Activity In Brain Homogenates Research Articles

Evaluating Antioxidant Enzyme Parameters in Rats Treated with Berberine-Loaded Bovine Serum Albumin Nanoparticles and Scopolamine

Abstract Introduction/Objective Introduction: Berberine (BER) has garnered attention for its antioxidant properties demonstrated in various studies, showing its ability to scavenge or inhibit reactive oxygen species (ROS) and reactive nitrogen species (RNS), including nitric oxide, superoxide anion, and peroxynitrites. Methods/Case Report Methods: Forty-two male Wistar rats were randomly assigned to seven groups, each comprising 6 rats: Sham control (no treatment), BSA-NPs orally administered, BRB-NPs orally administered, SCO intraperitoneally injected, BER followed by SCO injection, BSA-NPs with SCO injection, and BER-NPs with SCO injection. Treatments were administered daily for 28 days. The cholinergic status was evaluated by assessing acetylcholinesterase (AChE) activity in brain homogenates, and brain homogenate Aβ-42 levels were measured using the ELISA technique. Additionally, brain prooxidant markers (NO, TBARS, XO), nonenzymatic antioxidants (GSH), and enzymatic antioxidants (GPx, GST, and SOD) were measured. Results (if a Case Study enter NA) Results: The study revealed that treatment with BRB NPs resulted in the lowest AChE activity and Aβ-42 levels. Scopolamine administration significantly increased brain NO, TBARS, and XO activity, accompanied by a progressive depletion in GSH content (p<0.05). Treatment with BRB-free or BSA decreased NO levels, while the BSA or BRB-NPs groups exhibited higher brain TBARS levels than the sham group. All treated groups exhibited similar activity to the sham control, except for the BSA-treated group. Furthermore, all treated groups showed comparable GSH levels to the sham control, except for the scopolamine group. Treatment with BRB NPs normalized GPx activity and showed the highest GST activity. The BRB-NPs treated group also exhibited the highest SOD level. The p-value was <0.001 among all studied groups. Conclusion Conclusion: Injection of SCO induced oxidative impairments in brain tissue, evidenced by increased prooxidants such as NO and depletion of antioxidant capacity (GPx, GST, and GSH). SCO also disrupted glutathione metabolism, enhancing the level of lipid peroxidation in the brain. Treatment with BRB-NPs or free BRB progressively increased antioxidant capacity and mitigated the harmful effects of oxidative damage in the brain by reducing prooxidant levels.

Heavy metal toxicity arising from the industrial effluents repercussions on oxidative stress, liver enzymes and antioxidant activity in brain homogenates of Oreochromis niloticus

Industrial effluents reaching to the aquatic ecosystem is one of the major causes of environmental pollution and exposure to industrial effluents containing harmful substances may be a serious threat to human health. Therefore, the present study aimed to determine the sub-lethal (1/5th of predetermined LC50) impact of industrial effluents from Sundar Industrial Estate on Oreochromis niloticus with proper negative control. The physicochemical analysis of industrial effluents showed enormous loads of inorganic pollutants and exhibited high mean levels of heavy metals, Mn, Fe, Pb, Ni, Cr, Hg, As, Zn and Fe with statistically significant differences at p < 0.05. Highest level of Mn and Fe was detected in effluent’s samples as 147.36 ± 80.91 mg/L and 90.52 ± 32.08 mg/L, respectively. Exposure led to increase in serum biochemical parameters alanine aminotransferase + 25%, aspartate aminotransferase + 20% and alkaline phosphatase + 7% over control although superoxide dismutase, catalase, glutathione peroxidase and reduced glutathione significantly increased as 3.42, 2.44, 4.8 and 8 folds, respectively in metabolically active tissue brain which indicated stress caused by industrial effluents. The results concluded that industrial effluent has potent oxidative stress inducers on one hand whereas histoarchitectural and physiological toxicity causing contaminants on the other. This condition may adversely affect the health of aquatic organisms, the fish and ultimately the human beings.

Вплив введення мезенхімальних стовбурових клітин на структуру та функцію нейропіля великих півкуль головного мозку щурів з експериментальною нітритіндукованою деменцією

The cerebral hemispheres neuropil of rats with experimental nitrite-induced Alzheimer’s type dementia was studied after mesenchymal stem cells (MSC) introduction. Rats were injected with an aqueous solution of sodium nitrite (50 mg/ kg) for 14 (group 1) and 28 days (group 3), and half of them additionally got intravenously MSC (500000 cells per rat) (groups 2 and 4). The control group received saline in the same way. The acetylcholine level, TBA-active substances contents, catalase and superoxide dismutase activities in brain homogenates, and the content of 2,3-diphofoglycerate (2,3- DFG) in erythrocytes were measured spectrophotometrically. Brain slices were stained with Congo red and according to the Einarson method. They were then examined on an Axiostar plus binocular microscope (“Zeiss”, Germany). The optical density of the cerebral hemispheres neuropil had been measured. In all experimental groups, an increase in the content of 2,3-DFG in erythrocytes and an imbalance in the pro- and antioxidant system, oxidative stress development in brain were observed. The neuropil structure of the cerebral hemispheres was changed: we observed focal zones of neurofilaments degeneration and atrophy and amyloid accumulation, especially in group 3. The optical density of neuropil was reduced; this was accompanied by a decrease in the content of acetylcholine. MSC injections resulted in a significant increase in the content of acetylcholine, decrease in the brain oxygen demand and the content of TBA-active substances. Consequently, prolonged sodium nitrite administration leads to the cerebral hemispheres neuropil structure and functional injury. MSC introduction contributes to the improvement of the neuropil morphofunctional state.

Cognition enhancing effects of Clausena lansium (Lour.) peel extract attenuate chronic restraint stress-induced memory deficit in rats

Chronic stress exposure is now accepted as a problem that can produce deleterious effects on both brain structure and function. Numerous studies have proposed the potential of fruit peels as vital sources for acetylcholinesterase (AChE) inhibitors and antioxidants. Clausena lansium (Lour.) or wampee (WP) fruit peel is a rich source of antioxidants and flavonoids that could prove beneficial for human health. Currently, there has been no scientific evidence supporting the potency of WP peel extract to combat or reverse the memory impairment induced by chronic restraint stress (CRS). Therefore, we aimed to investigate the AChE-inhibiting and neuroprotective effects of WP peel extracts against CRS-mediated oxidative stress and cognitive dysfunction in rats. Initial assessment of the extract revealed antioxidant capacity and high concentrations of polyphenols. Further, Wistar rats were dosed orally with the WP peel extract (200, 400, and 600 mg/kg daily) and kept in a restrainer for 4 h a day for 28 consecutive days. The object recognition and Morris water maze tests were used to determine cognitive functions. After sacrifice, biomarkers of oxidative stress and AChE inhibitory activity in brain homogenates of rats were also investigated. CRS exposure produced oxidative stress and increased AChE activity, changes that led to learning and memory impairment in the cognition tests. Improved memory, reduced AChE activity, and a decreased oxidative stress status were seen in rats treated with WP peel extract. Overall, supplementation with WP peel extract may exert cognitive-enhancing effects through antioxidative neuroprotection and inhibition of AChE activity against CRS-induced oxidative stress.

Promising Anti-stroke Signature of Voglibose: Investigation through In- Silico Molecular Docking and Virtual Screening in In-Vivo Animal Studies.

Postprandial hyperglycemia considered to be a major risk factor for cerebrovascular complications. The current study was designed to elucidate the beneficial role of voglibose via in-silico in vitro to in-vivo studies in improving the postprandial glycaemic state by protection against strokeprone type 2 diabetes. In-Silico molecular docking and virtual screening were carried out with the help of iGEMDOCK+ Pymol+docking software and Protein Drug Bank database (PDB). Based on the results of docking studies, in-vivo investigation was carried out for possible neuroprotective action. T2DM was induced by a single injection of streptozotocin (90mg/kg, i.v.) to neonates. Six weeks after induction, voglibose was administered at the dose of 10mg/kg p.o. for two weeks. After eight weeks, diabetic rats were subjected to middle cerebral artery occlusion, and after 72 hours of surgery, neurological deficits were determined. The blood was collected for the determination of serum glucose, CK-MB, LDH and lipid levels. Brains were excised for determination of brain infarct volume, brain hemisphere weight difference, Na+-K+ ATPase activity, ROS parameters, NO levels, and aldose reductase activity. In-silico docking studies showed good docking binding score for stroke associated proteins, which possibly hypotheses neuroprotective action of voglibose in stroke. In the present in-vivo study, pre-treatment with voglibose showed a significant decrease (p<0.05) in serum glucose and lipid levels. Voglibose has shown significant (p<0.05) reduction in neurological score, brain infarct volume, the difference in brain hemisphere weight. On biochemical evaluation, treatment with voglibose produced significant (p<0.05) decrease in CK-MB, LDH, and NO levels in blood and reduction in Na+-K+ ATPase, oxidative stress, and aldose reductase activity in brain homogenate. In-silico molecular docking and virtual screening studies and in-vivo studies in MCAo induced stroke, animal model outcomes support the strong anti-stroke signature for possible neuroprotective therapeutics.

Antioxidant nanomedicine with cytoplasmic distribution in neuronal cells shows superior neurovascular protection properties

This study investigated whether nitroxide radical (4-amino-TEMPOL)–containing nanoparticles (RNPs; antioxidant nanomedicine) can prevent neurovascular unit impairment caused by reactive oxygen species (ROS) after cerebral ischemia-reperfusion.C57BL/6J mice underwent transient middle cerebral artery occlusion (tMCAO). The mice were randomly divided and administered intra-arterial RNPs injection (9 mg/kg, 7 μM/kg), edaravone (3 mg/kg, 17 μM/kg), or phosphate-buffered saline (control group). Survival rate and neurological score were evaluated 24 h post-injection. RNPs distribution was determined using immunofluorescence staining and blood–brain barrier (BBB) disruption using Evans blue extravasation assay. Effect of RNPs and edaravone on microglia polarization into microglia M1 and M2 was evaluated. We also determined multiple ROS-scavenging activities in brain homogenates of RNPs- and edaravone-treated animals using an electron spin resonance-based spin-trapping method.Compared with edaravone, RNPs significantly improved the survival rate and neurological deficit, inhibited BBB disruption and supported polarization of microglia into M2 microglia. RNPs were localized in endothelial cells, the perivascular space, neuronal cell cytoplasm, astrocytes, and microglia. Scavenging capacities of hydroxyl, alkoxyl, and peroxyl radicals were significantly higher in the RNPs-treated group.RNPs show promising results as a future neuroprotective nanomedicine approach for cerebral ischemia-reperfusion injury.

REVERSAL OF CISPLATIN-INDUCED MEMORY IMPAIRMENT BY GALLIC ACID IN EXPERIMENTAL RAT MODEL

Objective: The objective of the study was to evaluate the protective effect of gallic acid on cisplatin-induced memory impairment (MI) in the rat model.&#x0D; Methods: Five groups of Wistar albino rats (n=6) were employed and the duration of the study was 22 days, excluding the pre-treatment period. Animals were pretreated with gallic acid for a period of 5 days and continued daily (200 mg/kg) for 22 days. The cisplatin (3 mg/kg) was given once in a week for 3 consecutive weeks to induce MI, whereas donepezil was used as standard. The evaluation was done by a change in body weight, memory activity by Morris water maze (MWM), locomotor activity by actophotometer, antioxidant activity by thiobarbituric acid reactive substance (TBARS), glutathione (GSH), and estimation of acetylcholinesterase (AChE) activity in brain homogenate.&#x0D; Results: Administration of cisplatin has induced MI by increasing in escape latency time, decrease in time spent in the target quadrant in the MWM task and it was reversed by gallic acid treatment. Decreased locomotor activity by cisplatin was also increased by gallic acid when tested by actophotometer. Cisplatin administration has induced oxidative stress by increasing TBARS and decreasing GSH levels. Gallic acid due to its proven antioxidant activity reversed the effects of cisplatin. The AChE level was significantly increased in the control group, whereas treatment groups have shown a decrease in AChE level.&#x0D; Conclusion: Gallic acid may serve as a primary agent to treat the cognitive impairment and oxidative stress associated memory dysfunctions. However, more extensive studies are needed before utilization in the clinical trial.

The Rat (Rattus norvegicus) as a Model Object for Acute Organophosphate Poisoning. 4. M1-Cholinoreceptors and Esterase Activity in Brain Homogenates

The Rat (Rattus norvegicus) as a Model Object for Acute Organophosphate Poisoning. 4. M1-Cholinoreceptors and Esterase Activity in Brain Homogenates

Detection of Phospholipase C Activity in the Brain Homogenate from the Honeybee.

The honeybee is a model organism for evaluating complex behaviors and higher brain function, such as learning, memory, and division of labor. The mushroom body (MB) is a higher brain center proposed to be the neural substrate of complex honeybee behaviors. Although previous studies identified genes and proteins that are differentially expressed in the MBs and other brain regions, the activities of the proteins in each region are not yet fully understood. To reveal the functions of these proteins in the brain, pharmacologic analysis is a feasible approach, but it is first necessary to confirm that pharmacologic manipulations indeed alter the protein activity in these brain regions. We previously identified a higher expression of genes encoding phospholipase C (PLC) in the MBs than in other brain regions, and pharmacologically assessed the involvement of PLC in honeybee behavior. In that study, we biochemically tested two pharmacologic agents and confirmed that they decreased PLC activity in the MBs and other brain regions. Here, we present a detailed description of how to detect PLC activity in honeybee brain homogenate. In this assay system, homogenates derived from different brain regions are reacted with a synthetic fluorogenic substrate, and fluorescence resulting from PLC activity is quantified and compared between brain regions. We also describe our evaluation of the inhibitory effects of certain drugs on PLC activity using the same system. Although this system is likely affected by other endogenous fluorescence compounds and/or the absorbance of the assay components and tissues, the measurement of PLC activity using this system is safer and easier than that using the traditional assay, which requires radiolabeled substrates. The simple procedure and manipulations allow us to examine PLC activity in the brains and other tissues of honeybees involved in different social tasks.

Mefenamic Acid Attenuates Chronic Alcohol Induced Cognitive Impairment in Zebrafish: Possible Role of Cholinergic Pathway.

Based on the scientific evidence supporting the neuroinflammatory response contributes the cognitive impairment associated with chronic alcoholism and the neuroprotective actions of mefenamic acid with reversalof memory loss and brain inflammation in mice, this study was designed to evaluate the effect of mefenamic acid against chronic alcohol induced cognitive impairment in zebrafish model. Zebrafish were grouped and subjected to normal behavioral analysis in light-dark chamber for 10days. The preference to dark compartment was noted in zebrafish. Zebrafish were grouped and exposed to escalating doses of alcohol for 28days with and without mefenamic acid exposure (100 and 200µg/L) and subjected to a fear conditioning passive avoidance task from day 13 of 28. The cognitive evaluation was performed for 10days and the brain tissue was isolated to estimate acetylcholinesterase activity. In cognitive evaluation study, the normal zebrafish retained the memory of the learned task and avoided the dark. The alcohol exposed zebrafish showed impairment in retaining the memory of learned task. Mefenamic acid exposed zebrafish showed a significant protection against cognitive impairment caused by alcohol and retained the memory of learned task with a significant decrease in AChE activity in brain homogenate compared to alcohol exposed zebrafish. The results of this study suggest that the memory enhancing activity of mefenamic acid might be due to activation of cholinergic transmission that has protected neuroinflammatory and neurodegenerative conditions caused by alcohol.

The Antioxidant Cofactor Alpha-Lipoic Acid May Control Endogenous Formaldehyde Metabolism in Mammals.

The healthy human body contains small amounts of metabolic formaldehyde (FA) that mainly results from methanol oxidation by pectin methylesterase, which is active in a vegetable diet and in the gastrointestinal microbiome. With age, the ability to maintain a low level of FA decreases, which increases the risk of Alzheimer's disease and dementia. It has been shown that 1,2-dithiolane-3-pentanoic acid or alpha lipoic acid (ALA), a naturally occurring dithiol and antioxidant cofactor of mitochondrial α-ketoacid dehydrogenases, increases glutathione (GSH) content and FA metabolism by mitochondrial aldehyde dehydrogenase 2 (ALDH2) thus manifests a therapeutic potential beyond its antioxidant property. We suggested that ALA can contribute to a decrease in the FA content of mammals by acting on ALDH2 expression. To test this assumption, we administered ALA in mice in order to examine the effect on FA metabolism and collected blood samples for the measurement of FA. Our data revealed that ALA efficiently eliminated FA in mice. Without affecting the specific activity of FA-metabolizing enzymes (ADH1, ALDH2, and ADH5), ALA increased the GSH content in the brain and up-regulated the expression of the FA-metabolizing ALDH2 gene in the brain, particularly in the hippocampus, but did not impact its expression in the liver in vivo or in rat liver isolated from the rest of the body. After ALA administration in mice and in accordance with the increased content of brain ALDH2 mRNA, we detected increased ALDH2 activity in brain homogenates. We hypothesized that the beneficial effects of ALA on patients with Alzheimer's disease may be associated with accelerated ALDH2-mediated FA detoxification and clearance.

Carbonic anhydrase activation enhances object recognition memory in mice through phosphorylation of the extracellular signal-regulated kinase in the cortex and the hippocampus

Rats injected with by d-phenylalanine, a carbonic anhydrase (CA) activator, enhanced spatial learning, whereas rats given acetazolamide, a CA inhibitor, exhibited impairments of fear memory consolidation. However, the related mechanisms are unclear. We investigated if CAs are involved in a non-spatial recognition memory task assessed using the object recognition test (ORT). Systemic administration of acetazolamide to male CD1 mice caused amnesia in the ORT and reduced CA activity in brain homogenates, while treatment with d-phenylalanine enhanced memory and increased CA activity. We provided also the first evidence that d-phenylalanine administration rapidly activated extracellular signal-regulated kinase (ERK) pathways, a critical step for memory formation, in the cortex and the hippocampus, two brain areas involved in memory processing. Effects elicited by d-phenylalanine were completely blunted by co-administration of acetazolamide, but not of 1-N-(4-sulfamoylphenyl-ethyl)-2,4,6-trimethylpyridinium perchlorate (C18), a CA inhibitor that, differently from acetazolamide, does not cross the blood brain barrier. Our results strongly suggest that brain but not peripheral CAs activation potentiates memory as a result of ERK pathway enhanced activation.

Effects of Mimosa pudica L. leaves extract on anxiety, depression and memory.

The present study was carried out to investigate the neuropharmacological activities of ethyl acetate extract of Mimosa pudica (EAMP) leaves on anxiety, depression and memory in a mouse model. Anti-anxiety potential of EAMP was evaluated by elevated plus maze (EPM), light-dark box (LDB) and social interaction (SI) tests in mice.Anti-depressant potential of EAMP was evaluated by forced swimming (FST), tail suspension (TST), and open field tests (OFT). The behavioral findings were further corroborated with estimation of neurotransmitters and their metabolites from mouse brain homogenate. Effect on learning and memory was evaluated by EPM, passive avoidance (PA) tests. Further, it was confirmed with assessment of acetylcholinesterase and caspase-3 activity in brain homogenate. EAMP showed significant anti-anxiety activity by increasing the time spent in open arm of EPM, light box of LDB. Social interaction time was increased significantly (p<0.01) as compared to vehicle control. There was also significant reduction of immobility time in both FST and TST without any changes in locomotor activity in the OFT. Monoamine neurotransmitters (dopamine and norepinephrine) concentrations were increased significantly (p<0.01) after 4 weeks of treatment as compared to stress control and substantiated the anti-depressant activity. Step down latency was increased (p<0.01) in PA test and transfer latency was decreased (p<0.01) in EPM test of EAMP-treated mice. Acetylcholinesterase and caspase-3 activity was significantly (p<0.05) changed in mice treated with EAMP (200 and 400 mg/kg). The results revealed that EAMP has anti-anxiety, anti-depressant and memory enhancing activities that are mediated through multiple mechanisms.

Advanced tests for early and accurate diagnosis of Creutzfeldt-Jakob disease.

Early and accurate diagnosis of Creutzfeldt-Jakob disease (CJD) is a necessary to distinguish this untreatable disease from treatable rapidly progressive dementias, and to prevent iatrogenic transmission. Currently, definitive diagnosis of CJD requires detection of the abnormally folded, CJD-specific form of protease-resistant prion protein (PrP(CJD)) in brain tissue obtained postmortem or via biopsy; therefore, diagnosis of sporadic CJD in clinical practice is often challenging. Supporting investigations, including MRI, EEG and conventional analyses of cerebrospinal fluid (CSF) biomarkers, are helpful in the diagnostic work-up, but do not allow definitive diagnosis. Recently, novel ultrasensitive seeding assays, based on the amplified detection of PrP(CJD), have improved the diagnostic process; for example, real-time quaking-induced conversion (RT-QuIC) is a sensitive method to detect prion-seeding activity in brain homogenate from humans with any subtype of sporadic CJD. RT-QuIC can also be used for in vivo diagnosis of CJD: its diagnostic sensitivity in detecting PrP(CJD) in CSF samples is 96%, and its specificity is 100%. Recently, we provided evidence that RT-QuIC of olfactory mucosa brushings is a 97% sensitive and 100% specific for sporadic CJD. These assays provide a basis for definitive antemortem diagnosis of prion diseases and, in doing so, improve prospects for reducing the risk of prion transmission. Moreover, they can be used to evaluate outcome measures in therapeutic trials for these as yet untreatable infections.

Neuroprotective effect of ethanolic extract of Heliotropium indicum against transient global ischemia induced brain damage in rats

Heliotropium indicum is a whole herb used as traditional medicine mainly in India for the treatment of mental disorders and as brain tonic since many years. The present study is to investigate the protective effects of ethanolic extract of whole herb of Heliotropium indicum on cerebral ischemia/reperfusion induced brain damage in rats. Cerebral ischemia was induced by occluding bilateral common carotid arteries for 60 min followed by 3h of reperfusion. Ischemia/reperfusion-induced neuronal injury was assessed by measurement of brain infarct area, biochemical estimations and histopathological studies. Pretreatment of Heliotropium indicum extract (200, 280 and 400 mg/kg, p.o.) significantly reduced the lipid peroxidation, increased the total thiol content, Catalase and glutathione-S-transferase activity in brain homogenates. The decreased cerebral infarction area in Extract-treated groups and histopathological sections confirmed the above findings. These observations reveal that Heliotropium indicum is a neuroprotective agent and may prove to be useful adjunct in the treatment of stroke and neurological disorders.

Influence of resveratrol and dihydroquercetin inclusion into phospholipid nanopatricles on their bioavailability and specific activity

The effects of natural polyphenols, resveratrol (RES) and dihydroquercetin (DHQ), included in phospholipid nanoparticles, have been compared with free substances of RES and DHQ in in vitro and in vivo experiments. Preincubation of healthy donor plasma low density lipoproteins (LDL) with RES or DHQ included in phospholipid nanoparticles caused a more pronounced decrease in Cu2+ induced lipid oxidation compared with the free substances, and reduced the formation of lipid peroxides products. Bioavailabilities of RES and DHQ in phospholipid formulations after oral administration in rats were increased by 1.5-2 times. In an acute hypoxia model in mice prophylactic two-week administration of RES or DHQ phospholipid formulations resulted in 25% increase in survival and 1.5-fold increase in catalase activity in brain homogenates compared to free substances. Using the model of endothelial dysfunction in rats induced by L-NAME it was shown, that RES markedly attenuated the inhibition effect of L-NAME on NO synthesis. RES in phospholipid nanoparticles had the same action at a dose 10 times lower compared to free RES. Load test with resistance (clamping of the ascending aorta for 30 sec) showed that phospholipid formulation of RES possessed more pronounced protective effect due to the stimulation of endothelial NO-synthase.

Differential neuromodulatory role of NO in anxiety and seizures: an experimental study

Nitric oxide is a simple, ubiquitous, diatomic molecule with complex neuromodulatory functions. Anxiety and seizures are closely similar neurobehavioral disorders and are regulated by limbic system. The present study evaluated the regulatory roles of NO in these pathophysiological states in experimental models. In test for anxiety, aminophylline induced anxiogenic responses were assessed by the elevated plus maze (EPM) test, and a low dose of the drug (50 mg/kg) reduced both open arm entries and open arm time in rats. Pretreatment with the NO mimetic, L-arginine (500 and 1000 mg/kg) and melatonin (50 mg/kg) attenuated aminophylline induced anxiogenesis whereas the NO synthase inhibitors, L-NAME and 7-NI (30 mg/kg) aggravated the anxiogeneic response. Such aminophylline induced neurobehavioral suppression in the EPM activity was accompanied by increases in MDA levels and reductions in GSH and NOx activity in brain homogenates – changes which were reversed by L-arginine and melatonin pretreatments. In tests for seizures, aminophylline induced seizures and mortality at higher dose levels of the drug (300 mg/kg). Interestingly, such seizures and mortality in rats were antagonized by L-NAME and 7-NI pretreatments. On the other hand, L-arginine tended to potentiate seizures after sub-convulsive dose (100 mg/kg) of this methylxanthine. Aminophylline induced seizures were accompanied by greater elevations in brain MDA levels, whereas, GSH levels were consistently lowered. Unlike that seen during anxiety, NOx levels were increased in brain homogenates of these rats. The changes in oxidative stress markers were neutralized by NO synthase inhibitors. Synergistic anticonvulsant effect on aminophylline seizures was seen when L-NAME was combined with melatonin. These pharmacological and biochemical data indicate that aminophylline induced anxiety and seizures are differentially modulated by NO.

P105 S-propargyl-cysteine (ZYZ-802), a novel water-soluble donor of endogenous hydrogen sulfide, attenuates impairment against cerebral ischemia–reperfusion injury in rats

Objective Cerebrovascular diseases can do great harm to human health including high rate of mutilation and high mortality and so on. Our Present study was performed in vivo to verify the hydrogen sulfide donor S-propargyl-cysteine, also named ZYZ-802, protective effect in ischemia–reperfusion rats and explore its probable mechanisms as well. Methods 150 SD rats were randomly divided into 6 groups: sham-operate group; focal cerebral ischemia/reperfusion injury group which were subjected to one hour of ischemia followed by 48 h of reperfusion; drug treatment groups (focal cerebral ischemia/reperfusion injury and treatment with different doses of drugs). The behavioral tests were used to evaluate the damage to central nervous system. 2,3,5-triphenyl tetrazolium chloride (TTC) staining method, PET-CT was used to assess the percentage of brain infarct area. H&E staining method was used to observe the pathologic histological changes of hippocampus CA1 region. Cat walk and Rota-Rod Test was used to detect the behavior function. SOD and GSH activity in brain homogenate was determined. Results Compared with sham-operate group, rats with one hour of ischemia followed by 48 h of reperfusion exhibited severe neural injury as shown in significant increase of neurological scores (P Conclusion SPRC exhibits neuroprotective effects on cerebral ischemia/reperfusion injury in rats.

The Cyanine Dye NK-4 Improves Scopolamine-Induced Memory Impairments in Mice

The aim of this study is to evaluate the effects of NK-4, a kind of cyanine dye, on cholinergic memory deficits in mice. We examined whether NK-4 could reverse scopolamine-induced amnesia in mice since NK-4 displays a potent and selective inhibitory effect on acetylcholinesterase (AChE) in vitro. Intraperitoneal administration of NK-4 significantly reversed scopolamine-induced cognitive impairments in mice in the Y maze and the passive avoidance tests, and NK-4 also improved spatial learning ability in the Morris water maze test. Despite NK-4 displaying remarkable AChE inhibitory activity in vitro, we could not detect a significant reduction of AChE activity in brain homogenates of NK-4-treated mice. Although the mechanism through which NK-4 reverses cognitive impairments in scopolamine-treated mice remains unclear, these data suggest that NK-4 may have potential as a therapeutic agent for the treatment of dementia.

Protective Effect of Embelin from Embelia ribes Burm. Against Transient Global Ischemia-Induced Brain Damage in Rats

Embelia ribes is being used in Indian traditional herbal medicine for the treatment of mental disorders and as brain tonic. The present study was designed to investigate the protective effects of embelin from E. ribes on global ischemia/reperfusion-induced brain injury in rats. Transient global ischemia was induced by occluding bilateral common carotid arteries for 30min followed by 24-h reperfusion. Neurological functions were measured using sensorimotor tests. Ischemia/reperfusion-induced neuronal injury was assessed by cerebral infarct area, biochemical and histopathological examination. Pretreatment of embelin (25 and 50mg/kg, p.o.) significantly increased locomotor activity and hanging latency time and decreased beam walking latency when compared with ischemic control. The treatment also reduced significantly the lipid peroxidation and increased the total thiol content and glutathione-S-transferase activity in brain homogenates. The decreased cerebral infarction area in embelin-treated groups and histopathological observations confirmed the above findings. These observations suggested that embelin is a neuroprotective agent and may prove to be useful adjunct in the treatment of stroke.