title: Treatment of rat spinal cord injury with the neurotrophic factor albumin-oleic acid: translational application for paralysis, spasticity and pain.
abstract: Sensorimotor dysfunction following incomplete spinal cord injury (iSCI) is often characterized by the debilitating symptoms of paralysis, spasticity and pain, which require treatment with novel pleiotropic pharmacological agents. Previous in vitro studies suggest that Albumin (Alb) and Oleic Acid (OA) may play a role together as an endogenous neurotrophic factor. Although Alb can promote basic recovery of motor function after iSCI, the therapeutic effect of OA or Alb-OA on a known translational measure of SCI associated with symptoms of spasticity and change in nociception has not been studied. Following T9 spinal contusion injury in Wistar rats, intrathecal treatment with: i) Saline, ii) Alb (0.4 nanomoles), iii) OA (80 nanomoles), iv) Alb-Elaidic acid (0.4/80 nanomoles), or v) Alb-OA (0.4/80 nanomoles) were evaluated on basic motor function, temporal summation of noxious reflex activity, and with a new test of descending modulation of spinal activity below the SCI up to one month after injury. Albumin, OA and Alb-OA treatment inhibited nociceptive Tibialis Anterior (TA) reflex activity. Moreover Alb-OA synergistically promoted early recovery of locomotor activity to 50 ± 10% of control and promoted de novo phasic descending inhibition of TA noxious reflex activity to 47 ± 5% following non-invasive electrical conditioning stimulation applied above the iSCI. Spinal L4-L5 immunohistochemistry demonstrated a unique increase in serotonin fibre innervation up to 4.2 ± 1.1 and 2.3 ± 0.3 fold within the dorsal and ventral horn respectively with Alb-OA treatment when compared to uninjured tissue, in addition to a reduction in NR1 NMDA receptor phosphorylation and microglia reactivity. Early recovery of voluntary motor function accompanied with tonic and de novo phasic descending inhibition of nociceptive TA flexor reflex activity following Alb-OA treatment, mediated via known endogenous spinal mechanisms of action, suggests a clinical application of this novel neurotrophic factor for the treatment of paralysis, spasticity and pain.
authors: Neurología Experimental, Hospital Nacional de Parapléjicos, Servicio de Salud de Castilla-La Mancha, Toledo, Castilla La-Mancha, Spain.
authors: Gerardo
authors: G
authors: Avila-Martin
authors: Iriana
authors: I
authors: Galan-Arriero
authors: Julio
authors: J
authors: Gómez-Soriano
authors: Julian
authors: J
authors: Taylor
mesh_terms: D000418:Albumins / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D009128:Muscle Spasticity / Q000188:drug therapy; D009829:Oleic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D010146:Pain / Q000188:drug therapy; D010243:Paralysis / Q000188:drug therapy; D051381:Rats; D017208:Rats, Wistar; D013119:Spinal Cord Injuries / Q000188:drug therapy*; D016896:Treatment Outcome
chemical_list: D000418:Albumins; D009829:Oleic Acids