Neuroscience Letters 554 (2013) 59–63 Contents lists available at ScienceDirect Neuroscience Letters jou rn al hom epage: www.elsevier.com/locate/neulet Plenary article Prophylactic neuroprotection with A91 improves the outcome of spinal cord injured rats A. Ibarra a,b,∗ , M. Sosa a , E. García a,b , A. Flores a,b , Y. Cruz a , H. Mestre a , S. Marti ˜ nón b , B.A. Pineda-Rodríguez a , G. Gutiérrez-Ospina c a Facultad de Ciencias de la Salud, Universidad Anáhuac México Norte, Av. Universidad Anáhuac # 46 Col. Lomas Anáhuac, Huixquilucan 52786, Estado de México, Mexico b Centro de Investigación del Proyecto CAMINA A.C. Calz. De Tlalpan # 4430 Col. Toriello Guerra, Del. Tlalpan 14050, Ciudad de México, Mexico c Departamento de Biología Celular y Fisiología, Instituto de Investigaciones Biomédicas, Universidad Nacional Autónoma de México, C.U., Distrito Federal, Coyoacán 04510, Ciudad de México, Mexico a r t i c l e i n f o Keywords: A91 Neural constituents Paraplegia Prophylactic neuroprotection Protective autoimmunity Vaccination a b s t r a c t 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. Immu- nization 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 pro- liferation. Prophylactic neuroprotection with an initial and subsequent booster dose of A91 may improve recovery after SC injury sustained during invasive spinal surgery procedures. © 2013 Elsevier Ireland Ltd. All rights reserved. 1. Introduction Iatrogenic SC injury is an unfortunate complication of many surgical procedures that take place on or around the vertebral col- umn. Recent reports suggest that the incidence of SC injury due to iatrogenic causes ranges from 0.59 to 14.7% [1,2]. Most of these hap- pen during invasive procedures like scoliosis corrective surgeries (0.55%) and spinal fusions (0.14%) [1,2]. Several risk factors for iatro- genic SC injury have been identified such as: age, gender, history of hypertension, preoperative SC function, and the involved seg- ments of the SC [3]. Considering the risk of SC injury surrounding Abbreviations: BBB, Basso, Beattie & Bresnahan open-field test; BD, booster dose; CFA, complete Freund’s adjuvant; CFSE, carboxifluorescein diester amine; MBP, myelin basic protein; MP, methylprednisolone; OVA, ovalbumin; RSNs, rubrospinal neurons; SC, spinal cord; SD, single dose; VHNs, ventral horn neurons. ∗ Corresponding author at: Av. Universidad Anáhuac No. 46 Col. Lomas Anáhuac, Huixquilucan, Edo. de México, Mexico. Tel.: +52 55 5627 0210x8524; fax: +52 55 5573 5545. E-mail addresses: iantonio65@yahoo.com, jose.ibarra@anahuac.mx (A. Ibarra). certain procedures and patient comorbidities, a preventive treat- ment prior to surgery would be of great clinical value. Previous attempts have used erythropoietin, melatonin, cyclosporine-A, and even methylprednisolone (MP) but have not achieved successful prophylactic neuroprotection [4]. Immunizing against altered pep- tide ligands designed from nervous tissue proteins has shown to promote neuroprotection and neural restoration after SC injury [5,6]. This phenomenon is known as protective autoimmunity. An example of these is A91, a non-encephalitogenic peptide derived from myelin basic protein (MBP) sequence 87–99 but with a lysine residue changed to alanine at position 91. In line with this, pre- vious studies in our laboratory have shown that immunization with a single dose of A91 after SC injury is capable of induc- ing significant tissue protection and motor recovery. A91 has also shown to induce a Th2 phenotype response that is capable of diminishing nitric oxide production and lipid peroxidation. This Th2 phenotype also releases neurotrophic factors after SC injury [7–9]. These effects explain, at least in part, the mechanisms by which protective autoimmunity ameliorates injury to the nervous system. 0304-3940/$ – see front matter © 2013 Elsevier Ireland Ltd. All rights reserved. http://dx.doi.org/10.1016/j.neulet.2013.08.048