Changes In Rat Brain Research Articles

Conventional Anti-glioblastoma Chemotherapy Affects Proteoglycan Composition of Brain Extracellular Matrix in Rat Experimental Model in vivo.

Temozolomide (TMZ) is a conventional chemotherapy drug for adjuvant treatment of glioblastoma multiforme (GBM), often accompanied by dexamethasone (DXM) to prevent brain oedema and alleviate clinical side effects. Here, we aimed to investigate an ability of the drugs to affect normal brain tissue in terms of proteoglycan (PG) composition/content in experimental rat model in vivo. Age- and brain zone-specific transcriptional patterns of PGs were demonstrated for 8, 60, and 120 days old rats, and syndecan-1, glypican-1, decorin, biglycan, and lumican were identified as the most expressed PGs. DXM treatment affected both PG core proteins expression (mainly syndecan-1, glypican-1, decorin, biglycan, lumican, versican, brevican, and NG2) and heparan sulphate (HS)/chondroitin sulphate (CS) content in organotypic brain slice culture ex vivo and experimental animals in vivo in a dose-dependent manner. TMZ treatment did not result in the significant changes in PG core proteins expression both in normal rat brain hippocampus and cortex in vivo (although generics did), but demonstrated significant effects onto polysaccharide HS/CS content in the brain tissue. The effects were age- and brain zone-specific and similar with the age-related PGs expression changes in rat brain. Combination of TMZ with DXM resulted in the most profound deterioration in PGs composition and content in the brain tissue both at core protein and glycosaminoglycan levels. Taken together, the obtained results demonstrate that conventional anti-glioblastoma therapy affects proteoglycan structure and composition in normal brain tissue, potentially resulting in deterioration of brain extracellular matrix and formation of the favourable tumorigenic niche for the expansion of the residual glioma cells. During the TMZ chemotherapy, dose and regimen of DXM treatment matter, and repetitive low DXM doses seem to be more sparing treatment compared with high DXM dose(s), which should be avoided where possible, especially in combination with TMZ.

Effects of recombinant activated coagulation factor VII on apoptosis and expressions of Bcl-2 and Bax in rats with intracerebral hemorrhage.

To investigate the effects of recombinant activated coagulation factor VII (rFVIIa) on apoptosis and the expressions of B-cell lymphoma 2 (Bcl-2) and Bcl-2-associated X protein (Bax) in rats with intracerebral hemorrhage (ICH). A total of 90 8-week-old male Sprague-Dawley (SD) rats with similar weight were selected and randomly divided into normal group (n=30), ICH control group (n=30), and rFVIIa treatment group (n=30). Five days later, hematoxylin-eosin (HE) staining was applied to observe pathological changes in rat brain in three groups. Cell apoptosis in rat brain was detected at 6 h, 12 h, 24 h, 48 h, 72 h, and 120 h, respectively. The relative expression levels of Bcl-2 and Bax in brain tissues were measured via fluorescence quantitative Polymerase Chain Reaction (qPCR) and Western blotting, respectively. Compared with those in ICH control group, rats in rFVIIa treatment group had fewer degenerated and necrotic nerve cells and milder pathological changes in the marginal zone. The number of apoptotic cells in ICH control group and rFVIIa group was gradually increased in a time-dependent manner, and achieved the peak at 72 h. The number of apoptotic cells in treatment group was significantly lower than that in ICH control group after 24 h (p<0.05). Both fluorescence qPCR and Western blotting results proved that in comparison with ICH control group, rFVIIa group had a higher relative expression level of Bcl-2 (p<0.05) and a lower expression level of Bax (p<0.05). Apoptosis mechanism may be involved in secondary brain injury after ICH. RFVIIa may have an important protective effect on neuronal injury after ICH by promoting the expression of Bcl-2 and inhibiting the expression of Bax protein.

Ascorbic acid protects male rat brain from oral potassium dichromate-inducedoxdative DNA damage and apoptotic changes: the expression patterns of caspase-3, P 53, Bax, and Bcl-2 genes.

Our study designed to study the potential of potassium dichromate (K2Cr2O7) oral exposure to induce damage in male rat brain and to compare the possible protective role of vitamin C (VC) either pre and/or concurrent supply against (K2Cr2O7) induced changes. Thirty male rats were divided into five groups. First control group received distilled water (C), second received 120mg/kg b.wt (VC), third received 25mg/kg b.wt K2Cr2O7 (Cr), fourth group received VC together with K2Cr2O7 by the same former doses (VC + Cr), and the fifth group received the same oral doses of VC 2weeks prior to and along with K2Cr2O7 for 6weeks (VC + Cr pro/co treated). The obtained results revealed that K2Cr2O7 induced a significant decrease in cholinergic activity, glutathione reductase GR activity, reduced glutathione content GSH and ATP levels. Furthermore, K2Cr2O7 induced a significant increase in oxidative DNA damage indicated by 8-hydroxy 2'-deoxyguanosine (8OH2'dG) and formation of apoptotic DNA ladders, significant increase in malondialdehyde (MDA), protein carbonyl, and lactate dehydrogenase enzyme. Increased mRNA expression of pro-apoptotic genes, including caspase-3, p53, and Bax, unlike Bcl-2 expression, was decreased. K2Cr2O7 increased caspase-3 and decreased Bcl-2 immuno-labeling. VC supply noticeably ameliorates K2Cr2O7-induced changes which were more significantly in VC pro and concurrent supplement rather than VC concurrent supply only. Finally, it is concluded that K2Cr2O7 oral administration induced oxidative apoptotic changes in rat brain and confirms the usefulness of VC pre and concurrent supply for the amelioration of K2Cr2O7-induced events more significantly than VC concurrent supply only.

The Significance of Sleep Deprivation in the Development of Local Epilepsy from the Point of View of Neuroplasticity

Objective. To study the neurological and electrophysiological manifestations of sleep deprivation (SD) in patients with local symptomatic forms of epilepsy and in healthy subjects and to investigate the neuromorphological patterns of SD in experimental conditions. Materials and methods. Complex clinical and electroencephalographic (video-EEG monitoring with sleep traces) studies were performed before and after SD for 48 h in 178 patients with locally originating epilepsy (LOE) and 45 healthy control subjects. Neurohistological and electron microscopic investigations of the brain were performed in rats after 48-h SD. Results and discussion. SD led to increases in epileptiform activity in patients with LOE (with increases in the frequency of epileptic seizures) and the onset of this activity in healthy subjects. Post-SD morphological changes in rat brains consisted of mitochondrial pleioconia, damage to elements of the blood-brain barrier, signs of astrocyte depletion, changes in gliocyte nuclei of the apoptotic and karyorrhectic types, and destruction of synapses; these were evidence of impairment to the mechanisms of neuroplasticity after SD. These results allow SD in patients to be regarded as a factor damaging the CNS and provoking the development of epileptic seizures in epilepsy. SD in experimental animals can be used as a model for further studies of the mechanisms of neuroplasticity.

Quantitative Mass Spectrometry Reveals Food Intake-Induced Neuropeptide Level Changes in Rat Brain: Functional Assessment of Selected Neuropeptides as Feeding Regulators

Endogenous neuropeptides are important signaling molecules that function as regulators of food intake and body weight. Previous work has shown that neuropeptide gene expression levels in a forebrain reward site, the nucleus accumbens (NAc), were changed by feeding. To directly monitor feeding-induced changes in neuropeptide expression levels within the NAc, we employed a combination of cryostat dissection, heat stabilization, neuropeptide extraction and label-free quantitative neuropeptidomics via a liquid chromatography-high resolution mass spectrometry platform. Using this methodology, we described the first neuropeptidome in NAc and discovered that feeding caused the expression level changes of multiple neuropeptides derived from different precursors, especially proSAAS-derived peptides such as Big LEN, PEN and little SAAS. We further investigated the regulatory functions of these neuropeptides derived from the ProSAAS family by performing an intra-NAc microinjection experiment using the identified ProSAAS neuropeptides, 'Big-LEN' and 'PEN'. Big LEN significantly increased rats' food and water intake, whereas both big LEN and PEN affected other behaviors including locomotion, drinking and grooming. In addition, we quantified the feeding-induced changes of peptides from hippocampus, hypothalamus and striatum to reveal the neuropeptide interplay among different anatomical regions. In summary, our study demonstrated neuropeptidomic changes in response to food intake in the rat NAc and other key brain regions. Importantly, the microinfusion of ProSAAS peptides into NAc revealed that they are behaviorally active in this brain site, suggesting the potential use of these peptides as therapeutics for eating disorders.

Acute Ammonia Intoxication-Induced Seizures but not Ammonia Per Se Contribute to the Electrophysiological Changes in Rat Brain

Background and Aim: Hepatic encephalopathy (HE) is a major complication in patients with mild to severe liver disease. HE is characterized by confusion, inverted sleep-wake cycles, disorientation, behavioral changes, impaired cognition, and motor disturbances, as well as increased brain edema and intracranial pressure. The molecular basis for these changes in HE remains unclear. Elevated blood and brain ammonia levels have been strongly implicated in its pathogenesis. Whether ammonia play any role in electrophysiological changes in HE that may be involved in neurobehavioral, biochemical and molecular changes observed in HE was examined. Methods: Male Wister albino rats were injected (i.p) with ammonium acetate (500 and 800 mg/kg) and liver toxin acetaminophen (AMPN, 500 mg/kg). Results: The AACE-treated group developed seizures within 10 min and survived post-treatment without any additional seizure incident. However, more than 70% of AMPN treated animals died after 56 hours. Hippocampal slices were prepared from these animals (1 hr after AACE and 40 h after AMPN, pre-coma stage) and electrophysiological changes were measured. A paired-pulse facilitation (PPF) sequence in which stimulation pulse pairs were delivered at intervals of 20-480 ms and the filed excitatory postsynaptic potential (EPSP) slope were calculated. A depressed PPF was observed in slices from both AACE and AMPN treated animals. Further, inhibition of seizures in AACE group showed reversal of these electrophysiological changes, while these inhibitors failed to prevent electrophysiological changes induced by AMPN. Additionally, seizure inducing agent's picrotoxin (PCT) and pentylenetetrazol (PTZ) showed electrophysiological changes similar to AACE, and that inhibition of PCT and PTZ induced seizures reversed electrophysiological changes. Conclusion: These findings suggest that the effect of acute ammonia intoxication on electrophysiological changes may be due to the effect of ammonia-induced seizures, but not due to ammonia per se. The author have none to declare.

STUDY OF CHRONIC TOXIC EFFECT OF DELTAMETHRIN AND DIMETHOATE ON BRAIN OF ADULT MALE ALBINO RATS

organophosphate pesticides are being increasingly used in combination with Pyrethroids. The effects of single molecules are being studied, but the risk associated with pesticide mixtures is still to estimate. So, the purpose of the current study was to evaluate the individual and combined toxic effects of deltamethrin (DLM) and dimethoate (DM) on brain of adult male albino rats. For this purpose, 60 adult male albino rats were randomized into 5equal groups: Group I: negative control, Group II: positive control received 1ml corn oil once daily. Group III received deltamethrin (5 mg/kg b.w./orally ∕daily), Group IV received dimethoate (20 mg/kg b.w./ orally ∕daily), Group V received deltamethrin (5 mg/kg b.w) and dimethoate(20 mg/kg b.w)orally ∕daily . At the end of the study (12 weeks); Body weight was evaluated then blood sample were obtained for estimation of oxidative stress markers malondialdehyde (MDA) glutathione (GSH), total antioxidant capacity TAC) and plasma cholinesterase (PCHE) level then rats were sacrificed. The brains were excised, prepared for histopathological, immunohistochemical examination and DNA damage estimation by comet assay. Results revealed that single DLM and DM exposure significantly had adverse effects on adult male Albino rats in the form of decrease in the body weight, increase in brain &serum MDA, decrease in TAC &GSH and decrease in PCHE level. Pathological changes in brain of rats included, pychnosis, neuronal degeneration, neuropil vacuolization, hemorrhage and congested blood vessels beside positive immuoreaction for bax. Also they caused DNA damage compared to control group. In conclusion, chronic exposure to DLM and DM singly and in combination induced significant oxidative damage in rat brain, associated with marked perturbations in antioxidant defense system in addition to genotoxicity detected by comet assay. Also, the mixture of the two pesticides caused greater damage on the brain of male albino rats, than the individual pesticides.

Antioxidant mediated response of Scoparia dulcis in noise-induced redox imbalance and immunohistochemical changes in rat brain.

Noise has been regarded as an environmental/occupational stressor that causes damages to both auditory and non-auditory organs. Prolonged exposure to these mediators of stress has often resulted in detrimental effect, where oxidative/nitrosative stress plays a major role. Hence, it would be appropriate to examine the possible role of free radicals in brain discrete regions and the "antioxidants" mediated response of S. dulcis. Animals were subjected to noise stress for 15 days (100 dB/4 hours/day) and estimation of endogenous free radical and antioxidant activity were carried out on brain discrete regions (the cerebral cortex, cerebellum, brainstem, striatum, hippocampus and hypothalamus). The result showed that exposure to noise could alleviate endogenous free radical generation and altered antioxidant status in brain discrete regions when compared to that of the control groups. This alleviated free radical generation (H2O2 and NO) is well supported by an upregulated protein expression on immunohistochemistry of both iNOS and nNOS in the cerebral cortex on exposure to noise stress. These findings suggest that increased free radical generation and altered anti-oxidative status can cause redox imbalance in the brain discrete regions. However, free radical scavenging activity of the plant was evident as the noise exposed group treated with S. dulcis[200 mg/(kg·b·w)] displayed a therapeutic effect by decreasing the free radical level and regulate the anti-oxidative status to that of control animals. Hence, it can be concluded that the efficacy of S. dulcis could be attributed to its free radical scavenging activity and anti-oxidative property.

Assessment the Protective Role of Quercetin on Acrylamide-Induced Oxidative Stress in Rats

This study aimed to elucidate whether quercetin treatment could modulate acrylamide (ACR)-induced DNA damage and oxidative changes in rat brain, liver, kidneys and testes tissues. Fifty adult albino rats were divided into five groups. The first group served as normal control, second group received 50 mg/kg quercetin (QTN) and third group received 20 mg/kg ACR. Fourth and fifth groups received dose of ACR along with 25 or 50 mg/kg QTN, respectively. ACR and QTN were given by oral administrations for 30 days. The results showed that, ACR administration induced significant elevation of alanine transferase, aspartate transferase activities, urea, creatinine and Malondialdehyde levels in serum, whereas, Acetylcholine esterase and testosterone levels were reduced after ACR administration. Moreover, ACR treatment increased Glutathione-S-transferase, Myeloperoxidase, Glutathione peroxidase activity, 8-hydroxy deoxyguanosine, tumor necrosis factor-α and nitric oxide contents in all tissues. QTN significantly improved the previous parameters. It played a role in ameliorating toxic effects of ACR in rats by reducing oxidative stress. Practical Applications Acrylamide was found in various fried, deep fried and oven-baked foods that are regularly consumed like chips, crisps and bread, also biscuits, crackers and breakfast cereals. Acrylamide exposure led to increase of alanine transferase, aspartate transferase activities, urea, creatinine and Malondialdehyde levels in serum, whereas, Acetylcholine esterase and testosterone levels were reduced. Moreover, ACR treatment increased Glutathione-S-transferase, Myeloperoxidase, Glutathione peroxidase activity, 8-hydroxy deoxyguanosine, tumor necrosis factor-α and nitric oxide contents in all tissues. Our study revealed the protective role of quercetin on acrylamide-induced oxidative stress in rats. Quercetin regulate the generation of inflammatory markers and increasing antioxidant enzyme activity in rat liver, kidneys, brain and testes tissues.

Age Associated Fluoride Induced Ultra Structural and Biochemical Changes in Rat Brain

Fluoride (F) ingestion is well known to be associated with oxidative stress in experimental animals, but the precise mechanism of its toxicity associated with advancing age has not yet been delineate. The present study attempts to assess the learning and memory capacity of rats using water maze test for cognitive functioning. The markers of oxidative stress i.e., Reacting oxygen species (ROS), protein carbonyl content (PC), lipid peroxide levels (LPx), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx) and reduced glutathione (GSH) were measured in the brain hippocampus of young and aged rats fed with fluoride (100 ppm) with drinking for 90 days. We observed significant changes of fluoride treated young and aged rat as compared with their respective controls. Lipofuscin content was significantly increased in fluoride treated aged rats. Ultra structural studies of the CA1 region in hippocampus of fluoride exposed rats revealed that the changes were more pronounced in the aged treated rats in terms of presence of clustered lipofuscin, vacuolization, lysosomal degradation and nucleolar fragmentation. On the basis of the results it may conclude that fluoride may be linked with neuro lipofuscinogenesis and alteration in neurobehavioral activity and these changes may be responsible for the development of age related disorders.

Age Associated Fluoride Induced Ultra Structural and Biochemical Changes in Rat Brain

Age Associated Fluoride Induced Ultra Structural and Biochemical Changes in Rat Brain

T1ρ relaxation time in brain regions increases with ageing: an experimental MRI observation in rats

T1ρ variation is associated with neurodegenerative diseases. This study aims to observe T1ρ relaxation time changes in rat brains associated with normal ageing in Sprague-Dawley (SD) rats, Wistar Kyoto (WKY) rats and spontaneously hypertension rats (SHRs). 18 male SD rats, 11 male WKY rats and 11 male SHRs were used. T1ρ measurement was performed at 3-T MR with a spin-lock frequency of 500 Hz. SD rats were scanned at the ages of 5, 8, 10 and 15 months. SHRs and WKY rats were scanned at the ages of 6, 9 and 12 months. For SD rats, T1ρ at the thalamus, hippocampus and frontal cortices increased significantly from 5 to 15 months (p < 0.05). For the WKY rats and SHRs, the T1ρ values in the thalamus, hippocampus and frontal cortices also increased significantly from 6 to 12 months (p < 0.05). Furthermore, T1ρ in the thalamus, hippocampus and frontal cortices of SHRs were consistently higher than those of WKY rats at the ages of 6, 9 and 12 months (p < 0.05). The percentage regional T1ρ differences between WKY rats and SHRs did not change during ageing. An increase in T1ρ was associated with age-related changes of the rat brain. An age-related and hypertension-related T1ρ increase in rat brain regions was observed in the thalamus, hippocampus and frontal cortical regions of the rat brain.

Cerebral glucose metabolism changes in rat brain upon forepaw electrical stimulation at different frequencies

PET imaging techniques and statistical parametric mapping analysis have been developed to identify neuronal functional activation from brain imaging. The purpose of this study was to examine the efficacy of the glucose metabolism in rat brain during forepaw electrical stimulation with different frequencies (3, 10, or 20 Hz) compared with a nonstimulated group (control). Fluorine-18 fluorodeoxyglucose was injected after confirmation of the range of normal physiology. For quantitative analysis, we used cerebral metabolism rate of glucose consumption (CMRglc) responses in the primary somatosensory cortex (S1FL) and motor cortex (M1). On comparing CMRglc responses in the contralateral S1FL and M1 with those of the ipsilateral areas in intragroup analysis, a significant increase (P<0.05) was observed in two electrical stimulation groups (10 and 20 Hz) but not at the 3 Hz level. In intergroup analysis, the CMRglc responses in the contralateral region of interest were compared with those of the control group to validate which electrical frequency conditions were appropriate to induce neuronal functional activation. Among the stimulation groups, significant increases in CMRglc response were only observed at 10 Hz (P<0.05). Therefore, 10 Hz is the most suitable frequency to confirm changes in CMRglc in the S1FL and M1 of the rat brain, and also fluorine-18 fluorodeoxyglucose PET could be useful to investigate recovery and plasticity in neurological diseases associated with primary sensory-motor cortex function.

Neuroplasticity Changes of Rat Brain by Musical Stimuli during Fetal Period.

Fetal development of the central nervous system is an important and sensitive stage which is affected by many external and internal stimuli. This study aimed to investigate effect of musical stimuli on fetal rat brain. In this experimental study, twelve female Wistar rats were selected and evenly assigned to control and musical groups. The females were mated with a male rat of the same genotype. Musical group was exposed to classic music with 60 dB power for 90 minutes twice per day from 2(nd) to 20(th) day of gestation. The control rats were handled similar to the musical group, but were not exposed to music. Before parturition, all the dams were anesthetized, and their blood samples were obtained and used for corticosterone (COS) measurement. They were transcardially perfused by electron microscope (EM) fixative agent. The fetal brains were extracted intact and used for slice preparation. Horizontal slices were made for electron microscope preparation, and images were taken and analyzed in terms of cell density and morphological changes. EM observation indicated significant morphological difference in cellular and intercellular spaces between the two groups. Music-treated fetuses had significantly higher cell density in parietal cortex and music-treated dams had lower COS level. It was concluded that prenatal music would have a great impact on neuroplasticity of fetal rat brain, at least indirectly. Although the rat fetuses cannot hear until birth, music-induced reduction in COS blood level of dams might be the reason for neuroplasticity of fetal brain.

Bacoside A: Role in Cigarette Smoking Induced Changes in Brain.

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

Discovering novel microRNAs and age-related nonlinear changes in rat brains using deep sequencing

Elucidating the molecular mechanisms of brain aging remains a significant challenge for biogerontologists. The discovery of gene regulation by microRNAs (miRNAs) has added a new dimension for examining this process; however, the full complement of miRNAs involved in brain aging is still not known. In this study, miRNA profiles of young, adult, and old rats were obtained to evaluate molecular changes during aging. High-throughput deep sequencing revealed 547 known and 171 candidate novel miRNAs that were differentially expressed among groups. Unexpectedly, miRNA expression did not decline progressively with advancing age; moreover, genes targeted by age-associated miRNAs were predicted to be involved in biological processes linked to aging and neurodegenerative diseases. These findings provide novel insight into the molecular mechanisms underlying brain aging and a resource for future studies on age-related brain disorders.

Calpains and their endo- and exogenous regulators in various models of neurodegeneration

On the basis of experimental series with murine models there was obtained the evidence on calcium-dependent protease activity changes in rat brain at induced neurodegeneration. The properties of the proteolytic and regulatory components of calpain system under the effect of neurotoxic stimuli--amyloid beta-peptide or glutamate--were characterized; the basic endogenous regulatory mechanisms of calcium-dependent proteolysis modulation were determined as well. Neuroprotective properties of exogenous calpain regulators differing in the mechanisms of action (sex steroids, calcium regulators) were tested on studied neurodegeneration models.

Potential efficacy of dopamine loaded-PVP/PAA nanogel in experimental models of Parkinsonism: possible disease modifying activity.

This study aimed to investigate the ability of dopamine (DA)-loaded polyvinylpyrrolidone-poly(acrylic acid) (PVP/PAAc) nanogel [synthesized by gamma (γ) radiation-induced template polymerization] [Nano-DA] to deliver DA across the blood brain barrier, and to evaluate the efficacy and safety of the acute and subchronic administration of Nano-DA in modulating motor activity and/or the biochemical changes in rat brain; induced by different models of Parkinsonism. In this respect, (PVP/PAAc) nanogel was synthesized by gamma radiation-induced polymerization of acrylic acid (AAc) in an aqueous solution of PVP as a template polymer, and then, it was used as a nano-drug carrier for DA. The PVP/PAAc and (PVP/PAAc loaded-DA nanogel particles were characterized by dynamic light scattering, infrared spectroscopy, and field emission-scanning electron microscopy. The loaded gel was administered in different doses and dosing regimens to Parkinsonian rats, and the catalepsy score and striatal DA levels were assessed. Then, the potential disease-modifying activity of this form of DA was investigated, through the assessment of the improvement in mitochondrial function, following the subchronic administration of Nano-DA to Parkinsonian rats. Significant disease-modifying effects were observed upon the administration of Nano-DA; in addition to normalization in their motor activity.

Finasteride improves motor, EEG, and cellular changes in rat brain in thioacetamide-induced hepatic encephalopathy.

Neurosteroids are involved in the pathogenesis of hepatic encephalopathy (HE). This study evaluated the effects of finasteride, inhibitor of neurosteroid synthesis, on motor, EEG, and cellular changes in rat brain in thioacetamide-induced HE. Male Wistar rats were divided into the following groups: 1) control; 2) thioacetamide-treated group, TAA (300 mg·kg(-1)·day(-1)); 3) finasteride-treated group, FIN (50 mg·kg(-1)·day(-1)); and 4) group treated with FIN and TAA (FIN + TAA). Daily doses of TAA and FIN were administered in three subsequent days intraperitoneally, and in the FIN + TAA group FIN was administered 2 h before every dose of TAA. Motor and reflex activity was determined at 0, 2, 4, 6, and 24 h, whereas EEG activity was registered about 24 h after treatment. The expressions of neuronal (NeuN), astrocytic [glial fibrilary acidic protein (GFAP)], microglial (Iba1), and oligodendrocyte (myelin oligodendrocyte glycoprotein) marker were determined 24 h after treatment. While TAA decreased all tests, FIN pretreatment (FIN + TAA) significantly improved equilibrium, placement test, auditory startle, head shake reflex, motor activity, and exploratory behavior vs. the TAA group. Vital reflexes (withdrawal, grasping, righting and corneal reflex) together with mean EEG voltage were significantly higher (P < 0.01) in the FIN + TAA vs. the TAA group. Hippocampal NeuN expression was significantly lower in TAA vs. control (P < 0.05). Cortical Iba1 expression was significantly higher in experimental groups vs. control (P < 0.05), whereas hippocampal GFAP expression was increased in TAA and decreased in the FIN + TAA group vs. control (P < 0.05). Finasteride improves motor and EEG changes in TAA-induced HE and completely prevents the development of hepatic coma.

High resolution mapping of modafinil induced changes in glutamate level in rat brain.

Modafinil is marketed in the United States for the treatment of narcolepsy and daytime somnolence due to shift-work or sleep apnea. Investigations of this drug in the treatment of cocaine and nicotine dependence in addition to disorders of executive function are also underway. Modafinil has been known to increase glutamate levels in rat brain models. Proton magnetic resonance spectroscopy (1HMRS) has been commonly used to detect the glutamate (Glu) changes in vivo. In this study, we used a recently described glutamate chemical exchange saturation transfer (GluCEST) imaging technique to measure Modafinil induced regional Glu changes in rat brain and compared the results with Glu concentration measured by single voxel 1HMRS. No increases in either GluCEST maps or 1HMRS were observed after Modafinil injection over a period of 5 hours. However, a significant increase in GluCEST (19±4.4%) was observed 24 hours post Modafinil administration, which is consistent with results from previous biochemical studies. This change was not consistently seen with 1HMRS. GluCEST mapping allows regional cerebral Glu changes to be measured and may provide a useful clinical biomarker of Modafinil effects for the management of patients with sleep disorders and addiction.