Neuroprotective effects of ultra-low-molecular-weight heparin on cerebral ischemia/reperfusion injury in rats: involvement of apoptosis, inflammatory reaction and  energy metabolism.
Previous experiments showed that ultra-low-molecular-weight heparin (ULMWH) reduced the infarct and neurologic deficit in rats followed by transient cerebral ischemia, but the mechanisms of its neuroprotective effect are unclear. This study reported the effect of ULMWH on energy metabolism, inflammatory reaction and neuronal apoptosis. Male Wistar rats were subjected to middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 24 h. ULMWH (0.5, 1 mg/kg, i.v.) was administered after the MCAO and reperfusion. 24 h after the reperfusion, Spectrophotometric assay was used to determine the activity of ATPase and the content of lactic acid in the brain. The ICAM-1 and Caspase-3 genes were investigated by RT-PCR. Furthermore, the apoptotic percentage of cells in hippocampus was quantified by flow cytometry. Compared with the model group, ULMWH significantly decreased lactic acid content and increased ATPase activity in ischemic brain. At the same time, ULMWH inhibited the neural apoptosis and decreased the expressions of ICAM-1 and Caspase-3 mRNA in hippocampus. These findings suggest that ULMWH exhibits a neuroprotective effect against cerebral ischemia/reperfusion injury, partly through improving energy metabolism, inhibiting apoptosis and attenuating inflammatory reaction.
Department of Pharmacy, the 88th Hospital of PLA, Hushan East Road, Tai'an 271000, Shandong, China. sdzhangqz@163.com.
Zhi-Guo
ZG
Zhang
Xin
X
Sun
Qing-Zhu
QZ
Zhang
Hua
H
Yang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001927:Brain Diseases / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D004734:Energy Metabolism / Q000187:drug effects*; D005343:Fibrinolytic Agents / Q000494:pharmacology*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology
D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight