Diabetes augments in vivo microvascular blood flow dynamics after stroke.

ABSTRACT

Stroke usually affects people with underlying medical conditions. In particular, diabetics are significantly more likely to have a stroke and the prognosis for recovery is poor. Because diabetes is associated with degenerative changes in the vasculature of many organs, we sought to determine how hyperglycemia affects blood flow dynamics after an ischemic stroke. Longitudinal in vivo two-photon imaging was used to track microvessels before and after photothrombotic stroke in a diabetic mouse model. Chronic hyperglycemia exacerbated acute (3-7 d) ischemia-induced increases in blood flow velocity, vessel lumen diameter, and red blood cell flux in peri-infarct regions. These changes in blood flow dynamics were most evident in superficial blood vessels within 500 µm from the infarct, rather than deeper or more distant cortical regions. Long-term imaging of diabetic mice not subjected to stroke indicated that these acute stroke-related changes in vascular function could not be attributed to complications from hyperglycemia alone. Treating diabetic mice with insulin immediately after stroke resulted in less severe alterations in blood flow within the first 7 d of recovery, but had more variable results at later time points. Analysis of microvessel branching patterns revealed that stroke led to a pruning of microvessels in peri-infarct cortex, with very few instances of sprouting. These results indicate that chronic hyperglycemia significantly affects the vascular response to ischemic stroke and that insulin only partially mitigates these changes. The combination of these acute and chronic alterations in blood flow dynamics could underlie diabetes-related deficits in cortical plasticity and stroke recovery.