The Beneficial Effects of Levetiracetam on Polyneuropathy in the Early Stage of Sepsis in Rats: Electrophysiological and Biochemical Evidence

Abstract

Critical illness polyneuropathy (CIP) is a common complication in long (>= 1 week) critical/intensive care hospitalizations. Rapidly progressing atrophy and weakness of the limb, trunk and, particularly, respiratory muscles may lead to severe morbidity or mortality. The aim of the present study was to investigate the protective effects of levetiracetam (LEV) on CIP in the early stage of sepsis in rats. We simulated CIP by a surgically induced sepsis model and verified it by lower-limb lectromyography (EMG) (amplitude and duration of CMAP, and distal latency). We evaluated the effects of various doses of LEV treatment (300, 600, and 1200 mg/kg i.p.) on CIP by performing electrophysiology, and determining plasma tumor necrosis factor (TNF)-alpha, lipid peroxides (malondialdehyde, MDA) levels, and total antioxidant capacity (TAC). Our data showed: (1) significant suppression of CMAP amplitude and prolongation of distal latency in the saline-treated sepsis group, and distal latency as well as CMAP amplitudes benefiting best from the 600 mg/kg LEV treatment; (2) significant rise in plasma TNF-alpha and MDA levels in the saline-treated sepsis group, but significant ameliorations by the 600 and 1200 mg/kg LEV treatment; (3) highly significant suppression of TAC in the saline-treated group, but profound reversals in all LEV-treated groups. We conclude that 300, 600, and 1200 mg/kg i.p. doses of post-septic treatment by LEV has possibly acted in a dose-dependent manner to both protect and restore the affected peripheral nerves' axon and myelin following surgical disturbance of the cecum to induce sepsis and consequent polyneuropathy.