Date on Master's Thesis/Doctoral Dissertation


Document Type

Doctoral Dissertation

Degree Name

Ph. D.


Pharmacology and Toxicology

Committee Chair

Hagg, Theo


Nerves--Regeneration; Spinal cord--Wounds and injuries--Treatment


These studies set out to identify strategies to rescue and repair the adult nervous system. First, we investigated the role of ciliary neurotrophic factor (CNTF) in 5HT1A receptor-induced neurogenesis in the rodent brain. Systemic treatment with an agonist, 8-OH-DPAT, increased neurogenesis only in rats and not mice, and only in one of the two neurogenic regions. This increase was not mediated by CNTF. These data suggest that translation of 5HT1A-based studies to human cell replacement therapies should be reconsidered. Secondly, the role of the plasticity-associated metalloprotease ADAM21 after spinal cord injury was investigated by comparing ADAM21-deficient mice to their wildtype littermates. No differences in behavioral or histology were found. However, a comprehensive metalloproteinase gene array revealed that ADAM21 regulates a cluster of inflammatory genes following injury. This leaves a potential for discovery of specific pharmaceutical ADAM21 inhibitors to reduce detrimental inflammatory processes following spinal cord injury.