A new antioxidant compound H-290151 attenuates spinal cord injury induced expression of constitutive and inducible isoforms of nitric oxide synthase and edema formation in the rat.
The role of oxidative stress in spinal cord injury (SCI) induced upregulation of constitutive or inducible isoforms of nitric oxide synthase (cNOS or iNOS) is not well known. The present investigation was undertaken to examine the influence of an antioxidant compound H-290/51 (Astra-Zeneca, Mölndal, Sweden) on SCI induced cNOS and iNOS upregulation in a rat model. SCI induced by incision into the right dorsal horn of the T10-11 segment resulted in marked NOS upregulation. Upregulation of cNOS was most prominent in the uninjured T9 and T12 segments. On the other hand, iNOS expression was most marked in the injured T10-11 segments. These NOS immunoreactivities were mainly confined to the injured cells located in the edematous regions of the cord exhibiting profound leakage of Evans blue and [131]Iodine-sodium tracers. Pre-treatment with H-290/51 markedly attenuated the trauma-induced cNOS and iNOS expression along with the microvascular permeability disturbances, edema formation and cell injury. These results suggest that (i) oxidative stress is involved in SCI induced induction of cNOS and iNOS, (ii) NO plays an important role in the cord pathology, and (iii) that the compound H-290/51 has a potential therapeutic value in SCI.
Sharma
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HS
Laboratory of Neuroanatomy, Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden. Sharma@medcellbiol.uu.se
Sjöquist
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Alm
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D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002199:Capillary Permeability / Q000187:drug effects; D004487:Edema / Q000517:prevention & control*; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000098:blood supply / Q000201:enzymology / Q000473:pathology; D013118:Spinal Cord Diseases / Q000517:prevention & control*; D013119:Spinal Cord Injuries / Q000201:enzymology* / Q000473:pathology; D015854:Up-Regulation / Q000187:drug effects
D000975:Antioxidants; C088233:H290-51; D007211:Indoles; D018696:Neuroprotective Agents; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; C496322:Nos1 protein, rat; C496318:Nos2 protein, rat