Mild hypothermia protects against early brain injury in rats following subarachnoid hemorrhage via the TrkB/ERK/CREB signaling pathway.
Subarachnoid hemorrhage (SAH) is a severe neurological disease, which is associated with a significant number of cases of premature mortality and disability worldwide. Mild hypothermia (MH) has been proposed as a potential therapeutic strategy to reduce neuronal injury following SAH. The present study aimed to investigate the mechanisms of MH's protective role in the process of SAH. The present study demonstrated that MH was able to protect against early brain injury in a rat model of SAH. Treating SAH rats with MH reduced the release of reactive oxygen species and prevented activation of apoptotic cascades. Furthermore, the protective effects of MH were shown to be mediated by enhanced activity of the tropomyosin receptor kinase B/extracellular signal‑regulated kinases/cAMP response element binding protein (TrkB/ERK/CREB) pathway. Inhibition of TrkB/ERK/CREB activity using a small molecule inhibitor largely abolished the beneficial effects of MH in SAH rats. These results outline an endogenous mechanism underlying the neuroprotective effects of MH in SAH.
Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Ou
O
Lv
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Fenggang
F
Zhou
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Yongri
Y
Zheng
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Qingsong
Q
Li
Department of Neurosurgery, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Jianjiao
J
Wang
Department of Neurology, The Second Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang 150086, P.R. China.
Yulan
Y
Zhu
D000818:Animals; D001930:Brain Injuries / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D007036:Hypothermia, Induced / Q000379:methods*; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000378:metabolism*; D015398:Signal Transduction; D013345:Subarachnoid Hemorrhage / Q000150:complications* / Q000378:metabolism / Q000473:pathology / Q000628:therapy
D017362:Cyclic AMP Response Element-Binding Protein; D020813:Receptor, trkB; D048049:Extracellular Signal-Regulated MAP Kinases