnoid Hemorrhage

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Wei Huang

2016-01-01

Full Text Available Sirtuin3 (SIRT3 is an important protein deacetylase which predominantly presents in mitochondria and exhibits broad bioactivities including regulating energy metabolism and counteracting inflammatory effect. Since inflammatory cascade was proved to be critical for pathological damage following subarachnoid hemorrhage (SAH, we investigated the overall expression and cell-specific distribution of SIRT3 in the cerebral cortex of Sprague-Dawley rats with experimental SAH induced by internal carotid perforation. Results suggested that SIRT3 was expressed abundantly in neurons and endothelia but rarely in gliocytes in normal cerebral cortex. After experimental SAH, mRNA and protein expressions of SIRT3 decreased significantly as early as 8 hours and dropped to the minimum value at 24 h after SAH. By contrast, SOD2 expression increased slowly as early as 12 hours after experimental SAH, rose up sharply at the following 12 hours, and then was maintained at a higher level. In conclusion, attenuated SIRT3 expression in cortical neurons was associated closely with enhanced reactive oxygen species generation and cellular apoptosis, implying that SIRT3 might play an important neuroprotective role during early brain injury following SAH.

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.

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.

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

Comprehensive Evaluation of Neuroprotection Achieved by Extended Selective Brain Cooling Therapy in a Rat Model of Penetrating Ballistic-Like Brain Injury

Science.gov (United States)

Shear, Deborah A.; Deng-Bryant, Ying; Leung, Lai Yee; Wei, Guo; Chen, Zhiyong; Tortella, Frank C.

2016-01-01

Brain hypothermia has been considered as a promising alternative to whole-body hypothermia in treating acute neurological disease, for example, traumatic brain injury. Previously, we demonstrated that 2-hours selective brain cooling (SBC) effectively mitigated acute (≤24 hours postinjury) neurophysiological dysfunction induced by a penetrating ballistic-like brain injury (PBBI) in rats. This study evaluated neuroprotective effects of extended SBC (4 or 8 hours in duration) on sub-acute secondary injuries between 3 and 21 days postinjury (DPI). SBC (34°C) was achieved via extraluminal cooling of rats' bilateral common carotid arteries (CCA). Depending on the experimental design, SBC was introduced either immediately or with a 2- or 4-hour delay after PBBI and maintained for 4 or 8 hours. Neuroprotective effects of SBC were evaluated by measuring brain lesion volume, axonal injury, neuroinflammation, motor and cognitive functions, and post-traumatic seizures. Compared to untreated PBBI animals, 4 or 8 hours SBC treatment initiated immediately following PBBI produced comparable neuroprotective benefits against PBBI-induced early histopathology at 3 DPI as evidenced by significant reductions in brain lesion volume, axonal pathology (beta-amyloid precursor protein staining), neuroinflammation (glial fibrillary acetic protein stained-activated astrocytes and rat major histocompatibility complex class I stained activated microglial cell), and post-traumatic nonconvulsive seizures. In the later phase of the injury (7–21 DPI), significant improvement on motor function (rotarod test) was observed under most SBC protocols, including the 2-hour delay in SBC initiation. However, SBC treatment failed to improve cognitive performance (Morris water maze test) measured 13–17 DPI. The protective effects of SBC on delayed axonal injury (silver staining) were evident out to 14 DPI. In conclusion, the CCA cooling method of SBC produced neuroprotection measured across multiple

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

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Tortella Frank C

2009-08-01

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

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...

Effect of manganese on neonatal rat: manganese concentration and enzymatic alterations in brain

Energy Technology Data Exchange (ETDEWEB)

Seth, P K; Husain, R; Mushtaq, M; Chandra, S V

1977-01-01

Suckling rats were exposed for 15 and 30 days to manganese through the milk of nursing dams receiving 15 mg MnCl/sub 2/.4H/sub 2/O/kg/day orally and after which the neurological manifestations of metal poisoning were studied. No significant differences in the growth rate, developmental landmarks and walking movements were observed between the control and manganese-exposed pups. The metal concentration was significantly increased in the brain of manganese-fed pups at 15 days and exhibited a further three-fold increase over the control, at 30 days. The accumulation of the metal in the brain of manganese-exposed nursing dams was comparatively much less. A significant decrease in succinic dehydrogenase, adenosine triphosphatase, adenosine deaminase, acetylcholine esterase and an increase in monoamine oxidase activity was observed in the brain of experimental pups and dams. The results suggest that the developing brain may also be susceptible to manganese.

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

Science.gov (United States)

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.

The expression changes of inflammatory cytokines in the hippocampus following whole-brain irradiation in rats

International Nuclear Information System (INIS)

Yu De; Tian Ye; Ding Weijun; Zhu Yaqun; Liu Chunfeng

2004-01-01

To investigate the change pattern of some inflammatory cytokines in brain tissue at the acute phase after brain irradiated. The whole brain of SD rats was irradiated by the single dose of 2, 15 or 30 Gy of 4 MeV electron beam. The enzyme-linked immunosorbent assay (ELISA) was used for the measurement of IL-1 β, IL-6, and TNF-α content in hippocampus tissue of rats at 1h, 6h, 12h, 1d, 2 and 1 week post-irradiation. The mRNA of IL-1 β, IL-6, and TNF-α were detected by reverse-transcription polymerase chain reaction (RT-PCR) in the same experimental groups. It was analyzed about the influence of dosage and post-irradiation duration with the cytokines expression. Compared with both the normal control and the anesthetized with chloral hydrate but sham-irradiation groups, there were no difference about the three inflammatory cytokines expression in rats with 2 Gy irradiated. At 6h after irradiation with 15 Gy, 6 and 12h with 30 Gy groups, the content of IL-1β and TNF-α in hippocampus tissue were significantly increased, and were returned to normal level after 12 to 24h. The same change tendency of their mRNA relational level was observed in 15 and 30 Gy groups, but it happened earlier in 1h after exposure. Although the content of IL-6 in hippocampus kept stable in all the groups, its mRNA level raised obviously in 12h group. After 15-30 Gy whole-brain irradiation, the expression of some inflammatory cytokines increased abruptly in the hippocampus of SD rat within 1 day, but the interplay between inflammatory cytokines changes and the pathogenesis of radiation injury was incompletely understood at present. (authors)

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.

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.

Correlation between RNA Degradation Patterns of Rat's Brain and Early PMI at Different Temperatures.

Science.gov (United States)

Lü, Y H; Li, Z H; Tuo, Y; Liu, L; Li, K; Bian, J; Ma, J L; Chen, L

2016-06-01

To explore the correlation between early postmortem interval （PMI） and eight RNA markers of rat's brain at different temperatures. Total 222 SD rats were randomly divided into control group （PMI=0 h） and four experimental groups. And the rats in the experimental groups were sacrificed by cervical dislocation and respectively kept at 5 ℃, 15 ℃, 25 ℃ and 35 ℃ in a controlled environment chamber. The RNA was extracted from brain tissues, which was taken at 9 time points from 1 h to 24 h postmortem. The expression levels of eight markers, β-actin, GAPDH, RPS29, 18S rRNA, 5S rRNA, U6 snRNA, miRNA-9 and miRNA-125b, were detected using real-time fluorescent quantitative PCR, respectively. Proper internal reference was selected by geNorm software. Regression analysis of normalized RNA markers was performed by SPSS software. Mathematical model for PMI estimation was established using R software. Another 6 SD rats with known PMI were used to verify the mathematical model. 5S rRNA, miR-9 and miR-125b were suitable as internal reference markers for their stable expression. Both β-actin and GAPDH had well time-dependent degradation patterns and degraded continually with prolongation of PMI in 24 h postmortem. The mathematical model of the variation of ΔCt values with PMI and temperature was set up by R software and the model could be used for PMI estimation. The average error rates of model validation using β-actin and GAPDH were 14.1% and 22.2%, respectively. The expression levels of β-actin and GAPDH are well correlated with PMI and environmental temperature. The mathematical model established in present study can provide references for estimating early PMI under various temperature conditions. Copyright© by the Editorial Department of Journal of Forensic Medicine

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.

Science.gov (United States)

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.

Hippocampal-dependent spatial memory in the water maze is preserved in an experimental model of temporal lobe epilepsy in rats.

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Marion Inostroza

Full Text Available Cognitive impairment is a major concern in temporal lobe epilepsy (TLE. While different experimental models have been used to characterize TLE-related cognitive deficits, little is known on whether a particular deficit is more associated with the underlying brain injuries than with the epileptic condition per se. Here, we look at the relationship between the pattern of brain damage and spatial memory deficits in two chronic models of TLE (lithium-pilocarpine, LIP and kainic acid, KA from two different rat strains (Wistar and Sprague-Dawley using the Morris water maze and the elevated plus maze in combination with MRI imaging and post-morten neuronal immunostaining. We found fundamental differences between LIP- and KA-treated epileptic rats regarding spatial memory deficits and anxiety. LIP-treated animals from both strains showed significant impairment in the acquisition and retention of spatial memory, and were unable to learn a cued version of the task. In contrast, KA-treated rats were differently affected. Sprague-Dawley KA-treated rats learned less efficiently than Wistar KA-treated animals, which performed similar to control rats in the acquisition and in a probe trial testing for spatial memory. Different anxiety levels and the extension of brain lesions affecting the hippocampus and the amydgala concur with spatial memory deficits observed in epileptic rats. Hence, our results suggest that hippocampal-dependent spatial memory is not necessarily affected in TLE and that comorbidity between spatial deficits and anxiety is more related with the underlying brain lesions than with the epileptic condition per se.

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.

Brain Edema and Neurologic Deficits in Rat Stroke Model: The Effect of Hydroalcoholic Extract of Salvia Officinalis

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elham ghasemloo

2015-11-01

Full Text Available Bachground & Objectives: In the brain ischemia, the production of free radicals increases. Salvia is a rich source of antioxidant compounds; therefore, in this study we will examine the effects of Salvia extracts on brain edema and score of neurological deficits.  Materials & Methods: In this experimental study, 35 male Wistar rats were randomly divided into 5 groups, each containing 7 rats. The control group received distilled water, and the other three groups received intrapertioneally hydroalcoholic extracts of Salvia officinalis with dosages of 50, 75, and 100 mg/kg for 3 weeks (1+3=4, Where is the other group? There should be five groups but there are only four groups here.. Thereafter, each main group underwent 60 min middle cerebral artery occlusion 2 hours after the last injection of Salvia extracts .This occlusion caused ischemia in the right hemisphere. Then, the brain edema was assessed, and the neurologic deficits were analyzed. The sham group was not treated and no induction of brain ischemia. Brain edema was analyzed through SPSS18 software and LSD method, while the analysis of neurologic deficits was carried out by Mann-Whitney U. Results: Our study results indicate that the hydroalcoholic extracts of Salvia reduced permeability brain edema in three dosages of 50, 75, and 100mg/kg (83/29±0/42 , 82/10±0/32 and 81/29±0/48, respectively compared with the control group (85/31±0/58. They also reduced the neurologic deficits in experimental groups of 75 and 100 mg/kg (1/43±0/37 and 1±0/31, respectively compared with the control group (3/71±0/42 (p<0.05. Conclusion: Salvia officinalis apparently have a protective effect against stroke damage due to the reduced brain edema and neurological disorders.

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.

Effect of ethanol on enkephalinergic opioid system of rat brain

Energy Technology Data Exchange (ETDEWEB)

Belyayev, N.A.; Balakireva, N.N.; Brusov, O.S.; Panchenko, L.F.

1983-10-13

Specific binding of /sup 3/H-morphine and /sup 3/H-(D-Ala/sup 2/, D-Leu/sup 5/)-enkephalin (H-EN) with opiatic receptors was studied on white rats along with the content of Met- and Leu-enkephalin and the activity of enkephalinase in various brain segments after single dose (20% solution in 0.9% NaCl, IP; 1.5-4.5 g/kg body weight) and chronic injection (20% EtOH substituted for drinking water) of ethanol. The single injection of EtOH (1.5-4.5 g/kg) resulted in a depression of the specific binding of H-EN with opiate receptors. Doses of 1.5 and 2.5 g/kg led to a lower content of Leu-enkephalin in mid-brain but to an increase of Met-enkephalin; the 4.5 g/kg dose had no effect on the striatum. With chronic administration of EtOH, most of the values obtained on the experimental animals were similar to the control data. 23 references.

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.

The detection of brain ischaemia in rats by inductive phase shift spectroscopy

International Nuclear Information System (INIS)

González, C A; Villanueva, C; Vera, C; Flores, O; Reyes, R D; Rubinsky, B

2009-01-01

Ischaemia in the brain is an important clinical problem that is often monitored and studied with expensive devices such as MRI and PET, which are not readily available in low economical resource parts of the world. We have developed a new less expensive tool for non-invasive monitoring of ischaemia in the brain. This is a first feasibility study describing the concept. The system is based on the hypothesis that electromagnetic properties of the tissue change during ischaemia and that measuring the electromagnetic properties of the bulk of the brain with non-contact means can detect these changes. The apparatus we have built and whose design we describe here consists of two electromagnetic coils placed around the head. The system measures the bulk change in time of the phase difference between the electromagnetic signal on the two coils in a range of frequencies. A mathematical model simulating the device and the measurement is also introduced. Ischaemia was induced in the brain of rats by occlusion of the right cerebral and carotid arteries. Experimental subjects were monitored for 24 h. Inductive phase shift measurements were made at five frequencies in the range of 0.1–50 MHz eight times during the observation period. An ex vivo estimation of the percentage of necrosis in the ischemic subjects at t = 24 h was done. The mathematical model was also applied to the experimental tested situation. The results of both experiments and theory show significant phase shifts increase as a function of frequency and ischaemia time. The theoretical and experimental results suggest that the tested technique has the potential to detect the processes and level of ischaemia in the brain by non-invasive, continuous, bulk volumetric monitoring with a simple and inexpensive apparatus

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.

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

2012-09-01

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

Monochromatic Minibeams Radiotherapy: From Healthy Tissue-Sparing Effect Studies Toward First Experimental Glioma Bearing Rats Therapy

International Nuclear Information System (INIS)

Deman, Pierre; Vautrin, Mathias; Edouard, Magali; Stupar, Vasile; Bobyk, Laure; Farion, Régine; Elleaume, Hélène; Rémy, Chantal; Barbier, Emmanuel L.; Estève, François; Adam, Jean-François

2012-01-01

Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 × 5 × 4.8 mm 3 volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 × 8 × 7.8 mm 3 volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 ± 12.5 days versus 23.3 ± 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.

NMR: its application to the experimental study of hydrocephalus and brain edema

Energy Technology Data Exchange (ETDEWEB)

Asato, R; Murata, T; Mori, K; Handa, H [Kyoto Univ. (Japan). Faculty of Medicine

1981-06-01

The pulsed NMR technique is very sensitive to molecular movement because its observation frequency is in the range of the rates of molecular movement. Furthermore it makes it possible to study the interested molecules in the biological tissues physically and noninvasively. In this report we have investigated the experimental brain edema and hydrocephalus, in both of which the tissue fluid changes are main pathology, through /sup 1/H-NMR relaxation study of water molecule in the brain tissues. The longitudinal (T/sub 1/) and the transverse (T/sub 2/) relaxation times were measured with Varian-HR-220 spectrometer modified with Nicolet-TT-100 PFT system. The experimental materials were the adult male Wister rats suffering from cold injury edema and the adult canines suffering from kaolin hydrocephalus. The study showed firstly that in brain edema no particular changes were found for relaxation times in the white matter, whereas in the gray matter, discrepancy between the changes of T/sub 1/ and T/sub 2/ was observed. That is to say, there were 2 components of T/sub 2/ in contrast with single T/sub 1/ value in the same sample of the edematous gray matter, which indicates the existence of 2 fractions of tissue water, not exchanging on an NMR time scale. Secondary, a good correlation between the longitudinal (T/sub 1/) relaxation time and the tissue water content was found for the dog brains, which suggests that we can analyse the NMR relaxation data of the dog brains based on the two-fraction fast-exchange model.

Untangling dopamine-adenosine receptor-receptor assembly in experimental parkinsonism in rats

Directory of Open Access Journals (Sweden)

Víctor Fernández-Dueñas

2015-01-01

Full Text Available Parkinson’s disease (PD is a dopaminergic-related pathology in which functioning of the basal ganglia is altered. It has been postulated that a direct receptor-receptor interaction – i.e. of dopamine D2 receptor (D2R with adenosine A2A receptor (A2AR (forming D2R-A2AR oligomers – finely regulates this brain area. Accordingly, elucidating whether the pathology prompts changes to these complexes could provide valuable information for the design of new PD therapies. Here, we first resolved a long-standing question concerning whether D2R-A2AR assembly occurs in native tissue: by means of different complementary experimental approaches (i.e. immunoelectron microscopy, proximity ligation assay and TR-FRET, we unambiguously identified native D2R-A2AR oligomers in rat striatum. Subsequently, we determined that, under pathological conditions (i.e. in a rat PD model, D2R-A2AR interaction was impaired. Collectively, these results provide definitive evidence for alteration of native D2R-A2AR oligomers in experimental parkinsonism, thus conferring the rationale for appropriate oligomer-based PD treatments.

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 ...

The role of melatonin in radiation induced biochemical disturbances in brain and thyroid gland in adult male albino rats

International Nuclear Information System (INIS)

Abdel Kader, S.M.; EI-Sherbiny, E.M.

2007-01-01

Radiation induced changes in adult male albino male rats before and after melatonin administration were monitored to detect some biochemical changes in brain and thyroid gland. The parameters monitored were dopamine (DA), norepinephdne (NE) and gamma aminobutyric acid (GABA) in brain and triiodothyronine (T 3 ) thyroxine (T 4 ) and thyroid stimulating hormone (TSH) in serum of irradiated adult male albino rats before and after intraperitoneal injection of melatonin. Results indicated that 6.0 Gy whole body γ-irradiated rats showed gradual and significant decrease in DA, NE and GABA contents in different brain areas under investigation (cerebellum, pons+medulla oblongata, corpus striatum, cerebral cortex, hypothalamus, midbrain and hippocampus). The maximum effect of whole body γ-irradiation was observed after 21 days. Moreover, gradual and significant decrease in serum T 3 and T 4 levels were recorded after γ-irradiation. However, TSH level showed significant elevation throughout the experimental period. Melatonin at a dose level of 15 mg/kg b.wt. was intraperitoneally injected daily 30 minutes after 6.0 Gy whole body γ-irradiation, ameliorated DA, NE and GABA contents in different brain areas compared to those measured in irradiated rats. Moreover, melatonin gradually attenuated the effect of γ-irradiation on serum T 3 and T 4 levels to reach nearly the control level at day 21 after melatonin injection. However, melatonin ameliorated the elevated TSH level induced by γ-irradiation to reach its corresponding control value at day 21

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.

Chronic Opium Treatment Can Differentially Induce Brain and Liver Cells Apoptosis in Diabetic and Non-diabetic Male and Female Rats

OpenAIRE

Asiabanha, Majid; Asadikaram, Gholamreza; Rahnema, Amir; Mahmoodi, Mehdi; Hasanshahi, Gholamhosein; Hashemi, Mohammad; Khaksari, Mohammad

2011-01-01

It has been shown that some opium derivatives promote cell death via apoptosis. This study was designed to examine the influence of opium addiction on brain and liver cells apoptosis in male and female diabetic and non-diabetic Wistar rats. This experimental study was performed on normal, opium-addicted, diabetic and diabetic opium-addicted male and female rats. Apoptosis was evaluated by TUNEL and DNA fragmentation assays. Results of this study showed that apoptosis in opium-addicted and dia...

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.

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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.

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)

Hemodynamic measurements in rat brain and human muscle using diffuse near-infrared absorption and correlation spectroscopies

Science.gov (United States)

Yu, Guoqiang; Durduran, Turgut; Furuya, D.; Lech, G.; Zhou, Chao; Chance, Britten; Greenberg, J. H.; Yodh, Arjun G.

2003-07-01

Measurement of concentration, oxygenation, and flow characteristics of blood cells can reveal information about tissue metabolism and functional heterogeneity. An improved multifunctional hybrid system has been built on the basis of our previous hybrid instrument that combines two near-infrared diffuse optical techniques to simultaneously monitor the changes of blood flow, total hemoglobin concentration (THC) and blood oxygen saturation (StO2). Diffuse correlation spectroscopy (DCS) monitors blood flow (BF) by measuring the optical phase shifts caused by moving blood cells, while diffuse photon density wave spectroscopy (DPDW) measures tissue absorption and scattering. Higher spatial resolution, higher data acquisition rate and higher dynamic range of the improved system allow us to monitor rapid hemodynamic changes in rat brain and human muscles. We have designed two probes with different source-detector pairs and different separations for the two types of experiments. A unique non-contact probe mounted on the back of a camera, which allows continuous measurements without altering the blood flow, was employed to in vivo monitor the metabolic responses in rat brain during KCl induced cortical spreading depression (CSD). A contact probe was used to measure changes of blood flow and oxygenation in human muscle during and after cuff occlusion or exercise, where the non-contact probe is not appropriate for monitoring the moving target. The experimental results indicate that our multifunctional hybrid system is capable of in vivo and non-invasive monitoring of the hemodynamic changes in different tissues (smaller tissues in rat brain, larger tissues in human muscle) under different conditions (static versus moving). The time series images of flow during CSD obtained by our technique revealed spatial and temporal hemodynamic changes in rat brain. Two to three fold longer recovery times of flow and oxygenation after cuff occlusion or exercise from calf flexors in a

Establishment of an ideal time window model in hypothermic-targeted temperature management after traumatic brain injury in rats.

Science.gov (United States)

Zhao, Wan-Yong; Chen, Shao-Bo; Wang, Jing-Jing; Xu, Chao; Zhao, Ming-Liang; Dong, Hua-Jiang; Liang, Hai-Qian; Li, Xiao-Hong; Tu, Yue; Zhang, Sai; Chen, Chong; Sun, Hong-Tao

2017-08-15

Although hypothermic-targeted temperature management (HTTM) holds great potential for the treatment of traumatic brain injury (TBI), translation of the efficacy of hypothermia from animal models to TBI patientshas no entire consistency. This study aimed to find an ideal time window model in experimental rats which was more in accordance with clinical practice through the delayed HTTM intervention. Sprague-Dawley rats were subjected to unilateral cortical contusion injury and received therapeutic hypothermia at 15mins, 2 h, 4 h respectively after TBI. The neurological function was evaluated with the modified neurological severity score and Morris water maze test. The brain edema and morphological changes were measured with the water content and H&E staining. Brain sections were immunostained with antibodies against DCX (a neuroblast marker) and GFAP (an astrocyte marker). The apoptosis levels in the ipsilateral hippocampi and cortex were examined with antibodies against the apoptotic proteins Bcl-2, Bax, and cleaved caspase-3 by the immunofluorescence and western blotting. The results indicated that each hypothermia therapy group could improve neurobehavioral and cognitive function, alleviate brain edema and reduce inflammation. Furthermore, we observed that therapeutic hypothermia increased DCX expression, decreased GFAP expression, upregulated Bcl-2 expression and downregulated Bax and cleaved Caspase-3 expression. The above results suggested that HTTM at 2h or even at 4h post-injury revealed beneficial brain protection similarly, despite the best effect at 15min post-injury. These findings may provide relatively ideal time window models, further making the following experimental results more credible and persuasive. Copyright © 2017 Elsevier B.V. All rights reserved.

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

International Nuclear Information System (INIS)

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

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.

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.

Effect of MgSO4 on the expression of C-fos gene and the abilities of learning and memory in the rat brain with radiation induced injuries

International Nuclear Information System (INIS)

Zhang Wei; Wang Rui; Wang Lili; Zhou Juying; Tu Yu; Zou Rong; Zhou Weifang

2009-01-01

Objective: To investigate the effect of magnesium sulfate (MgSO 4 ) on the nerves function after hemisphere irradiation and explore possible mechanism of the effect. Methods: Mature Sprague-Dawley rats were randomly divided into 3 groups: blank control group (n = 26), experimental control group (n = 32) and experimental group (n = 32). To selecte rats randomly from the experimental control group and the experimental therapy group for 1/2 brain irradiation to a single-fraction maximal dose of 20 Gy using 5 MeV electrons. Magnesium sulfate was injected intraperitoneally into the rats that from the experimental group before and after irradiation for total seven times. The expression of c-fos gene was observed in the hippocampal formation of the rat brain with the immunofluorescence technique in 24 h after irradiation. The learning and memory results in Y-maze test were detected 8 weeks after irradiation respectively with the other rats and then had the pathomorphology observation. Results: Compared with the blank control group, the number of c-fos immunopositive cells in the hippocampal formation of experimental control group were increased markedly (P<0.01), and the learning and memory results of Y-maze test in the irradiation control group declined significantly (P<0.01). Compared with the irradiation control group, the experimental group's Fos immunopositive cells decreased significantly (P<0.05), and also the cognitive function of learning attempt times (at 4 and 8 weeks, P<0.01) and memory reappearance times (P<0.05) were significantly different from that in the irradiation control group. Conclusion: Magnesium sulfate can promote the recovery of the rats' cognitive impairment in the early stage after irradiation, and may play a role of protecting hippocampus neurons by the way of decreasing the expression of Fos protin in hippocampal formation. (authors)

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

Science.gov (United States)

Fries, Andreas W; Dadsetan, Sherry; Keiding, Susanne; Bak, Lasse K; Schousboe, Arne; Waagepetersen, Helle S; Simonsen, Mette; Ott, Peter; Vilstrup, Hendrik; Sørensen, Michael

2014-03-01

Ammonia has a key role in the development of hepatic encephalopathy (HE). In the brain, glutamine synthetase (GS) rapidly converts blood-borne ammonia into glutamine which in high concentrations may cause mitochondrial dysfunction and osmolytic brain edema. In astrocyte-neuron cocultures and brains of healthy rats, inhibition of GS by methionine sulfoximine (MSO) reduced glutamine synthesis and increased alanine synthesis. Here, we investigate effects of MSO on brain and interorgan ammonia metabolism in sham and bile duct ligated (BDL) rats. Concentrations of glutamine, glutamate, alanine, and aspartate and incorporation of (15)NH(4)(+) 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)NH(4)(+) into glutamine in all tissues. It did not affect alanine concentrations in any of the tissues but plasma alanine concentration increased; incorporation of (15)NH(4)(+) into alanine was increased in brain in sham and BDL rats and in kidney in sham rats. It inhibited GS in all tissues examined but only in brain was an increased incorporation of (15)N-ammonia into alanine observed. Liver and kidney were important for metabolizing blood-borne ammonia.

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

Science.gov (United States)

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.

Standardized Environmental Enrichment Supports Enhanced Brain Plasticity in Healthy Rats and Prevents Cognitive Impairment in Epileptic Rats

Science.gov (United States)

Kouchi, Hayet Y.; Bodennec, Jacques; Morales, Anne; Georges, Béatrice; Bonnet, Chantal; Bouvard, Sandrine; Sloviter, Robert S.; Bezin, Laurent

2013-01-01

Environmental enrichment of laboratory animals influences brain plasticity, stimulates neurogenesis, increases neurotrophic factor expression, and protects against the effects of brain insult. However, these positive effects are not constantly observed, probably because standardized procedures of environmental enrichment are lacking. Therefore, we engineered an enriched cage (the Marlau™ cage), which offers: (1) minimally stressful social interactions; (2) increased voluntary exercise; (3) multiple entertaining activities; (4) cognitive stimulation (maze exploration), and (5) novelty (maze configuration changed three times a week). The maze, which separates food pellet and water bottle compartments, guarantees cognitive stimulation for all animals. Compared to rats raised in groups in conventional cages, rats housed in Marlau™ cages exhibited increased cortical thickness, hippocampal neurogenesis and hippocampal levels of transcripts encoding various genes involved in tissue plasticity and remodeling. In addition, rats housed in Marlau™ cages exhibited better performances in learning and memory, decreased anxiety-associated behaviors, and better recovery of basal plasma corticosterone level after acute restraint stress. Marlau™ cages also insure inter-experiment reproducibility in spatial learning and brain gene expression assays. Finally, housing rats in Marlau™ cages after severe status epilepticus at weaning prevents the cognitive impairment observed in rats subjected to the same insult and then housed in conventional cages. By providing a standardized enriched environment for rodents during housing, the Marlau™ cage should facilitate the uniformity of environmental enrichment across laboratories. PMID:23342033

Standardized environmental enrichment supports enhanced brain plasticity in healthy rats and prevents cognitive impairment in epileptic rats.

Directory of Open Access Journals (Sweden)

Raafat P Fares

Full Text Available Environmental enrichment of laboratory animals influences brain plasticity, stimulates neurogenesis, increases neurotrophic factor expression, and protects against the effects of brain insult. However, these positive effects are not constantly observed, probably because standardized procedures of environmental enrichment are lacking. Therefore, we engineered an enriched cage (the Marlau™ cage, which offers: (1 minimally stressful social interactions; (2 increased voluntary exercise; (3 multiple entertaining activities; (4 cognitive stimulation (maze exploration, and (5 novelty (maze configuration changed three times a week. The maze, which separates food pellet and water bottle compartments, guarantees cognitive stimulation for all animals. Compared to rats raised in groups in conventional cages, rats housed in Marlau™ cages exhibited increased cortical thickness, hippocampal neurogenesis and hippocampal levels of transcripts encoding various genes involved in tissue plasticity and remodeling. In addition, rats housed in Marlau™ cages exhibited better performances in learning and memory, decreased anxiety-associated behaviors, and better recovery of basal plasma corticosterone level after acute restraint stress. Marlau™ cages also insure inter-experiment reproducibility in spatial learning and brain gene expression assays. Finally, housing rats in Marlau™ cages after severe status epilepticus at weaning prevents the cognitive impairment observed in rats subjected to the same insult and then housed in conventional cages. By providing a standardized enriched environment for rodents during housing, the Marlau™ cage should facilitate the uniformity of environmental enrichment across laboratories.

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

International Nuclear Information System (INIS)

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

Characterization of murine hepatitis virus (JHM) RNA from rats with experimental encephalomyelitis.

Science.gov (United States)

Jackson, D P; Percy, D H; Morris, V L

1984-09-01

When Wistar Furth rats are inoculated intracerebrally with the murine hepatitis virus JHM they often develop a demyelinating disease with resulting hind leg paralysis. Using an RNA transfer procedure and hybridization kinetic analysis, the virus-specific RNA in these rats was characterized. The pattern of JHM-specific RNA varied with individual infections of Wistar Furth rats. However, two species of JHM-specific RNA, the nucleocapsid and a 2.1-2.4 X 10(6)-Da RNA species were generally present. A general decrease in JHM-specific RNA in brains and spinal cord samples taken later than 20 days postinoculation was observed; however, JHM-specific RNA persisted in the spinal cord longer than in the brain of these rats.

Brain Aquaporin-4 in Experimental Acute Liver Failure

Science.gov (United States)

Rama Rao, Kakulavarapu V.; Jayakumar, Arumugam R.; Tong, Xiaoying; Curtis, Kevin M.; Norenberg, Michael D.

2016-01-01

Intracranial hypertension due to brain edema and associated astrocyte swelling is a potentially lethal complication of acute liver failure (ALF). Mechanisms of edema formation are not well understood but elevated levels of blood and brain ammonia and its byproduct glutamine have been implicated in this process. We examined mRNA and protein expression of the water channel protein aquaporin-4 (AQP4) in cerebral cortex in a rat model of ALF induced by the hepatotoxin thioacetamide. Rats with ALF showed increased AQP4 protein in the plasma membrane (PM). Total tissue levels of AQP4 protein and mRNA levels were not altered indicating that increased AQP4 is not transcriptionally mediated but is likely due to a conformational change in the protein, i.e. a more stable anchoring of AQP4 to the PM and/or interference with its degradation. By immunohistochemistry there was an increase in AQP4 immunoreactivity in the PM of perivascular astrocytes in ALF. Rats with ALF showed increased levels of α-syntrophin, a protein involved in the anchoring of AQP4 to perivascular astrocytic end-feet. Increased AQP4 and α-syntrophin levels were inhibited by L-histidine, an inhibitor of glutamine transport into mitochondria, suggesting a role for glutamine in the increase of PM levels of AQP4. These results indicate that increased AQP4 PM levels in perivascular astrocytic end-feet are likely critical to the development of brain edema in ALF. PMID:20720509

[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)

Activation of peripheral leukocytes in rat pregnancy and experimental preeclampsia

NARCIS (Netherlands)

Faas, MM; Schuiling, GA; Linton, EA; Sargent, IL; Redman, CWG

OBJECTIVE: The aim of this study was to search for activation markers of peripheral leukocytes in experimental preeclampsia in the rat. STUDY DESIGN: Experimental preeclampsia was induced in 14-day-pregnant rats by infusion of endotoxin (1.0 mu g/kg body weight). For comparison, rats with normal

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.

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.

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)

Comparative studies of D2 receptors and brain perfusion in hemi-parkinsonism rats

International Nuclear Information System (INIS)

Lin Yansong; Lin Xiangtong

2000-01-01

The relationship between dopamine D 2 receptors and brain perfusion in hemi-parkinsonism rats was studied. Hemi-parkinsonism rats were made by stereotaxic 6-hydroxy dopamine (6-OH-DA) lesions in substantia nigra (SN) and ventral tegmental area (VTA), apomorphine (Apo) which could induced the successful model rat rotates toward the intact side was used to select the rats, 125 I-IBZM ex-vivo autoradiography analysis and 99m Tc-HM-PAO regional cerebral biodistribution were used to evaluate D 2 receptors and cerebral blood flow. The HPLC-ECD were used to measure striatum DA and its metabolites content. The lesioned side striatum DA and its metabolites HVA DOPAC reduced significantly than that of the intact side and pseudo-operated group, striatum/cerebellum 125 I-IBZM uptake ratio was 8.04 +- 0.71 in lesioned side of hemi-parkinsonism rats, significantly increased compared with the intact side and the pseudo-operated group (p 0.05). These results indicated that in the 6-OH-DA lesioned side DA content decreased significantly and an up-regulation of striatum D 2 receptor binding sites was induced in hemi-parkinsonism rats, which showed good correlation with rotation behavior induced by Apo. Comparing with cerebral blood flow, D 2 receptor reflected by IBZM seems to be more specific and earlier to detect the cerebral functional impairment in experimental hemi-parkinsonism

Histological study of rat masseter muscle following experimental occlusal alteration.

Science.gov (United States)

Nishide, N; Baba, S; Hori, N; Nishikawa, H

2001-03-01

It has been suggested that occlusal interference results in masticatory muscle dysfunction. In our previous study, occlusal interference reduced the rat masseter energy level during masticatory movements. The purpose of this study was to investigate the histological alterations of rat masseter muscles following experimental occlusal alteration with unilateral bite-raising. A total of eight male adult Wistar rats were equally divided into control and experimental groups. The experimental rats wore bite-raising splints on the unilateral upper molar. However, 4 weeks after the operation, the anterior deep masseter muscles were removed and then stained for succinic acid dehydrogenase (SDH), haematoxylin eosin (HE) and myofibrillar ATPase. Most of the muscle fibres in experimental rats remained intact, although partial histological changes were observed, such as extended connective tissue, appearance of inflammatory cells in the muscle fibres and existence of muscle fibres with central nuclei and central cores. Moreover, the fibre area-fibre frequency histograms of experimental muscle indicated a broad pattern than that of controls. These results indicated that occlusal interference caused histological changes in masseter muscles and that this may be related to the fact that the masseter energy level was reduced during masticatory movements in unilateral bite-raised rats.

Influence of low frequency magnetic field used in magnetotherapy on interleukin 6 (IL-6 contents in rat heart and brain

Directory of Open Access Journals (Sweden)

Elżbieta Ciejka

2017-08-01

Full Text Available Background: The human population is exposed ever more frequently to magnetic fields (MF. This is due to both technological progress and development of the economy as well as to advances made in medical science. That is why the thorough understanding and systematized knowledge about mechanisms by which MF exerts its effects on living organisms play such an important role. In this context the health of MF-exposed people is the subject of particular concern. The aim of the study was to evaluate the effect of extremely low frequency magnetic field (ELFMF used in magnetotherapy on the concentration of interleukin 6 (IL-6 in rat heart and brain. Material and Methods: The male rats were randomly divided into 3 experimental groups: group I – control, without contact with magnetic field; group II − exposed to bipolar, rectangular magnetic field 40 Hz, induction “peak-to-peak” 7 mT 30 min/day for 2 weeks; and group III − exposed to bipolar, rectangular magnetic field 40 Hz, 7 mT 60 min/day for 2 weeks. Concentration of IL-6 in the heart and brain of animals was measured after MF exposure. Results: Exposure to ELFMF: 40 Hz, induction “peak-to-peak” 7 mT 30 min/day for 2 weeks caused a significant IL-6 increase in rat hearts compared to the control group (p < 0.05 and a non-significant IL-6 decrease in rat brain. The magnetic field applied for 60 min resulted in non-significant IL-6 increase in rat hearts compared to the control group and significant IL-6 decrease in rat brain (p < 0.05. Conclusions: The influence of magnetic field on inflammation in the body varies depending on the MF parameters and the affected tissues or cells. Med Pr 2017;68(4:517–523

[Influence of low frequency magnetic field used in magnetotherapy on interleukin 6 (IL-6) contents in rat heart and brain].

Science.gov (United States)

Ciejka, Elżbieta; Skibska, Beata; Gorąca, Anna

2017-06-27

The human population is exposed ever more frequently to magnetic fields (MF). This is due to both technological progress and development of the economy as well as to advances made in medical science. That is why the thorough understanding and systematized knowledge about mechanisms by which MF exerts its effects on living organisms play such an important role. In this context the health of MF-exposed people is the subject of particular concern. The aim of the study was to evaluate the effect of extremely low frequency magnetic field (ELFMF) used in magnetotherapy on the concentration of interleukin 6 (IL-6) in rat heart and brain. The male rats were randomly divided into 3 experimental groups: group I - control, without contact with magnetic field; group II - exposed to bipolar, rectangular magnetic field 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks; and group III - exposed to bipolar, rectangular magnetic field 40 Hz, 7 mT 60 min/day for 2 weeks. Concentration of IL-6 in the heart and brain of animals was measured after MF exposure. Exposure to ELFMF: 40 Hz, induction "peak-to-peak" 7 mT 30 min/day for 2 weeks caused a significant IL-6 increase in rat hearts compared to the control group (p < 0.05) and a non-significant IL-6 decrease in rat brain. The magnetic field applied for 60 min resulted in non-significant IL-6 increase in rat hearts compared to the control group and significant IL-6 decrease in rat brain (p < 0.05). The influence of magnetic field on inflammation in the body varies depending on the MF parameters and the affected tissues or cells. Med Pr 2017;68(4):517-523. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

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.

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

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...

Carbonated soft drinks induce oxidative stress and alter the expression of certain genes in the brains of Wistar rats.

Science.gov (United States)

El-Terras, Adel; Soliman, Mohamed Mohamed; Alkhedaide, Adel; Attia, Hossam Fouad; Alharthy, Abdullah; Banaja, Abdel Elah

2016-04-01

In Saudi Arabia, the consumption of carbonated soft drinks is common and often occurs with each meal. Carbonated soft drink consumption has been shown to exhibit effects on the liver, kidney and bone. However, the effects of these soft drinks on brain activity have not been widely examined, particularly at the gene level. Therefore, the current study was conducted with the aim of evaluating the effects of chronic carbonated soft drink consumption on oxidative stress, brain gene biomarkers associated with aggression and brain histology. In total, 40 male Wistar rats were divided into four groups: Group 1 served as a control and was provided access to food and water ad libitum; and groups 2‑4 were given free access to food and carbonated soft drinks only (Cola for group 2, Pepsi for group 3 and 7‑UP for group 4). Animals were maintained on these diets for 3 consecutive months. Upon completion of the experimental period, animals were sacrificed and serological and histopathological analyses were performed on blood and tissues samples. Reverse transcription‑polymerase chain reaction was used to analyze alterations in gene expression levels. Results revealed that carbonated soft drinks increased the serum levels of malondialdehyde (MDA). Carbonated soft drinks were also observed to downregulate the expression of antioxidants glutathione reductase (GR), catalase and glutathione peroxidase (GPx) in the brain when compared with that in the control rats. Rats administered carbonated soft drinks also exhibited decreased monoamine oxidase A (MAO‑A) and acetylcholine esterase (AChE) serum and mRNA levels in the brain. In addition, soft drink consumption upregulated mRNA expression of dopamine D2 receptor (DD2R), while 5-hydroxytryptamine transporter (5‑HTT) expression was decreased. However, following histological examination, all rats had a normal brain structure. The results of this study demonstrated that that carbonated soft drinks induced oxidative stress and

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

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

Monochromatic Minibeams Radiotherapy: From Healthy Tissue-Sparing Effect Studies Toward First Experimental Glioma Bearing Rats Therapy

Energy Technology Data Exchange (ETDEWEB)

Deman, Pierre [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Vautrin, Mathias [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); DOSIsoft, Cachan (France); Edouard, Magali [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Stupar, Vasile [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); Bobyk, Laure; Farion, Regine [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Elleaume, Helene [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France); Remy, Chantal; Barbier, Emmanuel L. [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); Esteve, Francois [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France); Adam, Jean-Francois, E-mail: adam@esrf.fr [INSERM, Grenoble (France); Universite Joseph Fourier, Institut des Neurosciences, Grenoble (France); European Synchrotron Radiation Facility, Grenoble (France); Grenoble University Hospital, Grenoble (France)

2012-03-15

Purpose: The purpose of this study was to evaluate high-dose single fraction delivered with monochromatic X-rays minibeams for the radiotherapy of primary brain tumors in rats. Methods and Materials: Two groups of healthy rats were irradiated with one anteroposterior minibeam incidence (four minibeams, 123 Gy prescribed dose at 1 cm depth in the brain) or two interleaved incidences (54 Gy prescribed dose in a 5 Multiplication-Sign 5 Multiplication-Sign 4.8 mm{sup 3} volume centered in the right hemisphere), respectively. Magnetic resonance imaging (MRI) follow-up was performed over 1 year. T2-weighted (T2w) images, apparent diffusion coefficient (ADC), and blood vessel permeability maps were acquired. F98 tumor bearing rats were also irradiated with interleaved minibeams to achieve a homogeneous dose of 54 Gy delivered to an 8 Multiplication-Sign 8 Multiplication-Sign 7.8 mm{sup 3} volume centered on the tumor. Anatomic and functional MRI follow-up was performed every 10 days after irradiation. T2w images, ADC, and perfusion maps were acquired. Results: All healthy rats were euthanized 1 year after irradiation without any clinical alteration visible by simple examination. T2w and ADC measurements remain stable for the single incidence irradiation group. Localized Gd-DOTA permeability, however, was observed 9 months after irradiation for the interleaved incidences group. The survival time of irradiated glioma bearing rats was significantly longer than that of untreated animals (49 {+-} 12.5 days versus 23.3 {+-} 2 days, p < 0.001). The tumoral cerebral blood flow and blood volume tend to decrease after irradiation. Conclusions: This study demonstrates the sparing effect of minibeams on healthy tissue. The increased life span achieved for irradiated glioma bearing rats was similar to the one obtained with other radiotherapy techniques. This experimental tumor therapy study shows the feasibility of using X-ray minibeams with high doses in brain tumor radiotherapy.

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

Science.gov (United States)

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.

Science.gov (United States)

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

Science.gov (United States)

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.

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

Gu Xiangjin

2014-02-01

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

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

Science.gov (United States)

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.

The expression and significance of tyrosine hydroxylase in the brain tissue of Parkinsons disease rats

OpenAIRE

Chen, Yuan; Lian, Yajun; Ma, Yunqing; Wu, Chuanjie; Zheng, Yake; Xie, Nanchang

2017-01-01

The expression and significance of tyrosine hydroxylase (TH) in brain tissue of rats with Parkinson's disease (PD) were explored and analyzed. A total of 120 clean-grade and healthy adult Wistar rats weighing 180–240 g were randomly divided equally into four groups according to the random number table method. Rats were sacrificed before and after the model establishment for 3, 6 or 8 weeks. The number of revolutions in rats was observed and the relative expression of TH mRNA in brain tissue w...

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

Science.gov (United States)

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.

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

Directory of Open Access Journals (Sweden)

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.

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.

Science.gov (United States)

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.

Science.gov (United States)

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.

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

Effects of insulin combined with idebenone on blood-brain barrier permeability in diabetic rats.

Science.gov (United States)

Sun, Yan-Na; Liu, Li-Bo; Xue, Yi-Xue; Wang, Ping

2015-04-01

This study investigates the effect of insulin combined with idebenone on blood-brain barrier (BBB) permeability in experimental streptozotocin-induced diabetic rats as well as the underlying mechanisms. With a diabetic rat model, we show that insulin and idebenone normalize body weight and water intake and restore BBB permeability and that their combination displays a synergistic effect. The results from transmission electron microscopy show that the combination of insulin and idebenone significantly closed the tight junction (TJ) in diabetic rats. The results from Western blotting in diabetic rats show that the upregulation of TJ-associated proteins occludin, and zonula occludens (ZO)-1 caused by the combination of insulin and idebenone is more remarkable than that with either agent alone. In addition, the activations of reactive oxygen species (ROS) and advanced glycation end products (AGEs) and the expression levels of receptors for advanced glycation end-products (RAGE) and nuclear factor-κB (NF-κB) were significantly decreased after treatment with insulin and idebenone in diabetic rats. These results suggest that the combination of insulin and idebenone could decrease the BBB permeability in diabetic rats by upregulating the expression of occludin, claudin-5, and ZO-1 and that the ROS/AGE/RAGE/NF-κB signal pathway might be involved in the process. © 2014 Wiley Periodicals, Inc.

Pathophysiological studies of experimental brain edema and cerebral ischemia using MRI/S

International Nuclear Information System (INIS)

Naruse, Shoji; Higuchi, Toshihiro; Horikawa, Yoshiharu; Tanaka, Chuzo; Hirakawa, Kimiyoshi

1987-01-01

Pathophysiological changes in experimental brain edema and cerebral ischemia were examined by the in vivo 1 H- and 31 P-NMR method. Two types of experimental brain edema were induced in rats by cold injury and by triethyltin (TET) intoxication. Experimental cerebral ischemia was induced in rats by the four-vessel occlusion method. During the course of these pathological conditions, the 1 H-MRIs and 31 P-NMR spectra were measured sequentially with a single NMR spectrometer (4.8 tesla, 9 cm bore magnet). In the cold-injury edema, high-intensity lesions were detected in the gray and white matters of the injured hemisphere by means of SE images with a long Te 3 hours after the injury. The intensity reached its maximum 16 to 24 hours after the injury, and then returned to normal 7 days later. These high-intensity lesions indicated an increase in the T2 value in the edematous tissue. There were no changes in the 31 P-NMR spectra during the course of edema formation and absorption. In the TET-induced edema, high-intensity lesions were also detected in the bilateral white matter by means of SE images with a long Te from the 3rd day up to the 7th day during the injection of TET. These high-intensity lesions subsided 42 days after the discontinuance of injecting TET. There were no changes in the 31 P-NMR spectra during the whole course of TET-induced edema. In the cerebral ischemia, no remarkable changes in the MRI were detected in either SE or IR images during the ischemic and recirculated periods. However, dynamic changes in the 31 P-NMR spectra were detected during the course of cerebral ischemia. In the pre-ischemic period, the peaks of the ATP, PCr, phosphodiesters (PDE), Pi, and phosphomonoesters (PME) were detected. After the induction of ischemia, the ATP and PCr peaks decreased, while one Pi peak increased rapidly. (J.P.N.)

Pathophysiological studies of experimental brain edema and cerebral ischemia using MRI/S

Energy Technology Data Exchange (ETDEWEB)

Naruse, S; Higuchi, T; Horikawa, Y; Tanaka, C; Hirakawa, K

1987-02-01

Pathophysiological changes in experimental brain edema and cerebral ischemia were examined by the in vivo /sup 1/H- and /sup 31/P-NMR method. Two types of experimental brain edema were induced in rats by cold injury and by triethyltin (TET) intoxication. Experimental cerebral ischemia was induced in rats by the four-vessel occlusion method. During the course of these pathological conditions, the /sup 1/H-MRIs and /sup 31/P-NMR spectra were measured sequentially with a single NMR spectrometer (4.8 tesla, 9 cm bore magnet). In the cold-injury edema, high-intensity lesions were detected in the gray and white matters of the injured hemisphere by means of SE images with a long Te 3 hours after the injury. The intensity reached its maximum 16 to 24 hours after the injury, and then returned to normal 7 days later. These high-intensity lesions indicated an increase in the T2 value in the edematous tissue. There were no changes in the /sup 31/P-NMR spectra during the course of edema formation and absorption. In the TET-induced edema, high-intensity lesions were also detected in the bilateral white matter by means of SE images with a long Te from the 3rd day up to the 7th day during the injection of TET. These high-intensity lesions subsided 42 days after the discontinuance of injecting TET. There were no changes in the /sup 31/P-NMR spectra during the whole course of TET-induced edema. In the cerebral ischemia, no remarkable changes in the MRI were detected in either SE or IR images during the ischemic and recirculated periods. However, dynamic changes in the /sup 31/P-NMR spectra were detected during the course of cerebral ischemia. In the pre-ischemic period, the peaks of the ATP, PCr, phosphodiesters (PDE), Pi, and phosphomonoesters (PME) were detected. After the induction of ischemia, the ATP and PCr peaks decreased, while one Pi peak increased rapidly.

Exploration of central dopamine D2 receptors by autoradiography, pathology and functional behaviour observation in rat model with experimental parkinsonism

International Nuclear Information System (INIS)

Lin Yansong; Lin Xiangtong

1996-01-01

The rat model with experimental parkinsonism mimic the course of human parkinsonism were made by cerebral-stereotaxic techniques. 125 I-IBZM was used to evaluate the D 2 receptors distribution by autoradiographic analysis of coronal brain section. In 6 parkinsonism model rats, on the lesioned side the striatum/frontal cortex ratio was 5.32 +- 0.37, it was significantly (P 125 I-IBZM as the ligand of D 2 receptor can well reflect the distribution and changes of D 2 receptors, and also as the theoretical basis for the clinical imaging diagnosis

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)

The effect of pre-nutrition of hydroalcoholic extractof Origanum vulgare on brain edema and neurologic deficits in a rat stroke model

Directory of Open Access Journals (Sweden)

Meysam Foroozandeh

2015-10-01

Full Text Available Background and Aim: Stroke is one of the most important factors of mortality and disability in the world. Free radicals are produced following ischemic stroke and they play a central role in breaking the blood-brain barrier and  causing brain edema formation. The aim of the current study was to evaluate the effect of hydro- alcoholic extract of Origanum vulgare on brain edema and neurologic deficit in a rat stroke model. Materials and Methods: In thisexperimental study, 35 male Wistar rats were randomly divided into 5 equal groups.  The first  two groups (control and Sham received distilled water, while three treatment groups received oral Origanum vulgare extract for 30days (50,75and 100 mg/kgdaily, respectively.  Two hours after the last dose of Origanum vulgare extract,each main group underwent  a 60 min middle cerebral artery occlusion.  Then, the assessment of blood brain edema, and neurologic deficits analysis were done . Brain edema (brain water content was analyzed by One-Way ANOVA using LSD method and neurologic deficits analysis by means of Mann-Whitney U, and P<0.05 was taken as the significant level. Results: Origanum vulgare extract reduced brain edema in the experimental groups of 50 (82.49±0.47, 75 (80.89±0.63 and 100 mg/kg/day (80.80±0.66 compared to the control group (84.46±0.67. The neurologic deficit scores in the experimental groups of 75and 100mg/kg/day, compared with control group, but neurologic deficit scores did not affect the group receiving the dose 50 mg/kg. Conclusion:  The obtained data indicate that Origanum vulgar extract via reduction of brain edema and neurologic deficits scorescan have a protective effect on the stroke model.

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)

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

Energy Technology Data Exchange (ETDEWEB)

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

Impact of bacteremia on the pathogenesis of experimental pneumococcal meningitis

DEFF Research Database (Denmark)

Brandt, Christian T; Holm, David; Liptrot, Matthew

2008-01-01

BACKGROUND: Bacteremia plays a major role in the outcome of pneumococcal meningitis. This experimental study investigated how bacteremia influences the pathophysiologic profile of the brain. METHODS: Rats with Streptococcus pneumoniae meningitis were randomized to 1 of 3 groups of infected study...... rats: (1) rats with attenuated bacteremia resulting from intravenous injection of serotype-specific pneumococcal antibody, (2) rats with early-onset bacteremia resulting from concomitant intravenous infection, or (3) a meningitis control group. The blood-brain barrier (BBB) breakdown, ventricle size......, brain water distribution, and brain pathologic findings were analyzed using magnetic resonance morphological and functional imaging. Laboratory data and clinical disease scores were obtained. RESULTS: Attenuation of the bacteremic component of pneumococcal meningitis improved clinical disease symptoms...

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

Directory of Open Access Journals (Sweden)

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.

Science.gov (United States)

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.

Determination of trace elements in kidneys, livers and brains of rats with sealer implants by ICP-MS

International Nuclear Information System (INIS)

Simsek, Neslihan; Akinci, Levent; Alan, Hilal; Gecör, Orhan; Özan, Ülkü

2017-01-01

Following root canal treatment, sealers may contact periapical tissue. The purpose of this study was to evaluate the systemic toxic effects of epoxy resin-based sealers (AH Plus and Obtuseal). Inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure levels of trace elements (beryllium, magnesium, aluminium, calcium, chromium, arsenic and lead) in the brain, kidney and liver of rats. Twenty sterilized polyethylene tubes were then filled with AH Plus and Obtuseal and implanted into the dorsal subcutaneous tissue of 10 rats; three unoperated animals were used as a control group. After 45 days, the rats were sacrificed by cervical dislocation following anaesthesia, and brains, kidneys and livers were removed from all experimental animals. ICP-MS analysis was used to determine levels of trace elements. Data were analysed using Kruskal– Wallis and Connover post hoc tests. No significant differences were found in aluminium and calcium levels, but brains, kidneys and livers showed significantly higher amounts of magnesium and chromium than the corresponding controls. In the kidney and liver samples, arsenic levels were found to be higher than in the control group. Lead was detected at higher levels only in liver samples from the AH Plus group. Beryllium was not detected in any organ. It was concluded that AH Plus and Obtuseal release minimal quantities of trace elements when in contact with subcutaneous tissue, and further studies are needed to understand the systemic effects of these materials

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.

Science.gov (United States)

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

Directory of Open Access Journals (Sweden)

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.

Evaluation of passive avoidance learning and spatial memory in rats exposed to low levels of lead during specific periods of early brain development.

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Rao Barkur, Rajashekar; Bairy, Laxminarayana K

2015-01-01

Widespread use of heavy metal lead (Pb) for various commercial purposes has resulted in the environmental contamination caused by this metal. The studies have shown a definite relationship between low level lead exposure during early brain development and deficit in children's cognitive functions. This study investigated the passive avoidance learning and spatial learning in male rat pups exposed to lead through their mothers during specific periods of early brain development. Experimental male rats were divided into 5 groups: i) the normal control group (NC) (N = 12) consisted of rat offspring born to mothers who were given normal drinking water throughout gestation and lactation, ii) the pre-gestation lead exposed group (PG) (N = 12) consisted of rat offspring, mothers of these rats had been exposed to 0.2% lead acetate in the drinking water for 1 month before conception, iii) the gestation lead exposed group (G) (N = 12) contained rat offspring born to mothers who had been exposed to 0.2% lead acetate in the drinking water throughout gestation, iv) the lactation lead exposed group (L) (N = 12) had rat offspring, mothers of these rats exposed to 0.2% lead acetate in the drinking water throughout lactation and v) the gestation and lactation lead exposed group (GL) (N = 12) contained rat offspring, mothers of these rats were exposed to 0.2% lead acetate throughout gestation and lactation. The study found deficit in passive avoidance learning in the G, L and GL groups of rats. Impairment in spatial learning was found in the PG, G, L and GL groups of rats. Interestingly, the study found that gestation period only and lactation period only lead exposure was sufficient to cause deficit in learning and memory in rats. The extent of memory impairment in the L group of rats was comparable with the GL group of rats. So it can be said that postnatal period of brain development is more sensitive to neurotoxicity compared to prenatal exposure. This work is available in Open

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

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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.

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

Correlation between AQP4 mRNA and PKC activity after gamma knife radiosurgery in rat brain

International Nuclear Information System (INIS)

Shen Guangjian; Xu Minhui; Gen Mingying; Tang Wenyuan; Sun Shanquan

2009-01-01

Objective: To explore the change of AQP4 mRNA expression and the correlation with PKC in rat brain irradiated by γ knife radiosurgery (GKS). Methods: 30 Wistar rats were used in the study. The experimental radiosurgery model was established by radiating rat left rotral caudate nucleus with GKS(one target, 100 Gy in isocenter dose and 4 mm in collimator), and was examined at 1,3,7,15,30 and 45 d post-irradiation. AQP4 mRNA expression, PKC activity and free intracellular calcium ion concentration ([Ca 2+ ] i ) of brain tissue were determined by RT-PCR, liquid scintillation counter and Fura-2/AM, respectively. Results: AQP4 mRNA expression increased gradually from 0.99 ± 0.05 in control group to 2.32 ± 0.10 at 30 d post-irradiation, and decreased to 2.21 ± 0.08 at 45 d post-irradiation. The PKC activity and the free [Ca 2+ ] i decreased gradually from 0.5896 ± 0.2101 and 455.82 ± 20.13 in control group to 0.0404 ± 0.0294 and 196.72 ± 9.87 at 30 d post- irradiation, and increased to 0.1050 ± 0.0607 and 219.26 ± 10.43 at 45 d post-irradiation, respectively. The significant differences were found between experimental group and control group except at 1 d post-irradiation (P 2+ ] i and the PKC activity was positive (P=0.001, r=0.959). Conclusions: The increased expression of AQP4 mRNA might result from the inhibition of PKC activity due to the reduction of free [Ca 2+ ] i after GKS. (authors)

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.

Imaging of aromatase distribution in rat and rhesus monkey brains with [11C]vorozole

International Nuclear Information System (INIS)

Takahashi, Kayo; Bergstroem, Mats; Fraendberg, Pernilla; Vesstroem, Eva-Lotta; Watanabe, Yasuyoshi; Langstroem, Bengt

2006-01-01

Aromatase is an enzyme that converts androgens to estrogens and may play a role in mood and mental status. The aim of this study was to demonstrate that brain aromatase distribution could be evaluated with a novel positron emission tomography (PET) tracer [ 11 C]vorozole. Vorozole is a nonsteroidal aromatase inhibitor that reversibly binds to the heme domain of aromatase. In vitro experiments in rat brain, using frozen section autoradiography, illustrated specific binding in the medial amygdala (MA), the bed nucleus of stria terminalis (BST) and the preoptic area (POA) of male rat brain. Specific binding in female rat brain was found in the MA and the BST; however, the signals were lower than those of males. The K d of [ 11 C]vorozole binding to aromatase in MA was determined to be 0.60±0.06 nM by Scatchard plot analysis using homogenates. An in vivo PET study in female rhesus monkey brain demonstrated the uptake of [ 11 C]vorozole in the amygdala, where the uptake was blocked by the presence of excess amounts of unlabeled vorozole. Thus, this tracer has a high affinity for brain aromatase and could have a potential for in vivo aromatase imaging. This technique might enable the investigation of human brain aromatase in healthy and diseased persons

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.

Stress-sensitive arterial hypertension, haemodynamic changes and brain metabolites in hypertensive ISIAH rats: MRI investigation.

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Seryapina, A A; Shevelev, O B; Moshkin, M P; Markel, A L; Akulov, A E

2017-05-01

hypothalamus of 3-month-old ISIAH rats, an increase in energetic activity and prevalence of excitatory over inhibitory neurotransmitters was noticed. The blood flow through the main arteries showed a positive correlation with glutamate and glutamine levels in the hypothalamus and a negative correlation with the hypothalamic GABA level. The blood pressure values were positively correlated with hypothalamic choline levels. Thus, the early development of stress-sensitive hypertension in the ISIAH rats is accompanied by considerable changes both in brain metabolite ratios and in the parameters of blood flow through the main arteries. © 2017 Institute of Cytology and Genetics (SB RAS). Experimental Physiology © 2017 The Physiological Society.

Fisetin alleviates early brain injury following experimental subarachnoid hemorrhage in rats possibly by suppressing TLR 4/NF-κB signaling pathway.

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Zhou, Chen-hui; Wang, Chun-xi; Xie, Guang-bin; Wu, Ling-yun; Wei, Yong-xiang; Wang, Qiang; Zhang, Hua-sheng; Hang, Chun-hua; Zhou, Meng-liang; Shi, Ji-xin

2015-12-10

Early brain injury (EBI) determines the unfavorable outcomes after subarachnoid hemorrhage (SAH). Fisetin, a natural flavonoid, has anti-inflammatory and neuroprotection properties in several brain injury models, but the role of fisetin on EBI following SAH remains unknown. Our study aimed to explore the effects of fisetin on EBI after SAH in rats. Adult male Sprague-Dawley rats were randomly divided into the sham and SAH groups, fisetin (25mg/kg or 50mg/kg) or equal volume of vehicle was given at 30min after SAH. Neurological scores and brain edema were assayed. The protein expression of toll-like receptor 4 (TLR 4), p65, ZO-1 and bcl-2 was examined by Western blot. TLR 4 and p65 were also assessed by immunohistochemistry (IHC). Enzyme-linked immunosorbent assay (ELISA) was performed to detect the production of pro-inflammatory cytokines. Terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) was perform to assess neural cell apoptosis. High-dose (50mg/kg) fisetin significantly improved neurological function and reduced brain edema at both 24h and 72h after SAH. Remarkable reductions of TLR 4 expression and nuclear factor κB (NF-κB) translocation to nucleus were detected after fisetin treatment. In addition, fisetin significantly reduced the productions of pro-inflammatory cytokines, decreased neural cell apoptosis and increased the protein expression of ZO-1 and bcl-2. Our data provides the evidence for the first time that fisetin plays a protective role in EBI following SAH possibly by suppressing TLR 4/NF-κB mediated inflammatory pathway. Copyright © 2015 Elsevier B.V. All rights reserved.

[Effect of space flight factors simulated in ground-based experiments on the behavior, discriminant learning, and exchange of monoamines in different brain structures of rats].

Science.gov (United States)

Shtemberg, A S; Lebedeva-Georgievskaia, K V; Matveeva, M I; Kudrin, V S; Narkevich, V B; Klodt, P M; Bazian, A S

2014-01-01

Experimental treatment (long-term fractionated γ-irradiation, antiorthostatic hypodynamia, and the combination of these factors) simulating the effect of space flight in ground-based experiments rapidly restored the motor and orienting-investigative activity of animals (rats) in "open-field" tests. The study of the dynamics of discriminant learning of rats of experimental groups did not show significant differences from the control animals. It was found that the minor effect of these factors on the cognitive performance of animals correlated with slight changes in the concentration ofmonoamines in the brain structures responsible for the cognitive, emotional, and motivational functions.

[Changes of the Expression of Brain Derived Neurotrophic Factors in Rats Trachea Induced by Acrolein Exposure].

Science.gov (United States)

Yuan, Bing; Yang, Rui-an; Zhao, Wei; Xu, Yan-yan; Dan, Qi-qin; Zhang, Yun-hui

2015-07-01

To investigate expressional changes of brain derived neurotrophic factor (BDNF) in the trachea of rats with acrolein inhalation. Twenty two SD rats were divided into 2 groups: the rats in experimental group were subjected to acrolein inhalation for the induce of trachea inflammatory injury, while the rats with saline (NS) inhalation were as control. All the rats were sacrificed in 1,3,6 weeks after acrolein (n = 11 at each time point) or saline inhalation (n = 11 at each time point), the samples of trachea epithelium were harvested. The immunohistochemistry and in situ hybridization was performed to detect the location of BDNF protein and mRNA in trachea. The expression of BDNF mRNA in the trachea tissues were determined by RT-PCR. There are positive cells in epithelium of trachea for BDNF protein and mRNA, with cytoplasm staining. The expression of BDNF mRNA in the trachea was increased at 1 week after acrolein inhalation (P 0.05). The inflammatory injury in trachea induced by acrolein exposure could be associated with the increased expression of BDNF. BDNF may be one of the crucial inflammatory factors in the process of inflammatory reaction in trachea with acrolein stimulation.

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...

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

Therapeutic effects of ellagic acid on memory, hippocampus electrophysiology deficits, and elevated TNF-α level in brain due to experimental traumatic brain injury

Directory of Open Access Journals (Sweden)

Shahram Mashhadizadeh

2017-04-01

Full Text Available Objective(s: Cognitive defects such as learning and memory impairment are amongst the most repetitious sequelae after sever and moderate traumatic brain injury (TBI. It was suggested that ellagic acid (EA, an innate phenol product, display neuroprotective properties against oxidative and inflammatory damages after brain injury. The object of the current study was therapeutic properties of EA on blood-brain barrier (BBB interruption and elevated content of TNF-α in brain tissue followed by neurologic aftereffects, cognitive and brain electrophysiology deficits as outcomes of diffuse TBI in rat. Materials and Methods: TBI was induced by a 200 g weight falling by a 2-m height through a free-falling tube onto the head of anesthetized rat. TBI rats treated immediately after trauma with EA             (100 mg/kg, IP once every 8 hr until 48 hr later. Neurologic outcomes, passive avoidance task (PAT, hippocampal long-term potentiation (LTP, BBB permeability and content of TNF-α in brain tissue were evaluated. Results: TBI induced significant impairments in neurological score, BBB function, PAT and hippocampal LTP in TBI+Veh group in compare with Sham+Veh (P

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

Science.gov (United States)

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.

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.

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.

Brain stem death as the vital determinant for resumption of spontaneous circulation after cardiac arrest in rats.

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Alice Y W Chang

Full Text Available BACKGROUND: Spontaneous circulation returns to less than half of adult cardiac arrest victims who received in-hospital resuscitation. One clue for this disheartening outcome arises from the prognosis that asystole invariably takes place, after a time lag, on diagnosis of brain stem death. The designation of brain stem death as the point of no return further suggests that permanent impairment of the brain stem cardiovascular regulatory machinery precedes death. It follows that a crucial determinant for successful revival of an arrested heart is that spontaneous circulation must resume before brain stem death commences. Here, we evaluated the hypothesis that maintained functional integrity of the rostral ventrolateral medulla (RVLM, a neural substrate that is intimately related to brain stem death and central circulatory regulation, holds the key to the vital time-window between cardiac arrest and resumption of spontaneous circulation. METHODOLOGY/PRINCIPAL FINDINGS: An animal model of brain stem death employing the pesticide mevinphos as the experimental insult in Sprague-Dawley rats was used. Intravenous administration of lethal doses of mevinphos elicited an abrupt cardiac arrest, accompanied by elevated systemic arterial pressure and anoxia, augmented neuronal excitability and enhanced microvascular perfusion in RVLM. This period represents the vital time-window between cardiac arrest and resumption of spontaneous circulation in our experimental model. Animals with restored spontaneous circulation exhibited maintained neuronal functionality in RVLM beyond this critical time-window, alongside resumption of baseline tissue oxygen and enhancement of local blood flow. Intriguingly, animals that subsequently died manifested sustained anoxia, diminished local blood flow, depressed mitochondrial electron transport activities and reduced ATP production, leading to necrotic cell death in RVLM. That amelioration of mitochondrial dysfunction and

Glucagon-like peptide-1 analogue, liraglutide, delays onset and reduces severity of experimental autoimmune encephalitis in Lewis rats

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Brian DellaValle

2016-11-01

Full Text Available AbstractIntroduction: Recent findings indicate that metabolic disturbances are involved in multiple sclerosis (MS pathology and influence the susceptibility to treatment, directing attention towards anti-diabetic drugs such as metformin and pioglitazone. Liraglutide, a drug of the glucagon-like peptide-1 (GLP-1 family, is also anti-diabetic and weight-reducing and is moreover, directly neuroprotective and anti-inflammatory in a broad spectrum of experimental models of brain disease. In this study we investigate the potential for this FDA-approved drug, liraglutide, as a treatment for MS by utilizing the experimental model, experimental autoimmune encephalitis (EAE.Methods: EAE was induced in 30 female Lewis rats that subsequently received twice-daily liraglutide (200 µg/kg s.c. or saline. Healthy controls were included (saline, n=6, liraglutide, n=7. Clinical score and weight were assessed daily by blinded observers. Animals were killed at peak disease severity (day 11 or if exceeding humane endpoint (clinical score ≥4. Protein levels of manganese superoxide dismutase (MnSOD, amyloid precursor protein (APP, and glial fibrillary acidic protein (GFAP were determined.Results: Liraglutide treatment delayed disease onset (group clinical score significantly >0 by two days and markedly reduced disease severity (median clinical score 2 vs. 5; p=0.0003. Fourteen of 15 (93% of vehicle-treated rats reached the humane endpoint (clinical score ≥4 by day 11 compared to 5 of 15 (33% of liraglutide-treated rats (p=0.0004. Liraglutide substantially increased the mitochondrial antioxidant MnSOD (p<0.01 and reduced the neurodegenerative marker APP (p=0.036 in the brain. GFAP levels were not significantly changed with drug treatment (p=0.09Conclusion: We demonstrate, for the first time, that liraglutide treatment delays onset of EAE in Lewis rats and is associated with improved protective capacity against oxidative stress. These data suggest GLP-1 receptor

Attenuation of Streptozotocin-Induced Lipid Profile Anomalies in the Heart, Brain, and mRNA Expression of HMG-CoA Reductase by Diosgenin in Rats.

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Hao, Shuang; Xu, Rihao; Li, Dan; Zhu, Zhicheng; Wang, Tiance; Liu, Kexiang

2015-07-01

Diabetes mellitus is associated with significant morbidity and mortality that contributes to pathogenesis of cardiovascular diseases. Diosgenin, a naturally occurring aglycone, is present abundantly in fenugreek. The steroidal saponin is being used as a traditional medicine for diabetes. The present study has investigated the effects of diosgenin on lipid profile in the heart and brain, mRNA expression, and hepatic HMG-CoA reductase (HMGR) activity of streptozotocin-induced diabetic rats. In our study, diosgenin was administered (40 mg/kg b.w.) orally for 45 days to control animals and experimentally induced diabetic rats. The effects of diosgenin on glucose, plasma insulin, cholesterol, triglycerides, free fatty acids, and phospholipids (PLs) in the heart and brain were studied. The levels of glucose, cholesterol, triglycerides, free fatty acids, PLs, and HMGR activity were increased significantly (P rats. Administration of diosgenin to diabetic rats significantly reduced blood glucose, cholesterol, triglycerides, free fatty acids, PLs levels, and also HMGR activity. In addition, the plasma insulin level was increased in diosgenin-treated diabetic rats. The above findings were correlated with histological observations of the heart and brain. The results showed that administration of diosgenin remarkably increased plasma insulin level with absolute reduction of blood glucose, lipid profile, and HMGR level when compared to diabetic control rats. The results have suggested that diosgenin prevents hypercholesterolemia and hepatosteatosis by modulation of enzymatic expression that is associated with cholesterol metabolism.

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

Discriminative stimulus properties and brain distribution of phencyclidine in rats following administration by injection and smoke inhalation

International Nuclear Information System (INIS)

Wessinger, W.D.; Martin, B.R.; Balster, R.L.

1985-01-01

Four male Sprague-Dawley rats were trained to discriminate IP injections of 3.0 mg/kg phencyclidine (PCP) from saline under a 2-lever fixed-ratio 32 schedule of food presentation. After reliable discriminative control of lever choice was established, other doses of injected PCP were tested resulting in dose-dependent increases in PCP-lever selection and dose-dependent decreases in rates of responding. When doses of PCP were administered by exposure to smoke from cigarettes containing PCP, a dose-dependent increase in PCP-lever responding was also observed. delta 9-Tetrahydrocannabinol administered via smoke exposure, up to doses which markedly suppressed response rates, did not result in PCP-appropriate responding, demonstrating the specificity of the PCP stimulus by the inhalation route. Brain levels and distribution of 3 H-PCP were determined in rats administered doses calculated to result in 50% generalization by the IP injection or smoke inhalation routes. By both routes of administration roughly equivalent brain levels were attained and the distribution was relatively even across the seven brain areas analyzed. These results demonstrate the validity of using the injection route of administration when studying PCP experimentally, in spite of the fact that PCP is abused primarily by smoking

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.

Alterations of metallothionein isomers in Hg{sup 0}-exposed rat brain

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Yasutake, A. [Biochemistry Section, National Institute for Minamata Disease, Minamata, Kumamoto 867-0008 (Japan); Nagano, M. [Morikawa Kenkodo Co., Ltd., 2170 Taguchi, Kosa, Kamimashiki, Kumamoto 861-4616 (Japan); Hirayama, K. [Kumamoto University College of Medical Science, Kuhonji, Kumamoto 862-0976 (Japan)

2003-01-01

Previously we found that exposure to mercury vapor effectively induced brain metallothionein (MT) in rats. Here, using FPLC-gel chromatography, we examined time-dependent alterations in the MT isomers, MT-I/II and MT-III, following 3 weeks of exposure. Rats were exposed to mercury vapor at 8.3 mg/m{sup 3} for 15 h in total over 5 consecutive days. Total MT levels in rat cerebrum and cerebellum increased by 65% and 155%, respectively, 24 h after the final exposure. The increased levels in both tissues remained unchanged for at least 2 weeks after termination of exposure. Interestingly, most MT in control rat cerebrum and cerebellum was accounted for by MT-III, with MT-I/II being less than 10%. Through mercury vapor exposure, MT-I/II was quickly induced to a significant extent in both tissues, reaching a level comparable to that of MT-III. The induction rate of MT-I/II in the cerebellum was somewhat higher than in the cerebrum. Chromatograms showed that the MT-I/II thus induced began to decline at an early stage in both tissues. In the cerebrum, the amount of MT-I/II on day 22 was about 30% of the maximum level on day 1. On the other hand, the induction of MT-III was not that dramatic, but it did become evident, at least in the latter stage, when MT-I/II had begun to decrease. Thus, though the induction rate of MT-III was not as high as MT-I/II, it was sustained throughout the experimental period. (orig.)

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

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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...

Charge effect of a liposomal delivery system encapsulating simvastatin to treat experimental ischemic stroke in rats

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Campos-Martorell M

2016-06-01

Full Text Available Mireia Campos-Martorell,1 Mary Cano-Sarabia,2 Alba Simats,1 Mar Hernández-Guillamon,1 Anna Rosell,1 Daniel Maspoch,2,3 Joan Montaner1,4 1Neurovascular Research Laboratory, Institut de Recerca Vall d’Hebron, Universitat Autònoma de Barcelona, Barcelona, 2Catalan Institute of Nanoscience and Nanotechnology (ICN2, CSIC and The Barcelona Institute of Science and Technology, Universitat Autònoma de Barcelona, Barcelona, 3Institució Catalana de Recerca i Estudis Avançats (ICREA, 4Neurovascular Unit, Department of Neurology, Universitat Autònoma de Barcelona, Hospital Vall d’Hebron, Barcelona, Spain Background and aims: Although the beneficial effects of statins on stroke have been widely demonstrated both in experimental studies and in clinical trials, the aim of this study is to prepare and characterize a new liposomal delivery system that encapsulates simvastatin to improve its delivery into the brain. Materials and methods: In order to select the optimal liposome lipid composition with the highest capacity to reach the brain, male Wistar rats were submitted to sham or transitory middle cerebral arterial occlusion (MCAOt surgery and treated (intravenous [IV] with fluorescent-labeled liposomes with different net surface charges. Ninety minutes after the administration of liposomes, the brain, blood, liver, lungs, spleen, and kidneys were evaluated ex vivo using the Xenogen IVIS® Spectrum imaging system to detect the load of fluorescent liposomes. In a second substudy, simvastatin was assessed upon reaching the brain, comparing free and encapsulated simvastatin (IV administration. For this purpose, simvastatin levels in brain homogenates from sham or MCAOt rats at 2 hours or 4 hours after receiving the treatment were detected through ultra-high-protein liquid chromatography. Results: Whereas positively charged liposomes were not detected in brain or plasma 90 minutes after their administration, neutral and negatively charged liposomes

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

Increase in seizure susceptibility in sepsis like condition explained by spiking cytokines and altered adhesion molecules level with impaired blood brain barrier integrity in experimental model of rats treated with lipopolysaccharides.

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Sewal, Rakesh K; Modi, Manish; Saikia, Uma Nahar; Chakrabarti, Amitava; Medhi, Bikash

2017-09-01

Epilepsy is a neurological disorder characterized by recurrent unprovoked seizures. Sepsis is a condition which initiates a cascade of a surge of inflammatory mediators. Interplay between seizures and inflammation other than of brain origin is yet to be explored. The present study was designed to evaluate the seizure susceptibility in experimental models of lipopolysaccharide (LPS) induced sepsis. Experimental sepsis was induced using lipopolysaccharides in Wistar rats. Valproic acid, dexametasone were given to two different groups of animals along with LPS. Two groups of animals were subjected to administration of vehicle and LPS respectively with no other treatment. 24h later, animals were subjected to seizures by using either maximal electro shock or pentylenetetrazole. Seizures related parameters, oxidative stress and TNF-α, IL-6, IL-1β, ICAM-1, ICAM-2, VCAM-1, MMP-9 level in serum and brain samples were evaluated. Histopathological and blood brain barrier permeability studies were conducted. Seizures were decreased in valproic acid treated animals. Reduced oxidative stress was seen in dexamethasone plus valproic acid treated groups as compared to LPS alone treated group. TNF-α, IL-6, IL-1β, ICAM-1, VCAM-1, MMP-9 levels were found increased in LPS treated animals whereas a reverse observation was noted for ICAM-2 level in brain and serum. Histopathological findings confirmed the successful establishment of sepsis like state in animals. Blood brain barrier permeability was found increased in LPS treated groups of animals. Seizure susceptibility may escalate during the sepsis like inflammatory conditions and curbing the inflammatory state might reverse the phenomenon. Copyright © 2017. Published by Elsevier B.V.

Doxorubicin induced neuro- and cardiotoxicities in experimental rats: Protection against oxidative damage by Theobroma cacao Stem bark

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A.M. Kosoko

2017-07-01

Full Text Available 80 rats, randomly selected, were divided into 3 treatment groups: pre-, co- and post-treatment; consisting of 6 sub-groups each (5 rats per sub-group: baseline, normal saline (2 mL, α-lipoic acid (20 mg/kg body weight, 200 mg/kg, 400 mg/kg or 800 mg/kg body weight Theobroma cacao stem bark aqueous extract (TCAE. All rats except for baseline group were intoxicated with 20 mg/kg body weight doxorubicin (DOX intraperitoneally. The animals in pre- or post-treatment group received a single dose of DOX (20 mg/kg body weight intraperitoneally 24 h before or after 7 days’ oral administration with TCAE respectively while those in co-treatment group were co-administered 2.86 mg/kg body weight of DOX with either normal saline, α- lipoic acid or TCAE orally for 7 days. Animals were sacrificed (pre- and post- treatment groups were sacrificed on the ninth day while the co-treatment group sacrificed on the 8th day. Brain and heart tissue samples were harvested for enzyme markers of toxicity, oxidative stress and histopathological examinations. DOX intoxication caused significant decrease in activities of LDH and ACP, and increase in γGT and ALP activities in brain tissues while causing a significant increase in LDH, ACP, γGT activities and decrease in ALP activity in the cardiac tissues. DOX intoxication caused a significant increase in concentrations of H2O2 generated, MDA and PC, XO, MPx and NOX activities with concomitant decrease in CAT, SOD, GPx and GST activities, and in concentrations of GSH, AsA and α-Toc in brain and cardiac tissues. Pre-, co- and post-treatment with TCAE at either 200 mg/kg, 400 mg/kg or 800 mg/kg body weight significantly reversed the oxidative damage to the organs induced by DOX-intoxication. The result affirmed that T. cacao stem bark aqueous extract protected against DOX induced oxidative damage in brain and cardiac tissues of experimental rats.

[¹⁸F]Altanserin and small animal PET: impact of multidrug efflux transporters on ligand brain uptake and subsequent quantification of 5-HT₂A receptor densities in the rat brain.

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Kroll, Tina; Elmenhorst, David; Matusch, Andreas; Celik, A Avdo; Wedekind, Franziska; Weisshaupt, Angela; Beer, Simone; Bauer, Andreas

2014-01-01

The selective 5-hydroxytryptamine type 2a receptor (5-HT(2A)R) radiotracer [(18)F]altanserin is a promising ligand for in vivo brain imaging in rodents. However, [(18)F]altanserin is a substrate of P-glycoprotein (P-gp) in rats. Its applicability might therefore be constrained by both a differential expression of P-gp under pathological conditions, e.g. epilepsy, and its relatively low cerebral uptake. The aim of the present study was therefore twofold: (i) to investigate whether inhibition of multidrug transporters (MDT) is suitable to enhance the cerebral uptake of [(18)F]altanserin in vivo and (ii) to test different pharmacokinetic, particularly reference tissue-based models for exact quantification of 5-HT(2A)R densities in the rat brain. Eighteen Sprague-Dawley rats, either treated with the MDT inhibitor cyclosporine A (CsA, 50 mg/kg, n=8) or vehicle (n=10) underwent 180-min PET scans with arterial blood sampling. Kinetic analyses of tissue time-activity curves (TACs) were performed to validate invasive and non-invasive pharmacokinetic models. CsA application lead to a two- to threefold increase of [(18)F]altanserin uptake in different brain regions and showed a trend toward higher binding potentials (BP(ND)) of the radioligand. MDT inhibition led to an increased cerebral uptake of [(18)F]altanserin but did not improve the reliability of BP(ND) as a non-invasive estimate of 5-HT(2A)R. This finding is most probable caused by the heterogeneous distribution of P-gp in the rat brain and its incomplete blockade in the reference region (cerebellum). Differential MDT expressions in experimental animal models or pathological conditions are therefore likely to influence the applicability of imaging protocols and have to be carefully evaluated. © 2013.

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

Radiation-induced cognitive dysfunction: an experimental model in the old rat

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Lamproglou, Ioannis; Chen, QI Ming; Boisserie, Gilbert; Mazeron, Jean-Jacques; Poisson, Michel; Baillet, Francois; Le Poncin, Monique; Delattre, Jean-Yves

1995-01-01

Purpose: To develop a model of radiation-induced behavioral dysfunction. Methods and Materials: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. Results: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p {<=} 0.001) and two-way avoidance (18% vs. 40%, p {<=} 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p {<=} 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. Conclusion: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes.

Radiation-induced cognitive dysfunction: an experimental model in the old rat

International Nuclear Information System (INIS)

Lamproglou, Ioannis; Chen, QI Ming; Boisserie, Gilbert; Mazeron, Jean-Jacques; Poisson, Michel; Baillet, Francois; Le Poncin, Monique; Delattre, Jean-Yves

1995-01-01

Purpose: To develop a model of radiation-induced behavioral dysfunction. Methods and Materials: A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. Results: Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p ≤ 0.001) and two-way avoidance (18% vs. 40%, p ≤ 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p ≤ 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. Conclusion: Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes

Radiation-induced cognitive dysfunction: An experimental model in the old rat

International Nuclear Information System (INIS)

Lamproglou, I.; Chen, Q.M.; Poisson, M.

1995-01-01

To develop a model of radiation-induced behavioral dysfunction. A course of whole brain radiation therapy (30 Gy/10 fractions/12 days) was administered to 26 Wistar rats ages 16-27 months, while 26 control rats received sham irradiation. Sequential behavioral studies including one-way avoidance, two-way avoidance, and a standard operant conditioning method (press-lever avoidance) were undertaken. In addition, rats were studied in a water maze 7 months postradiation therapy. Prior to radiation therapy, both groups were similar. No difference was found 1 and 3 months postradiation therapy. At 6-7 months postradiation therapy, irradiated rats had a much lower percentage of avoidance than controls for one-way avoidance (23% vs. 55%, p ≤ 0.001) and two-way avoidance (18% vs. 40%, p ≤ 0.01). Seven months postradiation therapy the reaction time was increased (press-lever avoidance, 11.20 s vs. 8.43 s, p ≤ 0.05) and the percentage of correct response was lower (water maze, 53% vs. 82%) in irradiated rats compared with controls. Pathological examination did not demonstrate abnormalities of the irradiated brains at the light microscopic level. Behavioral dysfunction affecting mainly memory can be demonstrated following conventional radiation therapy in old rats. This model can be used to study the pathogenesis of radiation-induced cognitive changes. 15 refs., 3 figs., 1 tab

Sleep deprivation attenuates experimental stroke severity in rats

DEFF Research Database (Denmark)

Moldovan, Mihai; Constantinescu, Alexandra Oana; Balseanu, Adrian

2010-01-01

Indirect epidemiological and experimental evidence suggest that the severity of injury during stroke is influenced by prior sleep history. The aim of our study was to test the effect of acute sleep deprivation on early outcome following experimental stroke. Young male Sprague-Dawley rats (n=20...... after stroke was monitored using a battery of behavioral tests investigating the asymmetry of sensorimotor deficit (tape removal test and cylinder test), bilateral sensorimotor coordination (rotor-rod and Inclined plane) and memory (T-maze and radial maze). Following MCAO, control rats had impaired...

Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue

Energy Technology Data Exchange (ETDEWEB)

Jost, Gregor; Frenzel, Thomas; Lohrke, Jessica; Pietsch, Hubertus [MR and CT Contrast Media Research, Bayer Pharma AG, Berlin (Germany); Lenhard, Diana Constanze [Charite, Institute of Vegetative Physiology, Berlin (Germany); Naganawa, Shinji [Nagoya University Graduate School of Medicine, Department of Radiology, Nagoya (Japan)

2017-07-15

Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study. GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry. Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h. In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs. (orig.)

Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue

International Nuclear Information System (INIS)

Jost, Gregor; Frenzel, Thomas; Lohrke, Jessica; Pietsch, Hubertus; Lenhard, Diana Constanze; Naganawa, Shinji

2017-01-01

Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study. GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry. Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h. In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs. (orig.)

Effect of ethanol in utero on higher nervous activity and protein and lipid metabolism in the rat brain

International Nuclear Information System (INIS)

Zabbudovskii, A.L.; Zhulin, V.V.

1985-01-01

The authors study parameters of protein phosphorylation and glycoprotein and phospholipid synthesis in the neocortex and hippocampus of adult rats and compare the findings with the results of an investigation of formation and preservation of defensive conditioned reflexes. The pattern of changes in these metabolic parameters are studied in response to stress. For the biochemical tests, the animals were lightly anesthetized with ether and injected with a mixture of (P 32)-orthophosphate and (H 3)-fucose. Phospholipids were identified with molybdate reagent and radioactivity of the protein digest and lipids was measured in Bray's scintillator. The study shows that the use of stress brought metabolic differences between the brain of the experimental and control rats more clearly to light

Caffeine and Cannabis Effects on Vital Neurotransmitters and Enzymes in the Brain Tissue of Juvenile Experimental Rats.

Science.gov (United States)

Owolabi, J O; Olatunji, S Y; Olanrewaju, A J

2017-05-01

Caffeine and cannabis are globally consumed and abused psychoactive substances. While caffeine is legally used in various forms, including in tea and coffee as beverages, it is also consumed in soda and energy drinks as additives. Cannabis, on the other hand, is considered illegal in most countries; albeit, it is being consumed globally particularly by adolescents. The adolescent stage marks a critical stage of brain development and maturation. Influences of agents on the brain at this stage may affect neuronal structural and functional attributes. To this end, the current experiment considered the effects of cannabis and caffeine on selected key neurotransmitters and enzymes in the brain tissues after regimented caffeine and cannabis treatment for 21 days. A total of 72 juvenile Wistar rats that were approximately 40 days old were divided into 6 groups A-F. The group A served as the control. Other groups were administered various dosages of caffeine or cannabis in distilled water, using oral gavages as follows: group B animals received 100 mg/kg body weight of caffeine, group C animals received 50 mg/kg body weight of caffeine, group D animals received 500 mg/kg body weight of cannabis, group E animals received 200 mg/kg body weight of cannabis, and group F received a low dose of cannabis (200 mg/kg body weight) plus a low dose of caffeine (50 mg/kg body weight). The animals were killed by cervical dislocation 24 h after the last administration. The brain tissues were excised and homogenized. The enzymes cytochrome C oxidase and glucose-6-phosphate dehydrogenase were assayed to observe tissue energy metabolism while the neurotransmitters gamma-amino butyric acid (GABA), glutamate, and dopamine were assayed to observe the effects of the psychoactive substances on their activities relative to mental activities. GABA, glutamate, and dopamine were generally higher in the treated groups of animals. The levels of G-6-PDH were higher in all treated animals' brains

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.

Glibenclamide reduces secondary brain damage after experimental traumatic brain injury.

Science.gov (United States)

Zweckberger, K; Hackenberg, K; Jung, C S; Hertle, D N; Kiening, K L; Unterberg, A W; Sakowitz, O W

2014-07-11

Following traumatic brain injury (TBI) SUR1-regulated NCCa-ATP (SUR1/TRPM4) channels are transcriptionally up-regulated in ischemic astrocytes, neurons, and capillaries. ATP depletion results in depolarization and opening of the channel leading to cytotoxic edema. Glibenclamide is an inhibitor of SUR-1 and, thus, might prevent cytotoxic edema and secondary brain damage following TBI. Anesthetized adult Sprague-Dawley rats underwent parietal craniotomy and were subjected to controlled cortical impact injury (CCI). Glibenclamide was administered as a bolus injection 15min after CCI injury and continuously via osmotic pumps throughout 7days. In an acute trial (180min) mean arterial blood pressure, heart rate, intracranial pressure, encephalographic activity, and cerebral metabolism were monitored. Brain water content was assessed gravimetrically 24h after CCI injury and contusion volumes were measured by MRI scanning technique at 8h, 24h, 72h, and 7d post injury. Throughout the entire time of observation neurological function was quantified using the "beam-walking" test. Glibenclamide-treated animals showed a significant reduction in the development of brain tissue water content(80.47%±0.37% (glibenclamide) vs. 80.83%±0.44% (control); pbeam-walking test throughout 7days. In accordance to these results and the available literature, glibenclamide seems to have promising potency in the treatment of TBI. Copyright © 2014 IBRO. Published by Elsevier Ltd. All rights reserved.

Validation of a simple and inexpensive method for the quantitation of infarct in the rat brain

Directory of Open Access Journals (Sweden)

C.L.R. Schilichting

2004-04-01

Full Text Available A gravimetric method was evaluated as a simple, sensitive, reproducible, low-cost alternative to quantify the extent of brain infarct after occlusion of the medial cerebral artery in rats. In ether-anesthetized rats, the left medial cerebral artery was occluded for 1, 1.5 or 2 h by inserting a 4-0 nylon monofilament suture into the internal carotid artery. Twenty-four hours later, the brains were processed for histochemical triphenyltetrazolium chloride (TTC staining and quantitation of the schemic infarct. In each TTC-stained brain section, the ischemic tissue was dissected with a scalpel and fixed in 10% formalin at 0ºC until its total mass could be estimated. The mass (mg of the ischemic tissue was weighed on an analytical balance and compared to its volume (mm³, estimated either by plethysmometry using platinum electrodes or by computer-assisted image analysis. Infarct size as measured by the weighing method (mg, and reported as a percent (% of the affected (left hemisphere, correlated closely with volume (mm³, also reported as % estimated by computerized image analysis (r = 0.88; P < 0.001; N = 10 or by plethysmography (r = 0.97-0.98; P < 0.0001; N = 41. This degree of correlation was maintained between different experimenters. The method was also sensitive for detecting the effect of different ischemia durations on infarct size (P < 0.005; N = 23, and the effect of drug treatments in reducing the extent of brain damage (P < 0.005; N = 24. The data suggest that, in addition to being simple and low cost, the weighing method is a reliable alternative for quantifying brain infarct in animal models of stroke.

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

A Simple and Reproducible Method to Prepare Membrane Samples from Freshly Isolated Rat Brain Microvessels.

Science.gov (United States)

Brzica, Hrvoje; Abdullahi, Wazir; Reilly, Bianca G; Ronaldson, Patrick T

2018-05-07

The blood-brain barrier (BBB) is a dynamic barrier tissue that responds to various pathophysiological and pharmacological stimuli. Such changes resulting from these stimuli can greatly modulate drug delivery to the brain and, by extension, cause considerable challenges in the treatment of central nervous system (CNS) diseases. Many BBB changes that affect pharmacotherapy, involve proteins that are localized and expressed at the level of endothelial cells. Indeed, such knowledge on BBB physiology in health and disease has sparked considerable interest in the study of these membrane proteins. From a basic science research standpoint, this implies a requirement for a simple but robust and reproducible method for isolation of microvessels from brain tissue harvested from experimental animals. In order to prepare membrane samples from freshly isolated microvessels, it is essential that sample preparations be enriched in endothelial cells but limited in the presence of other cell types of the neurovascular unit (i.e., astrocytes, microglia, neurons, pericytes). An added benefit is the ability to prepare samples from individual animals in order to capture the true variability of protein expression in an experimental population. In this manuscript, details regarding a method that is utilized for isolation of rat brain microvessels and preparation of membrane samples are provided. Microvessel enrichment, from samples derived, is achieved by using four centrifugation steps where dextran is included in the sample buffer. This protocol can easily be adapted by other laboratories for their own specific applications. Samples generated from this protocol have been shown to yield robust experimental data from protein analysis experiments that can greatly aid the understanding of BBB responses to physiological, pathophysiological, and pharmacological stimuli.

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.

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.

Accelerated regression of brain metastases in patients receiving whole brain radiation and the topoisomerase II inhibitor, lucanthone

International Nuclear Information System (INIS)

Rowe, John D. del; Bello, Jacqueline; Mitnick, Robin; Sood, Brij; Filippi, Christopher; Moran, Justin Ph.D.; Freeman, Katherine; Mendez, Frances; Bases, Robert

1999-01-01

Purpose: To determine if lucanthone crossed the blood-brain barrier in experimental animals; and to determine accelerated tumor regression of human brain metastases treated jointly with lucanthone and whole brain radiation. Methods and Materials: The organ distribution of 3 H lucanthone in mice and 125 I lucanthone in rats was determined to learn if lucanthone crossed the blood-brain barrier. Size determinations were made of patients' brain metastases from magnetic resonance images or by computed tomography before and after treatment with 30 Gy whole brain radiation alone or with lucanthone. Results: The time course of lucanthone's distribution in brain was identical to that in muscle and heart after intraperitoneal or intravenous administration in experimental animals. Lucanthone, therefore, readily crossed the blood-brain barrier in experimental animals. Conclusion: Compared with radiation alone, the tumor regression in patients with brain metastases treated with lucanthone and radiation was accelerated, approaching significance using a permutation test at p = 0.0536

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.

Experimentally-induced maternal hypothyroidism alters crucial enzyme activities in the frontal cortex and hippocampus of the offspring rat.

Science.gov (United States)

Koromilas, Christos; Tsakiris, Stylianos; Kalafatakis, Konstantinos; Zarros, Apostolos; Stolakis, Vasileios; Kimpizi, Despoina; Bimpis, Alexios; Tsagianni, Anastasia; Liapi, Charis

2015-02-01

Thyroid hormone insufficiency during neurodevelopment can result into significant structural and functional changes within the developing central nervous system (CNS), and is associated with the establishment of serious cognitive impairment and neuropsychiatric symptomatology. The aim of the present study was to shed more light on the effects of gestational and/or lactational maternal exposure to propylthiouracil (PTU)-induced hypothyroidism as a multilevel experimental approach to the study of hypothyroidism-induced changes on crucial brain enzyme activities of 21-day-old Wistar rat offspring in a brain region-specific manner. This experimental approach has been recently developed and characterized by the authors based on neurochemical analyses performed on newborn and 21-day-old rat offspring whole brain homogenates; as a continuum to this effort, the current study focused on two CNS regions of major significance for cognitive development: the frontal cortex and the hippocampus. Maternal exposure to PTU in the drinking water during gestation and/or lactation resulted into changes in the activities of acetylcholinesterase and two important adenosinetriphosphatases (Na(+),K(+)- and Mg(2+)-ATPase), that seemed to take place in a CNS-region-specific manner and that were dependent upon the PTU-exposure timeframe followed. As these findings are analyzed and compared to the available literature, they: (i) highlight the variability involved in the changes of the aforementioned enzymatic parameters in the studied CNS regions (attributed to both the different neuroanatomical composition and the thyroid-hormone-dependent neurodevelopmental growth/differentiation patterns of the latter), (ii) reveal important information with regards to the neurochemical mechanisms that could be involved in the way clinical hypothyroidism could affect optimal neurodevelopment and, ultimately, cognitive function, as well as (iii) underline the need for the adoption of more consistent

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

Penetration and distribution of gadolinium-based contrast agents into the cerebrospinal fluid in healthy rats: a potential pathway of entry into the brain tissue.

Science.gov (United States)

Jost, Gregor; Frenzel, Thomas; Lohrke, Jessica; Lenhard, Diana Constanze; Naganawa, Shinji; Pietsch, Hubertus

2017-07-01

Signal hyperintensity on unenhanced MRI in certain brain regions has been reported after multiple administrations of some, but not all, gadolinium-based contrast agents (GBCAs). One potential initial pathway of GBCA entry into the brain, infiltration from blood into the cerebrospinal fluid (CSF), was systematically evaluated in this preclinical study. GBCA infiltration and distribution in the CSF were investigated in healthy rats using repeated fluid-attenuated MRI up to 4 h after high-dose (1.8 mmol/kg) administration of six marketed and one experimental GBCA. Additionally, gadolinium measurements in CSF, blood and brain tissue samples (after 24 h) were performed using inductively coupled plasma mass spectrometry. Enhanced MRI signals in the CSF spaces with similar distribution kinetics were observed for all GBCAs. No substantial differences in the gadolinium concentrations among the marketed GBCAs were found in the CSF, blood or brain tissue. After 4.5 h, the concentration in the CSF was clearly higher than in blood but was almost completely cleared and lower than the brain tissue concentration after 24 h. In contrast to the brain signal hyperintensities, no differences in penetration and distribution into the CSF of healthy rats exist among the marketed GBCAs. • Gadolinium-based contrast agents can cross the blood-CSF barrier. • Fluid-attenuated MRI shows GBCA distribution with CSF flow. • GBCA structure and physicochemical properties do not impact CSF penetration and distribution. • GBCA clearance from CSF was almost complete within 24 h in rats. • CSF is a potential pathway of GBCA entry into the brain.

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.

Directory of Open Access Journals (Sweden)

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

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)

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

Science.gov (United States)

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.

Maternal Deprivation of Lewis Rat Pups Increases the Severity of Experi-mental Periodontitis in Adulthood.

Science.gov (United States)

Breivik, Torbjørn; Gundersen, Yngvar; Murison, Robert; Turner, Jonathan D; Muller, Claude P; Gjermo, Per; Opstad, Kristian

2015-01-01

Early life adverse events may influence susceptibility/resistance to chronic inflammatory diseases later in life by permanently dysregulating brain-controlled immune-regulatory systems. We have investigated the impact of infant-mother separation during early postnatal life on the severity of experimental periodontitis, as well as systemic stress and immune responses, in adulthood. Pups of periodontitis resistant Lewis rats were separated from their mothers for 3 h daily during postnatal days 2-14 (termed maternal deprivation; MD), separated for 15 min daily during the same time period (termed handling; HD), or left undisturbed. As adults, their behaviour was tested in a novel stressful situation, and ligature-induced periodontitis applied for 21 days. Two h before sacrifice all rats were exposed to a gram-negative bacterial lipopolysaccharide (LPS) challenge to induce a robust immune and stress response. Compared to undisturbed controls, MD rats developed significantly more periodontal bone loss as adults, whereas HD rats showed a tendency to less disease. MD and HD rats exhibited depression-like behaviour in a novel open field test, while MD rats showed higher glucocorticoid receptor (Gr) expression in the hippocampus, and HD rats had altered methylation of genes involved in the expression of hippocampal Gr. LPS provoked a significantly lower increase in circulating levels of the cytokine TGF-1β in MD and HD rats, but there were no significant differences in levels of the stress hormone corticosterone. Stressful environmental exposures in very early life may alter immune responses in a manner that influences susceptibility/resistance to periodontitis.

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

Science.gov (United States)

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

Science.gov (United States)

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

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.

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.

Oxidative stress in rats experimentally infected by Sporothrix schenckii.

Science.gov (United States)

Castro, Verônica S P; Da Silva, Aleksandro S; Thomé, Gustavo R; Wolkmer, Patrícia; Castro, Jorge L C; Costa, Márcio M; Graça, Dominguita L; Oliveira, Daniele C; Alves, Sydney H; Schetinger, Maria R C; Lopes, Sonia T A; Stefani, Lenita M; Azevedo, Maria I; Baldissera, Matheus D; Andrade, Cinthia M

2017-06-01

The aim of this study was to evaluate whether oxidative stress occurs in rats experimentally infected by Sporothrix schenckii, and its possible effect on disease pathogenesis. Thirty rats were divided into two groups: the group A (uninfected, n = 18) and the group B (infected by S. schenckii, n=21). Blood samples were collected on days 15, 30 and 40 post-infection (PI). At each sampling time, six rats of the group A, and seven of the group B were bled. TBARS (thiobarbituric acid reactive substances) levels in serum samples were measured to evaluate lipid peroxidation. In addition, catalase (CAT) and superoxide dismutase (SOD) activities, known as biomarkers of antioxidants levels, were verified in whole blood. Seric pro-inflammatory cytokine levels were measured (IFN-γ, TNF-α, and IL-6), which showed that these inflammatory mediators were at higher levels in the infected rats (P sporotrichosis showed significantly higher (p sporotrichosis is a likely mechanism for redox imbalance, and consequently cause the oxidative stress in experimentally infected rats. Copyright © 2017 Elsevier Ltd. All rights reserved.

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.

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.)

Suppressed Fat Appetite after Roux-en-Y Gastric Bypass Surgery Associates with Reduced Brain μ-opioid Receptor Availability in Diet-Induced Obese Male Rats.

Science.gov (United States)

Hankir, Mohammed K; Patt, Marianne; Patt, Jörg T W; Becker, Georg A; Rullmann, Michael; Kranz, Mathias; Deuther-Conrad, Winnie; Schischke, Kristin; Seyfried, Florian; Brust, Peter; Hesse, Swen; Sabri, Osama; Krügel, Ute; Fenske, Wiebke K

2016-01-01

Brain μ-opioid receptors (MORs) stimulate high-fat (HF) feeding and have been implicated in the distinct long term outcomes on body weight of bariatric surgery and dieting. Whether alterations in fat appetite specifically following these disparate weight loss interventions relate to changes in brain MOR signaling is unknown. To address this issue, diet-induced obese male rats underwent either Roux-en-Y gastric bypass (RYGB) or sham surgeries. Postoperatively, animals were placed on a two-choice diet consisting of low-fat (LF) and HF food and sham-operated rats were further split into ad libitum fed (Sham-LF/HF) and body weight-matched (Sham-BWM) to RYGB groups. An additional set of sham-operated rats always only on a LF diet (Sham-LF) served as lean controls, making four experimental groups in total. Corresponding to a stage of weight loss maintenance for RYGB rats, two-bottle fat preference tests in conjunction with small-animal positron emission tomography (PET) imaging studies with the selective MOR radioligand [ 11 C]carfentanil were performed. Brains were subsequently collected and MOR protein levels in the hypothalamus, striatum, prefrontal cortex and orbitofrontal cortex were analyzed by Western Blot. We found that only the RYGB group presented with intervention-specific changes: having markedly suppressed intake and preference for high concentration fat emulsions, a widespread reduction in [ 11 C]carfentanil binding potential (reflecting MOR availability) in various brain regions, and a downregulation of striatal and prefrontal MOR protein levels compared to the remaining groups. These findings suggest that the suppressed fat appetite caused by RYGB surgery is due to reduced brain MOR signaling, which may contribute to sustained weight loss unlike the case for dieting.

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.

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

Directory of Open Access Journals (Sweden)

Ching-Yi Tsai

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

Imaging of aromatase distribution in rat and rhesus monkey brains with [{sup 11}C]vorozole

Energy Technology Data Exchange (ETDEWEB)

Takahashi, Kayo [Division of Pharmacology, Department of Neuroscience, Uppsala University, Uppsala SE-75124 (Sweden); Uppsala Imanet, Uppsala SE-75109 (Sweden)]. E-mail: kayo.takahashi@uppsala.imanet.se; Bergstroem, Mats [Uppsala Imanet, Uppsala SE-75109 (Sweden); Department of Pharmaceutical Biosciences, Uppsala University, Uppsala SE-75124 (Sweden); Fraendberg, Pernilla [Uppsala Imanet, Uppsala SE-75109 (Sweden); Vesstroem, Eva-Lotta [Uppsala Imanet, Uppsala SE-75109 (Sweden); Watanabe, Yasuyoshi [Department of Physiology, Osaka City University Graduate School of Medicine, Osaka 545-8585 (Japan); Langstroem, Bengt [Uppsala Imanet, Uppsala SE-75109 (Sweden)

2006-07-15

Aromatase is an enzyme that converts androgens to estrogens and may play a role in mood and mental status. The aim of this study was to demonstrate that brain aromatase distribution could be evaluated with a novel positron emission tomography (PET) tracer [{sup 11}C]vorozole. Vorozole is a nonsteroidal aromatase inhibitor that reversibly binds to the heme domain of aromatase. In vitro experiments in rat brain, using frozen section autoradiography, illustrated specific binding in the medial amygdala (MA), the bed nucleus of stria terminalis (BST) and the preoptic area (POA) of male rat brain. Specific binding in female rat brain was found in the MA and the BST; however, the signals were lower than those of males. The K {sub d} of [{sup 11}C]vorozole binding to aromatase in MA was determined to be 0.60{+-}0.06 nM by Scatchard plot analysis using homogenates. An in vivo PET study in female rhesus monkey brain demonstrated the uptake of [{sup 11}C]vorozole in the amygdala, where the uptake was blocked by the presence of excess amounts of unlabeled vorozole. Thus, this tracer has a high affinity for brain aromatase and could have a potential for in vivo aromatase imaging. This technique might enable the investigation of human brain aromatase in healthy and diseased persons.

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 ...

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

Effects of protein restriction, melatonin administration, and short daylength on brain benzodiazepine receptors in prepubertal male rats

International Nuclear Information System (INIS)

Kennaway, D.J.; Royles, P.; Webb, H.; Carbone, F.

1988-01-01

The possibility that there are changes in brain benzodiazepine binding sites controlled by photoperiod was investigated in two strains of male rats. The hypothesis was tested by 3H-diazepam binding studies in various brain regions of prepubertal rats maintained in 14 or 10 h of light or treated with late-afternoon injections of melatonin (50 micrograms/day). Protein restriction was applied during the experiment to sensitize the animals to the treatments. Under the conditions employed, rats kept in short daylength throughout or kept on long photoperiod and given late-afternoon melatonin injections showed evidence of delayed puberty (seminal vesicle, ventral prostate, and testis weight decreased by 45%, 55%, and 60% respectively, compared to control rats). Binding measurements were made 1 h before and 2 and 5 h after the onset of darkness in the pubertal (42-day-old) or experimentally prepubertal rats. In the rats of the Porton strain (for which protein restriction was obligatory for the gonadal response) there was no consistent treatment or time effects on specific binding of 3H-diazepam to washed membranes of the hypothalamus, midbrain, or striatum. Similarly, there were no differences in the stimulation of 3H-diazepam binding by 100 microM GABA or the inhibition of binding by 50 microM N-acetyl 5 methoxy kynurenamine. By contrast, in Wistar rats, specific binding to midbrain membranes was reduced 5 h after dark compared to 2 h (37% saline; 20% melatonin) and the extent of stimulation by GABA in the hypothalamus was increased 5 h after darkness (35.6% to 46.7% saline; 37.4% to 50% melatonin). Melatonin treatment resulted in significantly higher specific binding in the hypothalamus 2 h after dark (10%, control fed; 20%, protein restricted) but reduced the GABA induced stimulation of binding in the midbrain (35.5% to 25%, control fed; 33.7% to 23.5%, protein restricted)

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.

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

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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.

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

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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

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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.

Quantitative-profiling of neurotransmitter abnormalities in the disease progression of experimental diabetic encephalopathy rat.

Science.gov (United States)

Zhou, Xueyan; Zhu, Qiuxiang; Han, Xiaowen; Chen, Renguo; Liu, Yaowu; Fan, Hongbin; Yin, Xiaoxing

2015-11-01

Diabetic encephalopathy (DE) is one of the most prevalent chronic complications of diabetes mellitus (DM), with neither effective prevention nor proven therapeutic regimen. This study aims to uncover the potential dysregulation pattern of the neurotransmitters in a rat model of streptozotocin (STZ)-induced experimental DE. For that purpose, male Sprague-Dawley (SD) rats were treated with a single intraperitoneal injection of STZ. Cognitive performance was detected with the Morris water maze (MWM) test. Serum, cerebrospinal fluid (CSF), and brain tissues were collected to measure the levels of neurotransmitters. Compared with the control rats, the acetylcholine (ACh) levels in serum, CSF, hippocampus, and cortex were all significantly down-regulated as early as 6 weeks in the STZ treatment group. In contrast, the glutamate (Glu) levels were decreased in CSF and the hippocampus, but unaffected in the serum and cortex of STZ-treated rats. As for γ-aminobutyric acid (GABA), it was down-regulated in serum, but up-regulated in CSF, hippocampus, and the cortex in the STZ-treated group. The mRNA expressions of neurotransmitter-related rate limiting enzymes (including AChE, GAD1, and GAD2) and pro-inflammatory cytokines (including IL-1β and TNF-α) were all increased in the DE rats. Our data suggest that DM induces isoform-dependent and tissue-specific neurotransmitter abnormalities, and that neuroinflammation may underlay the nervous system dysfunction observed in the progression of DE.

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

The Effect of Oral Feeding of Tribulus Terrestris Fruit on Some Markers of Oxidative Stress in the Brain of Diabetic Rats

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M Roghani

2013-06-01

Full Text Available Introduction: Chronic diabetes mellitus in the long run accompanies enhanced oxidative stress burden and decreases activity of antioxidant defense system. Due to significant role of these factors in development of some neurological disorders and with regard to antidiabetic and antioxidant effect of Tribulus terrestris (TT, this study was conducted to evaluate the effect of its oral administration on brain tissue level of some markers of lipid peroxidation and oxidative stress in diabetic rats. Methods: In this experimental study, rats were divided into 4 groups, i.e. control, TT-treated control, diabetic, and TT-treated diabetic groups. For induction of diabetes, streptozotcin (STZ was intraperitoneally administered (60mg/Kg. In addition, TT-treated groups received TT mixed with standard pelleted food at a weight ratio of 3% for 5 weeks. Level of malondialdehyde (MDA and nitrite as well as activity of superoxide dismutase (SOD in brain tissue were measured at the end of the study. Results: Diabetic rats showed a significant increase in tissue level of MDA (p<0.01 and nitrite (p<0.01 and a non-significant reduction of SOD activity. Furthermore, TT treatment significantly reduced level of MDA p<0.01 and nitrite (p<0.05. Also, SOD activity in treated-diabetic group was non-significantly higher as compared to diabetics. Conclusion: Chronic oral treatment with TT could attenuate some markers of lipid peroxidation and oxidative stress in brain tissue in diabetic rats which this could possibly prevent some neurological disorders due to enhanced oxidative stress.

Experimental Salmonella typhimurium infections in rats. I

DEFF Research Database (Denmark)

Hougen, H P; Jensen, E T; Klausen, B

1989-01-01

The course of experimentally induced Salmonella typhimurium infection was studied in three groups of inbred LEW rats: homozygous +/+, athymic rnu/rnu and isogeneic thymus-grafted rnu/rnu rats. In the first experiment the animals were inoculated intraperitoneally with 10(8) bacteria and all animals...... became severely septicemic and died within a week of inoculation, irrespective of presence or absence of thymus. In the second experiment the animals were inoculated with 10(6) bacteria, and both euthymic and thymus-grafted animals responded with high titres of anti bacterial antibodies while these were...... very low in the athymic nude animals. Polyclonal antibody production was only observed in the euthymic animals and only regarding IgG. Athymic rats were not able to clear the infection, while the thymus-grafted animals reacted like euthymic rats: Very few animals housed the bacteria four weeks after...

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)

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.

Science.gov (United States)

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.

Effects of an acute and a sub-chronic 900 MHz GSM exposure on brain activity and behaviors of rats

International Nuclear Information System (INIS)

Elsa Brillaud; Aleksandra Piotrowski; Anthony Lecomte; Franck Robidel; Rene de Seze

2006-01-01

Radio frequencies are suspected to produce health effects. Concerning the mobile phone technology, according to position during use (close to the head), possible effects of radio frequencies on the central nervous system have to be evaluated. Previous works showed contradictory results, possibly due to experimental design diversity. In the framework of R.A.M.P. 2001 project, we evaluated possible effect of a 900 MHz GSM exposure on the central nervous system of rat at a structural, a functional and a behavioral level after acute or sub-chronic exposures. Rats were exposed using a loop antenna system to different S.A.R. levels and durations, according to results of the French C.O.M.O.B.I.O. 2001 project. A functional effect was found (modification of the cerebral activity and increase of the glia surface) after an acute exposure, even at a low level of brain averaged S.A.R. (1.5 W/kg). No cumulative effect was observed after a sub-chronic exposure (same amplitude of the effect). No structural or behavioral consequence was noted. We do not conclude on the neurotoxicity of the 900 MHz GSM exposure on the rat brain. Our results do not indicate any health risk. (authors)

Effects of an acute and a sub-chronic 900 MHz GSM exposure on brain activity and behaviors of rats

Energy Technology Data Exchange (ETDEWEB)

Elsa Brillaud; Aleksandra Piotrowski; Anthony Lecomte; Franck Robidel; Rene de Seze [Toxicology Unit, INERIS, Verneuil en Halatte (France)

2006-07-01

Radio frequencies are suspected to produce health effects. Concerning the mobile phone technology, according to position during use (close to the head), possible effects of radio frequencies on the central nervous system have to be evaluated. Previous works showed contradictory results, possibly due to experimental design diversity. In the framework of R.A.M.P. 2001 project, we evaluated possible effect of a 900 MHz GSM exposure on the central nervous system of rat at a structural, a functional and a behavioral level after acute or sub-chronic exposures. Rats were exposed using a loop antenna system to different S.A.R. levels and durations, according to results of the French C.O.M.O.B.I.O. 2001 project. A functional effect was found (modification of the cerebral activity and increase of the glia surface) after an acute exposure, even at a low level of brain averaged S.A.R. (1.5 W/kg). No cumulative effect was observed after a sub-chronic exposure (same amplitude of the effect). No structural or behavioral consequence was noted. We do not conclude on the neurotoxicity of the 900 MHz GSM exposure on the rat brain. Our results do not indicate any health risk. (authors)

Morphofunctional analysis of experimental model of esophageal achalasia in rats.