Mouse spinal cord compression injury is ameliorated by intrathecal cationic manganese(III) porphyrin catalytic antioxidant therapy.

Published

Journal Article

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.

Full Text

Duke Authors

Cited Authors

  • Sheng, H; Spasojevic, I; Warner, DS; Batinic-Haberle, I

Published Date

  • August 2004

Published In

Volume / Issue

  • 366 / 2

Start / End Page

  • 220 - 225

PubMed ID

  • 15276251

Pubmed Central ID

  • 15276251

Electronic International Standard Serial Number (EISSN)

  • 1872-7972

International Standard Serial Number (ISSN)

  • 0304-3940

Digital Object Identifier (DOI)

  • 10.1016/j.neulet.2004.05.050

Language

  • eng