Molecular basis of brain injury and repair

Abstract

Injury to the central nervous system (CNS) is one of the leading causes of death and invalidity among all people below the age of 45 for which there are no specific treatments. The insight into the molecular pathophysiology of brain dysfunctions after the injury will provide indications for new effective therapeutic approaches that will limit damage, slow cell death and promote repair. The aim of this review is to highlight molecular mechanisms underlining primary and secondary injury. The initial impact or primary injury induces elevation of extracellular concentration of neurotransmitters leading to changes in electrical properties of neuronal membrane, net influx of Ca2+ and activation of diverse cellular signaling pathways. To restore neuronal homeostasis, the activities and expression of a variety of enzymes involved in control of extracellular concentration of biogenic amines and purine nucleotides/nucleosides, as well as the membrane potential are altered. The CNS has a limited capacity of self-repair. However, there are indications that the neonatal brain has a greater capacity for recovery than adult brain. The well known pathological hallmark of CNS injury is formation of the glial scar, the major impediment to axonal regeneration. Recently, it was shown that treatment with the purine nucleoside analogues attenuates and delays the process of reactive gliosis, and thus may be a useful approach for improving neurological recovery from head injury.