Protective effect of remote limb post conditioning via upregulation of heme oxygenase-1/BDNF pathway in rat model of cerebral ischemic reperfusion injury.

Abstract

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.

DOI: 10.1016/j.brainres.2017.05.016

Cite this paper

@article{Ramagiri2017ProtectiveEO, title={Protective effect of remote limb post conditioning via upregulation of heme oxygenase-1/BDNF pathway in rat model of cerebral ischemic reperfusion injury.}, author={Sruthi Ramagiri and Rajeev Taliyan}, journal={Brain research}, year={2017}, volume={1669}, pages={44-54} }