The Effects of Flunarizine on Survival Following Prolonged Cerebral Ischemia in the Gerbil

Cohan, Stanley; Lubitz, Dag Von; Redmond, David J.; Szathmary, S; Waksman, Joel

doi:10.1007/978-3-642-85863-5_62

Cited by 3 publications

(4 citation statements)

References 45 publications

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“…11 The onset of an isoelectric EEG within 15 seconds after bilateral carotid ligation is similar to the observations of others using a similar model of gerbil ischemia. 25 Although clinical seizure activity is frequently seen after cerebral ischemia in the gerbil, 26 - 28 we noted no clinical seizures or epileptiform discharges on EEG.…”

Section: Discussionsupporting

confidence: 88%

“…We have observed clinical seizures within 1 hour postischemia in 100% of gerbils from the same animal colony when they were subjected to 20 minutes of bilateral carotid occlusion. 11 An additional reason we may not have observed seizures is that the animals remained anesthetized in the postischemic period, in some cases up to 60 minutes.…”

Section: Discussionmentioning

confidence: 97%

“…Although flunarizine treatment either before or after ischemic insult to the brain reduces neuronal damage as viewed histologically, 5 -8 -10 prolongs animal survival, 11 and enhances functional recovery, 12 its pharmacological mechanisms of action are not well understood. Flunarizine does inhibit calcium-stimulated vasoconstriction, 15 and may increase cerebral blood flow, 16 the prevention of postischemic fall in cerebral blood flow being a potential protective mechanism of action.…”

Section: Discussionmentioning

confidence: 99%

“…1 - 7 One such compound is flunarizine. Although its mechanisms of action are not well understood, flunarizine has demonstrated protective effects following cerebral ischemia as manifested by improved survival of hippocampal neurons, 57 " 10 improved animal survival after prolonged global ischemia, 11 and improved functional recovery after focal ischemic insult, 12 even when the flunarizine is administered after termination of the ischemic event. It is also possible that flunarizine may be of prophylactic value in the population at increased risk for cerebral ischemia in enhancing the rate of cerebral recovery after an ischemic insult.…”

Section: N Umerous Researchers Have Suggested Thatmentioning

confidence: 99%

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Effect of flunarizine on electroencephalogram recovery and brain temperature in gerbils after brain ischemia.

Cohan

Redmond

Chen

1992

Stroke

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Background and Purpose: This study was designed to determine whether flunarizine enhances the rate of brain recovery as measured by electroencephalography after cerebral ischemia and whether these effects are attributable to changes in brain temperature.Methods: Male gerbils (n=81) were treated with either 10 mg/kg flunarizine or its vehicle, /3-cyclodextrin, intraperitoneally, 60 minutes before bilateral carotid occlusion of either 4 or 6 minutes' duration. The electroencephalogram was continuously recorded in the preischemic, ischemic, and postischemic stages of the experiment and rated for the time necessary for the return of 4-6, 7-10, and 11-15 Hz activity. In a second set of experiments, intracerebral temperature was monitored for 60 minutes before ischemia, during 10 minutes of carotid occlusion, and for 60 minutes after ischemia.Results: Flunarizine pretreatment resulted in significantly more rapid return of electroencephalographic activity in each of the three frequency categories monitored when compared with those animals pretreated with vehicle alone (p<0.001). Flunarizine had no effect on brain temperature before, during, or up to 60 minutes after termination of ischemia.Conclusions: Flunarizine, which has been of efficacy in reducing neuronal death, mortality, and functional impairment when administered after ischemic insults, may have prophylactic value in accelerating brain recovery from ischemia, but does not have this effect as a result of altered brain temperature. (Stroke 1992;23:229-233)

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