The Neuronal Apoptotic Death in Global Cerebral Ischemia in Gerbil: Important Role for Sodium Channel Modulator

被引:17
作者
Brahma, Manoja Kumar [1 ]
Dohare, Preeti [1 ]
Varma, Saurabh [2 ]
Rath, Srikanta Kumar [3 ]
Garg, Puja [1 ]
Biswal, Prasanta Kumar [1 ]
Chowdhury, Piyali Dhar [1 ]
Ray, Madhur [1 ]
机构
[1] Cent Drug Res Inst, Div Pharmacol, Lucknow 226001, Uttar Pradesh, India
[2] Indian Council Med Res, Inst Pathol, New Delhi, India
[3] Cent Drug Res Inst, Div Toxicol, Lucknow 226001, Uttar Pradesh, India
关键词
ischemic injury; gerbil; TTX; monensin; apoptosis; NOS; NITRIC-OXIDE SYNTHASE; ENDOTHELIAL-CELLS; FOCAL ISCHEMIA; BRAIN-INJURY; NA+ CHANNEL; INHIBITION; EXPRESSION; P53; ACCUMULATION; MECHANISMS;
D O I
10.1002/jnr.21960
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Global ischemia was induced in gerbil by bilateral occlusion of the common carotid arteries for 5 min. Sodium ionophore monensin or sodium channel blocker tetrodotoxin (TTX) was administered at doses of 10 mu g/kg, i.p., 30 min before ischemia induction; the dose was repeated after 22 hr. Subsequently, brain infarct occurred, determined at 24 hr after occlusion. Large, well-demarcated infarcts were observed in both hemispheres, an important observation because it critically influences the interpretation of the data. Because nitric oxide (NO) production is thought to be related to ischemic neuronal damage, we examined increases in Ca2+ influx, which lead to the activation of nitric oxide synthase (NOS). Then we evaluated the contributions of neuronal NOS, endothelial NOS, and inducible NOS to NO production in brain cryosections. The cytosolic release of apoptogenic molecules like cytochrome c and p53 were confirmed after 24 hr of reflow. TUNEL (terminal deoxynucleotidyl transferase dUTP nick-end labeling) labeling detected the apoptotic cells, which were confirmed in neuron-rich cell populations. After 24 hr, all the ischemic changes were amplified by monensin and significantly attenuated by TTX treatment. Additionally, the nesting behavior and histological outcomes were examined after 7 day of reflow. The neuronal damage in the hippocampal area and significant decrease in nesting scores were observed with monensin treatment and reduced by TTX pretreatment after day 7 of reflow. To our knowledge, this report is the first to highlight the involvement of the voltage-sensitive Na+ channel in possibly regulating in part NO system and apoptosis in a cytochrome c-dependent manner in global ischemia in the gerbil, and thus warrants further investigation. (C) 2008 Wiey-Liss, Inc.
引用
收藏
页码:1400 / 1411
页数:12
相关论文
共 41 条
[1]   Ca2+- and phosphatidylinositol 3-kinase-dependent nitric oxide generation in lung endothelial cells in situ with ischemia [J].
Al-Mehdi, AB ;
Song, C ;
Tozawa, K ;
Fisher, AB .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (51) :39807-39810
[2]   Nesting and shredding behavior as an indicator of hippocampal ischemic damage [J].
Antonawich, FJ ;
Melton, CS ;
Wu, P ;
Davis, JN .
BRAIN RESEARCH, 1997, 764 (1-2) :249-252
[3]   Core and penumbral nitric oxide synthase activity during cerebral ischemia and reperfusion [J].
Ashwal, S ;
Tone, B ;
Tian, HR ;
Cole, DJ ;
Pearce, WJ .
STROKE, 1998, 29 (05) :1037-1046
[4]   Comparative neuroprotective effect of sodium channel blockers after experimental spinal cord injury [J].
Ates, Ozkan ;
Cayli, Suleyman R. ;
Gurses, Ilal ;
Turkoz, Yusuf ;
Tarim, Ozcan ;
Cakir, Celal O. ;
Kocak, Ayhan .
JOURNAL OF CLINICAL NEUROSCIENCE, 2007, 14 (07) :658-665
[5]   Do sodium channel blockers have neuroprotective effect after onset of ischemic insult? [J].
Ates, Ozkan ;
Cayli, Suleyman R. ;
Gurses, Iclal ;
Karabulut, Aysun Bay ;
Yucel, Neslihan ;
Kocak, Ayhan ;
Cakir, Celal Ozbek ;
Yologlu, Saim .
NEUROLOGICAL RESEARCH, 2007, 29 (03) :317-323
[6]   Activation of voltage-sensitive sodium channels during oxygen deprivation leads to apoptotic neuronal death [J].
Banasiak, KJ ;
Burenkova, O ;
Haddad, GG .
NEUROSCIENCE, 2004, 126 (01) :31-44
[7]   Sodium calcium exchange: Its physiological implications [J].
Blaustein, MP ;
Lederer, WJ .
PHYSIOLOGICAL REVIEWS, 1999, 79 (03) :763-854
[8]   Roles of nitric oxide in brain hypoxia-ischemia [J].
Bolaños, JP ;
Almeida, A .
BIOCHIMICA ET BIOPHYSICA ACTA-BIOENERGETICS, 1999, 1411 (2-3) :415-436
[9]   Sodium-calcium exchanger contributes to membrane hyperpolarization of intact endothelial cells from rat aorta during acetylcholine stimulation [J].
Bondarenko, A .
BRITISH JOURNAL OF PHARMACOLOGY, 2004, 143 (01) :9-18
[10]   Expression of calcium-sensing receptor in rat colonic epithelium: evidence for modulation of fluid secretion [J].
Cheng, SX ;
Okuda, M ;
Hall, AE ;
Geibel, JP ;
Hebert, SC .
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY, 2002, 283 (01) :G240-G250