Early Administration of l-Arginine in Experimental Acute Spinal Cord Injury Impairs Long-Term Motor Function Recovery

Abstract

Recently, we reported that L-arginine, a nitric oxide precursor, reverses altered drug disposition induced by acute spinal cord injury (SCI) by increasing hepatic blood flow, without affecting mean arterial pressure and heart rate, whereas others have shown that it produces neuroprotection in several models of acute neurologic damage. Its use as a therapeutic agent for microcirculatory alterations associated with spinal shock seems promising. Therefore, here we have tested its influence on long-term morphofunctional neurologic outcome. Intravenous L-arginine (300 mg/kg per dose) was administered to adult rats after SCI of moderate intensity according to the following schemes (n=6): (1) single dose at 1 hour, (2) single dose at 24 hour, and (3) repeated doses first at 24 hour and then daily for 7 days. Control injured rats received the vehicle (saline solution). Contrary to our expectations, locomotor function, assessed using the Basso-Beattie-Bresnahan scale for 8 weeks, was significantly worse in the L-arginine treated groups compared with the control group. Areas of both spared white matter and myelin stain at the epicenter seemed reduced in rats that received L-arginine as a single dose at 1 hour after injury but were not significantly different from the control group. L-arginine as used here interfered with the functional outcome of rats subjected to SCI, suggesting that L-arginine or its metabolic products may be neurotoxic. Because of its potential utility for acute SCI suggested in the past, strategies should be designed to block its apparent neurotoxicity.