Inhibiting the aberrant PACT-p53 axis activation ameliorates spinal cord ischaemia-reperfusion injury in rats

Spinal cord ischaemia-reperfusion injury (SCII) induces multiple molecular and cellular changes, resulting in dyskinesia. Recently, it is reported that the p53 network plays a vital role in SCII. However, the roles of the PACT/PRKRA (interferon-inducible double-stranded RNA-dependent protein kinase activator A)-p53 axis in SCII are still unclear. The aim of this study was to elucidate the roles of the PACT-p53 axis in SCII. A Sprague-Dawley rat model of SCII was established by subjecting rats to a 14-min occlusion of the aortic arch. The Tarlov criteria, Western blotting, double immunofluorescence staining, haematoxylin and eosin (HE) staining, and transferase dUTP nick end labelling (TUNEL) assay were performed after SCII. Here, spinal cord ischaemia-reperfusion (SCI) caused hindlimb motor functional deficits as assessed by the Tarlov criteria. The protein expression of PACT was substantially upregulated at 48 h after SCII. Increased PACT fluorescence was mainly localized to neurons. Si-PACT pretreatment improved hindlimb motor function, ameliorated histological changes, and attenuated cell apoptosis after SCII. Si-PACT pretreatment reduced the protein expression of PACT, p53, Caspase-8 and IL-1β and the number of double-labelled PACT and p53. Taken together, inhibiting the aberrant PACT-p53 axis activation by si-PACT pretreatment ameliorates SCI-induced neuroapoptosis and neuroinflammation in rats. Silencing PACT expression is promising new therapeutic strategy for SCII.