PMID- 28535981 OWN - NLM STAT- MEDLINE DCOM- 20180412 LR - 20220310 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1669 DP - 2017 Aug 15 TI - Protective effect of remote limb post conditioning via upregulation of heme oxygenase-1/BDNF pathway in rat model of cerebral ischemic reperfusion injury. PG - 44-54 LID - S0006-8993(17)30212-3 [pii] LID - 10.1016/j.brainres.2017.05.016 [doi] AB - 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-alpha) 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-alpha. 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. CI - Copyright (c) 2017 Elsevier B.V. All rights reserved. FAU - Ramagiri, Sruthi AU - Ramagiri S AD - Laboratory of Neuropharmacology, Department of Pharmacy, BITS Pilani, Pilani Campus, Rajasthan 333031, India. FAU - Taliyan, Rajeev AU - Taliyan R AD - Laboratory of Neuropharmacology, Department of Pharmacy, BITS Pilani, Pilani Campus, Rajasthan 333031, India. Electronic address: taliyanraja@gmail.com. LA - eng PT - Journal Article DEP - 20170520 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Antioxidants) RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 3.1.1.7 (Acetylcholinesterase) SB - IM MH - Acetylcholinesterase/metabolism MH - Animals MH - Antioxidants/metabolism MH - Association Learning MH - Brain Ischemia/metabolism/pathology/*therapy MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Disease Models, Animal MH - Femoral Artery MH - Heme Oxygenase-1/antagonists & inhibitors/*metabolism MH - Hippocampus/metabolism/pathology MH - *Ischemic Postconditioning MH - Male MH - Memory MH - Motor Activity MH - Neurons/metabolism/pathology MH - Random Allocation MH - Rats, Wistar MH - Reperfusion Injury/metabolism/pathology/*therapy MH - Tumor Necrosis Factor-alpha/metabolism MH - Up-Regulation OTO - NOTNLM OT - BDNF OT - Cerebral ischemic reperfusion injury OT - Heme oxygenase OT - Neuroprotection OT - Remote ischemic post conditioning EDAT- 2017/05/26 06:00 MHDA- 2018/04/13 06:00 CRDT- 2017/05/25 06:00 PHST- 2017/02/11 00:00 [received] PHST- 2017/05/10 00:00 [revised] PHST- 2017/05/15 00:00 [accepted] PHST- 2017/05/26 06:00 [pubmed] PHST- 2018/04/13 06:00 [medline] PHST- 2017/05/25 06:00 [entrez] AID - S0006-8993(17)30212-3 [pii] AID - 10.1016/j.brainres.2017.05.016 [doi] PST - ppublish SO - Brain Res. 2017 Aug 15;1669:44-54. doi: 10.1016/j.brainres.2017.05.016. Epub 2017 May 20.