Controlling stress circuitry to enhance post-stroke recovery: targeting HPA Axis activation

• DOI: 10.55632/pwvas.v97i2.1198
• Publication Date: 2025-04-08T15:22:35Z
• Authors: Laurel Stone; Morgan Bridi

Ischemic stroke (IS) significantly impacts long-term health and quality of life, due in part to stress-induced hyperactivation the hypothalamic-pituitary-adrenal (HPA) axis. Elevated corticosterone hypercortisolism after exacerbate neuronal injury delay recovery. However, dynamics stress-responsive activity following IS, how these changes contribute outcomes, remain understudied. We hypothesize that corticotropin-releasing factor (CRF)+ neurons hypothalamic paraventricular nucleus (PVN) GAD+ bed stria terminalis (BNST) are progressively altered ischemic stroke. Additionally, we targeted chemogenetic modulation populations during acute recovery period reduces damage improves functional outcomes. Using mouse models transient middle cerebral artery occlusion (tMCAO), first investigated temporal patterns within PVN CRF+ BNST neurons. Fiber photometry was utilized longitudinally monitor synaptic input across subacute post-stroke periods. Next, used (DREADDs) critical window (days 1-7). Functional outcomes assessed included infarct size, hippocampal integrity, plasma levels, behaviors indicative anxiety cognitive deficits. These experiments clarify alters stress-related circuits whether can improve insights could lead novel strategies for mitigating stroke-induced enhancing