Tyrosine phosphatase inhibition attenuates early brain injury after subarachnoid hemorrhage in rats.
OBJECTIVE
Sodium orthovanadate (SOV) is a representative tyrosine phosphatase inhibitor and has been shown to ameliorate neuronal injury in cerebral ischemia. We hypothesized that tyrosine phosphatase inhibition by SOV might attenuate early brain injury after subarachnoid hemorrhage (SAH) in this study.


METHODS
The endovascular perforation model of SAH was produced and animals were randomly assigned to sham-operated rats, saline-treated (vehicle), and 10 mg/kg of SOV-treated SAH rats. Drugs were injected intraperitoneally immediately after SAH induction. Neurological score and brain water content (BWC) were assessed at 24 h after SAH. Cell injury was studied by terminal deoxynucleotidyl transferase-mediated uridine 5'-triphosphate-biotin nick end-labeling (TUNEL) at 24 h after SAH.


RESULTS
Severity of SAH and mortality in SOV-treated rats was similar to that of the saline group. SOV significantly decreased BWC and improved neurological score at 24 h after SAH compared with the saline group. SOV decreased TUNEL-positive cells at 24 h after SAH compared with the saline group.


CONCLUSIONS
These data suggest that tyrosine phosphatase inhibition by SOV ameliorates early brain injury after SAH.
Department of Physiology, Loma Linda University School of Medicine, Risley Hall, Room 223, Loma Linda, CA 92354, USA.
Yu
Y
Hasegawa
Hidenori
H
Suzuki
Prativa
P
Sherchan
Yan
Y
Zhan
Kamil
K
Duris
John H
JH
Zhang
D000818:Animals; D001929:Brain Edema / Q000188:drug therapy / Q000209:etiology; D001930:Brain Injuries / Q000188:drug therapy* / Q000201:enzymology* / Q000209:etiology / Q000401:mortality; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D020287:In Situ Nick-End Labeling / Q000379:methods; D008297:Male; D009460:Neurologic Examination; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012720:Severity of Illness Index; D013345:Subarachnoid Hemorrhage / Q000150:complications; D013997:Time Factors; D014638:Vanadates / Q000627:therapeutic use*
D014638:Vanadates; D017027:Protein Tyrosine Phosphatases