Development of Functional Recovery Therapy for Post-Stroke Sequelae: Towards a Future without Stroke Aftereffects.

Abstract

Stroke remains a leading cause of mortality and morbidity globally, posing significant challenges to healthcare systems due to its impact on Activities of Daily Living, Quality of Life, and healthcare costs. Current treatments primarily focus on acute management through thrombolytic therapy and thrombectomy, but only a limited number of patients benefit, underscoring the need for effective therapies to aid chronic stroke recovery. Despite ongoing clinical trials, cell therapy faces substantial logistical and cost-related hurdles, limiting its widespread adoption. Strategies to minimalize post-stroke sequelae emphasize preventing cerebral infarction deterioration, utilizing predictive scoring systems for focused treatment, and exploring drug repositioning. The complex interplay within the Neurovascular Unit and Oligovascular Niche highlights the role of various cell types and neurotrophic factors in stroke pathophysiology and recovery phases. Notably, microglia and astrocytes exhibit dual phenotypes ─ either inflammatory or protective ─ depending on the environment, influencing neural damage or repair processes post-stroke. Mitochondrial therapy emerges as a promising avenue, leveraging the organelles' ability to migrate between cells and mitigate inflammatory responses. Studies suggest that mitochondria transferred from astrocytes or other sources could transform inflammatory astrocytes into protective ones, thereby promoting white matter integrity and potentially reducing dementia progression associated with stroke sequelae. In conclusion, addressing stroke's multifaceted challenges requires innovative therapeutic approaches targeting inflammatory mechanisms and enhancing neuroprotection. Early detection and intervention, coupled with advancements in mitochondrial therapy and understanding intercellular interactions, hold promise for improving stroke outcomes and reducing long-term neurological complications.