Hydrogen Sulfide Protects the Brain Against Ischemic Reperfusion Injury in a Transient Model of Focal Cerebral Ischemia

被引:101
作者
Gheibi, Sevda [1 ]
Aboutaleb, Nahid [2 ,3 ]
Khaksari, Mehdi [4 ]
Kalalian-Moghaddam, Hamid [4 ]
Vakili, Abedin [5 ,6 ]
Asadi, Yasin [5 ,6 ]
Mehrjerdi, Fatemeh Zare [7 ]
Gheibi, Azam [8 ]
机构
[1] Shahid Beheshti Univ Med Sci, Sch Med, Dept Physiol, Tehran, Iran
[2] Iran Univ Med Sci, Sch Med, Physiol Res Ctr, Tehran, Iran
[3] Iran Univ Med Sci, Sch Med, Dept Physiol, Tehran, Iran
[4] Shahroud Univ Med Sci, Sch Med, Dept Physiol, Shahroud, Iran
[5] Semnan Univ Med Sci, Sch Med, Physiol Res Ctr, Semnan, Iran
[6] Semnan Univ Med Sci, Sch Med, Dept Physiol, Semnan, Iran
[7] Shahid Sadoghi Univ Med Sci, Sch Med, Dept Physiol, Yazd, Iran
[8] Univ Tehran Med Sci, Sch Adv Med Technol, Dept Med Biotechnol, Tehran, Iran
关键词
H2S; Apoptosis; Brain edema; Infarct volume; Transient focal cerebral ischemia; NECROSIS-FACTOR-ALPHA; MYOCARDIAL-ISCHEMIA; INDUCED APOPTOSIS; H2S PROTECTS; DAMAGE; EDEMA; MECHANISMS; EXPRESSION; RADICALS;
D O I
10.1007/s12031-014-0284-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Hydrogen sulfide (H2S), a well-known toxic gas, is regarded as endogenous neuromodulator and plays multiple roles in the central nervous system under physiological and pathological states, especially in secondary neuronal injury. Recent studies have shown relatively high concentrations of hydrogen sulfide (H2S) in the brain and also cytoprotective effects of endogenous and exogenous H2S in models of in vitro and in vivo ischemic injury. H2S protects neurons by functioning as an anti-oxidant, anti-inflammatory, and anti-apoptotic mediator and by improving neurological function. Moreover, it protects neurons from glutamate toxicity. Therefore, the present study aimed to determine whether H2S provides protection in transient focal cerebral ischemia. Focal ischemia was induced by 60-min middle cerebral artery occlusion (MCAO), followed by 23-h reperfusion. Saline as a vehicle and NaHS (H2S donor; 1 and 5 mg) were intraperitoneally injected (IP) at the beginning of ischemia. Infarct volume, brain edema, and apoptosis were assessed 24 h after MCAO. Treatment with NaHS at doses of 1 and 5 mg markedly reduced total infarct volumes by 29 and 51 %, respectively (P < 0.001). In addition, NaHS at doses of 1 and 5 mg reduced brain edema (P < 0.05) and inhibited apoptosis by decreasing positive TUNEL cells (P < 0.001). The present study shows that treatment with H2S reduces brain injuries and postischemic cerebral edema in a dose-dependent manner likely through the blocking programmed cell death. We propose that H2S might be a promising therapeutic target for stroke, although more researches are necessary to take into account the potential therapeutic effects of H2S in stroke patients.
引用
收藏
页码:264 / 270
页数:7
相关论文
共 35 条
[1]  
Abe K, 1996, J NEUROSCI, V16, P1066
[2]  
Abouzakhar Nasser, 2013, Proceedings of the 12th European Conference on Information Warfare and Security, P1
[3]   Tumor necrosis factor-alpha - A mediator of focal ischemic brain injury [J].
Barone, FC ;
Arvin, B ;
White, RF ;
Miller, A ;
Webb, CL ;
Willette, RN ;
Lysko, PG ;
Feuerstein, GZ .
STROKE, 1997, 28 (06) :1233-1244
[4]   Role of hydrogen sulfide in the cardioprotection caused by ischemic preconditioning in the rat heart and cardiac myocytes [J].
Bian, JS ;
Yong, QC ;
Pan, TT ;
Feng, ZN ;
Ali, MY ;
Zhou, SF ;
Moore, PK .
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS, 2006, 316 (02) :670-678
[5]   Expression of tumor necrosis factor alpha after focal cerebral ischaemia in the rat [J].
Buttini, M ;
Appel, K ;
Sauter, A ;
GebickeHaerter, PJ ;
Boddeke, HWGM .
NEUROSCIENCE, 1996, 71 (01) :1-16
[6]   Reactive oxygen radicals in signaling and damage in the ischemic brain [J].
Chan, PH .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2001, 21 (01) :2-14
[7]  
del Zoppo G, 2000, BRAIN PATHOL, V10, P95
[8]   Diabetic neuropathy: Mechanisms to management [J].
Edwards, James L. ;
Vincent, Andrea M. ;
Cheng, Hsinlin T. ;
Feldman, Eva L. .
PHARMACOLOGY & THERAPEUTICS, 2008, 120 (01) :1-34
[9]   Long-term hypothermia reduces infarct volume in aged rats after focal ischemia [J].
Florian, Baltromejus ;
Vintilescu, Raluca ;
Balseanu, Adrian Tudor ;
Buga, Ana-Maria ;
Grisk, Olaf ;
Walker, Lary C. ;
Kessler, Christof ;
Popa-Wagner, Aurel .
NEUROSCIENCE LETTERS, 2008, 438 (02) :180-185
[10]   Hydrogen sulfide attenuates lipopolysaccharide-induced inflammation by inhibition of p38 mitogen-activated protein kinase in microglia [J].
Hu, Li-Fang ;
Wong, Peter T. -H. ;
Moore, Philip K. ;
Bian, Jin-Song .
JOURNAL OF NEUROCHEMISTRY, 2007, 100 (04) :1121-1128