Abstract
It has recently been demonstrated that selective inhibition of both neuronal constitutive and inducible nitric oxide synthases (ncNOS and iNOS) is neuroprotective in a model of dynorphin (Dyn) A(1-17)-induced spinal cord injury. In the present study, various methods including the conversion of 3H-L-arginine to 3H-citrulline, immunohistochemistry and in situ hybridization are employed to determine the temporal profiles of the enzymatic activities, immunoreactivities, and mRNA expression for both ncNOS and iNOS after intrathecal injection of a neurotoxic dose (20 nmol) of Dyn A(1-17). The expression of ncNOS immunoreactivity and mRNA increased as early as 30 min after injection and persisted for 1-4 h. At 24-48 h, the number of ncNOS positive cells remained elevated while most neurons died. The cNOS enzymatic activity in the ventral spinal cord also significantly increased at 30 min-48 h, but no significant changes in the dorsal spinal cord were observed. However, iNOS mRNA expression increased later at 2 h, iNOS immunoreactivity and enzymatic activity increased later at 4 h and persisted for 24-48 h after injection of 20 nmol Dyn A(1-17). These results indicate that both ncNOS and iNOS are associated with Dyn-induced spinal cord injury, with ncNOS predominantly involved at an early stage and iNOS at a later stage. Copyright (C) 2000 Elsevier Science B.V.
Original language | English (US) |
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Pages (from-to) | 183-197 |
Number of pages | 15 |
Journal | Journal of chemical neuroanatomy |
Volume | 17 |
Issue number | 4 |
DOIs | |
State | Published - Jan 1 2000 |
Funding
The research was supported by grants from the National Natural Science Foundation of China and China Medical Board of New York. We thank Dr Solomon H. Snyder, Dr Ted M. Dawson and Dr Charles J. Lowenstein for their generous gifts of NOS antibodies and cDNA plasmids. We also thank Dr W. S. Lynn and Dr E. Ryan for critical reading and helpful discussion.
Keywords
- Dynorphin
- Neurotoxicity
- Nitric oxide
- Nitric oxide synthase
- Spinal cord injury
ASJC Scopus subject areas
- Cellular and Molecular Neuroscience