Oligodendrocyte dysfunction and regeneration failure: A novel hypothesis of delayed encephalopathy after carbon monoxide poisoning

Abstract

Carbon monoxide (CO) poisoning usually causes brain lesions and delayed encephalopathy, also known as delayed neurological sequelae (DNS). Demyelination of white matter (WM) is one of the most common sites of abnormalities in patients with DNS, but its mechanisms remain unclear. Oligodendrocytes (OLs) are myelinated cells that ensure the rapid conduction of neuronal axon signals and provide the nutritional factors necessary for maintaining nerve integrity in the central nervous system (CNS). OLs readily regenerate and replace damaged myelin membranes around axons in the adult mammalian CNS following demyelination. The ability to regenerate OLs depends on the availability of precursor cells (OPCs) in the CNS of adults. Multiple injury-related signals can induce OPC expansion followed by OL differentiation, axonal contact and myelin regeneration (remyelination). Therefore, OL dysfunction and regeneration failure in the deep WM of the brain are the key pathophysiological mechanisms leading to delayed brain injury after CO poisoning. CO-induced toxicity may interfere with OL function and render OPCs unable to regenerate OLs through some unclear mechanisms, leading to progressive demyelinating damage and resulting in DNS. In the future, combination therapies to reduce OL damage and promote OPC differentiation and remyelination may be important for the prevention and treatmentof DNS after CO poisoning.