title: Cerebral ischemia-induced mitochondrial changes in a global ischemic rat model by AFM.
abstract: Mitochondria play a central role in cell survival, and apoptotic cell death is associated with morphological changes in mitochondria. Quantification of the morphological and mechanical property changes in brain mitochondria is useful for evaluating the degree of ischemic injury and the neuroprotective effects of various drugs. This study was performed to investigate the changes in brain mitochondria in an 11-vessel occlusion ischemic model treated with magnesium sulfate (MgSO4), utilizing atomic force microscopy (AFM). Rats were randomly divided into three groups consisting of sham (n=6), global ischemia (GI, n=6), and MgSO4-treated global ischemia (MgSO4, n=6). The biophysical properties of brain mitochondria determined from AFM topographic images and adhesion force from force-distance measurements. The mean perimeter of ischemic mitochondria significantly increased to 2,396±541 nm (vs. 1,006±318 nm in control group, P<0.001). The MgSO4 treatment during global ischemia reduced the perimeter of ischemic mitochondria (1,127±399 nm, P<0.001). The other parameters including length, width and area were significantly different than the GI group. Besides, the adhesion force (23.2±3.9 nN) of isolated mitochondria from the MgSO4 group was close to normal levels (28.5±2.5 nN), compared with that of ischemic ones (17.7±3.3 nN, P<0.001). To confirm the neuroprotective effects of MgSO4, we performed Nissl staining. This study suggested that quantitative analysis of mitochondrial changes utilizing AFM could be effective for evaluating neuronal injury and drug effects.
authors.affiliation: Department of Medical Genetics, Ajou University School of Medicine, Suwon 443-721, Republic of Korea.
authors.forename: Eunkuk
authors.initials: E
authors.lastname: Park
authors.affiliation: Department of Neurosurgery, Kyung Hee University Hospital, Seoul 130-702, Republic of Korea.
authors.forename: Seok Keun
authors.initials: SK
authors.lastname: Choi
authors.affiliation: Department of Biomedical Engineering & Healthcare Industry Research Institute, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Sung Wook
authors.initials: SW
authors.lastname: Kang
authors.affiliation: Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Youngmi Kim
authors.initials: YK
authors.lastname: Pak
authors.affiliation: Department of Biomedical Engineering & Healthcare Industry Research Institute, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea. Electronic address: gjlee@khu.ac.kr.
authors.forename: Gi-Ja
authors.initials: GJ
authors.lastname: Lee
authors.affiliation: Department of Pharmacology & Kowhang Medical Research Institute, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Joo-Ho
authors.initials: JH
authors.lastname: Chung
authors.affiliation: Department of Biomedical Engineering & Healthcare Industry Research Institute, College of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea.
authors.forename: Hun-Kuk
authors.initials: HK
authors.lastname: Park
mesh_terms: D000818:Animals; D002545:Brain Ischemia / Q000473:pathology*; D004195:Disease Models, Animal; D006624:Hippocampus / Q000473:pathology; D008278:Magnesium Sulfate / Q000494:pharmacology; D008297:Male; D018625:Microscopy, Atomic Force / Q000379:methods*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000648:ultrastructure; D017207:Rats, Sprague-Dawley
chemical_list: D008278:Magnesium Sulfate
keywords: AFM; Brain mitochondria; Cerebral ischemia; Neuroprotective; Quantitative analysis