Prophylactic neuroprotection with A91 improves the outcome of spinal cord injured rats

Abstract

Iatrogenic injury to the spinal cord (SC) is not an uncommon complication of spinal surgery. In an attempt to establish a preventive therapy for anticipated SC injury, we tested the effect of a single dose (SD) vaccine vs. the addition of a booster dose (BD) of a neural-derived peptide (A91) prior to SC contusion. Immunization with A91 immediately after SC injury has demonstrated to induce significant tissue protection and motor recovery. After injury, only the BD vaccination schedule had a neuroprotective effect. It was capable of improving neurological recovery that was always significantly higher than the one observed in rats with SD immunization or those only treated with PBS. Toward the end of study, animals treated with an A91 BD presented a BBB score of 9.75±0.17 (mean±standard deviation) while rats treated with SD or PBS had a score of 6.6±0.7 and 5.6±0.6 respectively. In the next step we attempted to corroborate the neuroprotective effect induced by A91 immunization. For this purpose, we assessed the survival of rubrospinal neurons (RSNs) and ventral horn neurons (VHNs) sixty days after SC injury. BD vaccination induced a significant survival of both RSNs and VHNs after injury. Finally, the failure or success of this therapy (SD or BD respectively) was associated with a lower (SD) or higher (BD) A91-specific T cell proliferation. Prophylactic neuroprotection with an initial and subsequent booster dose of A91 may improve recovery after SC injury sustained during invasive spinal surgery procedures.

Keywords: A91; BBB; BD; Basso, Beattie & Bresnahan open-field test; CFA; CFSE; MBP; MP; Neural constituents; OVA; Paraplegia; Prophylactic neuroprotection; Protective autoimmunity; RSNs; SC; SD; VHNs; Vaccination; booster dose; carboxifluorescein diester amine; complete Freund's adjuvant; methylprednisolone; myelin basic protein; ovalbumin; rubrospinal neurons; single dose; spinal cord; ventral horn neurons.