The role of the sonic hedgehog signaling pathway in early brain injury after experimental subarachnoid hemorrhage in rats.
Previous studies have demonstrated that the sonic hedgehog (Shh) pathway plays a neuro-protective role. However, whether the Shh pathway is induced by subarachnoid hemorrhage (SAH) has not been investigated. We sought to investigate Shh activation in the cortex in the early stage of SAH, and assessed the effect of cyclopamine (a specific inhibitor of the Shh pathway) on Shh pathway regulation and evaluated the impact of cyclopamine on SAH. We found that the Shh pathway was up-regulated in the cortex after SAH, and that blocking the Shh pathway increased cell apoptosis. Early brain damages, including brain edema, blood-brain barrier impairment, and cortical apoptosis were significantly aggravated following with cyclopamine treatment compared with vehicle treatment. Our results suggest that the Shh pathway should be activated in the brain after SAH, and plays a beneficial role in SAH development, possibly by inhibiting cerebral oxidative stress through induction of antioxidant and detoxifying enzymes.
Beijing Tiantan Hospital, Capital Medical University, Beijing 100050, PR China; The First Hospital of Dalian Medical University, Dalian 116021, PR China.
Tao
T
Li
Jie
J
Zhang
Rong-Yao
RY
Liu
Zhi-Gang
ZG
Lian
Xiao-Lin
XL
Chen
Li
L
Ma
Hao-Min
HM
Sun
Yuan-Li
YL
Zhao
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000150:complications / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D002540:Cerebral Cortex / Q000293:injuries / Q000378:metabolism*; D053823:Hedgehog Proteins / Q000378:metabolism*; D008297:Male; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D013345:Subarachnoid Hemorrhage / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects; D014704:Veratrum Alkaloids / Q000494:pharmacology
D053823:Hedgehog Proteins; C546888:Shh protein, rat; D014704:Veratrum Alkaloids; C000541:cyclopamine
Cyclopamine; Early brain injury; Sonic hedgehog pathway; Subarachnoid hemorrhage