Selenium plays a modulatory role against cerebral ischemia-induced neuronal damage in rat hippocampus.
During cerebral ischemic cascade, a unifying factor which leads to mitochondrial dysfunctions is lack of oxygen followed by decrease in ATP production. The present study demonstrates the effect of selenium pretreatment (0.1 mg/kg as sodium selenite, i.p, 7 days) on cerebral ischemia-induced altered levels of mitochondrial ATP content, intracellular calcium (Ca(i)(2+)) in synaptosomes, expression of heat stress protein (Hsp70) and caspase-3 activity in hippocampus followed by neurobehavioral deficits and histopathological changes in Wistar rats. Cerebral ischemia was induced for 2 h followed by reperfusion for 22 h. It was observed that levels of (Ca(i)(2+)), Hsp70 and caspase-3 activity were significantly (p<0.01-0.001) higher with a marked decrease in ATP level in hippocampus of ischemic group as compared to sham values. Subsequently, a marked change was observed in neurobehavioral activities in ischemic animals as compared to control one. As a result of selenium pretreatment, a significant (p<0.05-0.001) trend of restoration was observed in the level of ATP, (Ca(i)(2+)), Hsp70, caspase-3 and behavioral outputs as compared to ischemic group. Histopathological analysis confirmed the protective effect of selenium against cerebral ischemia induced histological alterations as evidenced by lesser edema formation and separation of cells with minimal microglial cell infiltration in selenium pretreated group as compared to ischemic animals. The present study suggests that selenium may be able to salvage the ischemic penumbral zone neurons, thereby limiting ischemic cell death.
Yousuf
Seema
S
Neurotoxicology Laboratory, Department of Medical Elementology & Toxicology, Jamia Hamdard (Hamdard University), New Delhi 110062, India.
Atif
Fahim
F
Ahmad
Muzamil
M
Hoda
Md Nasrul
MN
Khan
M Badruzzaman
MB
Ishrat
Tauheed
T
Islam
Fakhrul
F
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology; D002118:Calcium / Q000378:metabolism; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004334:Drug Administration Schedule; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012643:Selenium / Q000008:administration & dosage / Q000494:pharmacology*; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors
D018840:HSP70 Heat-Shock Proteins; D018696:Neuroprotective Agents; D000255:Adenosine Triphosphate; D053148:Caspase 3; D012643:Selenium; D002118:Calcium