The Treatment Effect And Related Mechanism Of Exogenous Pyruvate In Early Brain Injury After Subarachnoid Hemorrhage

Objective 1.The purpose of this study is to construct a subarachnoid hemorrhage(SAH)rabbit model which can reflect the early pathophysiological changes after SAH.The stability and reliability of the animal model were verified via intracranial pressure monitor,SAH scores,neurological function scores,Terminal deoxynucleotidyl transferase dUTP nick end labeling(TUNEL)strain and Fluoro-jade B(FJB)strain.2.The treatment effect and related mechanism of exogenous pyruvate in early brain injury(EBI)after SAH were investigated from iconography,histology and molecular biology.MethodsA total of 97 New Zealand rabbits(weight=3±0.5kg)were used in the present study to investigate the method of constructing the SAH rabbit model and the treatment effect and related mechanism of exogenous pyruvate in EBI after SAH.The rabbits were divided randomly into sham operation group(undergoing super choice imaging carotid artery without puncture,n=10),other 87 rabbits underwent endovascular puncture under the guidance of digital subtraction angiography and were divided randomly into SAH6h+Vehicle(equal volume),SAH24h+Vehicle,SAH72h+Vehicle,SAH24h+EP(30mg/kg/d)and SAH72h+EP(n=10).The SAH scores were recorded to assess the amount of bleeding,the neurological scores were recorded to assess the neurological deficit,MRI was performed to estimate the reliability of the EBI,intraoperative changes of intracranial pressure(ICP)of animal were observed via ICP monitor,TUNEL and FJB staining were used to detect neuronal apoptosis and neurodegeneration respectively,hematoxylin and eosin(H&E)staining was used to assess the degree of vasospasm,ELISA kit was used to measure the level of tumor necrosis factor-?(TNF-?),and western blot was used to detect the expression of TNF-?,tJNK,pJNK,Bax and Bcl-2.Results 1.The success rate of SAH rabbit model was 57.47%(50/87).The degree of intracranial hemorrhage varied from each other and the neurological dysfunction was observed.ICP monitor showed an acute increasing ICP after endovascular puncture and TUNEL and FJB staning proved that the there were issue degeneration,necrosis and apoptosis both in the cortex and hippocampus after endovascular puncture.2.Our results demonstrated that exogenous pyruvate alleviated EBI in MRI and significantly improved neurological scores at 72 h after SAH,while there were no statistical differences between SAH+Vehicle and SAH+EP in SAH scores.Exogenous pyruvate decreased the level of TNF-? and downregulated pJNK/tJNK and Bax/Bcl-2 in cerebral cortex and hippocampus effectively both at 24 h and 72 h after SAH.Furthermore,exogenous pyruvate reduced TUNEL and FJB positive cells significantly.Simultaneously,exogenous pyruvate attenuated acute vasospasm after SAH.Conclusions 1.The endovascular puncture can introduce early brain injury after subarachnoid hemorrhage and stimulates changes in hemodynamics and pathophysiology successfully.2.The present study supported that EP attenuated early brain injury after subarachnoid hemorrhage,relieved neurological dysfunction,reduced the degree of vasopasm and afforded neuroprotective effects possibly via reducing TNF-? expression and inhibition of the JNK signaling pathway.