Pharmacological modification of the extracellular matrix to promote regeneration of the injured brain and spinal cord

Abstract

This chapter focuses on the role of the fibrous lesion scar as a major impediment for axonal regeneration in the injured central nervous system (CNS). We describe the appearance and complementary distribution of the glial and fibrous scar components in spinal cord lesions focusing on the morphology as well as on axon growth inhibitory molecular components accumulating in the collagenous and basement membrane-rich fibrous scar. We further report on the differential responses to fibrous scar of distinct fiber tracts in the injured spinal cord including the rubrospinal and corticospinal tracts as well as serotonergic, dopaminergic, and calcitonin gene-related peptide (CGRP) systems. Finally, we discuss therapeutic strategies to suppress fibrous scarring in traumatic CNS injury with particular emphasis on a unique pharmacological treatment using iron chelators and cyclic adenosine monophosphate (cAMP) to inhibit collagen biosynthesis. The latter treatment has been shown to promote long-distance axon growth, retrograde protection of injured neurons, and significant functional improvement.