Ting Yu1, Yunren Fan1, Yunfeng Xu1, Liangdie Xu1, Guangda Xu1, Fangchuan Cao1, Hailong Jiang2. 1. Department of Neurosurgery, Tiantai County People's Hospital, Laodong Road 335th, Taizhou, 317200, China. 2. Department of Neurosurgery, Tiantai County People's Hospital, Laodong Road 335th, Taizhou, 317200, China. Electronic address: nsjianghailong@163.com.
Abstract
BACKGROUND: Early brain injury (EBI) plays a critical role in determining the outcome of subarachnoid hemorrhage (SAH). The present study was designed to investigate the role of EGb 761, a standardized extract of Ginkgo biloba, in SAH-induced EBI and to explore its potential mechanism of action. METHOD: A rat SAH model was established by the endovascular perforation process. Doses of 10, 50 and 100 mg/kg EGb 761 were injected intraperitoneally 2 h after SAH was induced. Mortality, SAH grade, neurological score and brain water content were measured 24 h after SAH was induced. A Western blot assay was performed to assess the expression of the apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3, Akt and phosphorylated Akt (p-Akt). Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and neuronal nuclei (NeuN) double immunofluorescence staining were used to detect apoptotic neurons. RESULTS: Animals suffered from serious neurological deficits and increased brain water content after induction of SAH. Rats treated with EGb 761 experienced dose-dependent attenuation of neurological dysfunction and decreased brain water content. In addition, EGb 761 significantly activated Akt signaling accompanied by increased Bcl-2 levels and decreased expression of Bax and cleaved caspase-3. Moreover, EGb 761 decreased the number of TUNEL/NeuN-positive cells in a dose-dependent manner. However, all the beneficial effects of EGb 761 for SAH were abolished by the Akt inhibitor MK2206. CONCLUSION: Our results indicated that EGb 761 could ameliorate SAH-induced EBI and that the neuroprotective effects of EGb 761 against SAH were exerted via suppression of neuronal apoptosis through activation of the Akt pathway.
BACKGROUND: Early brain injury (EBI) plays a critical role in determining the outcome of subarachnoid hemorrhage (SAH). The present study was designed to investigate the role of EGb 761, a standardized extract of Ginkgo biloba, in SAH-induced EBI and to explore its potential mechanism of action. METHOD: A ratSAH model was established by the endovascular perforation process. Doses of 10, 50 and 100 mg/kg EGb 761 were injected intraperitoneally 2 h after SAH was induced. Mortality, SAH grade, neurological score and brain water content were measured 24 h after SAH was induced. A Western blot assay was performed to assess the expression of the apoptosis-related proteins Bax, Bcl-2, cleaved caspase-3, Akt and phosphorylated Akt (p-Akt). Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) and neuronal nuclei (NeuN) double immunofluorescence staining were used to detect apoptotic neurons. RESULTS: Animals suffered from serious neurological deficits and increased brain water content after induction of SAH. Rats treated with EGb 761 experienced dose-dependent attenuation of neurological dysfunction and decreased brain water content. In addition, EGb 761 significantly activated Akt signaling accompanied by increased Bcl-2 levels and decreased expression of Bax and cleaved caspase-3. Moreover, EGb 761 decreased the number of TUNEL/NeuN-positive cells in a dose-dependent manner. However, all the beneficial effects of EGb 761 for SAH were abolished by the Akt inhibitor MK2206. CONCLUSION: Our results indicated that EGb 761 could ameliorate SAH-induced EBI and that the neuroprotective effects of EGb 761 against SAH were exerted via suppression of neuronal apoptosis through activation of the Akt pathway.