Functional neuroprotective effect of CGS 26303, a dual ECE inhibitor, on ischemic-reperfusion spinal cord injury in rats.
Endothelin-1 (ET-1) has been implicated in many neurological diseases, including subarachnoid hemorrhage (SAH) and cerebral ischemia. ET-1 is also proved to deteriorate the ischemia-reperfusion injury in many organs. Our previous studies demonstrated that the endothelin-converting enzyme (ECE) inhibitor, CGS 26303, possessed beneficial effects for the treatment of SAH and transient middle cerebral artery occlusion. In this study, we investigated the neuroprotective effect of CGS 26303 on the locomotor function and mRNA expression of heme-oxygenase-1 (HO-1) in rats subjected to a 15-min spinal cord ischemia. The results showed that pretreatment with CGS 26303 significantly preserved the locomotor function and decreased the paraplegia rate at Days 1 and 3 as compared with a saline-treated group. Furthermore, rats pretreated with CGS 26303 had a significant increase in the levels of HO-1 mRNA expression at Day 3 when compared with animals pretreated with saline after spinal cord ischemia and the sham operation group. These results suggest that CGS 26303 may have a promising neuroprotective effect in the spinal cord after ischemia-reperfusion injury, and beneficial result may be due to an adaptive mechanism involved by HO-1 overexpression.
Chou
An-Kuo
AK
Department of Anesthesiology, Chang Gung Memorial Hospital-Kaohsiung Medical Center, Chang Gung University College of Medicine, Taiwan.
Chen
Tai-I
TI
Winardi
William
W
Dai
Ming-Hong
MH
Chen
Shih-Chieh
SC
Howng
Shen-Long
SL
Yen
Chun-Po
CP
Lin
Tzu-Kan
TK
Jeng
Arco Y
AY
Kwan
Aij-Lie
AL
D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000037:antagonists & inhibitors*; D000072396:Endothelin-Converting Enzymes; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D008124:Locomotion / Q000187:drug effects; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013116:Spinal Cord / Q000201:enzymology; D013119:Spinal Cord Injuries / Q000150:complications* / Q000503:physiopathology
D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D006419:Heme Oxygenase (Decyclizing); D016282:Aspartic Acid Endopeptidases; D008666:Metalloendopeptidases; D000072396:Endothelin-Converting Enzymes