
==== Front
J Cent Nerv Syst Dis
J Cent Nerv Syst Dis
spcns
CNS
Journal of Central Nervous System Disease
1179-5735
SAGE Publications Sage UK: London, England

10.1177_11795735241280805
10.1177/11795735241280805
Editorial
Unlocking the code for stroke treatment and care
Lou Ying
Sage Consulting (Beijing) Co. Ltd. , Beijing, China.
2024
3 9 2024
16 1179573524128080521 8 2024
20 8 2024
© The Author(s) 2024
2024
SAGE Publications Ltd unless otherwise noted. Manuscript content on this site is licensed under Creative Commons Licenses
https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).

typesetterts10
cover-dateJanuary-December 2024
==== Body
pmcStroke, 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
==== Refs
References

1 Sharma D Spring KJ Bhaskar SMM . Role of neutrophil-lymphocyte ratio in the prognosis of acute ischaemic stroke after reperfusion therapy: a systematic review and meta-analysis. J Cent Nerv Syst Dis. 2022;14 :11795735221092518.35492740
2 Yamashita T Nakano Y Sasaki R , et al. Safety and clinical effects of a muse cell-based product in patients with amyotrophic lateral sclerosis: results of a phase 2 clinical trial. Cell Transplant. 2023;32 :9636897231214370.38014622
3 Luo Y Qu J He Z , et al. Human umbilical cord mesenchymal stem cells improve the status of hypoxic/ischemic cerebral palsy rats by downregulating NogoA/NgR/Rho pathway. Cell Transplant. 2023;32 :9636897231210069.37982384
4 Milczarek O Swadźba J Swadźba P , et al. Comparative analysis of the results of stroke treatment with multiple administrations of Wharton's Jelly mesenchymal stem cells-derived HE-ATMP and standard conservative treatment: case series study. Cell Transplant. 2023;32 :9636897231195145.37644776
5 Huang S Li Y Zeng J , et al. Mesenchymal stem/stromal cells in asthma therapy: mechanisms and strategies for enhancement. Cell Transplant. 2023;32 :9636897231180128.37318186
6 Ogawa Y Akamatsu R Fuchizaki A , et al. Gap Junction-mediated transport of metabolites between stem cells and vascular endothelial cells. Cell Transplant. 2022;31 :9636897221136151.36401520
7 de Celis-Ruiz E Fuentes B Alonso de Leciñana M , et al. Final results of allogeneic adipose tissue-derived mesenchymal stem cells in acute ischemic stroke (AMASCIS): a Phase II, randomized, double-blind, placebo-controlled, single-center, pilot clinical trial. Cell Transplant. 2022;31 :9636897221083863.35301883
8 Fang Y Lao P Tang L , et al. Mechanisms of potential therapeutic utilization of mesenchymal stem cells in COVID-19 treatment. Cell Transplant. 2023;32 :9636897231184611.37395459
9 Minkelyte K Li D Li Y Ibrahim A . Transplantation of cryopreserved olfactory ensheathing cells restores loss of functions in an experimental model. Cell Transplant. 2023;32 :9636897231199319.37771302
10 Lin CY Ching YY Wu SF , et al. Coating-free culture medium for establishing and maintaining human induced pluripotent stem cells. Cell Transplant. 2023;32 :9636897231198172.37698258
11 Shigyo M Kobayashi Y Platoshyn O , et al. Derivation of Sendai-virus-reprogrammed human ipscs-neuronal precursors: in vitro and in vivo post-grafting safety characterization. Cell Transplant. 2023;32 :9636897231163232.36959733
12 Sun H Morihara R Feng T , et al. Human cord blood-endothelial progenitor cells alleviate intimal hyperplasia of arterial damage in a rat stroke model. Cell Transplant. 2023;32 :9636897231193069.37615293
13 Monsour M Gordon J Lockard G Borlongan CV . Stem cells attenuate the inflammation crosstalk between ischemic stroke and multiple sclerosis: a review. Cell Transplant. 2023;32 :9636897231184596.37515536
14 Brown JL Voth JP Person K Low WC . A technological and regulatory review on human-animal chimera research: the current landscape of biology, law, and public opinion. Cell Transplant. 2023;32 :9636897231183112.37599386
15 Tan S Yao Y Yang Q Yuan XL Cen LP Ng TK . Diversified treatment options of adult stem cells for optic neuropathies. Cell Transplant. 2022;31 :9636897221123512.36165292
16 Var SR Strell P Johnson ST Roman A Vasilakos Z Low WC . Transplanting microglia for treating CNS injuries and neurological diseases and disorders, and prospects for generating exogenic microglia. Cell Transplant. 2023;32 :9636897231171001.37254858
17 Gong D Wang W Yuan X Yu H Zhao M . Long-term clinical efficacy of human umbilical cord blood mononuclear cell transplantation by lateral atlanto-occipital space puncture (Gong's Puncture) for the treatment of multiple system atrophy. Cell Transplant. 2022;31 :9636897221136553.36354017
18 Sheikh AM Yano S Mitaki S Tabassum S Yamaguchi S Nagai A . Rho-Kinase inhibition decreases focal cerebral ischemia-induced glial activation in rats. J Cent Nerv Syst Dis. 2022;14 :11795735221123910.36106069
19 Rattanawong W Ongphichetmetha T Hemachudha T Thanapornsangsuth P . Neurofilament light is associated with clinical outcome and hemorrhagic transformation in moderate to severe ischemic stroke. J Cent Nerv Syst Dis. 2023;15 :11795735221147212.36632518
20 Mehta V Sharma A Jyoti D , et al. Fibrinogen as a predictor of early neurological deterioration in acute ischemic stroke - evidence from the indian population. J Cent Nerv Syst Dis. 2023;15 :11795735231156349.36779168
21 Yamada N Kashiwabara K Takekawa T , et al. Comparison of the effect and treatment sequence between a 2-week parallel repetitive transcranial magnetic stimulation and rehabilitation and a 2-week rehabilitation-only intervention during a 4-week hospitalization for upper limb paralysis after stroke: an open-label, crossover observational study. J Cent Nerv Syst Dis. 2022;14 :11795735211072731.35082548
22 Kikutsuji N Kataoka H Kiriyama T Sugie K . High-dose steroid-responsive COVID-19-related encephalopathy with a sudden onset of dysarthria mimicking stroke: a case report. J Cent Nerv Syst Dis. 2022;14 :11795735221147218.36579076
23 Md Noh MSF Yusof Khan AHK Mohd Sabri MN , et al. Vessel wall imaging in COVID-19 associated carotid atherothrombosis and stroke: a case report and literature review. J Cent Nerv Syst Dis. 2022;14 :11795735221112589.35832610
24 Bavikatte G Subramanian G Ashford S Allison R Hicklin D . Early identification, intervention and management of post-stroke spasticity: expert consensus recommendations. J Cent Nerv Syst Dis. 2021;13 :11795735211036576.34566442
