Introduction: Neurovascular coupling, as the local hyperemic response to neuronal activity, is impaired in peri-ischemic brain regions after stroke, with the mechanism being poorly understood. The mechanism is important for the control of brain blood flow, and its dysfunction after stroke, where reduced neurovascular coupling may contribute to futile reperfusion, as poor neurological outcome despite successful recanalization. Understanding these mechanisms is therefore critical for the development of targeted therapy.

Objective: The study aimed to assess neurovascular responses and capillary perfusion in the peri‐ischemic area before stroke and after ischemia reperfusion. It was hypothesized that impaired neurovascular coupling in the peri‐ischemic area is associated with disrupted capillary microcirculation.

Methods: Mice implanted with chronic cranial windows were trained for awake head-fixation prior to experiments. One-hour occlusion of the anterior middle cerebral artery branch was induced using single vessel photothrombosis. Cerebral perfusion and neurovascular coupling were assessed by optical coherence tomography and laser speckle contrast imaging. Capillaries and pericytes were studied in perfusion-fixed tissue by labelling lectin and platelet-derived growth factor receptor β.

Results: Arterial occlusion induced on average 11 spreading depressions over one hour associated with substantially reduced blood flow in the peri-ischemic cortex. Approximately half of the capillaries in the peri-ischemic area were no longer perfused after reperfusion (45% [95% CI, 33%, 58%] and 53% [95% CI, 39%, 66%] reduction in number of perfused capillaries at 3- and 24-hour follow-up, respectively; P < 0.0001, n = 6), which was associated with a reduced diameter of capillaries surrounded by pericytes. The capillaries in the peri-ischemic cortex that remained perfused showed an increased prevalence of flow stalling (0.5% [95% CI, 0.2%, 0.7%] at baseline, 5.1% [95% CI, 3.2%, 6.5%] and 3.2% [95% CI, 1.1%, 5.3%] at 3- and 24‐hour follow‐up, respectively; P < 0.001, n = 6). Blood flow velocity in the capillaries that remained perfused was similar to baseline at the 3-hour follow-up but increased at the 24-hour follow-up compared with baseline (1.16 mm/sec [95% CI, 1.08, 1.24 mm/sec] at baseline, and 1.29 mm/sec [95% CI, 0.97, 1.63 mm/sec] and 1.62 mm/sec [95% CI, 1.44, 1.79 mm/sec] at 3- and 24-hour follow-up, respectively; P < 0.05 n = 6). Whisker stimulation led to reduced neurovascular coupling responses in the sensory cortex corresponding to the peri-ischemic region 3 and 24 hours after reperfusion compared with baseline (19.2% [95% CI, 16.3%, 22.5%] blood flow increase at baseline, 13.4% [95% CI, 10.0%, 16.8%] at 3-hour follow-up, and 12% [95% CI, 9%, 15%] at 24-hour follow-up, P < 0.001, n = 6).

Conclusion. Arterial occlusion led to a reduced diameter of pericyte-surrounded capillaries in the peri-ischemic cortex associated with microcirculatory failure. This reduced capillary capacity may, at least in part, underlie impaired neurovascular coupling in peri-ischemic brain regions after reperfusion. Control and correction of capillary capacity may reduce the neurological dysfunction after stroke as a target for therapy.