Adiponectin protects hippocampal neurons against kainic acid-induced excitotoxicity.
Neuronal damage after seizure is correlated with blood-brain barrier (BBB) leakage. Adiponectin (Ad) has shown protective effects on endothelial function. In this study, we investigated the effects of Ad on cell survival and BBB integrity in the mouse hippocampus after kainic acid (KA) treatment. Twenty-four hours after intracerebroventricular injection of recombinant Ad, mice were treated with KA, and then sacrificed 48 h later. Decreased serum Ad and increased hippocampal Ad receptor 1 in the hippocampus of KA-treated mice were prevented by Ad pretreatment. Using cresyl violet staining, TUNEL analysis, and immunostaining for caspase-3, histological evaluation revealed that the marked cell death noted in the hippocampus of KA-treated mice was not observed in KA-treated mice pretreated with Ad. Impairment of the BBB, which was demonstrated by the presence of IgG, was inhibited by Ad pretreatment. Immunohistochemical analysis indicated that KA caused up-regulation of hippocampal VEGF, eNOS, and NF-kappaB levels, all of which were reduced in animals that received Ad pretreatment. These data indicate that Ad preserves the integrity of the BBB and has neuroprotective effects in an animal model of seizures.
Jeon
Byeong Tak
BT
Department of Anatomy and Neurobiology, Institute of Health Sciences, Medical Research Center for Neural Dysfunction, Gyeongsang National University School of Medicine, 92 Chilam-dong, Jinju, Gyeongnam, 660-751, Republic of Korea.
Shin
Hyun Joo
HJ
Kim
Jeong Bin
JB
Kim
Yu Kyeung
YK
Lee
Dong Hoon
DH
Kim
Kyu Hong
KH
Kim
Hyun Joon
HJ
Kang
Sang Soo
SS
Cho
Gyeong Jae
GJ
Choi
Wan Sung
WS
Roh
Gu Seob
GS
D052242:Adiponectin / Q000494:pharmacology*; D000818:Animals; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000473:pathology; D016923:Cell Death / Q000187:drug effects*; D019610:Cytoprotection; D006624:Hippocampus / Q000187:drug effects* / Q000473:pathology; D007608:Kainic Acid / Q000633:toxicity; D051379:Mice; D009474:Neurons / Q000187:drug effects* / Q000473:pathology
D052242:Adiponectin; D007608:Kainic Acid