FACTORS AFFECTING REGENERATION THROUGH THE GLIAL SCAR

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DESCRIPTION: (Adapted from the Applicant's Abstract.) The experiments in this proposal seek to compare and contrast the cellular and molecular mechanisms by which astroglia may inhibit the growth of axons in two regions of the spinal cord: 1) the roof plate, which is a transient boundary to dorsal column axons during development and 2) the glial dome of the dorsal root entry zone, which forms a doorway for afferents into the CNS during development but becomes a boundary to dorsal root afferent regeneration after birth. The applicant and his colleagues plan to correlate the development of the dorsal columns and the later forming dorsal commissure with morphogenesis of the midline glia and with the initial presence and subsequent disappearance of keratin sulfate/chondroitin sulfate glycosaminoglycans, putative boundary molecules that they have localized in this region. Enzyme digestion of the roof plate GAG's in an in vitro slice preparation will test whether dorsal column axons aberrantly cross the midline. For the studies on the DREZ, they plan first to describe the normal cellular and basal lamina elements at the CNS/PNS interface and the molecules that are expressed during the period of axonal ingrowth into the spinal cord. They will then compare these constituents with those of the DREZ in animals with crush injuries of the roots to determine if mechanical or chemical factors may contribute to regenerative failure in this region. Preliminary studies have shown that GAG's found in normal glial barriers such as the roof plate appear in reactive glia following root lesions. The putative astroglial boundary molecules of the roof plate and lesioned DREZ will be investigated in an in vitro assay system where the growing axons will be challenged with combination of putative pathway and boundary cells or molecules in various geometric patterns.