Editorial - Journal of Experimental Stroke & Translational Medicine (2025) Volume 17, Issue 2
White Matter Injury: Mechanisms, Clinical Impact, and Emerging Therapies
Elena Petrova*
Department of Neurology, Sechenov University, Moscow, Russia
- *Corresponding Author:
- Elena Petrova
Department of Neurology, Sechenov University, Moscow, Russia
E-mail: elena.petrova@sechenov.ru
Received: 01-March-2025, Manuscript No. jestm-25-170401; Editor assigned: 3-March-2025, PreQC No. jestm-25-170401 (PQ); Reviewed: 17-March-2025, QC No. jestm-25-170401; Revised: 24-March-2025, Manuscript No. jestm-25-170401 (R); Published: 31-March-2025, DOI: 10.37532/jestm.2024.16(6).331-332
Introduction
White matter injury (WMI) refers to structural and functional damage to the brain’s myelinated axons and their supporting cells. White matter, composed primarily of oligodendrocytes, axons, and glial cells, plays a central role in neural connectivity and efficient signal transmission. Injury to this system disrupts neuronal communication [1], resulting in cognitive, motor, and sensory deficits. WMI is observed across the lifespan, from premature infants with periventricular leukomalacia to adults with stroke, traumatic brain injury, multiple sclerosis, and neurodegenerative disorders. Because white matter constitutes nearly half of the human brain, understanding WMI is crucial for developing effective diagnostic and therapeutic approaches.
Mechanisms of White Matter Injury
The pathophysiology of WMI is multifactorial and involves complex interactions among vascular, inflammatory, and cellular processes.
Ischemia and Hypoxia: White matter is highly vulnerable to reduced blood flow and oxygen deprivation due to its limited collateral circulation and high metabolic demands.
Oxidative Stress: Excessive production of reactive oxygen species damages myelin and oligodendrocytes, impairing axonal conduction.
Excitotoxicity: Overactivation of glutamate receptors leads to calcium influx, triggering oligodendrocyte apoptosis and axonal injury [2].
Neuroinflammation: Activated microglia and infiltrating immune cells release cytokines, chemokines, and proteases that exacerbate demyelination and axonal damage.
Blood-Brain Barrier Dysfunction: BBB breakdown facilitates entry of inflammatory mediators and neurotoxic molecules, amplifying injury.
Maturational Vulnerability: In preterm infants, immature oligodendrocyte progenitors are particularly sensitive to oxidative stress and inflammation, predisposing them to WMI.
Clinical Manifestations
The clinical presentation of WMI varies depending on the extent, location, and timing of the injury.
In Neonates: WMI is a leading cause of cerebral palsy, cognitive impairment, and long-term motor deficits in premature infants.
In Adults: WMI contributes to stroke-related cognitive decline, gait disturbances, and post-stroke dementia.
In Neurodegenerative Diseases: White matter abnormalities are increasingly recognized in Alzheimer’s disease, Parkinson’s disease, and vascular dementia, where they contribute to progressive cognitive impairment.
In Traumatic Brain Injury (TBI): Diffuse axonal injury, a hallmark of TBI, results from shearing forces that disrupt axonal integrity and white matter connectivity.
Diagnostic Approaches
Early and accurate detection of WMI is critical for intervention and prognosis.
Magnetic Resonance Imaging (MRI): Diffusion tensor imaging (DTI) provides sensitive measures of white matter integrity, detecting microstructural changes not visible on conventional MRI.
Advanced Neuroimaging: Techniques such as magnetization transfer imaging and myelin water fraction imaging allow more precise evaluation of myelin health [3].
Biomarkers: Emerging serum and cerebrospinal fluid biomarkers, including neurofilament light chain and glial fibrillary acidic protein (GFAP) [4], may provide insights into white matter damage and repair.
Therapeutic Strategies
Currently, treatment of WMI remains largely supportive, but several promising strategies are under investigation:
Neuroprotection: Antioxidants, anti-inflammatory drugs, and glutamate receptor antagonists aim to reduce ongoing cellular injury.
Remyelination Therapies: Agents that promote oligodendrocyte progenitor cell differentiation and remyelination are being explored in preclinical and early clinical trials [5].
Cell-Based Therapies: Stem cell transplantation and exosome-based approaches show potential in promoting white matter repair and neuroregeneration.
Rehabilitation: Cognitive training, physical therapy, and occupational therapy remain essential for functional recovery in patients with WMI.
Preventive Measures: In neonates, strategies such as maternal care optimization, control of perinatal infections, and prevention of hypoxic events can reduce WMI risk.
Conclusion
White matter injury is a common and clinically significant phenomenon that contributes to a wide range of neurological disorders across the lifespan. Its pathogenesis involves ischemia, oxidative stress, excitotoxicity, inflammation, and BBB dysfunction, leading to impaired neuronal connectivity and functional deficits. Advances in neuroimaging and biomarker research have improved diagnostic accuracy, while novel therapeutic approaches—including remyelination strategies, neuroprotective agents, and regenerative medicine—offer hope for future interventions. Continued research aimed at understanding the mechanisms of WMI and translating experimental findings into clinical practice will be vital in reducing the burden of white matter-related neurological disability.
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