Multi-modal assessment of neurovascular coupling during cerebral ischaemia and reperfusion using remote middle cerebral artery occlusion

Hyperacute changes in cerebral blood flow (CBF) during cerebral ischemia and reperfusion is an important determinant of injury. CBF is regulated by neurovascular coupling (NVC), and disruption of NVC contributes to brain plasticity and repair problems. However, it is unknown how NVC is affected hyperacutely during cerebral ischemia and reperfusion. We have developed a remote middle cerebral artery occlusion (MCAO) model in the rat, which enables multi-modal assessment of NVC immediately prior to, during and immediately following reperfusion. Male Wistar rats were subjected to remote MCAO, where a long filament was advanced intraluminally through a guide cannula in the common carotid artery. Transcallosal stimulation evoked increases in blood flow, tissue oxygenation and neuronal activity, which were diminished by MCAO and partially restored during reperfusion. These evoked responses were not affected by administration of the thrombolytic alteplase at clinically used doses. Evoked CBF responses were fully restored at 24 hours post-MCAO indicating that neurovascular dysfunction was not sustained. These data show for the first time that the rat remote MCAO model coupled with transcallosal stimulation provides a novel method for continuous assessment of hyperacute NVC changes during ischemia and reperfusion, and offers unique insight into hyperacute ischemic pathophysiology.