EFFECTS OF ISRADIPINE, AN L-TYPE CALCIUM-CHANNEL BLOCKER ON PERMANENTAND TRANSIENT FOCAL CEREBRAL-ISCHEMIA IN SPONTANEOUSLY HYPERTENSIVE RATS

Permanent or transient focal cerebral ischemia was induced in spontane ously hypertensive rats (SHR) using the intraluminal filament method. Successful occlusion of the middle cerebral artery (MCA) was achieved using 4/O filaments (terminal diameter 0.20- 0.25 mm) coated with poly -L-lysine, The L-type calcium channel blocker isradipine (2.5 mg/kg) a dministered subcutaneously 30 min following permanent MCA occlusion si gnificantly reduced the volume of ischemic brain damage in the cerebra l hemisphere (25%; P = 0.0001), cerebral cortex (18%; P = 0.0034), and caudate nucleus (33%; P = 0.0002) when assessed at 24 h post-RICA occ lusion. Isradipine did not affect the functional deficit (measured usi ng a subjective neurological scoring system) induced by MCA occlusion. In SHR undergoing transient (2 h) MCA occlusion isradipine administer ed 30 min post-MCA occlusion produced a significant reduction (47%; P = 0.001) in hemispheric infarct volume, whereas isradipine administere d at the onset of reperfusion did not confer any significant neuroprot ection. No change in functional deficit was seen with isradipine with either dosing paradigm at 24 h post-MCA occlusion. These results demon strate that the intraluminal filament method of MCA occlusion can be u sed in the SHR strain and also substantiates the neuroprotective effic acy of isradipine in SHR models of permanent and transient focal cereb ral ischemia. (C) 1997 Academic Press.