Beneficial effects of nitric oxide synthase inhibition on the recovery of neurological function after spinal cord injury in rats.
We have demonstrated recently that treatment with N(G)-monomethyl-L-arginine (L-NMMA) accelerates electrophysiological recovery after transient spinal cord ischaemia in anaesthetized cats. To determine whether nitric oxide synthase (NOS) inhibition in the acute phase of spinal cord injury results in better functional recovery in the chronic phase, we evaluated the influence of L-NMMA on the time course of changes of neurological function and the histopathological changes after spinal cord compression in rats. Experimental spinal cord injury was produced in anaesthetized rats by short-term (5 min) compression with a thread placed around the spinal cord at T13. The recovery of motor function was assessed by a treadmill test 10, 20 and 30 days after spinal cord compression. The latency of potentials evoked by hindlimb stimulation was measured at the funiculus posterior at C1 10 days after the spinal cord injury in anaesthetized rats. Histological examinations were also performed at the same time. The compression-induced spinal cord injury resulted in motor dysfunction of hindlimbs, an increase in the latency of the evoked potentials and neuronal degeneration in funiculus posterior at T13. Repeated administration of L-NMMA for 1 day significantly accelerated the recovery of the motor function, shortened the latency of the evoked potentials and attenuated the myelin vacuolization in the spinal cord. These beneficial effects of L-NMMA on neurological function and histopathological changes were abolished by coadministration of L- but not D-arginine. These results suggest that NOS inhibition during the early stage of spinal cord injury has beneficial effects on the recovery of neurological function and the histopathological changes in the chronic stage.
Suzuki
T
T
Department of Pharmacology, Chiba University School of Medicine, Japan. stoshio@med.m.chiba-u.ac.jp
Tatsuoka
H
H
Chiba
T
T
Sekikawa
T
T
Nemoto
T
T
Moriya
H
H
Sakuraba
S
S
Nakaya
H
H
D000818:Animals; D001120:Arginine / Q000737:chemistry / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019054:Evoked Potentials, Motor / Q000187:drug effects; D007150:Immunohistochemistry; D008297:Male; D009043:Motor Activity / Q000187:drug effects; D009420:Nervous System / Q000187:drug effects / Q000503:physiopathology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000201:enzymology / Q000503:physiopathology*; D013237:Stereoisomerism; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D019323:omega-N-Methylarginine; D001120:Arginine; D019001:Nitric Oxide Synthase