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Evidence for the role of histaminergic pathways in neuroprotective mechanism of ischemic postconditioning in mice
Author(s) -
Kaur Indresh,
Kumar Amit,
Jaggi Amteshwar S.,
Singh Nirmal
Publication year - 2017
Publication title -
fundamental and clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.655
H-Index - 73
eISSN - 1472-8206
pISSN - 0767-3981
DOI - 10.1111/fcp.12275
Subject(s) - histaminergic , neuroprotection , pharmacology , morris water navigation task , acetylcholinesterase , tbars , anesthesia , medicine , chemistry , lipid peroxidation , histamine , oxidative stress , hippocampus , biochemistry , enzyme
The present study has been designed to investigate the possible role of histaminergic pathway in neuroprotective mechanism of ischemic postconditioning ( iPoC o). Bilateral carotid artery occlusion ( BCAO ) for 12 min followed by reperfusion for 24 h was employed to produce I/R‐induced cerebral injury in National Institutes of Health mice mice. iPoC o involving three episodes of carotid artery occlusion and reperfusion of 10 sec each was instituted immediately after BCAO just before prolonged reperfusion. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using Morris water maze test. Rotarod test, inclined beam‐walking test, and neurological severity score ( NSS ) were performed to assess motor incoordination and sensorimotor abilities. Brain acetylcholine esterase ( AC hE) activity, brain myeloperoxidase ( MPO ) activity, brain thiobarbituric acid‐reactive species ( TBARS ), and glutathione level ( GSH ) were also estimated. BCAO produced a significant rise in cerebral infarct size and NSS along with impairment of memory and motor coordination and biochemical alteration (↑ AC hE, ↑ MPO ↓ GSH , and ↑ TBARS ). iPoC o attenuated the deleterious effect of BCAO on infarct size, memory, NSS , motor coordination, and biochemical markers. Pretreatment of carnosine (a histamine [HA] precursor) potentiated the neuroprotective effects of iPoC o, whereas pretreatment of ketotifen (HA H1 receptor blocker and mast cell stabilizer) abolished the protective effects of iPoC o as well as that of carnosine on iPoC o. It may be concluded that neuroprotective effect of iPoC o probably involves activation of histaminergic pathways.