Protective Effect Of GKAB And Its Inhibitory Effect On NF-κB Signaling Pathway On Permanent Focal Cerebral Ischemia In Rats

Aim: To investigate the neuroprotective effects of Ginkgolide AB (GKAB) and the relationships between its neuroprotection and inhibition of NIK-IKK/IκB/NF-κB/c-Myc signaling pathway in rat model of permanent focal cerebral ischemia.Methods: Permanent middle cerebral artery occlusion (pMCAO) model was induced by using intraluminal filament technique in rats. GKAB (12.5, 25, 50mg/kg) was administrated intravenously(iv) at 10 min after the onset of ischemia. The neuroprotection of GKAB was analyzed by scoring neurological deficits, assessing brain infarction volume with 2,3,5-triphenyltetrazolium chloride (TTC), determining the brain water content and evaluating the morphologic changes and neuronal damage with Hematoxylin and eosin staining 24 h after ischemia. Western blot analysis was employed to determine alterations in NF-κB p65, IκBα, pIKKαin ischemic cortex and p-NIK in ischemic cortex or striatum or hippocampus at the indicated time. Brain sections were immunostained for NF-κB p65. RT-PCR was used to measure c-Myc mRNA levels.Results: GKAB (12.5, 25, 50mg/kg) reduced infarction volume in a dose-dependent manner (P< 0.05, P< 0.01) when administered at 10 min following the onset of ischemia in rats. GKAB (12.5, 25, 50mg/kg) also significantly ameliorated motor behavior deficits, diminished the increase in brain water content and reduced the extent of ischemic cell injury after cerebral ischemia (P< 0.05, P< 0.01). Western blot analysis revealed that GKAB(12.5,25,50mg/kg) significantly decreased overall protein levels of NF-κB p65 in the ischemic cortex at 12 h after ischemia (P< 0.01). In addition, GKAB (25,50mg/kg) markedly up-regulated the levels of IκBαin the ischemic cortex at 6 h after ischemia (P <0.05, P <0.01). GKAB(12.5,25,50mg/kg) significantly decreased the levels of pIKKα...