Neuroprotective Effect of DAHP via Antiapoptosis in Cerebral Ischemia

Behavioural Neurology
Yanhua QinMarong Fang

Abstract

Aberrant production of nitric oxide following inducible nitric oxide synthase (iNOS) expression has been implicated in cell death and contributes to ischemic brain injury. Tetrahydrobiopterin (BH4) is an essential cofactor of NOS activity. Herein, we evaluated antiapoptotic and anti-inflammatory effects of diamino-6-hydroxypyrimidine (DAHP), a guanosine 5'-triphosphate cyclohydrolase 1 (GTPCH1) inhibitor on focal cerebral ischemia-reperfusion injury by middle cerebral artery occlusion and reperfusion (MCAO) and investigated the underlying mechanism. Sprague-Dawley rats were divided into five groups. Experimental groups were subjected to 1.5 h transient MCAO. T2-weighted imaging was performed to evaluate brain edema lesions in the stroke rats. Infarct volume was estimated by 2,3,5-triphenyltetrazolium chloride (TTC) staining after 24 h reperfusion. Western blotting and immunohistochemistry were performed to detect iNOS, caspase-3, Bcl-2, COX-2, and TNF-α protein expressions. Apoptosis was determined by TUNEL staining. T2 hyperintensity changes were observed in primary ischemic region. DAHP pretreatment significantly suppressed iNOS overexpression, caspase-3, and TNF-α. There was also attenuation of neuronal apoptosis with decrem...Continue Reading

References

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Citations

Nov 14, 2019·Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas·Jing XuZhijuan Liu
Feb 3, 2018·Small·Guangzhao Qin, Ming Hu
Jan 17, 2019·Evidence-based Complementary and Alternative Medicine : ECAM·Tian XuFafeng Cheng

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Methods Mentioned

BETA
protein assay

Software Mentioned

Image
GraphPad Prism
SPSS
Pro Plus
Image Pro Plus

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