Predictable ventricular shift after focal cerebral ischaemia in rats: practical considerations for intraventricular therapeutic interventions

Abstract

Intracerebroventricular (ICV) route of administration is a useful experimental method to study the effects of chemicals or cellular grafts in the ventricular compartment of the brain after focal ischaemia. However, the induced oedema may cause structural dislocating phenomena and render a stereotaxic ICV invasion difficult and practically unavailable especially during the acute post-ischaemia phase. The aim of this study was to measure these structural ventricular dislocations and set new stereotaxic coordinates for successful and cost-effective ICV invasion 6–18 h after focal cerebral ischaemia. Wistar rats were subjected to 2 h middle cerebral artery occlussion (t-MCAO), were neurologically evaluated (modified Neurological Stroke Scale [mNSS], modified Bederson's Scale [mBS] and grid-walking test [GWT]) and brain slides were studied at 6 and 18 h post-occlusion for infarction volume, hemispheric oedema, middle line dislocation and stereotaxia of the lateral ventricles. Our data indicated that stereotaxic coordinates of the lateral ventricles in the infarcted and contralateral hemispheres significantly ( P < 0.05) changed at both time-points and were linearly correlated with the mNSS, mBS and some GWT scores ( P < 0.001). This correlation allowed for the calculation of simple (linear) mathematical equations (stereotaxic coordinate = b0 + b1*mNSS, where ‘ b0’ and ‘b1’ are fixed number and factor, respectively, calculated by regression analysis) that determined individually new coordinates for each animal. Verification experiments revealed that the new coordinates render ICV invasion feasible in up to 80% of infarcted rats (number needed to treat 1.65), compared with only 19.4% using the classical coordinates for normal rats. Therefore, we propose a new, time- and cost-effective methodology for practically feasible ICV invasion in rats 6–18 h after t-MCAO.