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

Abstract

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 (10 mg/kg) 20 mins before middle cerebral artery occlusion (pretreatment group); (ii) intracarotid cyclosporine A (10 mg/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: 16 ± 5% vs. 29 ± 11%, P = 0·004) and saline groups (16 ± 5% vs. 42 ± 12%, P = 0·015). No significant difference was observed between the post-treatment and saline groups (P = 0·065). 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.

Keywords: MRI; acute stroke therapy; cyclosporine; focal cerebral ischaemia; neuroprotection; reperfusion.