Sugar rush: A lone spike in blood glucose enhances thrombo-inflammation in the cerebral vasculature

Background: In healthy individuals, free of diabetes comorbidities, transient blood glucose spikes are a common event which reflects excessive food intake combined with adverse lifestyle conditions (stress, lack of exercise). How such blood glucose spikes contribute to cerebro-vascular disease has been a challenge to study under controlled conditions.

Methods: We present an approach to model brain thrombo-inflammation using laser ablation combined with 2-photon live imaging through a transcranial window in awake mice. Our system allows monitoring of the immediate cellular response to brain vascular tissue disruption under normal conditions or transient metabolic stress.

Results: Our data illustrates that transient hyperglycemia from a single injection of metabolically active D‑glucose but not inert L-glucose results in exacerbation of vascular damage, including rapid serum extravasation, platelet aggregation, and neutrophil recruitment, in healthy mice. Transient hyperglycemia aggravates thrombo-inflammation to a similar magnitude as chronic hyperglycemia (e.g. diabetic mice). Mechanistically, we show that exacerbation of thrombo-inflammation by transient hyperglycemia involves depletion of homeostatic nitric oxide by reactive oxygen species.

Conclusion: Our approach provides a controlled method to probe synergies of transient metabolic and physical brain vascular pathophysiology. Our work shows that a lone spike in blood glucose is sufficient to exacerbate thrombo-inflammation in response to vascular tissue disruption as may be spontaneously inflicted by aging, chemotherapy, and viral infection.