title: Alpha-lipoic acid treatment is neurorestorative and promotes functional recovery after stroke in rats.
abstract: The antioxidant properties of alpha-lipoic acid (aLA) correlate with its ability to promote neuroproliferation. However, there have been no comprehensive studies examining the neurorestorative effects of aLA administration after the onset of ischemia. The middle cerebral artery (MCA) of adult rats was occluded for 2 hours and then reperfused. aLA (20 mg/kg) was administered in 71 animals (aLA group) through the left external jugular vein immediately after reperfusion. An equivalent volume of vehicle was administered to 71 animals (control group). Functional outcome, levels of endogenous neural precursors with neurogenesis, glial cell activation, and brain metabolism were evaluated. Immediate aLA administration after reperfusion resulted in significantly reduced mortality, infarct size, and neurological deficit score (NDS) in the test group compared to the control group. Long-term functional outcomes, measured by the rotarod test, were markedly improved by aLA treatment. There was a significant increase in the number of cells expressing nestin and GFAP in the boundary zone and infarct core regions after aLA treatment. Furthermore, significantly more BrdU/GFAP, BrdU/DCX, and BrdU/NeuN double-labeled cells were observed along the boundary zone of the aLA group on days 7, 14, and 28 days, respectively. And brain metabolism using (18)F-FDG microPET imaging was markedly improved in aLA group. The effects of aLA was blocked by insulin receptor inhibitor, HNMPA (AM)3. These results indicate that immediate treatment with aLA after ischemic injury may have significant neurorestorative effects mediated at least partially via insulin receptor activation. Thus, aLA may be useful for the treatment of acute ischemic stroke.
authors.affiliation: Department of Neurology, Chonnam National University Hwasun Hospital, Hwasun, Korea. ckhchoikang@hanmail.net.|Department of Neurology, Chonnam National University Medical School, 8 Hak-dong, Dong-gu, Gwangju, 501-757, Korea. ckhchoikang@hanmail.net.
authors.forename: Kang-Ho
authors.initials: KH
authors.lastname: Choi
authors.affiliation: Department of Neurology, Chonnam National University Medical School, 8 Hak-dong, Dong-gu, Gwangju, 501-757, Korea. mspark@chonnam.ac.kr.
authors.forename: Man-Seok
authors.initials: MS
authors.lastname: Park
authors.affiliation: Department of Forensic medicine, Chonnam National University Medical School, 8 Hak-dong, Dong-gu, Gwangju, 501-757, Korea. veritas@jnu.ac.kr.
authors.forename: Hyung-Seok
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Anesthesiology and Pain Medicine, Inje University Ilsan Paik Hospital, Goyang, Korea. ktkim@paik.ac.kr.
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Kim
authors.affiliation: Department of Nuclear Medicine, Chonnam National University Hwasun Hospital, Hwasun, Korea. khs7998@daum.net.
authors.forename: Hyeon-Sik
authors.initials: HS
authors.lastname: Kim
authors.affiliation: Department of Neurology, Chonnam National University Medical School, 8 Hak-dong, Dong-gu, Gwangju, 501-757, Korea. jtkim@jnu.ac.kr.
authors.forename: Joon-Tae
authors.initials: JT
authors.lastname: Kim
authors.affiliation: Department of Neurology, Chonnam National University Medical School, 8 Hak-dong, Dong-gu, Gwangju, 501-757, Korea. Byeong.Kim@jnu.ac.kr.
authors.forename: Byeong-Chae
authors.initials: BC
authors.lastname: Kim
authors.affiliation: Department of Neurology, Chonnam National University Medical School, 8 Hak-dong, Dong-gu, Gwangju, 501-757, Korea. mkkim@jnu.ac.kr.
authors.forename: Myeong-Kyu
authors.initials: MK
authors.lastname: Kim
authors.affiliation: Department of Forensic medicine, Chonnam National University Medical School, 8 Hak-dong, Dong-gu, Gwangju, 501-757, Korea. jtpark@jnu.ac.kr.
authors.forename: Jong-Tae
authors.initials: JT
authors.lastname: Park
authors.affiliation: Department of Neurology, Chonnam National University Medical School, 8 Hak-dong, Dong-gu, Gwangju, 501-757, Korea. khcho@jnu.ac.kr.
authors.forename: Ki-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020520:Brain Infarction / Q000150:complications / Q000473:pathology; D001973:Bromodeoxyuridine / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000473:pathology; D007249:Inflammation / Q000473:pathology; D008297:Male; D064231:Nestin / Q000235:genetics / Q000378:metabolism; D049268:Positron-Emission Tomography; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D013194:Staining and Labeling; D020521:Stroke / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D013778:Tetrazolium Salts / Q000378:metabolism; D008063:Thioctic Acid / Q000494:pharmacology* / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; C000714848:Dcx protein, rat; D000089662:Doublecortin Protein; D005904:Glial Fibrillary Acidic Protein; D064231:Nestin; D012333:RNA, Messenger; D055748:SOXB1 Transcription Factors; D013778:Tetrazolium Salts; D008063:Thioctic Acid; C009591:triphenyltetrazolium; D001973:Bromodeoxyuridine; D005947:Glucose