Depletion of endogenous serotonin synthesis with p-CPA attenuates upregulation of constitutive isoform of heme oxygenase-2 expression, edema formation and cell injury following a focal trauma to the rat spinal cord.
The possibility that the upregulation of hemeoxygenase (HO) enzyme responsible for carbon monoxide (CO) formation in the spinal cord following trauma is involved in edema formation and cell damage was examined in a rat model. A focal trauma to the rat spinal cord by making an incision into the right dorsal horn of the T10-11 segment resulted in profound upregulation of HO-2 (the constitutive isoform of the enzyme) expression in the T9 and T12 segments 5 h after injury. In these segments a marked increase in edema formation, nerve cell damage, and expression of heat shock protein (HSP 72) were observed. Pretreatment with p-chlorophenylalanine (p-CPA, a serotonin synthesis inhibitor) significantly attenuated the trauma induced edema formation, cell injury, and HSP expression. Upregulation of HO-2 in p-CPA treated traumatised rats was considerably reduced. These observations suggest that (i) spinal cord injury has the capacity to induce an upregulation of HO-2 and HSP expression, (ii) abnormal production of CO as reflected by HO-2 expression is injurious to the cord, and (iii) that endogenous serotonin is involved in HO-2 expression in the cord.
Sharma
H S
HS
Laboratory of Neuroanatomy, Department of Medical Cell Biology, Biomedical Center, Uppsala University, Uppsala, Sweden. Sharma@medcellbiol.uu.se
Westman
J
J
D000818:Animals; D004487:Edema / Q000517:prevention & control*; D010134:Fenclonine / Q000494:pharmacology*; D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors*; D007150:Immunohistochemistry / Q000379:methods; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D012701:Serotonin / Q000378:metabolism*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D013119:Spinal Cord Injuries / Q000150:complications* / Q000473:pathology; D013194:Staining and Labeling; D015854:Up-Regulation / Q000187:drug effects
D050884:HSP72 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D012702:Serotonin Antagonists; D012701:Serotonin; D006419:Heme Oxygenase (Decyclizing); C105245:heme oxygenase-2; D010134:Fenclonine