Cytoprotection does not preserve brain functionality in rats during the acute post-stroke phase despite evidence of non-infarction provided by MRI

In animal models of stroke the promise of a therapy is commonly judged from infarct size measurements, assuming that a reduction in infarct size resul ts in reduction of the functional deficits. We have evaluated the validity of the concept that structural integrity translates into functional integri ty during the acute post-stroke period (24 h). Unilateral permanent middle cerebral artery occlusion (pMCAO) in Fischer F344 rats leads to infarcts co mprising the ipsilateral striatum and cortical structures, including the so matosensory cortex. Infarct volumes were assessed using magnetic resonance imaging (MRI) methods (T-2, diffusion, perfusion MRI). The functional integ rity of the somatosensory cortex was assessed by functional MRI (fMRI) meas uring changes in local cerebral blood volume, and by assessing the forelimb grip strength and the beam-walking performance of the animals. Treatment w ith the calcium antagonist isradipine (2.5 mg/kg injected s.c. immediately after pMCAO) reduced the total infarct size by more than 40% compared to ve hicle-injected controls. In particular, the ipsilateral somatosensory corte x appeared normal in diffusion- and T-2-weighted MRI images. In sham-operat ed rats simultaneous electrical stimulation of both forepaws led to similar activation of both somatosensory cortices, while in pMCAO animals given ve hicle only the contralateral cortex showed an fMRI response. Similarly, in pMCAO rats treated with isradipine, functional activation following bilater al electrical stimulation was only detected in the contralateral somatosens ory cortex despite the normal appearance of the ipsilateral cortex in MRI i mages. Furthermore, fMRI responses to pharmacological stimulation with bicu culline were virtually absent in the ipsilateral somatosensory cortices bot h in vehicle- and isradipine-treated rats. Finally there was no significant difference between vehicle- and isradipine-treated animals upon the perfor mance of beam-walking test or in forelimb grip strength. It is concluded th at during the acute (24 h) post-occlusion period, structural integrity in t he somatosensory cortex revealed by MRI does not translate into preservatio n of function. Copyright (C) 2000 John Wiley & Sons, Ltd.