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(Stroke. 1996;27:1578-1585.)
© 1996 American Heart Association, Inc.
Articles |
Long-lasting Neuroprotective Effect of Postischemic Hypothermia and Treatment With an Anti-inflammatory/Antipyretic Drug
Evidence for Chronic Encephalopathic Processes Following Ischemia
the Laboratory for Experimental Brain Research, Lund (Sweden) University, and Laboratory for Experimental Neurology, Escola Paulista de Medicina, Sao Paulo, Brazil (C.C.)
Correspondence to Dr Cicero Coimbra, Laboratory for Experimental Neurology, Escola Paulista de Medicina, R Botucatu 862, 04023-900, Sao Paulo, Brazil.
Background and Purpose It has been recognized that postischemic pharmacological interventions may delay the evolution of neuronal damage rather than provide long-lasting neuroprotection. Also, fever complicates recovery after stroke in humans. Here we report the effects of late postischemic treatment with hypothermia and an antipyretic/anti-inflammatory drug, dipyrone, on cell damage at 1 week and 2 months of survival.
Methods Rats were subjected to 10 minutes of forebrain ischemia. Hypothermia (33°C) was induced at 2 hours of recovery and maintained for 7 hours. Dipyrone (100 mg·kg-1IP) was given every 3 hours from 14 to 72 hours of recovery. Temperature was measured every 6 hours for 60 days. Neuronal damage was assessed at 7 days and 2 months of recovery.
Results From 17 to 72 hours of recovery, a period of hyperthermia was observed, which dipyrone abolished but postischemic hypothermia treatment did not. Dipyrone treatment diminished neuronal damage by 43% at 7 days, and at 2 months of survival, a minor (16%) protection was seen. Postischemic hypothermia treatment alone delayed neuronal damage. In contrast, combined treatment of hypothermia followed by dipyrone markedly diminished neuronal damage by more than 50% at both 7 days and 2 months of recovery.
Conclusions Neuronal degeneration may be ongoing for months after a transient ischemic insult, and prolonged protective measures need to be instituted for long-lasting neuroprotective effects. Hyperthermia during recovery worsens ischemic damage, and processes associated with inflammation may contribute to the development of neuronal damage. An early and extended period of postischemic hypothermia provides a powerful and long-lasting protection if followed by treatment with anti-inflammatory/antipyretic drugs.
Editorial Comment
Evidence for Chronic Encephalopathic Processes Following Ischemia
Division of Basic Medical SciencesFaculty of MedicineMemorial University of NewfoundlandSt John's, NF, Canada
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