Mn (III) Tetrakis (4-Benzoic Acid) Porphyrin Protects Against Neuronal and Glial Oxidative Stress and Death After Spinal Cord Injury

Lokanatha      Valluru; Yao      Diao; Jorge      E. Hachmeister; Danxia      Liu

doi:10.2174/187152712803581056

Abstract

This study explores the ability of a catalytic antioxidant, Mn (III) tetrakis (4-benzoic acid) porphyrin (MnTBAP), to protect against neuronal and glial oxidative stress and death after spinal cord injury (SCI). Nine different doses of MnTBAP were administered into the intrathecal space of the rat spinal cord immediately following moderate SCI to establish dose - response curves for prevention of lipid peroxidation and neuron death. An optimal dose was determined by comparing the effectiveness of MnTBAP protection among doses. The optimal dose was then administered and the cords were removed 24 h post-administration and processed for staining. The cells in the cord sections at different distances from the epicenter were counted to obtain the spatial profiles of MnTBAP protection. Comparison of the counts between MnTBAP- and vehicle-treated groups in the sections double immuno-fluorescence-stained with oxidative and cellular markers demonstrated that MnTBAP significantly reduced numbers of nitrotyrosine- and DNP-positive (stained with an antibody against 2,4-dinitrophenyl hydrazine (DNPH)-labeled protein carbonyls) neurons, astrocytes, and oligodendrocytes. Comparison of the counts between the two treatments in the sections immuno-stained with cellular markers revealed that MnTBAP significantly increased numbers of neurons, motoneurons, astrocytes, and oligodendrocytes. MnTBAP more effectively reduced neuronal than glial cell death. Post-injury treatment with the optimal dose of MnTBAP at 6, 12, 24, 48, and 72 h post-SCI demonstrated that the effective time window for reducing protein nitration and neuron death was at least 12 h. Our results demonstrated that MnTBAP combats oxidative stress, thereby attenuating all types of cell death after SCI.

Keywords: Antioxidant therapy, membrane lipid peroxidation, Mn (III) tetrakis (4-benzoic acid) porphyrin, neuronal and glial death, optimal dose, oxidation and nitration of proteins, spinal cord injury, effective time window, ANOVA, MnTBAP