Reduction in ischemic brain injury in rabbits by the anion transport inhibitor L-644,711.

Abstract

BACKGROUND AND PURPOSE:

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.

• Authors: J J Kohut, M M Bednar, H K Kimelberg, T L McAuliffe, C E Gross
• Journal: Stroke (Stroke) Vol. 23 Issue 1 Pg. 93-7 (Jan 1992) ISSN: 0039-2499 [Print] United States
• PMID: 1731427 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Fluorenes
• L 644711

Topics

• Animals
• Astrocytes (pathology)
• Blood Pressure (drug effects)
• Brain Ischemia (drug therapy, pathology, physiopathology)
• Cerebrovascular Circulation (drug effects)
• Cerebrovascular Disorders (drug therapy, pathology)
• Female
• Fluorenes (pharmacology, therapeutic use)
• Intracranial Embolism and Thrombosis (physiopathology)
• Intracranial Pressure
• Male
• Rabbits