Aim: Remote ischemic post conditioning (RIPOC) has shown to be neuroprotective against cerebral ischemic reperfusion (I/R) injury. However, the RIPOC protection against I/R injury induced cognitive abnormalities still remains elusive. Abundant evidence from earlier studies highlighted the role of heme oxygenase-1 (HO-1) in neuronal survival in various neurodegenerative disorders. Thus, in the present study, we investigated the possible contribution of HO-1 in RIPOC mediated neuroprotection against cerebral I/R injury and associated cognitive deficits.
Experimental procedure: Rats were subjected to bilateral common carotid occlusion model to induce I/R injury. RIPOC was achieved by 3 cycles of ischemia (10min) and reperfusion (10min) of bilateral femoral artery. Behavioral, biochemical and histological evaluation was performed. The levels of Tumor Necrosis Factor (TNF-α) were estimated. To further confirm molecular mechanism, HO-1 and Brain Derived Neurotrophic Factor (BDNF) activities were estimated.
Results: Ischemic injury resulted in severe neurological deficits and cognitive abnormalities besides elevating oxidative stress and neuroinflammation. RIPOC intervention improved the behavioral parameters and anti-oxidant content. In addition, RIPOC decreased the levels of oxidative markers and pro-inflammatory cytokines like TNF-α. Moreover, RIPOC significantly upregulated HO-1 and neurotrophin including BDNF. Marked reduction in hippocampal structural abnormalities were observed with RIPOC intervention. SnPP treatment reversed the protective effects of RIPOC.
Conclusion: These findings suggest that the neuroprotective effects of RIPOC during early reperfusion may be mediated through upregulation of HO-1 and BDNF, as the conditioning stimulus was found ineffective in presence of HO-1 inhibitor.
Keywords: BDNF; Cerebral ischemic reperfusion injury; Heme oxygenase; Neuroprotection; Remote ischemic post conditioning.
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