TY - JOUR
T1 - Neuroprotective effects of nitric oxide synthase inhibitors in spinal cord injury-induced pathophysiology and motor functions
T2 - An experimental study in the rat
AU - Sharma, Hari Shanker
AU - Badgaiyan, Rajendra D.
AU - Alm, Per
AU - Mohanty, S.
AU - Wiklund, Lars
PY - 2005
Y1 - 2005
N2 - 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.
AB - 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.
KW - Blood-spinal cord barrier
KW - Cell injury
KW - Edema formation
KW - Endothelial NOS
KW - L-NAME
KW - L-NMMA
KW - L-NNA
KW - Motor dysfunction
KW - Neuronal NOS
KW - Nitric oxide
KW - Nitric oxide synthase
KW - Spinal cord injury
KW - Spinal cord pathology
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U2 - 10.1196/annals.1344.037
DO - 10.1196/annals.1344.037
M3 - Article
C2 - 16179549
AN - SCOPUS:29744446628
SN - 0077-8923
VL - 1053
SP - 422
EP - 434
JO - Annals of the New York Academy of Sciences
JF - Annals of the New York Academy of Sciences
ER -