Neuroprotective effects of nitric oxide synthase inhibitors in spinal cord injury-induced pathophysiology and motor functions: An experimental study in the rat.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/209304
- author
- Sharma, HS ; Badgaiyan, RD ; Alm, Per LU ; Mohanty, S and Wiklund, L
- organization
- publishing date
- 2005
- 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
- Wiley-Blackwell
- external identifiers
-
- pmid:16179549
- wos:000235109800043
- scopus:29744446628
- ISSN
- 0077-8923
- DOI
- 10.1196/annals.1344.037
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000)
- id
- 1b37390b-d069-41b2-8d10-22187fa1e949 (old id 209304)
- date added to LUP
- 2016-04-01 16:56:40
- date last changed
- 2022-03-15 04:00:16
@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}},
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}},
language = {{eng}},
pages = {{422--434}},
publisher = {{Wiley-Blackwell}},
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}},
doi = {{10.1196/annals.1344.037}},
volume = {{1053}},
year = {{2005}},
}