The effects of L-arginine on neurological function, histopathology, and expression of hypoxia-inducible factor-1 alpha following spinal cord ischemia in rats.
The aim of this study was to investigate the effects of L-arginine (L-Arg) on neurological function, histopathology, and expression of hypoxia-inducible factor-1 alpha (HIF-1alpha) following spinal cord ischemia in rats, and the interaction between therapy with the nitric oxide donor L-Arg and up-regulation of the expression of HIF-1alpha. Thirty Wistar rats weighing between 200 and 250 g were divided into three groups, each containing 10 rats: group 1, sham operation; group 2, untreated ischemia-reperfusion (I-R); group 3, I-R plus L-Arg treatment. Spinal cord ischemia was applied for 20 min. There were no significant differences in mean arterial pressures, temperatures, and blood gas levels among the groups. In group 2, malondialdehyde values were significantly increased compared with groups 1 and 3. The rats with aortic occlusion in group 2 had paraplegia or paraparesis. In group 3, all animals were neurologically intact. In group 3, spinal motor neurons did not decrease significantly, and little proliferation of microglia was observed compared with those in group 2. In group 2, spinal motor neurons in ventral gray matter decreased significantly compared with those in groups 1 and 3. HIF-1alpha-positive immunostaining was mildly detected in group 2 animals. The expression of immunoreactive cells was intensely increased in spinal cord tissue from I-R/L-Arg rats. In conclusion, our findings suggest that HIF-1alpha-positive immunostaining may be critical factors in the pathophysiology of inflammatory spinal cord injury induced by I-R. Nitric oxide may play an important role in the immunohistochemical expression of these molecules, and the neuroprotective benefit of L-Arg may be attributed to preventing neural cell necrosis.
Tuncer
M Cudi
MC
Department of Anatomy, Dicle University, Medical School, Diyarbakir, Turkey. cudi@dicle.edu.tr
Hatipoglu
E Savas
ES
Ozturk
H
H
Kervancioglu
P
P
Buyukbayram
H
H
D000818:Animals; D001120:Arginine / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D007150:Immunohistochemistry; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D020760:Spinal Cord Ischemia / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D015854:Up-Regulation / Q000187:drug effects
C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018696:Neuroprotective Agents; D001120:Arginine