Reduction in ischemic brain injury in rabbits by the anion transport inhibitor L-644,711.
OBJECTIVE
We studied the anion transport inhibitor L-644,711, which is known to reduce astrocyte swelling and excitotoxin release in primary astrocyte culture, in two models of thromboembolic stroke to assess its capacity to influence ischemic brain injury.


METHODS
New Zealand White rabbits were used in this study. The two models include autologous clot embolized to the brain via the carotid artery, with one model using a transient period of systemic hypotension. Cerebral blood flow was determined by the hydrogen clearance method, intracranial pressure was measured with a fiberoptic transducer, and infarct size was assessed with triphenyltetrazolium chloride staining of the coronally sectioned brain. Both models received a 2-hour infusion of L-644,711 (total dose, 12 mg/kg) beginning 20 minutes before embolization.


RESULTS
In both the normotensive (p less than 0.01) and the hypotensive (p less than 0.05) model, treatment with L-644,711 resulted in a significant reduction in infarct size and a significant improvement in regional cerebral blood flow (p less than 0.03, normotensive model, and p less than 0.05, hypotensive model). Raised intracranial pressure, unique to the hypotensive model, was abolished by the administration of L-644,711 (p less than 0.05). A hyperglycemic response associated with embolization, also unique to the hypotensive model, was significantly reduced by the administration of L-644,711 (p less than 0.05).


CONCLUSIONS
The ability of L-644,711 to limit brain injury in two related models of thromboembolic stroke suggests a potential therapeutic role for anion channel blockers in cerebral ischemia.
Kohut
J J
JJ
Division of Neurosurgery, Albany Medical College, New York.
Bednar
M M
MM
Kimelberg
H K
HK
McAuliffe
T L
TL
Gross
C E
CE
D000818:Animals; D001253:Astrocytes / Q000473:pathology*; D001794:Blood Pressure / Q000187:drug effects; D002545:Brain Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D002560:Cerebrovascular Circulation / Q000187:drug effects; D002561:Cerebrovascular Disorders / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D005449:Fluorenes / Q000494:pharmacology / Q000627:therapeutic use*; D002542:Intracranial Embolism and Thrombosis / Q000503:physiopathology; D007427:Intracranial Pressure; D008297:Male; D011817:Rabbits
D005449:Fluorenes; C053396:L 644711