Cyclosporin-A enhances non-functional axonal growing after complete spinal cord transection.
Therapeutic approaches that promote both neuroprotection and neuroregeneration would be valuable for spinal cord (SC) injury therapies. Cyclosporin-A (CsA) is an immunosuppressant that, due to its mechanism of action, could both protect and regenerate the neural tissue after injury. Previous studies have already demonstrated that intraperitoneal administration of CsA at a dose of 2.5 mg/kg/12 h during the first 2 days after SC contusion, followed by 5 mg/kg/12 h orally, diminishes tissue damage and improves motor recovery. In order to evaluate the effect of this CsA dosing regimen on axonal growth, we assessed motor recovery, presence of axons establishing functional connections and expression of GAP-43 in rats subjected to a complete SC transection. The Basso-Beattie-Bresnahan rating scale did not show difference in motor recovery of CsA or vehicle-treated rats. Moreover, somato-sensorial evoked potentials demonstrated no functional connections in the SC of these animals. Nevertheless, histological studies showed that: i) a significant number of CsA-treated rats presented growing axons, although they deviated perpendicularly at the edge of the stumps, surrounding them, ii) the expression of GAP-43 in animals treated with CsA was higher than that observed in the control group. Finally, anterograde tracing of the corticospinal tract of rats subjected to an incomplete SC transection showed no axonal fibers reaching the caudal stump. In summary, CsA administered at the dosing-regimen that promotes neuroprotection in SC contused rats induces both GAP-43 expression and axonal growth; however, it failed to generate functional connections in SC transected animals.
Ibarra
Antonio
A
Unidad de Investigación Médica en Enfermedades Neurológicas, HE, CMN Siglo XXI, IMSS, Av. Cuauhtemoc No. 330, Col. Doctores, C.P. 06720, México City, Mexico. iantonio65@yahoo.com
Hernández
Edson
E
Lomeli
Joel
J
Pineda
Dante
D
Buenrostro
Maribel
M
Martiñón
Susana
S
Garcia
Elisa
E
Flores
Nayeli
N
Guizar-Sahagun
Gabriel
G
Correa
Dolores
D
Madrazo
Ignacio
I
D000818:Animals; D001369:Axons / Q000187:drug effects*; D015153:Blotting, Western; D016572:Cyclosporine / Q000494:pharmacology*; D004594:Electrophysiology; D005260:Female; D019922:GAP-43 Protein / Q000096:biosynthesis / Q000187:drug effects; D007150:Immunohistochemistry; D009416:Nerve Regeneration / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000494:pharmacology*; D011712:Pyramidal Tracts / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D013119:Spinal Cord Injuries
D019922:GAP-43 Protein; D018696:Neuroprotective Agents; D016572:Cyclosporine