title: Aging causes exacerbated ischemic brain injury and failure of sevoflurane post-conditioning: role of B-cell lymphoma-2.
abstract: Aging is associated with exacerbated brain injury after ischemic stroke. Herein, we explored the possible mechanisms underlying the age-associated exacerbated brain injury after ischemic stroke and determined whether therapeutic intervention with anesthetic post-conditioning would provide neuroprotection in aged rats. Male Fisher 344 rats (young, 4 months; aged, 24 months) underwent 2h of middle cerebral artery occlusion (MCAO) followed by 24-h reperfusion, with or without sevoflurane post-conditioning for 15 min immediately at the onset of reperfusion. Compared with young rats, aged rats showed larger infarct size, worse neurological scores and more TUNEL-positive cells in the penumbral cerebral cortex at 24h after MCAO. However, edema formation and motor coordination were similar in both groups. Sevoflurane reduced the infarct size, edema formation, and TUNEL-positive cells, and improved the neurological outcome in young rats but not in aged rats. Molecular studies revealed that basal expression of the anti-apoptotic molecule B-cell lymphoma-2 (Bcl-2) in the brain was lower in aged rats compared with young rats before MCAO, while basal expression of the pro-apoptotic molecule Bcl-2-associated X protein (Bax) showed similar levels in both groups. MCAO reduced Bcl-2 expression and increased Bax expression in both groups; however, Bax increase was more pronounced in aged rats. In young rats, sevoflurane reversed the above MCAO-induced changes. In contrast, sevoflurane failed to enhance Bcl-2 expression but decreased Bax expression in aged rats. These findings suggest that aging-associated reduction in basal Bcl-2 expression in the brain contributes to increased neuronal injury by enhancing cell apoptosis after ischemic stroke. Sevoflurane post-conditioning failed to provide neuroprotection in aged rats, probably due to its inability to increase Bcl-2 levels and prevent apoptosis in the brain.
authors.affiliation: Department of Anesthesiology, Qilu Hospital, Shandong University, No. 44 Wenhua Xi Road, Jinan City, Shandong Province 250012, China.
authors.forename: P
authors.initials: P
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, The People's Hospital of Chiping, No. 136 Wenhua Road, Chiping City, Shandong Province 252100, China.
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Department of Anesthesiology, The First People's Hospital of Jining, No. 6 Jiankang Road, Jining City, Shandong Province 272011, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Gynaecology and Obstetrics, Qilu Hospital, Shandong University, No. 44 Wenhua Xi Road, Jinan City, Shandong Province 250012, China.
authors.forename: J
authors.initials: J
authors.lastname: Dong
authors.affiliation: Department of Anesthesiology, Qilu Hospital, Shandong University, No. 44 Wenhua Xi Road, Jinan City, Shandong Province 250012, China.
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Qilu Hospital, Shandong University, No. 44 Wenhua Xi Road, Jinan City, Shandong Province 250012, China.
authors.forename: D
authors.initials: D
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Qilu Hospital, Shandong University, No. 44 Wenhua Xi Road, Jinan City, Shandong Province 250012, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, Qilu Hospital, Shandong University, No. 44 Wenhua Xi Road, Jinan City, Shandong Province 250012, China.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Anesthesiology, Qilu Hospital, Shandong University, No. 44 Wenhua Xi Road, Jinan City, Shandong Province 250012, China.
authors.forename: B
authors.initials: B
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, Qilu Hospital, Shandong University, No. 44 Wenhua Xi Road, Jinan City, Shandong Province 250012, China. Electronic address: lei-wf@hotmail.com.
authors.forename: W
authors.initials: W
authors.lastname: Lei
mesh_terms: D000367:Age Factors; D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D004195:Disease Models, Animal; D057775:Ischemic Postconditioning / Q000379:methods*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D011916:Rats, Inbred F344; D000077149:Sevoflurane; D020521:Stroke / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D016896:Treatment Outcome
chemical_list: D008738:Methyl Ethers; D018696:Neuroprotective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D000077149:Sevoflurane
keywords: Aging; Anesthetic post-conditioning; Apoptosis; B-cell lymphoma-2; Ischemic stroke