Diabetes-Induced Cerebral Ischemia Mechanisms

Diabetes markedly increases both the incidence and severity of cerebral ischaemia through a constellation of interrelated mechanisms. Chronic hyperglycaemia and insulin resistance promote endothelial dysfunction, characterised by reduced nitric oxide availability and disordered angiogenesis, which in turn compromises cerebrovascular reactivity and collateral perfusion. Structural remodelling of cerebral microvessels often leads to tortuosity, aberrant neovascularisation and heightened risk of haemorrhagic transformation following reperfusion. Breakdown of the blood–brain barrier (BBB) ensues via degradation of tight junction proteins and basement membrane components, facilitating influx of plasma proteins and inflammatory cells. Sustained neuroinflammation, driven by activated microglia and upregulated adhesion molecules, exacerbates neuronal injury through the release of pro-inflammatory cytokines and matrix metalloproteinases. Mitochondrial dysfunction, oxidative stress and impaired antioxidant defence further compromise neuronal survival, reducing ATP production and promoting apoptotic and necrotic pathways. Collectively, these processes hinder endogenous repair and plasticity, resulting in larger infarct volumes, poor neurological recovery and increased post-stroke cognitive impairment in diabetic individuals.

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Diabetes-Induced Cerebral Ischemia Mechanisms publication trend

The graph below shows the total number of articles in diabetes-induced cerebral ischemia mechanisms across all publications each year (not limited to Nature Index journals).

Technical terms

Insulin resistance: A state in which cells fail to respond adequately to insulin, leading to impaired glucose uptake and hyperglycaemia.

Blood–brain barrier (BBB): A selective endothelial interface that regulates molecule and cell passage between the circulation and the brain parenchyma.

Neuroinflammation: Activation of glial cells and release of inflammatory mediators within the central nervous system.

Reactive oxygen species (ROS): Highly reactive molecules derived from oxygen that can damage proteins, lipids and nucleic acids.

Middle cerebral artery occlusion (MCAO): An experimental procedure in which blood flow through the middle cerebral artery is transiently blocked to model ischaemic stroke.

Mitochondrial membrane potential: The electrochemical gradient across the inner mitochondrial membrane essential for ATP synthesis.

References

1. The Pre-Stroke Induction and Normalization of Insulin Resistance Respectively Worsens and Improves Functional Recovery. International Journal of Molecular Sciences (2023).
2. Microglia knockdown reduces inflammation and preserves cognition in diabetic animals after experimental stroke. Journal of Neuroinflammation (2020).
3. Melatonin protects against focal cerebral ischemia-reperfusion injury in diabetic mice by ameliorating mitochondrial impairments: involvement of the Akt-SIRT3-SOD2 signaling pathway. Aging (2021).