Mouse spinal cord compression injury is ameliorated by intrathecal cationic manganese(III) porphyrin catalytic antioxidant therapy.
This study evaluated the effects of the cationic manganese(III) tetrakis(N,N'-diethylimidazolium-2-yl)porphyrin catalytic antioxidant Mn(III)TDE-2-ImP5+ (AEOL 10150) on outcome from spinal cord compression (SCC) in the mouse. C57BL/6J mice were subjected to 60 min thoracic SCC after discontinuation of halothane anesthesia. In Experiment 1, mice were given intravenous Mn(III)TDE-2-ImP5+ (0.5 mg/kg bolus followed by 1 mg kg(-1) h(-1) for 24 h), methylprednisolone (30 mg/kg bolus followed by 5.4 mg kg(-1) h(-1) for 24 h), or vehicle (n = 25 per group). In Experiment 2, mice were given intrathecal Mn(III)TDE-2-ImP5+ (2.5 or 5.0 microg/kg) or vehicle (n = 18 per group). In both experiments, treatment began 5 min post-SCC onset. Rotarod performance was measured on post-SCC days 3, 7, 14, and 21. On post-SCC day 21, the spinal cord was histologically examined and a total damage score was calculated. Neither intravenous Mn(III)TDE-2-ImP5+ nor methylprednisolone altered rotarod performance (accelerated rate P = 0.11, fixed rate P = 0.11) or mean +/- S.D. total damage score (Mn(III)TDE-2-ImP5+ = 21 +/- 9, methylprednisolone = 24 +/- 8, vehicle = 22 +/- 10; P = 0.47; shams = 0). Intrathecal Mn(III)TDE-2-ImP5+ (both 2.5 and 5.0 microg) given at SCC-onset improved rotarod performance (P = 0.05) and total damage score (2.5 microg = 19 +/- 10, P = 0.04; 5.0 microg =19 +/- 8, P = 0.03) versus vehicle (26 +/- 10). These studies demonstrate sustained benefit from manganese(III) porphyrin catalytic antioxidant therapy after SCC. However, efficacy was dependent upon route of administration suggesting that bioavailability is critical in defining efficacy.
Department of Anesthesiology, Duke University Medical Center, Durham, NC 27710, USA.
Huaxin
H
Sheng
Ivan
I
Spasojevic
David S
DS
Warner
Ines
I
Batinic-Haberle
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000627:therapeutic use*; D002384:Catalysis; D007275:Injections, Intravenous; D007278:Injections, Spinal; D008665:Metalloporphyrins / Q000008:administration & dosage / Q000627:therapeutic use*; D051379:Mice; D008810:Mice, Inbred C57BL; D013117:Spinal Cord Compression / Q000188:drug therapy* / Q000473:pathology
C472668:AEOL 10150; D000975:Antioxidants; D008665:Metalloporphyrins