The Current Update of Conventional and Innovative Treatment Strategies for Central Nervous System Injury
Abstract
:1. Introduction
2. Pathogenesis of CNS Trauma
2.1. Primary Injury
2.1.1. Focal Contusions and Hematomas
2.1.2. Diffuse Axonal Injury (DAI)
2.1.3. Swelling
2.2. Secondary Injury
2.2.1. Inflammatory Response
2.2.2. Oxidative Stress
2.2.3. Excitotoxicity
2.2.4. Apoptosis and Necrosis
2.2.5. Blood–Brain Barrier (BBB) Disruption
2.3. The Classification and Severity of CNS Trauma
2.3.1. TBI Are Classified Into Three Categories Based on Severity
2.3.2. SCI Common Standardized and Classified System
- ASIA A (Complete): No motor or sensory function is preserved in the sacral segments S4–S5. It indicates a complete spinal cord injury where no motor or sensory function is preserved below the level of injury, including the anal and perineal area.
- ASIA B (Incomplete): Sensory but not motor function is preserved below the neurological level of injury and extends through the sacral segments. This grade reflects some preservation of sensory function below the injury level, with no motor function below the level.
- ASIA C (Incomplete): Motor function is preserved below the neurological level, and more than half of key muscle functions below the neurological level have a muscle grade less than 3. It indicates partial preservation of motor functions, where some movements are possible but not strong enough to overcome gravity.
- ASIA D (Incomplete): Motor function is preserved below the neurological level, and at least half of key muscle functions below the neurological level have a muscle grade of 3 or more. It represents a less severe form of incomplete injury, with more significant preservation of motor function and ability to move against gravity.
- ASIA E (Normal): Motor and sensory function are normal. The individual has regained normal function, though they may have had a spinal cord injury previously or had transient deficits.
3. Treatment Strategies of CNS Injury
3.1. Current Approaches
3.1.1. Surgical Treatment
3.1.2. Medical Treatment
3.1.3. Rehabilitation
3.1.4. Weight-Supported Locomotor Training (WSLT)
3.1.5. Occupational Therapy
3.1.6. Functional Electrical Stimulation (FES)
3.2. Innovative Therapies
3.2.1. Stem Cell Therapies
3.2.2. Modulation of Inflammatory and Immune Responses
3.2.3. Combination Therapies
4. Clinical Implications and Future Directions in CNS Injuries
5. Limitations in the Treatment of CNS Injuries
6. Discussion on Challenges in Clinical Translation
Bridging Experimental and Clinical Realms
- Regulatory Challenges: Many promising therapies encounter regulatory barriers that delay approval processes, limiting rapid integration into clinical use. Regulatory bodies demand extensive data on safety and efficacy, which requires prolonged and costly clinical trials.
- Scalability and Accessibility: Even if a therapy shows promise in controlled experimental settings, scaling it to be widely accessible poses logistical and manufacturing challenges. The cost implications are often prohibitive, affecting the equitable distribution of these advanced treatments.
- Ethical Concerns: Particularly with therapies like stem cell treatment, ethical debates can impede progress. Issues around stem cell sourcing and the long-term impact of genetically modified cells in humans need resolution within ethical frameworks before such treatments can become mainstream.
- Long-Term Efficacy and Safety: Many experimental treatments lack long-term data, making it difficult to predict their future impact. Clinicians and patients may be wary of potential long-term complications or side effects that have not yet been fully understood.
7. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Primary Injury | Secondary Injury | |
---|---|---|
Timing | Immediate | Delayed (minutes to months after trauma) |
Causes | External mechanical forces (impact, penetration, etc.) | Biochemical and cellular response to primary injury |
Pathophysiology | Physical disruption of CNS tissue | Inflammation, oxidative stress, excitotoxicity, BBB disruption |
Clinical Manifestations | Contusions, hematomas, DAI, tissue swelling | Cerebral edema, ischemia, cell death |
Treatment Objectives | Physical disruption of CNS tissue | Physical disruption of CNS tissue |
Stem Cell Type | Source | Key Characteristics | Therapeutic Actions | Clinical Application |
---|---|---|---|---|
Mesenchymal Stem Cells (MSCs) | Bone marrow, adipose tissue, dental tissues, etc. | Low immunogenicity, multipotent, can differentiate into various tissue types | Can differentiate into cell types that replace damaged tissue, secrete anti-inflammatory and regenerative factors | Numerous clinical trials, showing potential to improve functional outcomes, safe and potentially effective |
Exosomes and Extracellular Vesicles | Derived from MSCs and other cell types | Contain proteins, lipids, and nucleic acids that facilitate intercellular communication | Transfer regenerative molecules to injured cells, promote neurogenesis and angiogenesis | Research focused on their role in modulating inflammation and delivering growth factors for tissue repair and regeneration |
Neural Stem Cells (NSCs) | Derived from embryonic or adult neural tissues | Can differentiate into neurons, astrocytes, and oligodendrocytes | Integrate into the host spinal cord, replace lost neurons and glial cells, reduce inflammation, support recovery | Preclinical and some early clinical studies show promise in enhancing recovery of motor functions |
Human Induced Pluripotent Stem Cells (hiPSCs) | Adult cells reprogrammed to an embryonic stem-cell-like state | Pluripotent, can differentiate into any cell type, personalized therapy option with reduced rejection risks | Differentiate into neural cells to promote nerve regeneration, reduce lesion size | Experimental stages; promising results in animal models for improving outcomes in SCI |
Embryonic Stem Cells (ESCs) | Derived from preimplantation embryos | Pluripotent, capable of differentiating into any cell type | Differentiate into oligodendrocytes for remyelination of neurons, essential for SCI repair | Ethical concerns limit use, but research continues under controlled settings for potential in treating severe SCI |
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Tsai, M.-H.; Wu, C.-Y.; Wu, C.-H.; Chen, C.-Y. The Current Update of Conventional and Innovative Treatment Strategies for Central Nervous System Injury. Biomedicines 2024, 12, 1894. https://doi.org/10.3390/biomedicines12081894
Tsai M-H, Wu C-Y, Wu C-H, Chen C-Y. The Current Update of Conventional and Innovative Treatment Strategies for Central Nervous System Injury. Biomedicines. 2024; 12(8):1894. https://doi.org/10.3390/biomedicines12081894
Chicago/Turabian StyleTsai, Meng-Hsuan, Chi-Ying Wu, Chao-Hsin Wu, and Chun-Yu Chen. 2024. "The Current Update of Conventional and Innovative Treatment Strategies for Central Nervous System Injury" Biomedicines 12, no. 8: 1894. https://doi.org/10.3390/biomedicines12081894