Postischemic hypothermia and IL-10 treatment provide long-lasting neuroprotection of CA1 hippocampus following transient global ischemia in rats

W. Dalton Dietrich, Raul Busto, John R. Bethea

Research output: Contribution to journalArticle

104 Scopus citations

Abstract

Experimental studies have demonstrated that postischemic therapeutic interventions may delay rather than provide long-lasting neuroprotection. The purpose of this study was to determine whether mild hypothermia (33-34°C) combined with the anti-inflammatory cytokine interleukin-10 (IL-10) would protect the CA1 hippocampus 2 months after ischemia. Rats were subjected to 12.5 min of normothermic (37°C) forebrain ischemia by two-vessel occlusion followed immediately by: (a) 4 h of normothermic (37°C) reperfusion (n = 5); (b) 4 h of postischemic hypothermia (3334°C) (n = 5); (c) 4 h of normothermia plus IL-10 (5 μg) treatment 30 min after ischemia and at 3 days (n = 5); or (d) 4 h of hypothermia plus IL-10 treatment (n = 5). Rats survived for 2 months and were perfusion fixed for quantitative histopathological assessment of CA1 hippocampus. Postischemic normothermia and hypothermia, as well as normothermia plus IL-10 treatment led to severe damage of the CA1 hippocampus. In contrast, the combined treatment of hypothermia with IL-10 treatment improved overall neuronal survival by 49% compared to normothermic ischemia (P < 0.01). These data emphasize the detrimental consequences of secondary inflammatory responses on ischemic neutonal damage after transient global ischemia. In postinjury settings where restricted durations of mild hypothermia can be induced, anti-inflammatory treatments, including IL-10, may promote chronic neuroprotection.

Original languageEnglish (US)
Pages (from-to)444-450
Number of pages7
JournalExperimental Neurology
Volume158
Issue number2
DOIs
StatePublished - Aug 1999

Keywords

  • Anti- inflammatory agents
  • Cytokines
  • Hypothermia
  • IL-10
  • Neuronal damage
  • Rats
  • Temperature

ASJC Scopus subject areas

  • Neurology
  • Neuroscience(all)

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