Correspondence between neurological deficit, cerebral infarct size, and Rho-kinase activity in a rat cerebral thrombosis model.
Whether Rho-kinase activity is really associated with the pathogenesis of cerebral infarction remains unclear. To consider this question, we investigated correspondences between severity of neurological deficit, infarct size, amount of various marker proteins, and Rho-kinase activity in a rat cerebral infarction model. Sodium laurate was injected into the left internal carotid artery, inducing cerebral infarction in the ipsilateral hemisphere in rats. We prepared rats with various severities of neurological deficit (mild to severe) 3 days after injection of laurate, then measured infarct size and amount of various marker proteins, phosphorylation of substrates of Rho-kinase, myosin-binding subunit (MBS), myosin light chain (MLC), ezrin/radixin/moesin (ERM), and adducin using Western blot methods. First, infarct size increased corresponding to the severity of neurological deficit. Second, amounts of activating transcription factor 3, nestin, CD68, proliferating cell nuclear antigen, and heat shock protein 70 were increased, whereas neurofilament and myelin-associated glycoprotein were decreased corresponding to the severity of neurological deficit and infarct size. Finally, Rho-kinase activity (phospho-MBS/MBS, phospho-MLC/MLC, phospho-ERM/ERM, and phospho-adducin/adducin) was increased corresponding to the severity of neurological deficit and infarct size. Rho-kinase thus appears to play a crucial role in the pathogenesis of cerebral infarction.
Kawasaki
Koh
K
Laboratory for Pharmacology, Asahi Kasei Pharma, 632-1 Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan. kawasaki.km@om.asahi-kasei.co.jp
Yano
Kazuo
K
Sasaki
Kunie
K
Tawara
Shunsuke
S
Ikegaki
Ichiro
I
Satoh
Shin-Ichi
S
Ohtsuka
Yuji
Y
Yoshino
Yuki
Y
Kuriyama
Hiroshi
H
Asano
Toshio
T
Seto
Minoru
M
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002544:Cerebral Infarction / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D020767:Intracranial Thrombosis / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D023421:Models, Animal; D051381:Rats; D017207:Rats, Sprague-Dawley; D054460:rho-Associated Kinases / Q000378:metabolism*
D015415:Biomarkers; D054460:rho-Associated Kinases