ABSTRACT
Neuronal apoptosis is one of the essential mechanisms of early brain injury after subarachnoid hemorrhage (SAH). Recently, HLY78 has been shown to inhibit apoptosis in tumor cells and embryonic cells caused by carbon ion radiation through activation of the Wnt/β-catenin pathway. This study was designed to explore the anti-apoptotic role of HLY78 in experimental SAH. The results demonstrated that HLY78 attenuated neuronal apoptosis and the neurological deficits after SAH through the activation of low-density lipoprotein receptor-related protein 6 (LRP6), which subsequently increased the level of phosphorylated glycogen synthesis kinase 3 beta (p-GSK3β) (Ser9), β-catenin, and Bcl-2, accompanied by a decrease of p-β-catenin, Bax, and cleaved caspase 3. An LRP6 small-interfering ribonucleic acid reversed the effects of HLY78. In conclusion, HLY78 attenuates neuronal apoptosis and improves neurological deficits through the LRP6/GSK3β/β-catenin signaling pathway after SAH in rats. HLY78 is a promising therapeutic agent to attenuate early brain injury after SAH.
ABSTRACT
Neuronal apoptosis is one of the essential mechanisms of early brain injury after subarachnoid hemorrhage (SAH). Recently, HLY78 has been shown to inhibit apoptosis in tumor cells and embryonic cells caused by carbon ion radiation through activation of the Wnt/β-catenin pathway. This study was designed to explore the anti-apoptotic role of HLY78 in experimental SAH. The results demonstrated that HLY78 attenuated neuronal apoptosis and the neurological deficits after SAH through the activation of low-density lipoprotein receptor-related protein 6 (LRP6), which subsequently increased the level of phosphorylated glycogen synthesis kinase 3 beta (p-GSK3β) (Ser9), β-catenin, and Bcl-2, accompanied by a decrease of p-β-catenin, Bax, and cleaved caspase 3. An LRP6 small-interfering ribonucleic acid reversed the effects of HLY78. In conclusion, HLY78 attenuates neuronal apoptosis and improves neurological deficits through the LRP6/GSK3β/β-catenin signaling pathway after SAH in rats. HLY78 is a promising therapeutic agent to attenuate early brain injury after SAH.
ABSTRACT
Although the treatment of aneurysmal subarachnoid hemorrhage (SAH) has made considerable progress in recent years,its mortality and disability have not been effectively controlled.Ischemic brain injury after SAH is considered to be an important reason for the poor prognosis of patients; however,its mechanism is still not fully understood.Studies have shown that the cerebral microcirculation disturbance after SAH is closely associated with ischemic brain injury.This article reviews the advances in research on cerebral microcirculation disturbance and ischemic brain injury after SAH.
ABSTRACT
Objective To explore the dynamic changes of blood brain barrier(BBB)permeability after experimental subarachnoid hemorrhage(SAH)in rats.Methods Eighty female SD rats were divided into normal saline control group(n=10)and SAH group(n=70).The SAH model was induced by injecting 300 ?l of autologous arterial blood into the subarachnoid space near the circle of Willis via a cannula in an artificial hole between the olfactory bulb and frontal lobe.BBB permeability in cerebral cortex of SAH and normal saline rats was assessed at 6,12,24,36,48,60,and 72 h after SAH establishment by fluorescence spectrophotometer and fluorescence microscopy for Evans Blue(EB)extravasation.The ultrastructural changes in BBB were observed with transmission electron microscope.Results Compared with the control group,the changes of Evans Blue content and extravasation in cerebral cortex of SAH group peaked at 36 h(P0.05).The severe ultrastructural abnormality was found at 36 h after SAH.Conclusion The changes of BBB permeability develop at the acute stage of SAH,resulting from multiple factors together.The BBB after SAH possesses a self-repairable property.
ABSTRACT
0.05).ICP increased rapidly to the maximum 1min after SAH(P