THE EFFECTS OF MK-801, IFENPRODIL, JO-1784, JO-1994 AND JO-1997 ON PK-11195 RECEPTOR-BINDING, NITRIC-OXIDE SYNTHASE (NO SYNTHASE) ACTIVITY AND INFARCT VOLUME IN A MOUSE MODEL OF FOCAL CEREBRAL-ISCHEMIA

Middle cerebral artery occlusion (MCAO) is a widely used surgical proc edure for inducing focal cortical ischaemia in mice. In the present st udy, all experiments were performed on 4-week-old, male Swiss mice (OF -1 Iffa Credo, France), 20-25 g at the time of surgery. Sham-operated mice were subjected to simple exposure of the middle cerebral artery. Mice were injected with either MK-801, ifenprodil, JO 1784, JO 1994 or 30 1997 al the following time points after surgery; 5, 15, 45 min and 3, 6, 24, 30, 48 and 54 h. Mice were sacrificed 72 h after surgery an d both ipsilateral and contralateral cortices were dissected in their entirety, weighed, and assayed for [H-3]PK 11195 binding while the bra in-stem and cerebellum were assayed for nitric oxide synthase (NO synt hase) activity. In a separate experiment the area of ischaemic damage was determined planimetrically by means of an image analysis system. C oagulation of the middle cerebral artery induced a marked enhancement of the ipsilateral cortical omega(3) peripheral-type benzodiazepine bi nding site (PTBB'S) densities, an increase in NO synthase activity in the brain-stem and cerebellum and an increase in the cortical infarct area. MK-801, ifenprodil, JO 1784. JO 1994 and JO 1997 demonstrated co mparable neuroprotective effects on all three indices of cortical dama ge. A down-regulation of cortical omega(3) peripheral-type benzodiazep ine binding site (PTBB'S) densities and a decrease in NOS activity occ urred following pharmacological intervention. In contrast to JO 1784, JO 1994 and JO 1997 have a bimodal effect on omega(3) PTBB'S densities . Copyright (C) 1996 Elsevier Science Ltd.