Increased leukocyte ROCK activity in patients after acute ischemic stroke.
BACKGROUND
Rho-kinase (ROCK) is a downstream effector of Rho GTPase that is known to regulate various pathological processes important to the development of ischemic stroke, such as thrombus formation, inflammation, and vasospasm. Inhibition of ROCK leads to decreased infarct size in animal models of ischemic stroke. This study tests the hypothesis that ROCK activity increases during the acute phase of ischemic stroke.


METHODS
Serial blood samples were drawn from 10 patients with acute ischemic stroke presenting within 24 h of symptom onset and with NIHSS scores >or=4. Samples were taken at 24, 48, and 72 h. Leukocyte ROCK activity was determined by immunoblotting leukocyte lysates with antibodies to the phosphorylated form of myosin-binding subunit (P-MBS) of myosin light chain phosphatase (MLCP). MBS and P-MBS contents were normalized to alpha-tubulin, and ROCK activity was expressed as the ratio of P-MBS to MBS. ROCK activities in these 10 patients were compared to baseline ROCK activities in 10 control subjects without acute illness and matched for sex, age, and number of vascular risk factors using a two-tailed Student's t-test.


RESULTS
The mean NIHSS score in patients with stroke was 15.4. ROCK activity was significantly increased at 24 and 48 h in patients after acute ischemic stroke when compared to control values, with peak elevations at 48 h after stroke onset. There was no apparent correlation between ROCK activity and stroke severity based on NIHSS.


CONCLUSIONS
Leukocyte ROCK activity is increased in patients after acute ischemic stroke with maximal activity occurring about 48 h after stroke onset. These findings suggest that activation of ROCK may play a role in the pathogenesis of ischemic stroke in humans.
Feske
Steven K
SK
Vascular Medicine Research, Brigham and Women's Hospital, 65 Landsdowne Street, Cambridge, MA 02139, USA.
Sorond
Farzaneh A
FA
Henderson
Galen V
GV
Seto
Minoru
M
Hitomi
Asako
A
Kawasaki
Koh
K
Sasaki
Yasuo
Y
Asano
Toshio
T
Liao
James K
JK
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / Q000031:analogs & derivatives / Q000494:pharmacology; D000368:Aged; D015153:Blotting, Western; D002545:Brain Ischemia / Q000201:enzymology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D007962:Leukocytes / Q000201:enzymology*; D008297:Male; D043263:Myosin-Light-Chain Phosphatase / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D020521:Stroke / Q000201:enzymology*; D014404:Tubulin / Q000378:metabolism; D054460:rho-Associated Kinases / Q000037:antagonists & inhibitors / Q000097:blood*
D004791:Enzyme Inhibitors; D014404:Tubulin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D054460:rho-Associated Kinases; D043263:Myosin-Light-Chain Phosphatase; C049347:fasudil