BACKGROUND AND PURPOSE: Recent studies reported that apoptosis was involved in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). The aim of this study was to examine whether sodium orthovanadate (SOV) prevents post-SAH apoptosis by modulating growth factors and its downstream receptor tyrosine kinases. Method- Rats were operated on with the endovascular perforation model. SAH animals were treated with vehicle, 3 mg/kg and 10 mg/kg SOV, and evaluated regarding neurofunction and brain edema. The expression of growth factors such as mature brain-derived neurotrophic factor, insulin-like growth factor-1, and vascular endothelial growth factor and phosphorylation of tropomyosin-related kinase B, which is a receptor tyrosine kinase for brain-derived neurotrophic factor and the downstream pathway in antiapoptosis, was examined by Western blot analysis. Neuronal cell death was measured with terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling staining. We also administered K252a, a tropomyosin-related kinase B antagonist, to examine the mechanisms for neuroprotective effects by SOV. RESULTS: SOV significantly improved neurofunction and reduced brain edema after SAH. SOV increased mature brain-derived neurotrophic factor and prevented post-SAH tropomyosin-related kinase B inactivation and caspase-3 activation, resulting in attenuation of neuronal cell death in the cortex and hippocampal CA1 region. Preinjection of K252a abolished the beneficial effects of SOV. CONCLUSIONS: The current study showed that brain-derived neurotrophic factor-induced tropomyosin-related kinase B activation by SOV was necessary for protection against early brain injury after SAH.
BACKGROUND AND PURPOSE: Recent studies reported that apoptosis was involved in the pathogenesis of early brain injury after subarachnoid hemorrhage (SAH). The aim of this study was to examine whether sodium orthovanadate (SOV) prevents post-SAH apoptosis by modulating growth factors and its downstream receptor tyrosine kinases. Method- Rats were operated on with the endovascular perforation model. SAH animals were treated with vehicle, 3 mg/kg and 10 mg/kg SOV, and evaluated regarding neurofunction and brain edema. The expression of growth factors such as mature brain-derived neurotrophic factor, insulin-like growth factor-1, and vascular endothelial growth factor and phosphorylation of tropomyosin-related kinase B, which is a receptor tyrosine kinase for brain-derived neurotrophic factor and the downstream pathway in antiapoptosis, was examined by Western blot analysis. Neuronal cell death was measured with terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling staining. We also administered K252a, a tropomyosin-related kinase B antagonist, to examine the mechanisms for neuroprotective effects by SOV. RESULTS:SOV significantly improved neurofunction and reduced brain edema after SAH. SOV increased mature brain-derived neurotrophic factor and prevented post-SAHtropomyosin-related kinase B inactivation and caspase-3 activation, resulting in attenuation of neuronal cell death in the cortex and hippocampal CA1 region. Preinjection of K252a abolished the beneficial effects of SOV. CONCLUSIONS: The current study showed that brain-derived neurotrophic factor-induced tropomyosin-related kinase B activation by SOV was necessary for protection against early brain injury after SAH.
Authors: Kamil Duris; Anatol Manaenko; Hidenori Suzuki; William B Rolland; Paul R Krafft; John H Zhang Journal: Stroke Date: 2011-09-29 Impact factor: 7.914
Authors: Mutsumi Fujii; Prativa Sherchan; Paul R Krafft; William B Rolland; Yoshiteru Soejima; John H Zhang Journal: J Neurol Sci Date: 2014-04-30 Impact factor: 3.181