Understanding Molecular Pathology along Injured Spinal Cord Axis: Moving Frontiers toward Effective Neuroprotection and Regeneration

Abstract

Spinal cord injury (SCI) is a severe, often life threatening, traumatic condition leading to serious neurological dysfunctions. The pathological hallmarks of SCI include inflamma tion, reactive gliosis, axonal demyelination, neuronal death, and cyst formation. Although much has been learned about the progression of SCI pathology affecting a large number of biochemical cascades and reactions, the roles of proteins involved in these processes are not well understood. Advances in proteomic technologies have made it possible to examine the spinal cord proteome from healthy and experimental animals and disclose a detailed overview on the spatial and temporal regionalization of these secondary processes. Data clearly demonstrated that neurotrophic molecules dominated in the segment above the central lesion, while the proteins associated with necrotic/apoptotic pathways abound the segment below the lesion. This knowledge is extremely important in finding optimal targets and pathways on which complementary neuroprotective and neuroregenerative approaches should be focused on. In terms of neuroprotection, several active substances and cell-based therapy together with biomaterials releasing bioactive substances showed partial improvement of spinal cord injury. However, one of the major challenges is to select specific therapies that can be combined safely and in the appropriate order to provide the maximum value of each individual treatment. and caudal axes, with expression of neurotrophic and immunomodula-tory factors in the in contrast to in the caudal These data indicate the importance of by inhibiting and to M2 clear impact on findings