Brain temperature and the neuroprotective action of enadoline and dizocilpine in the gerbil model of global ischaemia.
Mongolian gerbils were subjected to transient forebrain ischaemia by occluding both common carotid arteries for 7 min. Subcutaneous administration of either the kappa-opioid receptor agonist enadoline (CI-977; 1 mg kg-1), or the non-competitive NMDA receptor antagonist dizocilpine (MK-801; 3 mg kg-1), at induction of ischaemia prevented neurodegeneration of CA1-CA2 pyramidal neurones in the dorsal hippocampus. It was shown by continuously monitoring intrahippocampal temperature that brain temperature drops by approximately 4 degrees C during ischaemia, when rectal temperature is maintained normothermic. Enadoline at no time point tested affected brain temperature, whereas dizocilpine statistically lowered brain temperature following ischaemia. These findings suggest that enadoline affords neuroprotection in the absence of any hypothermic episode, whilst in the case of dizocilpine, the small transient hypothermia observed following ischaemia may act synergistically or additively with the drug to yield neuroprotection.
Hayward
N J
NJ
Parke-Davis Neuroscience Research Centre, Addenbrookes Hospital Site, Cambridge, UK.
McKnight
A T
AT
Woodruff
G N
GN
D000818:Animals; D001572:Benzofurans / Q000627:therapeutic use*; D001831:Body Temperature / Q000187:drug effects; D001921:Brain / Q000187:drug effects; D016291:Dizocilpine Maleate / Q000627:therapeutic use*; D005260:Female; D005849:Gerbillinae; D002546:Ischemic Attack, Transient / Q000473:pathology / Q000517:prevention & control*; D008954:Models, Biological; D011759:Pyrrolidines / Q000627:therapeutic use*
D001572:Benzofurans; D011759:Pyrrolidines; D016291:Dizocilpine Maleate; C067110:enadoline