Ômega-conotoxina MVIIC e/ou dantrolene no trauma medular agudo de ratos

Abstract

Acute spinal cord injury causes damage to the nervous tissue by primary and secondary mechanisms. Excessive intracellular calcium concentration is a key element to the development of secondary injury. It occurs by several mechanisms: influx of calcium through membrane voltage-gated calcium channels and mobilization of intracellular reserves from the endoplasmic reticulum. The purpose of this study was to evaluate the neuroprotective effect of the association of calcium channel blockers, -conotoxin MVIIC and dantrolene, on experimental acute spinal cord injury. Twenty male Wistar rats were randomly distributed into five groups: CN (negative control), CP (positive control), T (-conotoxina MVIIC), D (dantrolene) and T+D (-conotoxina MVIIC + dantrolene). Animals of the CN group underwent T12 laminectomy and intrathecal PBS injection. The other groups underwent T12 laminectomy and compressive spinal trauma due to a 10 gram stem drop from the height of 25 mm at the MASCIS Impactor spinal trauma induction system. The CP group received intrathecal PBS injection, the T group received intrathecal 20 pmol/10 l of -conotoxin MVIIC, group D received 10 mg/kg dantrolene intraperitoneally and the T + D group received 20 pmol/10 L of -conotoxin MVIIC intrathecally and 10 mg/kg dantrolene intraperitoneally. Neurological examination was performed daily for seven days and consisted with Basso, Beatie, Bresnahan test for the evaluation of motor function. Eight days after treatment, the animals were euthanized and the blood samples were collected for hematological and biochemistry analysis, and spinal cords samples were colleted for quantification of reactive oxygen species, lipid peroxidation and the evaluation of the gene expression of factors related to apoptosis (Bax, caspase 3, 8 and 9). It was observed that only group D improved motor function with significant difference after seven days evaluation by BBB test (p<0,05). Values for hematological and biochemistry profiles were within the reference intervals in all groups, with the exception of urea values that were higher in all animals. There was no statistical difference between the values of quantification of reactive oxygen species, lipid peroxidation and gene expression of related factors to apoptosis. It was conclude that dantrolene promoted motor recovery. There was not effect of pharmacological addition on the association MVIIC and dantrolene.