Neurobiological Factors in Ischemic Stroke Outcomes

Ischaemic stroke arises from arterial occlusion leading to rapid loss of oxygen and glucose supply, triggering a cascade of cellular and molecular events. Energy failure induces glutamate-mediated excitotoxicity, oxidative stress and a robust neuroinflammatory response. Microglial activation and peripheral immune cell infiltration exacerbate blood–brain barrier disruption and neuronal apoptosis. Concurrently, neurotrophic support via factors such as brain-derived neurotrophic factor (BDNF) and downstream MAPK/ERK signalling influences synaptic plasticity and repair mechanisms. Dysregulation of the hypothalamic–pituitary–adrenal (HPA) axis modulates cortisol release, impacting inflammation and remote hippocampal integrity. Genetic variants governing endothelial adhesion, mitochondrial resilience and cytokine production further shape lesion size and functional recovery. Psychosocial variables, including social interaction, can alter neuroendocrine stress responses and neurotrophic factor expression, underscoring the interplay between environment and intrinsic repair pathways. Recent advances have identified novel targets for anti-inflammatory therapy, stress hormone modulation and neurotrophic enhancement, paving the way for personalised interventions to improve long-term outcomes.

Research from Nature Portfolio

Studies in aged murine models have demonstrated that post-stroke social isolation markedly increases infarct volume and serum interleukin-6 levels, delays functional recovery and downregulates genes critical for synaptic plasticity. By contrast, pair-housing fosters activation of BDNF-MAPK/ERK signalling, restores myelin basic protein and enhances neurobehavioural performance over weeks. These findings highlight the profound influence of the social environment on neurotrophic pathways and inflammatory tone after focal cerebral ischaemia, suggesting that non-pharmacological interventions may potentiate endogenous repair.

Neurobiological Factors in Ischemic Stroke Outcomes publication trend

The graph below shows the total number of articles in neurobiological factors in ischemic stroke outcomes across all publications each year (not limited to Nature Index journals).

Technical terms

Neuroinflammation: Activation of central and peripheral immune cells leading to cytokine and chemokine release that influences neuronal survival and repair.

Excitotoxicity: Neuronal injury caused by excessive glutamate receptor activation, resulting in calcium overload and cell death.

HPA axis: The neuroendocrine network comprising hypothalamus, pituitary and adrenal glands that regulates stress hormone (cortisol/corticosterone) release.

Brain-derived neurotrophic factor (BDNF): A key protein that promotes neuronal survival, growth, synaptic plasticity and repair after injury.

MAPK/ERK signalling: A kinase cascade that transduces extracellular signals to the nucleus, regulating gene expression involved in cell survival and plasticity.

References

1. Post-Stroke Neuropsychiatric Complications: Types, Pathogenesis, and Therapeutic Intervention. Aging and Disease (2023).
2. Impact of social isolation on corticosterone release and recovery after stroke in aged rats: A behavioral and biochemical analysis. Experimental Gerontology (2024).
3. Ischemic Stroke, Glucocorticoids, and Remote Hippocampal Damage: A Translational Outlook and Implications for Modeling. Frontiers in Neuroscience (2021).
4. Dysregulated Hypothalamic–Pituitary–Adrenal Axis Is Associated With Increased Inflammation and Worse Outcomes After Ischemic Stroke in Diabetic Mice. Frontiers in Immunology (2022).
5. Reversal of the Detrimental Effects of Post-Stroke Social Isolation by Pair-Housing is Mediated by Activation of BDNF-MAPK/ERK in Aged Mice. Scientific Reports (2016).
6. Social interaction plays a critical role in neurogenesis and recovery after stroke. Translational Psychiatry (2014).