Faculty Collaboration Database

Reduction in ischemic brain injury in rabbits by the anion transport inhibitor L-644,711. Stroke 1992 Jan;23(1):93-7

Date

01/01/1992

Pubmed ID

1731427

DOI

10.1161/01.str.23.1.93

Scopus ID

2-s2.0-0026501391 (requires institutional sign-in at Scopus site)   25 Citations

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.

Author List

Kohut JJ, Bednar MM, Kimelberg HK, McAuliffe TL, Gross CE

Author

Timothy L. McAuliffe PhD Professor in the Psychiatry and Behavioral Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Animals
Astrocytes
Blood Pressure
Brain Ischemia
Cerebrovascular Circulation
Cerebrovascular Disorders
Female
Fluorenes
Intracranial Embolism and Thrombosis
Intracranial Pressure
Male
Rabbits