Transient neurovascular coupling impairment in brain penetrating arterioles of streptozotocin treated mice post recurrent nonsevere hypoglycemia

Hypoglycemia is a major complication of insulin therapy, particularly in type 1 diabetes mellitus. During hypoglycemia, the brain initiates vascular adaptations to maintain adequate blood flow. Here, we examined the effects of non-severe recurrent hypoglycemia (RH) on brain vascular diameter and neurovascular coupling (NVC)-the functional mechanism adapting local blood flow to neuronal energetic demand-in a streptozotocin (STZ)-induced hyperglycemia mouse model. We assessed stimulus-induced dilation of penetrating arterioles (PAs) in the somatosensory cortex of awake mice using <i>in vivo</i> two-photon microscopy. NVC remains preserved after 8 weeks of sustained hyperglycemia. Non-severe RH episodes, however, cause a transient delay in NVC, which resolves within 24 h. These results suggest that PAs maintain vascular autoregulatory mechanisms despite the metabolic challenges posed by hyperglycemia and RH, highlighting the resilience of brain PAs to systemic glucose fluctuations. We conclude that hyperglycemia per se is not a disruptor of NVC in PAs in the diabetic pathology.