Postischemic (S)-emopamil therapy ameliorates focal ischemic brain injury in rats

Eiharu Morikawa, Myron Ginsberg, W. Dalton Dietrich, Robert C. Duncan, Raul Busto

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

(S)-Emopamil is a calcium channel blocker of the phenylalkylamine class, having potent serotonin S2 antagonistic properties and high blood-brain barrier penetrability. Previous studies have documented cerebroprotective effects in animal models of both focal and global ischemia. The present study was undertaken to define the postischemic "window" of therapeutic efficacy for this agent. Sprague-Dawley rats were subjected to permanent proximal middle cerebral artery occlusion, combined with an initial 30-minute period of halothane-induced hypotension (50 mm Hg). (S)-Emopamil (20 mg/kg) was administered intraperitoneally either 20-30 minutes prior to middle cerebral artery occlusion or 1 hour, 2 hours, or 3 hours following occlusion. Treated groups received a second similar dose 2.5 hours later and twice daily for 2 days thereafter. Brains were perfusion-fixed on the third day. Planimetric analysis of hemotoxylin and eosin-stained coronal brain sections documented a cortical infarct averaging 72.9±33.3 mm3 (mean±SD) in untreated rats. Cortical infarct volume was reduced by 48% (to 37.6±27.6 mm3) when therapy was initiated 1 hour postischemia (p<0.05). When treatment was deferred to 2 hours postischemia, mean cortical infarct volume was reduced by 34%, but this difference did not attain statistical significance. Infarct volume in rats with treatment initiated at 3 hours postischemia was indistinguishable from that in controls. Striatal infarct volume was similar in all groups. These results document a postischemic therapeutic window of cerebroprotection for (S)-emopamil lying between 1 and 2 hours after middle cerebral artery occlusion.

Original languageEnglish
Pages (from-to)355-360
Number of pages6
JournalStroke
Volume22
Issue number3
StatePublished - Mar 1 1991

Fingerprint

Middle Cerebral Artery Infarction
Brain Injuries
Controlled Hypotension
Corpus Striatum
Brain
Calcium Channel Blockers
Halothane
Hematoxylin
Eosine Yellowish-(YS)
Blood-Brain Barrier
Sprague Dawley Rats
Serotonin
Therapeutics
Ischemia
Animal Models
Perfusion
emopamil

Keywords

  • Calcium channel blockers
  • Neuroprotection
  • Rats

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Postischemic (S)-emopamil therapy ameliorates focal ischemic brain injury in rats. / Morikawa, Eiharu; Ginsberg, Myron; Dalton Dietrich, W.; Duncan, Robert C.; Busto, Raul.

In: Stroke, Vol. 22, No. 3, 01.03.1991, p. 355-360.

Research output: Contribution to journalArticle

Morikawa, Eiharu ; Ginsberg, Myron ; Dalton Dietrich, W. ; Duncan, Robert C. ; Busto, Raul. / Postischemic (S)-emopamil therapy ameliorates focal ischemic brain injury in rats. In: Stroke. 1991 ; Vol. 22, No. 3. pp. 355-360.
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