Protective effects of memantine against ischemia-reperfusion injury in spontaneously hypertensive rats

A. Dogan, M. A. Eras, V. L. Raghavendra Rao, Robert J. Dempsey

Research output: Contribution to journalArticle

30 Scopus citations

Abstract

Memantine, an uncompetitive NMDA open-channel blocker, has been shown to be effective in preventing neuronal damage after permanent focal cerebral ischemia. Reperfusion after a long period of ischemia may aggravate the progression of neuronal damage. Those drugs that show protective effects after permanent cerebral ischemia, therefore, might fail to do so against ischemia-reperfusion injury. In this study we evaluated the effects of memantine on brain edema formation and ischemic injury volume after transient cerebral ischemia. Male Spontaneously Hypertensive Rats (SHR) weighing 250-300 g were anesthetized with halothane and subjected to 1 hour of temporary middle cerebral artery occlusion by an intraluminal suture. 20 mg/kg of memantine or saline were injected intraperitoneally 5 min. after the induction of ischemia. Physiological parameters and regional cerebral blood flow were monitored during the surgical procedure. Brain water content and ischemic injury volume were measured with the wet dry method and 2,3,5-triphenyl tetrazolium chloride monohydrate (TTC) staining, respectively, at 24 hours after occlusion. There were no statistically significant differences between the groups regarding physiological parameters during the procedure. Memantine treatment (n = 9) reduced the brain water content significantly in the cortex compared to saline treatment (n = 8; 83.1 ± 0.7% vs. 84.5 ± 1.5%, respectively, p < 0.05). The total volume of ischemic brain injury was 300 ± 49 mm3 in the animals treated with saline (n = 13). Treatment with 20 mg/kg memantine (n = 14) reduced the ischemic injury volume to 233 ± 61 mm3 (P < 0.01). These results demonstrate that the harmful effects of recirculation after a period of ischemia can be attenuated by the treatment of memantine, perhaps by its action at the NMDA receptors.

Original languageEnglish (US)
Pages (from-to)1107-1113
Number of pages7
JournalActa Neurochirurgica
Volume141
Issue number10
DOIs
StatePublished - Nov 2 1999

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Keywords

  • Cerebral edema
  • Memantine
  • NMDA receptor
  • Transient cerebral ischemia

ASJC Scopus subject areas

  • Surgery
  • Clinical Neurology

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