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

Abstract

Hyperacute changes in cerebral blood flow during cerebral ischaemia and reperfusion are important determinants of injury. Cerebral blood flow is regulated by neurovascular coupling, and disruption of neurovascular coupling contributes to brain plasticity and repair problems. However, it is unknown how neurovascular coupling is affected hyperacutely during cerebral ischaemia and reperfusion. We have developed a remote middle cerebral artery occlusion model in the rat, which enables multi-modal assessment of neurovascular coupling immediately prior to, during and immediately following reperfusion. Male Wistar rats were subjected to remote middle cerebral artery occlusion, 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 middle cerebral artery occlusion and partially restored during reperfusion. These evoked responses were not affected by administration of the thrombolytic alteplase at clinically used doses. Evoked cerebral blood flow responses were fully restored at 24 h post–middle cerebral artery occlusion indicating that neurovascular dysfunction was not sustained. These data show for the first time that the rat remote middle cerebral artery occlusion model coupled with transcallosal stimulation provides a novel method for continuous assessment of hyperacute neurovascular coupling changes during ischaemia and reperfusion, and offers unique insight into hyperacute ischaemic pathophysiology.

Dual-modal in vivo assessment for electrophysical and hemodynamic characteristics of cerebral edema induced by lipopolysaccharide

“…Similarly, Brad et al . monitored that brain activity and the time-dependent neurophysiological and hemodynamic response during the cerebral ischemia and reperfusion process [ 10 ]. Damage to the BBB is one of the consequences of stroke with the greatest impact.…”

Research on the classification of early‐stage brain edema by combining intrinsic optical signal imaging and laser speckle contrast imaging

“…Sullender presented a dual‐modality imaging system to simultaneously map cortical blood flow and oxygen tension for studying the pathological features in the acute photothrombotic stroke [44]. Buchan used a multimodal approach to assess hyperacute changes in cerebral blood flow during cerebral ischemia and reperfusion by combining LSCI and microelectrode techniques, offering unique insights into the pathophysiology of hyperacute ischemia [45].…”

Transcranial contrast-enhanced ultrasound in the rat brain reveals substantial hyperperfusion acutely post-stroke

“…However, it has been reported that hyperemia following stroke can actually result in low tissue oxygenation due to impaired capillary transit time heterogeneity, 44 along with the increased risk of oxidative injury during hyperperfusion post-stroke 45 and a dysfunction of neurovascular coupling. 13 This may represent an ischemia-reperfusion injury paradigm in the brain that has recently been proposed but not confirmed in human subjects due to the paucity of appropriate blood flow imaging techniques able to detect these changes. 6,7 Interestingly, another study showed that hyperperfusion within one day post-MCAO was associated with smaller lesions but sustained hyperperfusion at four days post-MCAO was associated with infarct growth.…”

“…The use of animal models of stroke allows continuous measurement of blood flow with greater spatial and temporal resolution than the techniques used in humans. Techniques such as Laser Doppler Flowmetry (LDF), Laser Speckle Contrast Imaging, 14 C-iodoantipyrine autoradiography and hydrogen clearance [12][13][14][15] but also optical techniques such as optical coherence tomography, photoacoustic microscopy, optical imaging spectroscopy and two-photon microscopy 16 have been used in animal studies. These techniques require invasive surgical (i.e.…”