Pre- and post-treatment with cyclosporine A in a rat model of transient focal cerebral ischaemia with multimodal MRI screening

Background Irreversible damage may occur at reperfusion after sustained cerebral ischaemia. Aims We investigated the value of cyclosporine A for reducing the infarct size in a model of transient middle cerebral artery occlusion. Methods Twenty-seven Sprague-Dawley rats sustained a middle cerebral artery occlusion of one-hour. Acute multimodal Magnetic Resonance Imaging (MRI) was used during occlusion to confirm the success of surgery and measure baseline lesion size. Animals were randomly treated by: (i) intracarotid cyclosporine A (10mg/kg) 20mins before middle cerebral artery occlusion (pretreatment group); (ii) intracarotid cyclosporine A (10mg/kg) immediately after reperfusion (post-treatment group); and (iii) intracarotid saline immediately after reperfusion. Results Histopathological measurements on day 1 showed a significant reduction of infarct size in the pretreatment group compared to the post-treatment (percentage values of ipsilateral hemispheres: 165% vs. 29 +/- 11%, P=0 center dot 004) and saline groups (16 +/- 5% vs. 42 +/- 12%, P=0 center dot 015). No significant difference was observed between the post-treatment and saline groups (P=0 center dot 065). Behavioural examinations on day 1 showed no significant difference between groups. Immunohistochemistry showed a statistically significant reduction of microglial cell count in the pretreatment group compared to either saline or cyclosporine A post-treatment groups. Conclusions We conclude that intracarotid cyclosporine A is effective in reducing infarct size when given prior to ischaemia, but not when administered at reperfusion.