Unlocking the code for stroke treatment and care

Stroke, a devastating cerebrovascular event, remains a leading cause of death and disability worldwide. ¹ The quest for effective treatments has led researchers to the frontiers of regenerative medicine, where cell-based therapies are emerging as promising contenders. ²

Stem cells, particularly mesenchymal stem cells (MSCs), have emerged as key players in regenerative medicine, with their immunomodulatory and tissue regenerative effects showing promise in the context of stroke.^3-7 The safety and potential efficacy of MSCs have been demonstrated in clinical trials for conditions such as ALS, suggesting their potential as a novel regenerative medicine for stroke as well. ² The potential of MSCs extends to their role in treating severe COVID-19, a condition marked by a hyperinflammatory state that parallels the pathophysiology of stroke. ⁸ This overlap highlights the versatility of MSCs in addressing the complications associated with stroke.

Cryopreserved olfactory ensheathing cells (OECs) have shown promise in the repair of CNS injuries, hinting at their potential application in stroke recovery. ⁹ The development of coating-free culture mediums for human pluripotent stem cells (hPSCs) represents an innovation that could significantly enhance the efficiency and clinical applicability of hPSC expansion for stroke therapy. ¹⁰

Shigyo et al., investigated the generation and characterization of neural precursor cells derived from human-induced pluripotent stem cells (hiPSCs), which have potential therapeutic applications in treating neurodegenerative disorders, including stroke. The study demonstrates the safety and efficacy of these hiPSC-derived NPCs in in vitro and in vivo models, suggesting their utility in stroke treatment by potentially replacing damaged neurons and providing neuroprotection. ¹¹

Ischemic stroke, a leading cause of global disability and death, has seen mechanical thrombectomy (MT) emerge as the preferred treatment. However, the potential vascular complications post-stroke has led to investigations into the use of human cord blood–endothelial progenitor cells (hCB-EPCs) to alleviate arterial damage. ¹²

The intersection of stroke with conditions like multiple sclerosis (MS) has been noted, with stem cell therapies showing promise in reducing neuroinflammation associated with both conditions. This highlights the potential of stem cells in addressing the chronic inflammatory phase in stroke and MS. ¹³

The therapeutic potential of human-animal chimeras for regenerative medicine has been discussed, which could have implications for treating stroke by providing an alternative source of organs for transplantation. ¹⁴ This approach could circumvent limitations of traditional organ transplantation.

In the context of optic neuropathies, the potential of stem cell therapy has been recognized, with conditions like demyelinating optic neuritis sharing pathophysiological mechanisms with stroke. Adult stem cells, such as MSCs and hematopoietic stem cells, have shown neuroprotective properties and have been applied in clinical trials for optic neuropathies. ¹⁵

Microglial transplantation has demonstrated potential in stroke recovery, with studies indicating improvements in neurological deficits and functional recovery in rodent models. ¹⁶ The preconditioning of microglia has been shown to enhance angiogenesis and axonal outgrowth, significantly mitigating the adverse outcomes of stroke.

Human umbilical cord blood mononuclear cells (hUCB-MCs) have shown neuroprotective effects and the ability to improve local brain microenvironments in neurodegenerative diseases, including stroke. ¹⁷ Early treatment with hUCB-MC transplantation may be beneficial, highlighting the need for further research and clinical trials.

Precision therapies, such as the Rho-kinase inhibitor Fasudil, have demonstrated their ability to mitigate the damage caused by stroke in preclinical models. By reducing stroke volume and the associated cerebral edema, these therapies target the very heart of the injury, offering hope for more effective post-stroke care. ¹⁸

The quest for reliable biomarkers has led to the discovery of neurofilament light chain (NFL), a protein that can predict the trajectory of a patient’s recovery and the risk of hemorrhagic transformation. ¹⁹ This marker’s ability to forecast outcomes is a significant step towards personalized medicine in the realm of stroke treatment.

Mild stroke, defined by a National Institutes of Health Stroke Scale (NIHSS) score of less than 5, has variable outcomes and is more likely to be associated with small vessel disease. The presence of cerebral microbleeds (CMB) and muscle weakness as a symptom are associated with poor discharge outcomes, indicating the need for closer monitoring and potential thrombolytic treatment. ²⁰

Rehabilitation remains a cornerstone of stroke management, and the NEURO® program exemplifies the benefits of a combined approach, integrating rTMS with occupational therapy to enhance motor function recovery. ²¹ This strategy’s success underscores the importance of tailored rehabilitation programs that can adapt to the individual needs of stroke survivors.

Despite these advances, the journey towards effective stroke management is fraught with challenges. The overlap between stroke and other neurological conditions, particularly in the context of COVID-19, complicates diagnosis and requires a nuanced approach to patient care.^22,23 Additionally, the prevalence of post-stroke spasticity calls for vigilant monitoring and timely intervention to optimize the quality of life for survivors. ²⁴

In summary, the treatment of stroke is a complex mosaic that integrates immediate intervention, innovative therapies, and a dedication to rehabilitation.

To advancing our understanding and improving clinical practice in acute stroke care, Journal of Central Nervous System Disease is organizing a special collection on Unlocking the Code of Stroke: Deciphering Time, Tissue, and Systems for Better Outcomes. Readers are encouraged to explore more information on the collection page: https://journals.sagepub.com/topic/collections-cns/cns-1-special_collection_on_unlocking_the_code_of_stroke?journalCode=cns