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

Sharma, HS; Badgaiyan, RD; Alm, Per LU ; Mohanty, S and Wiklund, L (2005) In Annals of the New York Academy of Sciences 1053. p.422-434
Abstract
The role of nitric oxide (NO) in spinal cord injury (SCI)-induced 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... (More)
The role of nitric oxide (NO) in spinal cord injury (SCI)-induced 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-induced 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 neuro-protection, and the disturbances in motor function following SCI are associated with the state of spinal cord pathology. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
cell injury, formation, edema, blood-spinal cord barrier, endothelial NOS, L-NMMA, neuronal NOS, L-NNA, L-NAME, nitric oxide synthase, spinal cord injury, nitric oxide, motor dysfunction, spinal cord pathology
in
Annals of the New York Academy of Sciences
volume
1053
pages
422 - 434
publisher
New York Academy of Sciences
external identifiers
  • pmid:16179549
  • wos:000235109800043
  • scopus:29744446628
ISSN
0077-8923
DOI
10.1196/annals.1344.037
language
English
LU publication?
yes
id
1b37390b-d069-41b2-8d10-22187fa1e949 (old id 209304)
date added to LUP
2007-08-20 14:03:36
date last changed
2017-07-02 04:28:35
@article{1b37390b-d069-41b2-8d10-22187fa1e949,
  abstract     = {The role of nitric oxide (NO) in spinal cord injury (SCI)-induced 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-induced 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 neuro-protection, and the disturbances in motor function following SCI are associated with the state of spinal cord pathology.},
  author       = {Sharma, HS and Badgaiyan, RD and Alm, Per and Mohanty, S and Wiklund, L},
  issn         = {0077-8923},
  keyword      = {cell injury,formation,edema,blood-spinal cord barrier,endothelial NOS,L-NMMA,neuronal NOS,L-NNA,L-NAME,nitric oxide synthase,spinal cord injury,nitric oxide,motor dysfunction,spinal cord pathology},
  language     = {eng},
  pages        = {422--434},
  publisher    = {New York Academy of Sciences},
  series       = {Annals of the New York Academy of Sciences},
  title        = {Neuroprotective effects of nitric oxide synthase inhibitors in spinal cord injury-induced pathophysiology and motor functions: An experimental study in the rat.},
  url          = {http://dx.doi.org/10.1196/annals.1344.037},
  volume       = {1053},
  year         = {2005},
}