Delayed administration of dapsone protects from tissue damage and improves recovery after spinal cord injury.
After spinal cord injury (SCI), a complex cascade of pathophysiological processes increases the primary damage. The inflammatory response plays a key role in this pathology. Recent evidence suggests that myeloperoxidase (MPO), an enzyme produced and released by neutrophils, is of special importance in spreading tissue damage. Dapsone (4,4'-diaminodiphenylsulfone) is an irreversible inhibitor of MPO. Recently, we demonstrated, in a model of brain ischemia/reperfusion, that dapsone has antioxidant, antiinflammatory, and antiapoptotic effects. The effects of dapsone on MPO activity, lipid peroxidation (LP) processes, motor function recovery, and the amount of spared tissue were evaluated in a rat model of SCI. MPO activity had increased 24.5-fold 24 hr after SCI vs. the sham group, and it had diminished by 38% and 19% in the groups treated with dapsone at 3 and 5 hr after SCI, respectively. SCI increased LP by 45%, and this increase was blocked by dapsone. In rats treated with dapsone, a significant motor function recovery (Basso-Beattie-Bresnahan score, BBB) was observed beginning during the first week of evaluation and continuing until the end of the study. Spontaneous recovery 8 weeks after SCI was 9.2 ± 1.12, whereas, in the dapsone-treated groups, it reached 13.6 ± 1.04 and 12.9 ± 1.17. Spared tissue increased by 42% and 33% in the dapsone-treated groups (3 and 5 hr after SCI, respectively) vs. SCI without treatment. Dapsone significantly prevented mortality. The results show that inhibition of MPO by dapsone significantly protected the spinal cord from tissue damage and enhanced motor recovery after SCI.
Departamento de Neuroquímica, Instituto Nacional de Neurología y Neurocirugía Manuel Velasco Suárez S.S.A., México D.F., México.
Araceli
A
Diaz-Ruiz
Hermelinda
H
Salgado-Ceballos
Sergio
S
Montes
Gabriel
G
Guizar-Sahagún
Noemi
N
Gelista-Herrera
Marisela
M
Mendez-Armenta
Sofia
S
Diaz-Cintra
Camilo
C
Ríos
D000818:Animals; D003622:Dapsone / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D005493:Folic Acid Antagonists / Q000008:administration & dosage*; D015227:Lipid Peroxidation / Q000187:drug effects; D009043:Motor Activity / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function / Q000187:drug effects*; D013119:Spinal Cord Injuries / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D018709:Statistics, Nonparametric; D016019:Survival Analysis; D013997:Time Factors
D005493:Folic Acid Antagonists; D003622:Dapsone; D009195:Peroxidase