급성 뇌경색에서의 항혈전 및 신경보호 치료

허성혁,장대일 대한의사협회 2009 대한의사협회지 Vol.52 No.4

As, until now, many studies have failed to establish the clinical effect of numerous neuroprotectives, antithrombotic therapy must be emphasized as one of critical options among limited treatment strategies in acute ischemic stroke. Based on the accumulating evidences that platelets and coagulating proteins play an important role in the thrombus formation, antiplatelets and anticoagulants are served as antithrombotics. Recently, major advances have been made in understanding the effects of antiplatelets and anticoagulants. Large randomized clinical trials have highlighted the effectiveness and safety of early and continuous antiplatelet therapy in reducing atherothrombotic stroke recurrence. Urgent anticoagulation has been used often to prevent early recurrent stroke and to improve neurological outcomes, however, its formal use in acute stroke has been the subject of debate even in cardioembolic stroke. That’s because anticoagulants also increase the risk of fatal or disabling intracranial hemorrhage and it is difficult to monitor proper anticoagulation. Although early administration of anticoagulants should be considered to prevent the secondary injury and the propagation of thrombosis in patients with atherothrombotic stroke, more evidences are needed especially in patients with infractions secondary to large artery thrombosis or cardioembolism. This review discusses recent advances related to antithrombotic strategies and putative neuroprotectives.

품종별 곶감(Diospyros kaki)의 영양성분 분석, 산화방지 효과 및 뇌 신경세포 보호효과

김종민(Jong Min Kim),박선경(Seon Kyeong Park),강진용(Jin Yong Kang),박상현(Sang Hyun Park),박수빈(Su Bin Park),유슬기(Seul Ki Yoo),한혜주(Hye Ju Han),이수광(Su-Gwang Lee),이욱(Uk Lee),허호진(Ho Jin Heo) 한국식품과학회 2018 한국식품과학회지 Vol.50 No.2

본 연구에서는 떫은감의 5가지 공시품종인 상주둥시, 고종시, 고동시, 갑주백목, 청도반시를 이용하여 가공된 곶감의 유리당, 지방산, 무기성분, 구성 아미노산, 바이타민 C와 같은 영양성분 분석을 진행하였고, 총 페놀성 화합물의 함량을 측정함과 동시에 in vitro 상에서 ABTS, DPPH 라디칼 제거 활성을 측정하였고, FRAP, 지방질과산화물 생성 억제효과, 아세틸콜린 분해효소 억제효과를 확인하였다. 이를 토대로 MC-IXC 뇌 신경세포에서 신경세포 생존율과 산화적 스트레스 억제효과, 세포막 보호효과를 확인하였다. 유리당 분석에서는 상주둥시 품종이 포도당(glucose), 과당(fructose) 함량이 가장 높았고, 지방산 함량은 상주둥시 품종에서는 올레산(oleic acid)이, 고동시, 고종시, 갑주백목, 반시에서는 팔미트산(palmitic acid)이 가장 높은 비율을 나타내었다. 포타슘과 인의 함량이 다른 무기성분들에 비해 월등히 높았으며, 주요 아미노산으로는 아스파트산(aspartic acid)과 글루탐산(glutamic acid)이 상대적으로 높았고, 바이타민 C 역시 5 품종 모두 검출되었다. 또한, 총 페놀성 화합물을 상주둥시의 95% 에탄올 추출물이 가장 높았고, ABTS, DPPH 라디칼 제거 활성과 FRAP, 지방질 과산화물 생성 억제활성 그리고 아세틸콜린 분해효소 억제 활성에서 갑주백목의 80% 에탄올 추출물이 가장 높은 활성을 나타내었다. 산화적 스트레스에 대한 뇌 신경세포 생존율은 갑주백목이 가장 높은 생존율을 나타내었으며, 산화적 스트레스 생성 억제와 뇌 신경세포 세포막 보호효과 역시 갑주백목이 가장 큰 억제 활성과 보호효과를 보였다. 이와 같은 결과로 보아 곶감은 뛰어난 산화방지 효과를 가지고 있으며, 이를 근간으로 뇌 신경세포 보호효과도 우수한 것으로 나타났다. 이러한 생리활성능력은 임산물의 고부가가치 소재개발에 있어 산업적 활용 가능성을 재고하는데 도움이 될 것으로 판단된다. 다만 생리활성 물질의 검증이 부족하고, 산화방지활성이 in vitro 상의 효과에 국한된 점에서 향후 물질분석과 인기지능 개선 효과 검증을 통해 인기지능 개선 건강기능식품 소재로서 연구될 수 있을 것으로 판단된다. This study was conducted to compare nutritional analysis and neuroprotective effect of 5 cultivars of Diospyros kaki (Dungsi, Godongsi, Gojongsi, Gabjubaekmok, and Bansi). In nutritional analysis, three free sugars: sucrose, glucose, and fructose, and six fatty acids: tartaric acid, hexadecanoic acid, palmitic acid, oleic acid, octadecenamide, and octadecane, were detected. Potassium and phosphorus levels were the highest in inorganic component analysis, and glutamic acid and aspartic acid were the highest contents in amino acid analysis. Vitamin C was detected in all cultivars. Total phenolic content was the highest in Dungsi. Antioxidant activities such as ABTS (3-ethylbenzothiazoline-6-sulfonic acid), DPPH (1,1-diphenyl-2-picrylhydrazyl) radical scavenging activities, FRAP (ferric reducing/antioxidant power), and MDA (malondialdehyde) inhibitory effect were the highest in Gabjubaekmok. Acetylcholinesterase inhibitory activity, cell viability, intracellular reactive oxygen species (ROS) accumulation, and lactate dehydrogenase (LDH) release were measured to confirm the neuroprotective effect in MC-IXC cells. Gabjubaekmok showed significant acetylcholinesterase (AChE) inhibition and neuroprotection.

Centella asiatica enhances neurogenesis and protects neuronal cells against H2O2-induced oxidative injury

Haeun Kim,Jin Tae Hong,Mi Hee Park 충북대학교 동물의학연구소 2015 Journal of Biomedical and Translational Research Vol.16 No.3

Traditionally, Centella asiatica leaf extracts are used to treat neurodegenerative diseases in India. Centella asiatica is reportedly used to enhance memory and treat dementia, but its promoting effect on neural stem cell differentiation has not been studied yet. In the present study, we investigated whether or not Centella asiatica leaf extracts act on neuronal precursor cells and neuronal cell lines to induce neuronal differentiation, neurite outgrowth, and neuroprotection. The neurogenesis-promoting potential of Centella asiatica leaf extracts was determined by differentiation assay on neural stem cells isolated from mouse embryos and PC12 cell lines. To understand the contribution of specific neural cell types towards increase after Centella asiatica treatment, neural stem cells were differentiated into various neural subtypes and checked by Western blotting using neural cell lineage-specific antibody markers. Neuroprotective activity of Centella asiatica was analyzed in PC12 cells exposed to 100 μM of H2O2. Cell growth was analyzed by MTT assay while cell death was analyzed by Western blotting detection of apoptosis-related proteins. Cells treated with Centella asiatica had significantly longer primary and secondary neurites as well as a higher number of neurites per cell compared to control cells. Expression levels of TUBBIII, TH, NF, and BDNF increased upon Centella asiatica treatment, suggesting that Centella asiatica has a neurogenesis-promoting effect. Centella asiatica also inhibited oxidative stress-induced neural cell damage through regulation of apoptosis- and cell cycle-related proteins. Thus, leaf extracts of Centella asiatica might promote neurogenesis, neuroregeneration, and neuroprotection in the context of neurodegenerative diseases.

Neuroprotective effects of resveratrol via anti-apoptosis on hypoxic-ischemic brain injury in neonatal rats

신진영,서민애,최은진,김진경,서억수,이준화,정혜리,김우택 대한소아청소년과학회 2008 Clinical and Experimental Pediatrics (CEP) Vol.51 No.10

Purpose : Resveratrol, extracted from red wine and grapes, has an anti-cancer effect, an antiinflammatory effect, and an antioxidative effect mainly in heart disease and also has neuroprotective effects in the adult animal model. No studies for neuroprotective effects during the neonatal periods have been reported. Therefore, we studied the neuroprotective effect of resveratrol on hypoxic-ischemic brain damage in neonatal rats via anti-apoptosis. Methods : Embryonic cortical neuronal cell culture of rat brain was performed using pregnant Sprague-Dawley (SD) rats at 18 days of gestation (E18) for the in vitro approach. We injured the cells with hypoxia and administered resveratrol (1, 10, and 30 µg/mL) to the cells at 30 minutes before hypoxic insults. In addition, unilateral carotid artery ligation with hypoxia was induced in 7-day-old neonatal rats for the in vivo approach. We injected resveratrol (30 mg/kg) intraperitoneally into animal models. Real-time PCR and Western blotting were performed to identify the neuroprotective effects of resveratrol through anti-apoptosis. Results : In the in vitro approach of hypoxia, the expression of Bax, caspase-3, and the ratio of Bax/Bcl-2, indicators of the level of apoptosis, were significantly increased in the hypoxia group compared to the normoxia group. In the case of the resveratrol-treated group, expression was significantly decreased compared to the hypoxia group. And the results in the in vivo approach were the same as in the in vitro approach. Conclusion : The present study demonstrates that resveratrol plays neuroprotective role in hypoxic-ischemic brain damage during neonatal periods through the mechanism of anti-apoptosis. Purpose : Resveratrol, extracted from red wine and grapes, has an anti-cancer effect, an antiinflammatory effect, and an antioxidative effect mainly in heart disease and also has neuroprotective effects in the adult animal model. No studies for neuroprotective effects during the neonatal periods have been reported. Therefore, we studied the neuroprotective effect of resveratrol on hypoxic-ischemic brain damage in neonatal rats via anti-apoptosis. Methods : Embryonic cortical neuronal cell culture of rat brain was performed using pregnant Sprague-Dawley (SD) rats at 18 days of gestation (E18) for the in vitro approach. We injured the cells with hypoxia and administered resveratrol (1, 10, and 30 µg/mL) to the cells at 30 minutes before hypoxic insults. In addition, unilateral carotid artery ligation with hypoxia was induced in 7-day-old neonatal rats for the in vivo approach. We injected resveratrol (30 mg/kg) intraperitoneally into animal models. Real-time PCR and Western blotting were performed to identify the neuroprotective effects of resveratrol through anti-apoptosis. Results : In the in vitro approach of hypoxia, the expression of Bax, caspase-3, and the ratio of Bax/Bcl-2, indicators of the level of apoptosis, were significantly increased in the hypoxia group compared to the normoxia group. In the case of the resveratrol-treated group, expression was significantly decreased compared to the hypoxia group. And the results in the in vivo approach were the same as in the in vitro approach. Conclusion : The present study demonstrates that resveratrol plays neuroprotective role in hypoxic-ischemic brain damage during neonatal periods through the mechanism of anti-apoptosis.

4-vessel occlusion으로 誘發한 흰쥐 前腦虛血의 神經細胞 損傷에 대한 大黃의 防禦效果

安德均,元道喜,金鍾虎 대한본초학회 1999 大韓本草學會誌 Vol.14 No.1

Neuroprotective and prophylatic neuroprotective effects of the Rhei Rhizoma on the rat's transient forebrain ischemia caused by 4-vessel-occlusion are concluded as following. 1. The neuroprotective effects of i.p. injection and oral administration on the neuronal density of hypothermic rats in the CA1 region of the hippocampus 7 days after 10-minute 4-BO. provided significant neuroprotection at the dose of 500 and 1000 ㎎/㎏. 2. The neuroprotective effects of Rhei Rhizoma extracts i.p. injection and oral administration on the neuronal density of normothermic rats in the CA1 region of the hippocampus 7 days after 10-minute 4-VO. provided significant neuroprotection at the dose of 500 and 1000 ㎎/㎏ against the ischemia-induced cell death when i.p injection and administration was initiated immediately after occlusion. 3. The prophylactic neuroprotective effects of Rhei Rhizoma extracts i.p. injection and oral administration pretreatment on the neuronal density of hypothermic rats in the CA1 region of the hippocampus 7 days after 10-minute 4-VO, provided significant prophylactic neuroprotection at the dosage of 500 and 1000 ㎎/㎏ against the ischemia-induced cell death when i.p. injection administration was initiated immediately after occlusion. 4. The prophylactic neuroprotective effects of Rhei Rhizoma extracts i.p. injection and oral administration pretreatment on the neuronal densith of normothermic rats in the CA1 region of the hippocampus 7 days after 10-minute 4-VO. provided significant prophylactic neuroprotection at the dosage of 1000 ㎎/㎏ against the ischemia-induced cell death when i.p. injection and administration was initiated immediately after occlution. According to the above results, Rhei Rhizoma has showed neruoprotective and prophylatic neuroprotective effects on the rats' transient forebrain ischemia caused by 4-vessel-occlusion. Therefore Rhei Rhizoma is recommended to be used for the prevention and curing of ischamia diseases.

Multi Target Neuroprotective and Neurorestorative Anti-Parkinson and Anti-Alzheimer Drugs Ladostigil and M30 Derived from Rasagiline

Moussa B.H. Youdiim 한국뇌신경과학회 2013 Experimental Neurobiology Vol.22 No.1

Present anti-PD and -AD drugs have limited symptomatic activity and devoid of neuroprotective and neurorestorative property that is needed for disease modifying action. The complex pathology of PD and AD led us to develop several multi-target neuroprotective and neurorestorative drugs with several CNS targets with the ability for possible disease modifying activity. Employing the pharmacophore of our anti-parkinson drug rasagiline (Azilect, N-propagrgyl-1-R-aminoindan), we have developed a series of novel multi-functional neuroprotective drugs (A) [TV-3326 (N-propargyl-3R-aminoindan-5yl)-ethyl methylcarbamate)], with both cholinesterase-butyrylesterase and brain selective monoamine-oxidase (MAO) A/B inhibitory activities and (B) the iron chelator-radical scavenging-brain selective monoamine oxidase (MAO) A/B inhibitor and M30 possessing the neuroprotective and neurorescuing propargyl moiety of rasagiline, as potential treatment of AD, DLB and PD with dementia. Another series of multi-target drugs (M30, HLA-20 series) which are brain permeable iron chelators and potent selective brain MAO inhibitors were also developed. These series of drugs have the ability of regulating and processing amyloid precursor protein (APP) since APP and alpha-synuclein are metaloproteins (iron-regulated proteins), with an iron responsive element 5”UTR mRNA similar to transferring and ferritin. Ladostigil inhibits brain acetyl and butyrylcholinesterase in rats after oral doses. After chronic but not acute treatment, it inhibits MAO-A and -B in the brain. Ladostigil acts like an anti-depressant in the forced swim test in rats, indicating a potential for anti-depressant activity. Ladostigil prevents the destruction of nigrostriatal neurons induced by infusion of neurotoxin MPTP in mice. The propargylamine moiety of ladostigil confers neuroprotective activity against cytotoxicity induced by ischemia and peroxynitrite in cultured neuronal cells. The multi-target iron chelator M30 has all the properties of ladostigil and similar neuroprotective activity to ladostigil, but is not a ChE inhibitor. M30 has a neurorestorative activity in post-lesion of nigrostriatal dopamine neurons in MPTP, lacatcystin and 6-hydroxydopamine animal models of PD. The neurorestorative activity is related to the ability of the drug to activate hypoxia inducing factor (HIF) which induces the production of such neurotrophins as brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF) and erythropoietin as well as glia-derived neurotrophic factor (GDNF). The unique multiple actions of ladostigil and M30 make the potentially useful drugs for the treatment of dementia with Parkinsonian-like symptoms and depression.

Taurine exerts neuroprotective effects via anti-apoptosis in hypoxic-ischemic brain injury in neonatal rats

정지은,김태열,박혜진,이계향,이정훈,최은진,김진경,정혜리,서억수,김우택 대한소아청소년과학회 2009 Clinical and Experimental Pediatrics (CEP) Vol.52 No.12

Purpose:Taurine (2-aminoethanesulfonic acid) is a simple sulfur-containing amino acid. It is abundantly present in tissues such as brain, retina, heart, and skeletal muscles. Current studies have demonstrated the neuroprotective effects of taurine, but limited data are available for such effects during neonatal period. The aim of this study was to determine whether taurine could reduce hypoxic-ischemic (HI) cerebral injury via anti-apoptosis mechanism. Methods:Embryonic cortical neurons isolated from Sprague-Dawley (SD) rats at 18 days gestation were cultured in vitro. The cells were divided into hypoxia group, taurine-treated group before hypoxic insult, and taurine-treated group after HI insult. In the in vivo model, left carotid artery ligation was performed in 7-day-old SD rat pups. The pups were exposed to hypoxia, administered an injection of 30 mg/kg of taurine, and killed at 1 day, 3 days, 1 week, 2 weeks, and 4 weeks after the hypoxic insult. We compared the expressions of Bcl-2, Bax, and caspase-3 among the 3 groups by using real- time polymerase chain reaction (PCR) and western blotting. Results:The cells in the taurine-treated group before hypoxic insult, although similar in appearance to those in the normoxia group, were lesser in number. In the taurine-treated group, Bcl-2 expression increased, whereas Bax and caspase-3 expressions reduced. Conclusion:Taurine exerts neuroprotective effects onperinatal HI brain injury due to its anti-apoptotic effect. The neuroprotective effect was maximal at 1–2 weeks after the hypoxic injury. Purpose:Taurine (2-aminoethanesulfonic acid) is a simple sulfur-containing amino acid. It is abundantly present in tissues such as brain, retina, heart, and skeletal muscles. Current studies have demonstrated the neuroprotective effects of taurine, but limited data are available for such effects during neonatal period. The aim of this study was to determine whether taurine could reduce hypoxic-ischemic (HI) cerebral injury via anti-apoptosis mechanism. Methods:Embryonic cortical neurons isolated from Sprague-Dawley (SD) rats at 18 days gestation were cultured in vitro. The cells were divided into hypoxia group, taurine-treated group before hypoxic insult, and taurine-treated group after HI insult. In the in vivo model, left carotid artery ligation was performed in 7-day-old SD rat pups. The pups were exposed to hypoxia, administered an injection of 30 mg/kg of taurine, and killed at 1 day, 3 days, 1 week, 2 weeks, and 4 weeks after the hypoxic insult. We compared the expressions of Bcl-2, Bax, and caspase-3 among the 3 groups by using real- time polymerase chain reaction (PCR) and western blotting. Results:The cells in the taurine-treated group before hypoxic insult, although similar in appearance to those in the normoxia group, were lesser in number. In the taurine-treated group, Bcl-2 expression increased, whereas Bax and caspase-3 expressions reduced. Conclusion:Taurine exerts neuroprotective effects onperinatal HI brain injury due to its anti-apoptotic effect. The neuroprotective effect was maximal at 1–2 weeks after the hypoxic injury.

Ginsenoside Rb1 exerts neuroprotective effects through regulation of Lactobacillus helveticus abundance and GABA_A receptor expression

Chen, Huimin,Shen, Jiajia,Li, Haofeng,Zheng, Xiao,Kang, Dian,Xu, Yangfan,Chen, Chong,Guo, Huimin,Xie, Lin,Wang, Guangji,Liang, Yan The Korean Society of Ginseng 2020 Journal of Ginseng Research Vol.44 No.1

Background: Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure. Purpose: The present study aimed to elucidate the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects of Rb1 based on regulation of microflora. Methods: A pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 were compared between conventional and PGF rats. The relative abundances of common probiotics were quantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressions of the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (α2, β2, and γ2) and GABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/R+Rb1 rat hippocampus and striatum were assessed to reveal the neuroprotective mechanism of Rb1. Results: The results showed that microbiota plays a key role in neuroprotection of Rb1. The relative abundance of Lactobacillus helveticus (Lac.H) increased 15.26 fold after pretreatment with Rb1. I/R surgery induced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were prevented by colonizing the rat gastrointestinal tract with Lac.H (1 × 10⁹ CFU) by gavage 15 d before I/R surgery. Both Rb1 and Lac.H upregulated expression of GABA receptors in I/R rats. Coadministration of a GABA_A receptor antagonist significantly attenuated neuroprotective effects of Rb1 and Lac.H. Conclusion: In sum, Rb1 exerts neuroprotective effects by regulating Lac.H and GABA receptors rather than through direct distribution to the target sites.

Ginsenoside Rb1 exerts neuroprotective effects through regulation of Lactobacillus helveticus abundance and GABA<SUB>A</SUB> receptor expression

Huimin Chen,Jiajia Shen,Haofeng Li,Xiao Zheng,Dian Kang,Yangfan Xu,Chong Chen,Huimin Guo,Lin Xie,Guangji Wang,Yan Liang 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.1

Background: Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exerts excellent neuroprotective effects even though it has low intracephalic exposure. Purpose: The present study aimed to elucidate the apparent contradiction between the pharmacokinetics and pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects of Rb1 based on regulation of microflora. Methods: A pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 were compared between conventional and PGF rats. The relative abundances of common probiotics were quantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressions of the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (α2, β2, and γ2) and GABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/RþRb1 rat hippocampus and striatum were assessed to reveal the neuroprotective mechanism of Rb1. Results: The results showed that microbiota plays a key role in neuroprotection of Rb1. The relative abundance of Lactobacillus helveticus (Lac.H) increased 15.26 fold after pretreatment with Rb1. I/R surgery induced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1β, IL-6, and TNF-α) were prevented by colonizing the rat gastrointestinal tract with Lac.H (1×10<SUP>9</SUP> CFU) by gavage 15 d before I/R surgery. Both Rb1 and Lac.H upregulated expression of GABA receptors in I/R rats. Coadministration of a GABAA receptor antagonist significantly attenuated neuroprotective effects of Rb1 and Lac.H. Conclusion: In sum, Rb1 exerts neuroprotective effects by regulating Lac.H and GABA receptors rather than through direct distribution to the target sites.

Ginsenoside Rb1 exerts neuroprotective effects through regulation of Lactobacillus helveticus abundance and GABAA receptor expression

Huimin Chen,Jiajia Shen,Haofeng Li,Xiao Zheng,Dian Kang,Yangfan Xu,Chong Chen,Huimin Guo,Lin Xie,Guangji Wang,Yan Liang 고려인삼학회 2020 Journal of Ginseng Research Vol.44 No.1

Background: Ginsenoside Rb1 (Rb1), one of the most abundant protopanaxadiol-type ginsenosides, exertsexcellent neuroprotective effects even though it has low intracephalic exposure. Purpose: The present study aimed to elucidate the apparent contradiction between the pharmacokineticsand pharmacodynamics of Rb1 by studying the mechanisms underlying neuroprotective effects ofRb1 based on regulation of microflora. Methods: A pseudo germ-free (PGF) rat model was established, and neuroprotective effects of Rb1 werecompared between conventional and PGF rats. The relative abundances of common probiotics werequantified to reveal the authentic probiotics that dominate in the neuroprotection of Rb1. The expressionsof the gamma-aminobutyric acid (GABA) receptors, including GABAA receptors (a2, b2, and g2) andGABAB receptors (1b and 2), in the normal, ischemia/reperfusion (I/R), and I/RþRb1 rat hippocampus andstriatum were assessed to reveal the neuroprotective mechanism of Rb1. Results: The results showed that microbiota plays a key role in neuroprotection of Rb1. The relativeabundance of Lactobacillus helveticus (Lac.H) increased 15.26 fold after pretreatment with Rb1. I/R surgeryinduced effects on infarct size, neurological deficit score, and proinflammatory cytokines (IL-1b, IL-6, andTNF-a) were prevented by colonizing the rat gastrointestinal tract with Lac.H (1 109 CFU) by gavage 15d before I/R surgery. Both Rb1 and Lac.H upregulated expression of GABA receptors in I/R rats. Coadministrationof a GABAA receptor antagonist significantly attenuated neuroprotective effects of Rb1 and Lac.H. Conclusion: In sum, Rb1 exerts neuroprotective effects by regulating Lac.H and GABA receptors ratherthan through direct distribution to the target sites.