Thrombin inhibition by argatroban ameliorates early brain injury and improves neurological outcomes after experimental subarachnoid hemorrhage in rats.
OBJECTIVE
We investigated the role of thrombin in early brain injury after subarachnoid hemorrhage (SAH).


METHODS
The standard intravascular perforation model was used to produce experimental SAH in Sprague Dawley rats. Low-dose (0.3 mg/h) and high-dose (0.9 mg/h) argatroban, a direct thrombin inhibitor, were evaluated for effects on brain edema, blood-brain barrier (BBB) disruption, apoptotic cell death, inflammatory marker, and neurological outcomes after SAH.


RESULTS
Both doses of argatroban attenuated BBB disruption; however, only high-dose was effective in lowering edema in all brain regions, reducing cell death, and inflammatory marker expression, and improving neurological outcomes.


CONCLUSIONS
Thrombin inhibition by argatroban improves neurological outcomes and provides neuroprotection against acute events after SAH such as BBB disruption, brain edema, and cell death.
Sugawara
Takashi
T
Department of Physiology, Loma Linda University, Loma Linda, Calif 92354, USA.
Jadhav
Vikram
V
Ayer
Robert
R
Chen
Wanqiu
W
Suzuki
Hidenori
H
Zhang
John H
JH
D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D001120:Arginine / Q000031:analogs & derivatives; D001812:Blood-Brain Barrier / Q000187:drug effects; D001929:Brain Edema / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D016923:Cell Death / Q000187:drug effects; D004195:Disease Models, Animal; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D010875:Pipecolic Acids / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function / Q000187:drug effects*; D013345:Subarachnoid Hemorrhage / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D013449:Sulfonamides; D013917:Thrombin / Q000037:antagonists & inhibitors*
D000925:Anticoagulants; D010875:Pipecolic Acids; D013449:Sulfonamides; D001120:Arginine; D013917:Thrombin; C031942:argatroban