Neuroprotective effects of nitric oxide synthase inhibitors in spinal cord injury-induced pathophysiology and motor functions: An experimental study in the rat

Hari Shanker Sharma, Rajendra D. Badgaiyan, Per Alm, S. Mohanty, Lars Wiklund

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63 Scopus citations

Abstract

The role of nitric oxide (NO) in spinal cord injary (SCI)-indnced motor dysfunction, breakdown of the blood-spinal cord barrier (BSCB), edema formation, and cell injury was examined using a pharmacological approach. We used three types of nitric oxide synthase (NOS) inhibitors: a nonselective blocker, L-NAME; an irreversible inhibitor of all isoforms of NOS, L-NMMA; and a long-term competitive inhibitor of neuronal NOS with equal potency to inhibit endothelial NOS, L-NNA. The compounds were administered once daily in separate groups of rats for 7 days. On the 8th day, SCI was performed by making a longitudinal incision into the right dorsal horn of the T10-11 segments, and the rats were allowed to survive 5 h after injury. Long-term treatment with L-NNA attenuated SCI-induced NOS upregulation, BSCB breakdown, edema formation, and cell injury, whereas comparatively less neuroprotection is offered by L-NMMA. The magnitude of neuroprotection is much less evident in injured animals that received L-NAME. Interestingly, SCI-indaced motor dysfunction measured according to the Tarlov scale showed close correlation with the magnitude of neuroprotection. Thus, an improvement in motor function was seen in animals pretreated with L-NNA, whereas rats treated with L-NAME or L-NMMA did not show any influence on motor dysfunction after SCI. This observation suggests that inhibition of neuronal NOS is important for neuroprotection, and the disturbances in motor function following SCI are associated with the state of spinal cord pathology.

Original languageEnglish (US)
Pages (from-to)422-434
Number of pages13
JournalAnnals of the New York Academy of Sciences
Volume1053
DOIs
StatePublished - 2005

Keywords

  • Blood-spinal cord barrier
  • Cell injury
  • Edema formation
  • Endothelial NOS
  • L-NAME
  • L-NMMA
  • L-NNA
  • Motor dysfunction
  • Neuronal NOS
  • Nitric oxide
  • Nitric oxide synthase
  • Spinal cord injury
  • Spinal cord pathology

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