Demyelination as a rational therapeutic target for ischemic or traumatic brain injury

Abstract

Previous research on stroke and traumatic brain injury (TBI) heavily emphasized pathological alterations in neuronal cells within gray matter. However, recent studies have highlighted the equal importance of white matter integrity in long-term recovery from these conditions. Demyelination is a major component of white matter injury and is characterized by loss of the myelin sheath and oligodendrocyte cell death. Demyelination contributes significantly to long-term sensorimotor and cognitive deficits because the adult brain only has limited capacity for oligodendrocyte regeneration and axonal remyelination. In the current review, we will provide an overview of the major causes of demyelination and oligodendrocyte cell death following acute brain injuries, and discuss the crosstalk between myelin, axons, microglia, and astrocytes during the process of demyelination. Recent discoveries of molecules that regulate the processes of remyelination may provide novel therapeutic targets to restore white matter integrity and improve long-term neurological recovery in stroke or TBI patients.

A Post-stroke Therapeutic Regimen with Omega-3 Polyunsaturated Fatty Acids that Promotes White Matter Integrity and Beneficial Microglial Responses after Cerebral Ischemia

“…Therefore, the damage or insufficient repair of white matter contributes to the development of long-term neurological deficits [42]. On the one hand, ischemia/reperfusion induces cell death of the myelin-producing oligodendrocytes and, consequently, white matter demyelination [7]. On the other hand, the continuous presence of oligodendrocyte progenitor cells (OPCs) in the brain provides an opportunity for oligodendrocyte regeneration and white matter repair [2, 43, 44].…”

“…White matter injury is characterized by demyelination and loss of axonal integrity [2, 7]. Demyelination, or destruction of the myelin sheath, if unrepaired, causes degradation of the naked axons, eventually leading to irreversible neurological disability [1].…”

“…Demyelination, or destruction of the myelin sheath, if unrepaired, causes degradation of the naked axons, eventually leading to irreversible neurological disability [1]. White matter repair, including axonal regeneration, oligodendrogenesis, and the myelination of demyelinated or newly generated axons, rebuilds the neuronal circuits and restores axonal conduction [7–11]. Both white matter injury and repair are remarkably influenced by the functional status of the surrounding glial cells, such as astrocytes and microglia [12, 13].…”

White matter damage after traumatic brain injury: A role for damage associated molecular patterns

“…In addition to producing focal damage, the differential movement of grey and white matter during acceleration-deceleration results in widespread, diffuse axonal tearing at grey-white matter junctions [21]. As diffuse axonal injury and loss of white matter integrity are strongly associated with chronic sensorimotor, cognitive, and psychiatric dysfunction in both pre-clinical and clinical TBI [22–28], therapies that limit white matter damage and enhance remyelination may profoundly improve long-term clinical outcomes.…”

Implantation of Brain-derived Extracellular Matrix Enhances Neurological Recovery after Traumatic Brain Injury

“…Recent studies have highlighted the importance of white matter integrity in long-term recovery after stroke and TBI. 17,28 White matter, consisting of myelinensheathed axons and myelin-producing oligodendrocytes, is known to play a critical role in signal transduction and communication across brain regions. 29 White matter destruction is an integral component of most human TBI cases 30,31 and accounts for profound sensorimotor and cognitive impairments.…”