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

**Authors:** Irene Fernandez Ugidos, Jennifer Calvo Iglesias, Heather Sendall, Víctor Manuel Calero-Hernandez, Courtney M. Dugas, Andrea Zsombok, Prasad V.G. Katakam, Ricardo Mostany

PMC · DOI: 10.1016/j.isci.2025.114371 · iScience · 2025-12-09

## TL;DR

The study finds that brain blood vessels in diabetic mice can maintain blood flow during glucose fluctuations, except for a temporary delay after repeated mild low-glucose episodes.

## Contribution

The study reveals that recurrent non-severe hypoglycemia transiently impairs neurovascular coupling in diabetic mice.

## Key findings

- Neurovascular coupling remains preserved in brain penetrating arterioles under chronic hyperglycemia.
- Recurrent non-severe hypoglycemia causes a transient delay in neurovascular coupling response.
- Penetrating arterioles show resilience to systemic glucose fluctuations.

## Abstract

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 in vivo 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.

•Neurovascular coupling is preserved under chronic hyperglycemia in brain penetrating arterioles•Recurrent hypoglycemia transiently delays NVC response in hyperglycemic mice•Brain penetrating arterioles are resilient to systemic glucose fluctuations

Neurovascular coupling is preserved under chronic hyperglycemia in brain penetrating arterioles

Recurrent hypoglycemia transiently delays NVC response in hyperglycemic mice

Brain penetrating arterioles are resilient to systemic glucose fluctuations

Physiology; Neuroscience

## Linked entities

- **Diseases:** type 1 diabetes mellitus (MONDO:0005147)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Diseases:** Hypoglycemia (MESH:D007003), hyperglycemia (MESH:D006943), type 1 diabetes mellitus (MESH:D003922), diabetic (MESH:D003920)
- **Chemicals:** glucose (MESH:D005947), insulin (MESH:D007328), STZ (MESH:D013311)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12886521/full.md

## References

65 references — full list in the complete paper: https://tomesphere.com/paper/PMC12886521/full.md

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Source: https://tomesphere.com/paper/PMC12886521