Cognitive Deficits In Rats Research Articles

A study of the neuroprotective role of Punica granatum and rosuvastatin in scopolamine induced cognitive deficit in rats

Background: The present work has been planned to find out the effect of Punica granatum and Rosuvastatin on learning and memory in Scopolamine induced cognitive deficits in rats. Scopolamine being an anticholinergic agent is used fervently in experimental models for memory deficits and has been widely implicated for the screening of cognitive dysfunction. Punica granatum (Pomegranate) has shown to suppress tumor neuronal cells, hence it can be a potential agent in providing neuroprotection for preventing the development and progression of AD. There are conflicting reports indicating the role of statins as a neuroprotective agent. This contradiction led us to investigate the effect of the role of Rosuvastatin on memory. The test agents were further compared to the standard treatment group acetylcholinesterase inhibitor i.e. Donepezil.Methods: Male wistar rats 150-200gms were divided into 4 groups of 6 rats each. Amnesia was induced by scopolamine 3mg/kg ip at day 5 in all the groups. Group1 (amnesic control) given distilled water; group 2(standard treatment i.e. Donepezil 0.5mg/kg orally); group 3(Rosuvastatin group10mg/kg orally); group 4 (Punica granatum juice 500mg/kg orally) The methods for validating cognition deficits were behavioural tests like Cook’s pole response and Passive Avoidance response.Results: It was evident from our research that the Punica granatum juice and Rosuvastatin effectively antagonized the scopolamine induced cognitive impairment in the paradigms studied. The neuroprotective effect of Punica granatum juice was better as compared to the Rosuvastatin group and the effects of the former were comparable with the standard treatment i.e. Donepezil group.Conclusions: Punica granatum has a remarkable protective role in memory function, learning, cognition and behavior in Scopolamine induced amnesia model of Alzheimer’s disease which was better than Rosuvastatin treatment.

Allicin attenuates tunicamycin-induced cognitive deficits in rats via its synaptic plasticity regulatory activity.

Objective(s):To illuminate the functional effects of allicin on rats with cognitive deficits induced by tunicamycin (TM) and the molecular mechanism of this process.Materials and Methods:200–250 g male SD rats were divided into three groups at random: control group (n=12), TM group (5 μl, 50 μM, ICV, n=12), and allicin treatment group (180 mg/kg/d with chow diet, n=12). After 16 weeks of allicin treatment, the learning ability and memory were tested using novel object recognition (NOR) testing on rats with 72 hr TM treatment (5 μl, 50 μM, ICV); meanwhile, the variation of field excitatory postsynaptic potential (fEPSP) in the Schaffer Collateral (SC)-CA1 synapse was detected by extracellular electrophysiological recordings and the morphology of dendritic spine was observed by Golgi staining as well as detecting several synaptic plasticity-related proteins by Western blot.Results:The density of dendritic spine was increased significantly in allicin-treated groups and the correspondence slope of fEPSP in TM-induced cognitive deficits group was enhanced and expression of synaptophysin and glutamate receptor-1(GluR1) in hippocampal neurons was up-regulated.Conclusion:The results indicate that allicin plays an important role in synaptic plasticity regulation. These finding showed that allicin could be used as a pharmacologic treatment in TM-induced cognitive deficits.

Zeaxanthin improves diabetes-induced cognitive deficit in rats through activiting PI3K/AKT signaling pathway

Published studies have shown that cognitive deficit is a characteristic manifestation of neurodegenerative disease in diabetes. However, there is no effective prevention and treatment for this diabetes-associated behavior disorder. In the present study, we attempted to elucidate the effect of zeaxanthin on cognitive deficit and the change in the hippocampus correlated with cognitive decline in diabetic rats. Diabetic rats in this study were induced by high-fat diet and low-dose streptozocin (STZ), cognitive ability of rats were evaluated use morris water maze (MWM) and morphology change in hippocampus was assessed by cresyl violet stain. Moreover, we detected the expression of phosphorylated serine/threonine kinase (p-AKT) and Cleaved caspase-3, and the activity of nuclear factor-κB (NF-κB) use western-blot (WB).Results displayed that supplementation with zeaxanthin reduce blood glucose, improve cognitive deficit, survive neural cell, increase p-AKT level, inhibit Cleaved caspase-3 level and NF-κB nuclear transcription in hippocampus. This study demonstrated that zeaxanthin ameliorate diabetes-related cognitive deficit may by means of protecting neural cell from hyperglycemia involved in AKT/NF-κB signaling pathway. This study may provide a potential therapeutic approach for the prevention of diabetes- associated cognitive deficit.

Changes in the expression of metabotropic glutamate receptor 5 (mGluR5) in a ketamine-based animal model of schizophrenia

It has been shown that the metabotropic glutamate receptor subtype 5 (mGluR5) is functionally associated with the NMDA subtype of the glutamate receptor family (NMDA receptors). These two receptors colocalize in brain regions associated with schizophrenia. Although the role of the NMDA receptor in cognitive and negative symptoms of schizophrenia is well studied, information about the role of mGluR5 receptors in schizophrenia is sparse. In our work, we show that subchronic administration of ketamine, a well-studied, non-competitive antagonist of NMDA receptors, caused cognitive deficits in rats as shown by testing novel object recognition (NOR). Moreover, we reveal that subchronic administration of ketamine increased the mRNA and protein expression levels of mGluR5 receptors in regions CA1 and CA3 of the dorsal part of the hippocampus, both of which are strongly associated with the formation of visual memory, which is tested via NOR. We postulate that increased expression of mGluR5 receptors in the dorsal part of the hippocampus may reflect compensatory changes to imbalanced glutamate neurotransmission associated with the hypoactivation of NMDA receptors.

Modulating Oxidative Stress Relieves Stress-Induced Behavioral and Cognitive Impairments in Rats.

Background:Persistent psychological stress often leads to anxiety disorders and depression. Benzodiazepines and selective serotonin reuptake inhibitors are popular treatment options but have limited efficacy, supporting the need for alternative treatment. Based on our recent preclinical work suggesting a causal link between neurobehavioral deficits and elevated oxidative stress, we hypothesized that interventions that mitigate oxidative stress can attenuate/overcome neurobehavioral deficits.Methods:Here, we employed the rat social defeat model of psychological stress to determine whether increasing antioxidant levels using grape powder would prevent and/or reverse social defeat-induced behavioral and cognitive deficits. Furthermore, a hippocampal-derived HT22 cell culture model of oxidative stress was employed to identify the individual beneficial constituent(s) of grape powder and the underlying mechanism(s) of action.Results:Grape powder treatment prevented and reversed social defeat-induced behavioral and cognitive deficits and also decreased social defeat-induced increase in plasma corticosterone and 8-isoprostane (systemic and oxidative stress markers, respectively). And grape powder treatment replenished social defeat-induced depleted pool of key antioxidant enzymes glyoxalase-1, glutathione reducatse-1, and superoxide dismutase. Grape powder constituents, quercetin and resveratrol, were most effective in preventing oxidative stress-induced decreased cellular antioxidant capacity. Grape powder protected oxidative stress-induced cell death by preventing calcium influx, mitochondrial dysfunction, and release of cytochrome c.Conclusions:Grape powder treatment by increasing antioxidant pool and preventing cell damage and death prevented and reversed social defeat-induced behavioral and cognitive deficits in rats. Quercetin and resveratrol are the major contributors towards beneficial effects of grape powder.

Resveratrol reversed chronic restraint stress-induced impaired cognitive function in rats.

Chronic stress occurs in everyday life, and often results in memory impairments and depressive symptoms. Resveratrol is a natural polyphenol that possesses numerous biological properties, including potent antidepressant‑like effects. The present study aimed to examine the effects of resveratrol treatment on chronic restraint stress (CRS)‑induced cognitive impairment and to explore the underlying molecular mechanisms. Male Wistar rats were exposed to CRS for 21days in order to induce depressive‑like behavior. The results demonstrated that CRS (6h/day, 21days) was able to induce cognitive deficits in rats, as evidenced by Morris water maze and novel object recognition tests. In addition, CRS exposure significantly decreased the mRNA and protein expression levels of hippocampal brain‑derived neurotrophic factor (BDNF) in the rats. Conversely, chronic treatment with resveratrol (80mg/kg, i.p.; 21days) significantly prevented the behavioral and biochemical alterations induced by CRS. The effects of resveratrol were nearly identical to those observed with fluoxetine treatment. In conclusion, the present study demonstrated that resveratrol may be a potential therapeutic agent for the treatment of chronic stress‑induced cognitive impairments, and its underlying molecular mechanism may be associated with the increased levels of hippocampal BDNF.

β-Caryophyllene/Hydroxypropyl-β-Cyclodextrin Inclusion Complex Improves Cognitive Deficits in Rats with Vascular Dementia through the Cannabinoid Receptor Type 2 -Mediated Pathway.

This work was conducted to prepare β-caryophyllene-hydroxypropyl-β-cyclodextrin inclusion complex (HPβCD/BCP) and investigate its effects and mechanisms on cognitive deficits in vascular dementia (VD) rats. First, HPβCD/BCP was prepared, optimized, characterized, and evaluated. HPβCD/BCP and AM630 were then administered to VD rats to upregulate and downregulate the cannabinoid receptor type 2 (CB2). Results showed that HPβCD/BCP can significantly increase the bioavailability of BCP. Through the Morris water maze test, HPβCD/BCP can attenuate learning and memory deficits in rats. Cerebral blood flow (CBF) monitoring results indicated that HPβCD/BCP can promote the recovery of CBF. Moreover, molecular biology experiments showed that HPβCD/BCP can increase the expression levels of CB2 in brain tissues, particularly the hippocampus and white matter tissues, as well as the expression levels of PI3K and Akt. Overall, the findings demonstrated the protective effects of HPβCD/BCP against cognitive deficits induced by chronic cerebral ischemia and suggested the potential of HPβCD/BCP in the therapy of vascular dementia in the future.

RESVERATROL ATTENUATES INSULIN RESISTANCE–ASSOCIATED COGNITIVE DEFICITS IN RATS

RESVERATROL ATTENUATES INSULIN RESISTANCE–ASSOCIATED COGNITIVE DEFICITS IN RATS

Icariside II, a novel phosphodiesterase-5 inhibitor, attenuates streptozotocin-induced cognitive deficits in rats

Beta-amyloid (Aβ) deposition and neuroinflammation are involved in Alzheimer’s disease (AD)-type neurodegeneration with cognitive deficits. Phosphodiesterase-5 (PDE5) inhibitors have recently been studied as a potential target for cognitive enhancement by reducing inflammatory responses and Aβ levels. The present study was designed to investigate the effects of icariside II (ICS II), a novel PDE5 inhibitor derived from the traditional Chinese herb Epimedium brevicornum, on cognitive deficits, Aβ levels and neuroinflammation induced by intracerebroventricular-streptozotocin (ICV-STZ) in rats. The results demonstrated that ICV-STZ exhibited cognitive deficits and neuronal morphological damage, along with Aβ increase and neuroinflammation in the rat hippocampus. ICS II improved cognitive deficits, attenuated neuronal death, and decreased the levels of Aβ1-40, Aβ1-42 and PDE5 in the hippocampus of STZ rats. Furthermore, administration of ICS II at the dose of 10mg/kg for 21days significantly suppressed the expression of beta-amyloid precursor protein (APP), beta-secretase1 (BACE1) and increased the expressions of neprilysin (NEP) together with inhibited interleukin-1β (IL-1β), tumor necrosis factor (TNF)-α, cyclooxygenase-2 (COX-2) and transforming growth factor-β1 (TGF-β1) levels. In addition, ICS II exerted a beneficial effect on inhibition of IκB-α degradation and NF-κB activation induced by STZ. Taken together, the present study demonstrated that ICS II was a potential therapeutic agent for AD treatment.

Fermented Saccharina japonica (Phaeophyta) improves neuritogenic activity and TMT-induced cognitive deficits in rats

(FSJ) on the memory deficient rats, which were induced by trimethyltin chloride (TMT), was investigated by assessing the Morris water maze test and by performing choline acetyltransferase (ChAT), cAMP response element binding protein (CREB), and brain derived neuro -trophic factor (BDNF) immunohistochemistry. The neurite outgrowth of Neuro2a cells was assessed in order to examine the underlying mechanisms of the memory enhancing effects of FSJ. Treatment with FSJ tended to shorten the latency to find the platform in the acquisition test of the Morris water maze at the second and fourth day compared to the control group. In the probe trial, the FSJ treated group increased time spent in the target quadrant, compared to that of the con-trol group. Consistent with the behavioral data, these treatments recovered the loss of ChAT, CREB, and BDNF immune-positive neurons in the hippocampus produced by TMT. Treatment with FSJ markedly stimulated neurite outgrowth of the Neuro2a cells as compared to that of the controls. These findings demonstrate that FSJ may be useful for improving the cognitive function via regulation of neurotrophic marker enzyme activity.

Docosahexaenoic Acid Protects against 1-Bromopropane Induced Cognitive Deficits in Rats involving in GSK-3β Activation and Oxidative Stress Inhibition

A number of organic solvent are known to be neurotoxic substance, which can cause neurotoxicological effects in humans. 1-Bromopropane (1-BP) is an alternative to ozone-depleting solvent that widely used in industrial production. Occupational exposure to 1-BP becomes a major health concern due to its neurotoxicity displayed in animals and humans. Docosahexaenoic acid (DHA), long chain n-3 polyunsaturated fatty acids (PUFA) and the main component of fish oil, is essential for normal neurological development and displays potent neuroprotective capacity. Here we investigate the protective effects and underlying mechanisms of DHA against 1-BP-induced deficits of spatial learning and memory ability in rats. Cognitive performance was assessed by Morris Water Maze test (MWM). Neuronal injury was determined by Nissl staining and TUNEL staining. The apoptosis-related proteins, including cleaved caspase-3, Bcl-2 and Bax, and proteins modified by 4-hydroxy-2-nonenal (4-HNE) or acrolein, in the brain were determined by Western blot. The inactive glycogen synthase kinase-3β (GSK-3β) in the brain of rats was also detected by specific antibody. Exposure to 1-BP resulted in learning deficits and memory loss of rats, neuronal apoptosis in the hippocampus cornu ammonis 3 (CA3) and prefrontal cortex, accompanied with significant GSK-3β inhibition by phosphorylation. Importantly, we found that pre-treatment with DHA significantly improved MWM performances of rats intoxicated with 1-BP, as well as the abrogation of neuron loss, alleviation of redox unbalance and GSK-3β activation in the brain. Our findings suggested that DHA supplementation would be a promising intervention for the central neurotoxicity of 1-BP, which might be correlated with oxidative stress and GSK-3β inhibition.

Effects of novel tacrine-related cholinesterase inhibitors in the reversal of 3-quinuclidinyl benzilate-induced cognitive deficit in rats—Is there a potential for Alzheimer’s disease treatment?

Inhibitors of cholinesterase are important drugs for therapy of Alzheimer’s disease and the search for new modifications is extensive, including dual inhibitors or multi-target hybrid compounds. The aim of the present study was a preliminary evaluation of pro-cognitive effects of newly-developed 7-MEOTA-donepezil like hybrids (compounds no. 1 and 2) and N-alkylated tacrine derivatives (compounds no. 3 and 4) using an animal model of pharmacologically-induced cognitive deficit.Male Wistar rats were subjected to tests of learning and memory in a water maze and step-through passive avoidance task. Cognitive impairment was induced by 3-quinuclidinyl benzilate (QNB, 2mgkg−1), administered intraperitoneally 1h before training sessions. Cholinesterase inhibitors were administered as a single therapeutic dose following the QNB at 30min at the following dose rates; 1 (25.6mgkg−1), 2 (12.3mgkg−1), 3 (5.7mgkg−1), 4 (5.2mgkg−1).The decrease in total path within the 10-swim session (water maze), the preference for target quadrant (water maze) and the entrance latency (passive avoidance) were taken as indicators of learning ability in rats. The effects of novel compounds were compared to that of standards tacrine (5.2mgkg−1) and donepezil (2.65mgkg−1).QNB significantly impaired spatial navigation as well as fear learning. Generally, the performance of rats was improved when treated with novel inhibitors and this effect reached efficiency of standard donepezil at selected doses. There was a significant improvement in the groups treated with compounds 2 and 3 in all behavioral tasks. The rest of the novel compounds succeed in the passive avoidance test. In summary, the potential of novel inhibitors (especially compounds 2 and 3) was proved and further detailed evaluation of these compounds as potential drugs for Alzheimer’s disease treatment is proposed.

Fructus mume extracts alleviate cognitive impairments in 5XFAD transgenic mice.

Background Fructus mume (F. mume) has been used as a traditional treatment for ulcer, cough, and digestive problems for many years in Asian countries. Previous studies have demonstrated that F. mume extracts alleviate cognitive deficits in rats with chronic cerebral hypoperfusion and in mice with scopolamine treatments. The present experiment was conducted to examine the effects of F. mume on cognitive impairments in 5XFAD transgenic mice with five familial Alzheimer’s disease (AD) mutations.Methods F. mume was administered daily to 5XFAD mice at 12 weeks of age and continued for 90 days. Cognitive function was evaluated using a spatial memory version of the Morris water maze task, the object/location novelty recognition test, and contextual fear conditioning at 24 weeks of age. To elucidate the possible mechanisms underlying the memory improving effects of F. mume in 5XFAD mice, we examined alterations in hippocampal cholinergic function.ResultsVehicle-treated 5XFAD mice exhibited hippocampus-dependent memory impairments compared with non-transgenic littermates, which was reversed in F. mume-treated 5XFAD mice. In addition, reduced hippocampal choline acetyltransferase (ChAT) levels in 5XFAD mice were reversed by F. mume treatment, indicating that F. mume enhances the effects of cholinergic neuronal function.Conclusions F. mume may have therapeutic effects on cognitive impairments in AD.

Delayed neuroprotection against cerebral ischemia reperfusion injury: putative role of BDNF and GSK-3β

Aim: Numerous studies have demonstrated the possible neuroprotective role of lithium treatment against neurological disorders. However, the role of lithium in delayed phase of neuronal death against focal ischemia has not been explored. Therefore, the present study was designed to investigate the effect and molecular mechanisms of post-lithium treatment against cerebral ischemic reperfusion (I/R) injury and associated cognitive deficits in rats. Methods: I/R injury was induced by right middle cerebral artery occlusion and lithium (40 and 60 mg/kg) were given intraperitoneally, 24 h after the insult and continued for 1 week with 24-h interval. Using Lasser Doppler, cerebral blood flow was monitored before, during and after MCAO induction. Besides behavioral, biochemical, and histological evaluation, levels of tumor necrosis factor alpha (TNF-α) and brain-derived neurotrophic factor (BDNF) were also estimated. Results: I/R injury resulted in significant elevation of neurological deficits, oxidative stress, neuroinflammation, and cognitive impairments. We found that lithium injection, 24 h after I/R-injury continued for 1 week, dose dependently prevented behavioral abnormality and cognitive impairments. Moreover, lithium attenuated the levels of oxidative stress and pro-inflammatory-cytokines TNF-α level. Further, lithium treatments significantly reduced neuronal damage and augmented healthy neuronal count and improved neuronal density in hippocampus. These neuroprotective effects of delayed lithium treatment were associated with upregulation of neurotrophic factor BDNF levels. Conclusion: Delayed lithium treatment provides neuroprotection against cerebral I/R injury and associated cognitive deficits by upregulating BDNF expression that opens a new avenue to treat I/R injury even after active cell death.

Docosahexaenoic Acid-Phosphatidylcholine Improves Cognitive Deficits in an Aβ23-35-Induced Alzheimer's Disease Rat Model.

Both Docosahexaenoic acid (DHA) and Phosphatidylcholine (PC) have been shown to halt the pathogenesis of Alzheimer disease (AD) and vascular dementia. This study aimed to investigate the role of DHA-containing PC (DHA-PC) in the improvement of Aβ25-35-induced cognitive deficits in rats. Aβ25-35-induced AD rats were treated for 30 days with DHA-PC, which was extracted from Sthenoteuthis oualaniensis spawns. Cognitive improvement of the AD rats was detected using the Morris water maze (MWM). The results demonstrated that DHA-PC could improve the learning and memory abilities of AD rats in a dose-dependent pattern. Further analyses showed that expression of phosphorylated tau decreased, and the neuronal morphology recovered in brains of DHA-PC-treated AD rats, as compared with mock-treated AD rats. In addition, DHAPC treatment increased the activity of GSH-Px and SOD in the cortex and hippocampus of AD rats. Taken together, these data suggest that DHA-PC is able to improve the cognitive deficits in AD rats, probably through decreasing the phosphorylation of tau in the cortex and hippocampus CA1 area, and increasing the GSH-Px and SOD activities in the brain of AD rats.

Dietary Cholesterol Protects Anesthesia-Induced Cognitive Deficits in Wistar Rats

Purpose : To evaluate the effect of cholesterol on frequent exposure of anesthesia-induced cognitive impairment in wistar rats. Methods : Healthy wistar rats were divided in two groups, the gp I rats fed with regular diet and gp II with cholesterol diet. These groups were further divided into sub-groups as gp Ia (n=8) and gp IIa (n=8). These sub-groups received weekly exposure of anesthesia for 6 weeks. Animals were anesthetized by subcutaneous sodium thiopental injection. Cortical nerve growth factor levels were measured by indirect sandwich enzyme-linked immunosorbent assay (ELISA) while total protein was determined by Bradford protein assay. Results : Group IIa (cholesterol-fed animals) as well as Group IIb (cholesterol-fed followed by anesthesia) showed significant increase in body weight (25 to 50 g, p < 0.03), but no such increase was observed in other groups. However, group Ib showed a significant (43.07 %, p ˂ 0.001) decrease in the level of nerve growth factor when compared with group Ia. Moreover, significantly decreased cytokines IL-1β levels (59.09 %, p < 0.005) and TNF-α (20 %, p < 0.025) of group IIa more effectively than in group Ia rats. Microglial marker showed significantly increase (16.66 %, p < 0.025) in cholesterol diet group. Overall increase in leakage of anti-rat IgG (blood brain barrier marker) was found in both groups (IIa and IIb). Conclusion : The results suggest that dietary cholesterol protects or neutralizes anesthesia-induced cognitive deficits in rats. Keywords : Cognitive deficit, Cholesterol diet, Blood-brain barrier, Nerve growth factor, Inflammation marker, Microglial marker, Cytokines

Radix Angelica Sinensis Promotes Synaptic Plasticity During Cognitive Recovery in Chronically Stressed Rats.

The accumulation of chronic stress is associated with cognitive dysfunction. Radix Angelica Sinensis (RAS) has been shown to have neuroprotective potential for treating Alzheimer's disease and vascular dementia. However, the impact of RAS on cognitive impairment induced by chronic stress has not been studied. In the present study, RAS significantly alleviated cognitive deficits in rats subjected to chronic restraint stress. This neuroprotective effect was associated with enhancement of synaptic efficacy by improving field excitatory postsynaptic potential amplitudes, alleviating adverse alterations in the structure of synapses and neurons in the hippocampus, and increasing the levels of brain-derived neurotrophic factor, microtubule-associated protein-2, and synaptophysin in the hippocampus. These findings provide initial evidence for the therapeutic potential of RAS for the treatment of neuronal deterioration caused by chronic stress.

Resveratrol attenuates insulin resistance-induced cognitive deficits in rats

Resveratrol attenuates insulin resistance-induced cognitive deficits in rats

Impairment of cognitive function by chemotherapy: association with the disruption of phase-locking and synchronization in anterior cingulate cortex.

BackgroundPatients following prolonged cancer chemotherapy are at high risk of emotional and cognitive deficits. Research indicates that the brain neuronal temporal coding and synaptic long-term potentiation (LTP) are critical in memory and perception. We studied the effects of cisplatin on induction of LTP in the basolateral amygdala (BLA)-anterior cingulate cortex (ACC) pathway, characterized the coordination of spike timing with local theta oscillation, and identified synchrony in the BLA-ACC network integrity.ResultsIn the study presented, the impacts of cisplatin on emotional and cognitive functions were investigated by elevated plus-maze test, Morris water maze test, and rat Iowa gambling task (RGT). Electrophysiological recordings were conducted to study long-term potentiation. Simultaneous recordings from multi-electrodes were performed to characterize the neural spike firing and ongoing theta oscillation of local field potential (LFP), and to clarify the synchronization of large scale of theta oscillation in the BLA-ACC pathway. Cisplatin-treated rats demonstrated anxiety- like behavior, exhibited impaired spatial reference memory. RGT showed decrease of the percentage of good decision-makers, and increase in the percentage of maladaptive behavior (delay-good decision-makers plus poor decision-makers). Cisplatin suppressed the LTP, and disrupted the phase-locking of ACC single neural firings to the ongoing theta oscillation; further, cisplatin interrupted the synchrony in the BLA-ACC pathway.ConclusionsWe provide the first direct evidence that the cisplatin interrupts theta-frequency phase-locking of ACC neurons. The block of LTP and disruption of synchronized theta oscillations in the BLA-ACC pathway are associated with emotional and cognitive deficits in rats, following cancer chemotherapy.

NSC23766, A Specific Inhibitor of Rac1 GTPase, Attenuated Delayed Neuronal Cell Death and Cognitive Deficit in Rats with Cardiac Arrest

Background: Recent studies have implicated that inhibition of Rac1 GTPase protects the neuronal cells from cerebral ischemic injury, although its effects in a cardiac arrest (CA) global cerebral ischemia model have not been examined. The purpose of the current study was to examine the regulatory and functional role of the Rac1 in reactive oxygen species (ROS) generation and neuronal cell death/cognitive dysfunction following global cerebral ischemia in the rats.Methods: A rat model of CA was established by the delivery of alternating current between the esophagus and chest wall to induce ventricular fibrillation. Rats were randomly assigned to the following groups: 1) sham group, 2) CA group, 3) CA + NSC23766 group (NSC), and 4) CA + saline group. NSC23766 (50 μg, intracerebroventricular injection) or isotonic saline was administered 15 minutes before CA. Neurological function of rats after reperfusion was scored using the neurological deficit score evaluation method. Survival rates, neuronal counts, Rac1 activation, mitochondrial ROS formation and expression of thioredoxin2 (Trx2) and peroxiredoxin3 (Prx3) in the hippocampal CA1 region were assessed after reperfusion. Morris water maze task was used to quantify spatial learning and memory deficits after reperfusion.Results: NSC23766, the specific inhibitor of Rac1 GTPase, significantly attenuated neuronal damage and reduced the spatial learning and memory deficits associated with global cerebral ischemia induced by CA (P<0.05). Furthermore, NSC23766 exerted its neuroprotective function by decreasing the ROS generation (P<0.05). However, there was no significant difference of Trx2 and Prx3 protein expression in hippocampal CA1 region between the CA group and NSC group after 1 day reperfusion (P<0.05). Conclusions: Our findings suggested that NSC23766 not only ameliorated post-ischemic neuronal cell death, but also improved learning and memory deficits in a cerebral ischemia animal model through down-regulating ROS generation. Citation: Juan Liao, Chang Xu, Chang Liu, Na Wang, Guo-Qing Huang, Chang-Sheng Huang, et al. NSC23766, a specific inhibitor of Rac1 GTPase, attenuated delayed neuronal cell death and cognitive deficit in rats with cardiac arrest. J Anesth Perioper Med 2015; 2: 136-45. doi: 10.24015/JAPM.2015.0019This is an open-access article, published by Evidence Based Communications (EBC). This work is licensed under the Creative Commons Attribution 4.0 International License, which permits unrestricted use, distribution, and reproduction in any medium or format for any lawful purpose. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.