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Neuroprotective Effect of the χ‐Agonist Enadoline (CI‐977) in Rat Models of Focal Cerebral Ischaemia
Author(s) -
Hayward Neil James,
McKnight Alexander Thorburn,
Woodruff Geoffrey Neil
Publication year - 1993
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.1993.tb00947.x
Subject(s) - neuroprotection , medicine , ischemia , anesthesia , agonist , isoflurane , cerebral blood flow , middle cerebral artery , infarction , pharmacology , receptor , myocardial infarction
The neuroprotective efficacy of the χ‐opioid agonist enadoline (CI‐977) was examined in two acute rat models of focal cerebral ischaemia [non‐recovery (4 h) and recovery (24 h)]. In the non‐recovery model, Sprague ‐ Dawley rats were anaesthetized throughout the study period. Focal ischaemia was produced by the permanent occlusion of the left middle cerebral artery (MCA). The amount of early ischaemic damage was assessed in coronal sections at nine pre‐determined stereotaxic planes. Enadoline at doses of 0.1, 0.3 and 1.0 mg/kg ( n = 8), administered s.c. 30 min prior to ischaemia, produced dose‐dependent amelioration of cortical damage. Importantly, enadoline had no significant effect on any of the physiological parameters monitored (blood pressure, blood gases, glucose, pH). In the recovery model the left MCA was permanently occluded under isoflurane anaesthesia. Animals were allowed to recover and were killed 24 h later. The amount of ischaemic brain damage and swelling was assessed histologically. In this model pretreatment with enadoline at either 0.1, 0.3, or 1.0 mg/kg s.c. was followed by continuous s.c. infusion at 0.017, 0.05 or 0.17 mg/kg/h respectively ( n = 8–17). Enadoline produced dose‐dependent reductions in the volumes of infarction and brain swelling; the greatest reductions were seen at 1.0 mg/kg plus 0.17 mg/kg/h in both infarction (reduced by 37.4% from controls) and swelling (reduced by 47.8%). Therefore the χ‐opioid agonist enadoline affords dose‐dependent neuroprotection in both the non‐recovery and recovery models of focal cerebral ischaemia in the rat. In the recovery model enadoline was effective in reducing infarction and oedema; the reduction in brain swelling occurs in parallel with the reduction in ischaemic damage.