Sruthi Ramagiri1, Rajeev Taliyan2. 1. Laboratory of Neuropharmacology, Department of Pharmacy, BITS Pilani, Pilani Campus, Rajasthan 333031, India. 2. Laboratory of Neuropharmacology, Department of Pharmacy, BITS Pilani, Pilani Campus, Rajasthan 333031, India. Electronic address: taliyanraja@gmail.com.
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.
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.