TITLE: PROTECTIVE ROLE OF ENDOTHELIAL NITRIC OXIDE SYNTHASE FOLLOWING PRESSURE- INDUCED INSULT TO THE OPTIC NERVE Authors: Chandrakumar Balaratnasingam

Although intracranial pressure (ICP) elevation can induce significant structural and functional changes within the central nervous system (CNS), almost complete neuronal recovery is possible if ICP and associated pathogenic factors are restored in the acute phase of the disease process. Nitric oxide synthase (NOS) isoforms have been implicated in the pathogenesis of many CNS diseases and may play an important role in the development of neuronal tolerance in the early stages of pressure elevation. In this paper we use the pig optic nerve, a typical central white matter tract, to study the time-dependent sequence of NOS isoform change following pressure elevation. The timing of NOS isoform change in relationship to structural and functional changes to axons and glial cells is also discussed. This study demonstrates that endothelial cell nitric oxide synthase (ecNOS), an enzyme that plays a protective role in the CNS, is up-regulated in a time-dependent manner after pressure elevation. ecNOS levels increase after axonal and astrocyte injury, suggesting that it might be a compensatory response that is initiated in an effort to preserve CNS function. Inducible NOS (iNOS) and neuronal NOS (nNOS), which are known to have a deleterious effect on the CNS, were not detected in this study. The increase in ecNOS demonstrated in this study is significantly different to the increase in iNOS and nNOS previously demonstrated following traumatic brain injury. Changes in ecNOS levels may therefore be important in the development of neuronal tolerance in the early stages of CNS diseases such as hydrocephalus. 3