Global Cerebral Ischemia In Rats Research Articles

Burst-Suppression EEG Reactivity to Photic Stimulation-A Translational Biomarker in Hypoxic-Ischemic Brain Injury.

The reactivity of an electroencephalogram (EEG) to external stimuli is impaired in comatose patients showing burst-suppression (BS) patterns following hypoxic-ischemic brain injury (HIBI). We explored the reactivity of BS induced by isoflurane in rat models of HIBI and controls using intermittent photic stimulation (IPS) delivered to one eye. The relative time spent in suppression referred to as the suppression ratio (SR) was measured on the contralateral fronto-occipital cortical EEG channel. The BS reactivity (BSR) was defined as the decrease in the SR during IPS from the baseline before stimulation (SRPRE). We found that BSR increased with SRPRE. To standardize by anesthetic depth, we derived the BSR index (BSRi) as BSR divided by SRPRE. We found that the BSRi was decreased at 3 days after transient global cerebral ischemia in rats, which is a model of brain injury after cardiac arrest. The BSRi was also reduced 2 months after experimental perinatal asphyxia in rats, a model of birth asphyxia, which is a frequent neonatal complication in humans. Furthermore, Oxytocin attenuated BSRi impairment, consistent with a neuroprotective effect in this model. Our data suggest that the BSRi is a promising translational marker in HIBI which should be considered in future neuroprotection studies.

Tangeretin confers neuroprotection, cognitive and memory enhancement in global cerebral ischemia in rats.

Global cerebral ischemia is commonly associated with neurological deficits, including cognitive and memory impairments. The present study aims to investigate the neuroprotective, cognitive, and memory enhancement effects of Tangeretin, a flavonoid against global cerebral ischemia in rats. Bilateral common carotid artery occlusion (BCCAO) and reperfusion injury method was used to induce global cerebral ischemia in rats. Motor, cognitive, and memory functions were evaluated using rotarod, grip strength, Y-maze, and Morris water maze. Further, acetylcholine esterase (AchE) enzyme activity, acetylcholine (Ach), oxidative stress markers (ROS, SOD, MDA, and CAT), inflammation (IL-6 and TNF-α), and apoptotic markers (cytochrome C, caspase 9, and caspase 3) in BCCAO rats were measured following Tangeretin (5,10, and 20mg/kg, oral) treatment. Our findings show that Tangeretin treatment significantly improved cognition and memory by enhancing Ach levels through the amelioration of AchE enzyme activity in BCCAO rats. Moreover, Tangeretin exhibited neuroprotective effects through the mitigation of oxidative stress, inflammation, and apoptosis in the BCCAO rats. In summary, the current findings suggested that Tangeretin exhibited neuroprotection, cognitive and memory enhancement against global cerebral ischemia.

Blood-Brain Barrier Rescue by Roflumilast After Transient Global Cerebral Ischemia in Rats.

Phosphodiesterase 4 inhibitors (PDE4-I), which selectively increase cyclic adenosine monophosphate (cAMP) levels, have shown neuroprotective effects after several neurological injuries inducing blood-brain barrier (BBB) damage including local/focal cerebral ischemia. The present investigated whether roflumilast confers BBB neuroprotection in the hippocampus after transient global cerebral ischemia (TGCI) in rats. TGCI resulted in whole BBB disruption as measured by the increase of Evans blue (EB) and IgG extravasation, neurodegeneration, and downregulation of claudin-5 and endothelial nitric oxide synthase (eNOS) levels in the CA1 hippocampal subfield of ischemic rats. Roflumilast attenuated BBB disruption and restored the levels of eNOS in the CA1 hippocampal area. Moreover, roflumilast increased the levels of B2 cell lymphoma (BcL-2) and neuron-glial antigen-2 (NG2) in the CA1 subfield after global ischemia in rats. The protective effects of roflumilast against TGCI-induced BBB breakdown might involve preservation of BBB integrity, vascularization and angiogenesis, and myelin repair.

The Regulation of Autophagy by p38 MAPK-PPARγ Signaling During the Brain Ischemic Tolerance Induced by Cerebral Ischemic Preconditioning.

Several studies indicated that autophagy activation participates in brain ischemic tolerance (BIT) induced by cerebral ischemic preconditioning (CIP). However, the mechanism of autophagy activation during the process still remains unclear. The present study aimed to evaluate the role of p38 MAPK-peroxisome proliferator-activated receptor γ (PPARγ) signaling cascade in autophagy during the CIP-induced BIT. The results shown that, initially, autophagy activation was observed after CIP in the model of global cerebral ischemia in rats, as was indicated by the upregulation of Beclin 1 expression, an increase in LC3-II/LC3-I ratio, the enhanced LC3 immunofluorescence, and a rise in the number of autophagosomes in the neurons of the hippocampal CA1 area. Besides, the inhibitor of autophagy 3-methyladenine obliterated the neuroprotection induced by CIP. Furthermore, the upregulation of p-p38 MAPK and PPARγ expressions was earlier than autophagy activation after CIP. In addition, pretreatment with SB203580 (the inhibitor of p38 MAPK) reversed CIP-induced PPARγ upregulation, autophagy activation, and neuroprotection. Pretreatment with GW9662 (the inhibitor of PPARγ) reversed autophagy activation and neuroprotection, while it had no effect on p-p38 MAPK upregulation induced by CIP. These data suggested that the p38 MAPK-PPARγ signaling pathway participates in autophagy activation during the induction of BIT by CIP.

Proteasome and Neuroprotective Effect of Hyperbaric Oxygen Preconditioning in Experimental Global Cerebral Ischemia in Rats

ObjectivesWe investigated the involvement of the proteasome in the mechanism of preconditioning with hyperbaric oxygen (HBO-PC).MethodsThe experiments were performed on male Wistar rats subjected to a transient global cerebral ischemia of 5 min duration (2-vessel occlusion model) and preconditioned or not with HBO for 5 preceding days (1 h HBO at 2.5 atmosphere absolute [ATA] daily). In subgroups of preconditioned rats, the proteasome inhibitor MG132 was administered 30 min prior to each preconditioning session. Twenty-four hours and 7 days post-ischemia, after neurobehavioral assessment, the brains were collected and evaluated for morphological changes and quantitative immunohistochemistry of cell markers and apoptosis-related proteins.ResultsWe observed reduced damage of CA1 pyramidal cells in the HBO preconditioned group only at 7 days post-ischemia. However, both at early (24 h) and later (7 days) time points, HBO-PC enhanced the tissue expression of 20S core particle of the proteasome and of the nestin, diminished astroglial reactivity, and reduced p53, rabbit anti-p53 upregulated modulator of apoptosis (PUMA), and rabbit anti-B cell lymphoma-2 interacting mediator of cell death (Bim) expressions in the hippocampus and cerebral cortex. HBO-PC also improved T-maze performance at 7 days. Proteasome inhibitor abolished the beneficial effects of HBO-PC on post-ischemic neuronal injury and functional impairment and reduced the ischemic alterations in the expression of investigated proteins.SignificancePreconditioning with hyperbaric oxygen-induced brain protection against severe ischemic brain insult appears to involve the proteasome, which can be linked to a depletion of apoptotic proteins and improved regenerative potential.

Evaluation of the effect of the PIR-12 compound on anxiety and locomotor activity in experimental global cerebral ischemia in rats

A study was carried out to assess the effect of a new pyrimidine derivative (PIR-12 50 mg/kg) on anxiety and locomotor activity under conditions of global cerebral ischemia in rats. It was confirmed that the investigated compound PIR-12 helps to reduce the degree of anxiety, which is manifested in an increase in the indicators "Time at the central site" and "Time in the open arms of the maze" in 3,2 (p<0,05) and 3,1% (p<0,05). "Time in the closed arms of the labyrinth" and "the number of grooming acts" decreased against the background of the introduction of PIR-12 by 28,9% (p<0,05) and 4,1 times (p<0,05) compared with the control group animals, which surpasses the effect of the reference drug Cavinton. In addition, PIR-12 promotes an increase in the motor activity of ischemic rats: the number of hanging and standing rats was 7,4 times higher (p<0,05), 4,2 times (p<0,05), relative to the NC rat group, and the effect is comparable to the group of animals that received Cavinton.

THE EFFECT OF PIR-20 COMPOUND ON COGNITIVE DEFICIT REDUCTION IN EXPERIMENTAL GLOBAL CEREBRAL ISCHEMIA IN RATS

A study was conducted to assess the effect of a new pyrimidine derivative PIR-20 (50 mg/kg) on the development of cognitive deficits in the conditions of global cerebral ischemia in rats. The study was performed on 40 male Wistar rats weighing 200–220 g, divided into 4 groups of 10 individuals. False-operated rats and negative control animals were injected with a suspension of purified water and tween-80, the third group of animals received Cavinton (3,2 mg/kg), the fourth — PIR-20 (50 mg/kg). All test subjects were injected intraperitoneally for ten days prior to surgery. The number of dives increased to 100%, while the decision-making time decreased by 55,2% (p<0,05) in the extrapolation escape test against the background of the PIR-20 compound administration. 75% of the animals treated with PIR-20 did not re-visit the dark compartment, and the time of entering the dark chamber increased by 172,9% (p<0,05) as compared to the group of negative control rats in the test of passive avoidance of the avesir environment. It was confirmed that the studied compound PIR-20 contributes to the improvement of cognitive and mnestic functions, which is confirmed by the results of tests of passive and active aversive environment avoidance. The obtained effect exceeded the results of the control group and the reference drug Cavinton.

Effect of Mild Hypothermia on the Catalytic Characteristics of Synaptic Acetylcholinesterase during Subtotal Global Cerebral Ischemia in Rats

Effect of Mild Hypothermia on the Catalytic Characteristics of Synaptic Acetylcholinesterase during Subtotal Global Cerebral Ischemia in Rats

The Effects of Atorvastatin on Global Cerebral Ischemia-Induced Neuronal Death.

(1) Background and Purpose: Global cerebral ischemia-induced severe hypoxic brain damage is one of the main causes of mortality and long-term neurologic disability even after receiving early blood reperfusion. This study aimed to test the hypothesis that atorvastatin potentially has neuroprotective effects in global cerebral ischemia (GCI). (2) Methods: We performed two sets of experiments, analyzing acute (1-week) and chronic (4-week) treatments. For the vehicle (Veh) and statin treatments, 1 mL of 0.9% saline and 5 mg/kg of atorvastatin (ATOR) were administered orally. For histological analysis, we used the following staining protocols: Fluoro-Jade B and NeuN, 4-hydroxynonenal, CD11b and GFAP, IgG, SMI71, and vWF. Finally, we evaluated the cognitive function with a battery of behavioral tests. (3) Results: The GCI-ATOR group showed significantly reduced neuronal death, oxidative stress, inflammation, and BBB disruption compared with the GCI-Veh group. Moreover, the GCI-ATOR group showed decreased endothelial damage and VV proliferation and had significantly improved cognitive function compared with the GCI-Veh group in both models. (4) Conclusions: ATOR has neuroprotective effects and helps recover the cognitive function after GCI in rats. Therefore, administration of atorvastatin may be a therapeutic option in managing GCI after CA.

Activation of p38 MAPK participates in the sulbactam-induced cerebral ischemic tolerance mediated by glial glutamate transporter-1 upregulation in rats

Our previous studies have shown that sulbactam can play a neuroprotection role in hippocampal neurons by upregulating the expression and function of glial glutamate transporter-1 (GLT-1) during ischemic insult. Here, using rat global cerebral ischemia model, we studied in vivo the role of p38 mitogen-activated protein kinases (MAPK) in the sulbactam-induced GLT-1 upregulation and neuroprotection against ischemia. The hippocampal CA1 field was selected as observing target. The expressions of phosphorylated-p38 MAPK and GLT-1 were assayed with western blot analysis and immunohistochemistry. The condition of delayed neuronal death (DND) was assayed with neuropathological evaluation under thionin staining. It was shown that administration of sulbactam protected CA1 hippocampal neurons against ischemic insult accompanied with significantly upregulation in the expressions of phosphorylated-p38 MAPK and GLT-1. The time course analysis showed that sulbactam activated p38 MAPK before the GLT-1 upregulation in either normal or global cerebral ischemic rats. Furthermore, inhibiting p38 MAPK activation by SB203580 blocked the GLT-1 upregulation and neuroprotection induced by sulbactam. The above results suggested that p38 MAPK, at least partly, participated in the sulbactam-induced brain tolerance to ischemia mediated by GLT-1 upregulation in rats.

Time-related metabolomics study in the rat plasma after global cerebral ischemia and reperfusion: Effect of ischemic preconditioning.

Cardiac arrest is one of the major causes of death and disability. The aim of the study was to identify dynamic time-dependent metabolomic changes reflected in rat plasma induced by cerebral ischemia and reperfusion with the focus on the protective effect of ischemic preconditionig. Global cerebral ischemia in rats was induced by the four-vessel occlusion. Blood plasma was collected in three reperfusion times: an early post-acute 3 hr, then 24 hr, as an incipient time for delayed neuronal death induction and 72 hr as prolonged reperfusion period. The metabolomic measurements were conducted via untargeted nuclear magnetic resonance spectroscopy. Plasma of ischemized rats manifested dynamic metabolomic changes over the reperfusion time, such as increased levels of ketone bodies, decreased levels of pyruvate, alanine, and citrate. All three branched chain amino acids showed common pattern during reperfusion time: a decrease in 3 hr compared to sham, then a highest level in 24 hr and decrease in 72 hr reperfusion time, similar to their corresponding ketoacids. The protective effect of ischemic preconditioning was demonstrated by a faster tendency of plasma metabolites to normalize. Results also proved the remarkable metabolomic differences between the control (naïve) and sham-operated anesthetized animals, what warrants for critical evaluation of surgery/anaesthesy in the algorithm of metabolomic animal studies.

Angelica sinensis extract protects against ischemia-reperfusion injury in the hippocampus by activating p38 MAPK-mediated p90RSK/p-Bad and p90RSK/CREB/BDNF signaling after transient global cerebral ischemia in rats

Ethnopharmacological relevanceAngelica sinensis (Oliv.) Diels, commonly known as Dang Gui (DG), is one of the most popular traditional Chinese herbal medicines for the treatment of stroke. However, the effects of DG on transient global cerebral ischemia (GCI) and its precise mechanisms remain unclear.Aim of the study: This study aimed to investigate the effects of the DG extract on ischemia-reperfusion (I/R) injury in the hippocampus 7 d after transient GCI and to identify the potential mitogen-activated protein kinase (MAPK)-related signaling pathway in the hippocampus involved in the effects. Materials and methodsRats were intragastrically administered DG at doses of 0.25 g/kg (DG-0.25g), 0.5 g/kg (DG-0.5g), or 1 g/kg (DG-1g) 1, 3, and 5 d after GCI. ResultsDG-0.5g and DG-1g treatments effectively promoted hippocampal cornu ammonis 1 (CA1) neuronal survival. DG-0.5g and DG-1g treatments markedly increased phospho-p38 MAPK (p-p38 MAPK), phospho-90-kDa ribosomal S6 kinase (p-p90RSK), cytosolic and mitochondrial phospho-Bad (p-Bad), phospho-cAMP response element-binding protein (p-CREB), brain-derived neurotrophic factor (BDNF), and p-CREB/BDNF expression; decreased 4-hydroxy-2-nonenal, cytochrome c (Cytc), and cleaved caspase-3 expression, and inhibited apoptosis in the hippocampal CA1 region. Pretreatment with a specific inhibitor of p38 MAPK, SB203580, completely blocked the effects of DG-1g on the expression of the aforementioned proteins. ConclusionsDG-0.5g and DG-1g treatments exerted neuroprotective effects on I/R injury by activating p38 MAPK-mediated p90RSK/p-Bad-induced anti-apoptotic-Cytc/caspase-3-related and p90RSK/CREB/BDNF survival signaling in the hippocampus 7 d after transient GCI.

Развитие периферической сенсорной гиперсенситизации после глобальной ишемии головного мозга у крыс (краткое сообщение)

Развитие периферической сенсорной гиперсенситизации после глобальной ишемии головного мозга у крыс (краткое сообщение)

Post-ischemic salubrinal administration reduces necroptosis in a rat model of global cerebral ischemia.

Ischemic stroke is one of the most important causes of death and disability worldwide. Subroutines underlying cell death after stroke are largely unknown despite their importance in the design of novel therapies for this pathology. Necroptosis, a recently described form of regulated cell death, has been related with inflammation and, in some models, with endoplasmic reticulum (ER) stress. We hypothesize that alleviation of ER stress following a salubrinal treatment will reduce the ischemic-dependent necroptosis. To probe the hypothesis, we measured, at 48 and 72h after transient global cerebral ischemia in rat, in cerebral cortex and cornu ammonis 1, the main hallmarks of necroptosis: mRNA levels and phosphorylation of mixed lineage kinase domain like pseudokinase as well as receptor interacting serine/threonine protein kinase 3, along the years 2017-2018. Selective neuronal loss after 7days of the ischemic insult, and other markers related with the inflammatory response were also measured. This study shows that necroptosis in cerebral cortex can be detected after 72h of the insult and seems to be elicited before 48h of reperfusion. The type of necroptosis here observed seems to be tumor necrosis factor receptor 1 independent. Necroptotic response is less evident in the cornu ammonis 1 hippocampal area than in cerebral cortex. The treatment with salubrinal administered 1 and 24h after the ischemia, decreased the necroptotic marker levels and reduced the areas of selective neuronal loss, supporting the presence of ischemic-dependent necroptosis, and the notion that ER stress is involved in the necroptotic response. Open Science: This manuscript was awarded with the Open Materials Badge For more information see: https://cos.io/our-services/open-science-badges/.

A study on neuroprotective effect of cod liver oil in bilateral common carotid artery occlusion induced global cerebral ischemia in rats

A study on neuroprotective effect of cod liver oil in bilateral common carotid artery occlusion induced global cerebral ischemia in rats

Neuroglobin mediates neuroprotection of hypoxic postconditioning against transient global cerebral ischemia in rats through preserving the activity of Na+/K+ ATPases

Hypoxic postconditioning (HPC) is an innovative neuroprotective strategy with cytoprotective effects on the hippocampal neurons against transient global cerebral ischemia (tGCI) in adult rats. However, its molecular mechanisms have not yet been adequately elucidated. Neuroglobin (Ngb) is an endogenous neuroprotectant with hypoxia-inducible property, and its role in experimental stroke has been increasingly attractive. Hence, the purpose of this study is to explore the involvement of Ngb in HPC-mediated neuroprotection and to further investigate its underlying molecular mechanism. We found that HPC increased Ngb expression in CA1 subregion after tGCI. Also, the inhibition of Ngb expression with Ngb antisense oligodeoxynucleotide (AS-ODNs) eliminated the neuroprotective effect mediated by HPC, whereas overexpression of Ngb ameliorated neuronal damage in CA1 after tGCI, indicating that HPC conferred neuroprotective effects via upregulation of Ngb. We further showed that HPC increased the membranous level of Na+/K+ ATPases β1 subunit (Atp1b1) in CA1 after tGCI. Furthermore, we demonstrated that Ngb upregulation in CA1 after HPC maintained the membranous level of Atp1b1 through Ngb–Atp1b1 interaction and reduced the glutathionylation of membranous Atp1b1 via suppression of reactive oxygen species (ROS), ultimately preserving the activity of NKA. Taken together, these data indicate that Ngb is involved in the neuroprotection of HPC against tGCI via maintenance of NKA activity in the hippocampal CA1.

Pharmacological Neuroprotection in Cardiac Surgery: Effectiveness of Pharmacologic-Preconditioning with Erythromycin.

Regardless of the degree of advances in neuroprotective strategies, and despite the technological progress in neuromonitoring, brain injury still remains the "Achilles' heel" in cardiac surgery. A large number of pharmacological and non-pharmacological therapeutic interventions have been investigated during the last two decades. Recently, both theoretical and experimental findings suggest benefits of pharmacological cerebral protection, although, there is no conclusive evidence of clinical superiority of specific agents that have been applied as neuroprotectants, in human randomized controlled trials. Pre-ischemic conditioning has also been used in an attempt to reduce the incidence of brain injury following cardiac surgery. In light of previous evidence showing that pharmacologic preconditioning with a single dose of erythromycin induces tolerance against transient global cerebral ischemia in rats, we examined whether erythromycin would reduce the number of apoptotic neurons in the neocortex in our acute porcine model of hypothermic circulatory arrest (HCA). Pre-ischemic conditioning with a single dose of the antibiotic erythromycin, applied 12 h before HCA, significantly reduced neuronal injury in the neocortex of the porcine brain, suggesting that cerebral protection may be achieved with erythromycin pharmacological preconditioning in cardiac surgery on an experimental basis. Since erythromycin has been effectively used in clinical practice with few side effects, these findings suggest that it could be a promising candidate for potential clinical neuroprotective strategy.

Ethyl-acetate fraction of Trichilia catigua protects against oxidative stress and neuroinflammation after cerebral ischemia/reperfusion

Ethnopharmacological relevanceTrichilia catigua A. Juss (Meliaceae) preparations have been used in folk medicine to alleviate fatigue, stress, and improve memory. Antinociceptive, antiinflammatory, and in vitro neuroprotective effects have been observed in animals. Cerebral ischemia/reperfusion (I/R) leads to severe neuropsychological deficits that are largely associated with oxidative stress, inflammation and neurodegeneration. We reported previously that an ethyl-acetate fraction (EAF) of T. catigua reduced brain ischemia-induced learning and memory impairments in the absence of histological protection. Aim of the studyContinuing those studies, here we aimed to investigate the antioxidant and antiinflammatory properties of T. catigua in an in vivo model of I/R. Material and methodsRats were subjected to 15 min of brain ischemia (4-VO model) followed by up to 15 days of reperfusion. Vehicle was given by gavage 30 min before ischemia and at 1 h of reperfusion. In a first experiment, brain ischemia-induced changes in oxidative stress markers, i.e., reduced glutathione (GSH), oxidized glutathione (GSSG), superoxide dismutase (SOD), catalase (CAT), malondialdehyde (MDA), and protein carbonyl groups (PCGs) were measured on days 1, 3, and 5 post-ischemia. Similar time course analysis was done for neuroinflammation markers, i.e., microglia (OX42 immunorreactivity) and astrocytes (GFAP immunorreactivity), in the hippocampus. In a second experiment, the time points at which these markers of oxidative stress and neuroinflammation peaked were used to test the effects of T. catigua (400 mg/kg, p.o.). ResultsOxidative stress markers peaked on day 1 post-ischemia. GSH decreased (−23.2%) while GSSG increased (+ 71.1%), which yielded a significant reduction in the GSH/GSSG ratio (−39.1%). The activity of CAT was largely reduced by ischemia (−54.6% to −65.1%), while the concentration of PCG almost doubled in the brain of ischemic rats (+99.10%) in comparison to sham. Treatment with the EAF of T. catigua normalized these changes in oxidative markers to the control levels (GSH: +27.5%; GSSG: −23.8%; GSH/GSSG: +44.6%; PCG: −80.3%). In the hippocampus, neuroinflammation markers peaked on day 5 post-ischemia, with microglial and astrocytic responses increasing to 54.8% and 37.1%, respectively. The elevation in glial cells response was completely prevented by EAF. ConclusionThese results demonstrate that T. catigua has both antioxidant and antiinflammatory activities after transient global cerebral ischemia in rats, which may contribute to the previously reported memory protective effect of T. catigua.

Pre-Treatment with Metformin in Comparison with Post-Treatment Reduces Cerebral Ischemia Reperfusion Induced Injuries in Rats.

To explore the effects of pre versus post ischemic treatment with metformin after global cerebral ischemia in rats. Male Wister rats underwent forebrain ischemia by bilateral common carotid artery occlusion for 17 min. Metformin (200 mg/kg) or vehicle was given orally by gavage for 7-14 days. Rats were divided into: control, metformin pre-treatment, metformin post-treatment and metformin pre and post continuous treatment groups. Cerebral infarct size, histopathology, myeloperoxidase and serum malondialdehyde were measured 7 days after ischemia. Histopathological analysis showed that metformin pre-treatment significantly decreased leukocyte infiltration, myeloperoxidase activity and also malondialdehyde level. Metformin pre-treatment and metformin post-treatment reduced infarct size compared with the control group, but it was not significant in the pre and post continuous treatment group. Our findings suggest that pre-treatment with metformin in comparison with post-treatment in experimental stroke can reduce the extent of brain damage and is more neuroprotective at least in part by inhibiting oxidative stress and inflammation.

BFGF plays a neuroprotective role by suppressing excessive autophagy and apoptosis after transient global cerebral ischemia in rats

Transient global cerebral ischemia (tGCI) is a cerebrovascular disorder that can cause apoptotic neuronal damage and functional deficits. Basic fibroblast growth factor (bFGF) was reported to be highly expressed in the central nervous system (CNS) and to exert neuroprotective effects against different CNS diseases. However, the effects of bFGF on tGCI have not been studied intensively. This study was conducted to investigate the effect of bFGF and its underlying mechanism in an animal model of tGCI. After intracerebroventricular (i.c.v.) injection of bFGF, functional improvement was observed, and the number of viable neurons increased in the ischemia-vulnerable hippocampal CA1 region. Apoptosis was induced after tGCI and could be attenuated by bFGF treatment via inhibition of p53 mitochondrial translocation. In addition, autophagy was activated during this process, and bFGF could inhibit activation of autophagy through the mTOR pathway. Rapamycin, an activator of autophagy, was utilized to explore the relationship among bFGF, apoptosis, and autophagy. Apoptosis deteriorated after rapamycin treatment, which indicated that excessive autophagy could contribute to the apoptosis process. In conclusion, these results demonstrate that bFGF could exert neuroprotective effects in the hippocampal CA1 region by suppressing excessive autophagy via the mTOR pathway and inhibiting apoptosis by preventing p53 mitochondrial translocation. Furthermore, our results suggest that bFGF may be a promising therapeutic agent to for treating tGCI in response to major adverse events, including cardiac arrest, shock, extracorporeal circulation, traumatic hemorrhage, and asphyxiation.