Title:Mn (III) Tetrakis (4-Benzoic Acid) Porphyrin Protects Against Neuronal and Glial Oxidative Stress and Death After Spinal Cord Injury
Volume: 11
Issue: 6
Author(s): Lokanatha Valluru, Yao Diao, Jorge E. Hachmeister and Danxia Liu
Affiliation:
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
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.
