Neurotrauma—From Injury to Repair: Clinical Perspectives, Cellular Mechanisms and Promoting Regeneration of the Injured Brain and Spinal Cord

Abstract

Traumatic injury to the brain and spinal cord (neurotrauma) is a common event across populations and often causes profound and irreversible disability. Pathophysiological responses to trauma exacerbate the damage of an index injury, propagating the loss of function that the central nervous system (CNS) cannot repair after the initial event is resolved. The way in which function is lost after injury is the consequence of a complex array of mechanisms that continue in the chronic phase post-injury to prevent effective neural repair. This review summarises the events after traumatic brain injury (TBI) and spinal cord injury (SCI), comprising a description of current clinical management strategies, a summary of known cellular and molecular mechanisms of secondary damage and their role in the prevention of repair. A discussion of current and emerging approaches to promote neuroregeneration after CNS injury is presented. The barriers to promoting repair after neurotrauma are across pathways and cell types and occur on a molecular and system level. This presents a challenge to traditional molecular pharmacological approaches to targeting single molecular pathways. It is suggested that novel approaches targeting multiple mechanisms or using combinatorial therapies may yield the sought-after recovery for future patients.

Applications of Stem Cell-Derived Extracellular Vesicles in Nerve Regeneration

“…CNS injuries, including spinal cord injury (SCI), traumatic brain injury (TBI) and optic nerve injury (ONI), therefore, represent a complex problem in biology with an unmet clinical need. Since this review focuses on the utility of EVs in nerve regeneration, the reader is directed to some excellent recent reviews on CNS and PNS regeneration elsewhere [ 100 , 101 , 102 , 103 ].…”

“…Mature NG2+ oligodendrocytes are not only reduced in number but display altered morphology at the lesion site that results in reduced myelination, whilst oligodendrocyte precursor cells (OPCs) are activated and secrete axon growth inhibitory chondroitin sulphate proteoglycans (CSPGs) [ 175 ]. As well as this, the degenerating myelin sheath unravels myelin-derived axon growth inhibitory molecules such as Nogo, oligodendrocyte-derived myelin glycoprotein (OMgp), myelin-associated glycoprotein (MAG) [ 102 ].…”

“…More recently, combinations of biomaterials, stem cells, growth factors and drugs have led to improvements in axon regeneration over single treatments [ 178 ]. For more information on these research areas, the reader is directed to some excellent reviews elsewhere [ 102 , 179 , 180 , 181 , 182 , 183 ].…”