Spinal cord changes consequent to peripheral nerve injury: neuroprotective role of thioctic acid enantiomers

Peripheral neuropathies are in general characterized by hyperalgesia and allodynia with alterations of muscular sensitivity and functions. The antioxidant has been proposed as a potential therapeutic agent in the treatment or prevention of several pathologies related to oxidative stress. Thioctic acid is an antioxidant existing in nature and expressed in two optical isomers. (+)-Thioctic acid is the naturally occurring enantiomer, although synthetic thioctic acid is mainly the mixture of (+) and (-)-enantiomers. The present study assessed if compression of sciatic nerve, induced by loose ligation, is accompanied by a central nervous system (CNS) changes and if thioctic acid enantiomers treatment has a possible protective role. Loose ligation of the right sciatic nerve was performed in spontaneously hypertensive rats (SHR), used as a model of increased oxidative stress, and in normotensive Wistar-Kyoto rats (WKY) as control group. Animals with sciatic nerve ligation were left untreated or were treated intraperitoneally for 14 days with (+/-)-(25 and 50 mg/Kg/day), (+)-(25 mg/Kg/day), (-)-(25 mg/Kg/day) thioctic acid. Analysis was centered on injury phenomena at level of dorsal root ganglia and spinal cord with immunochemical and immunohistochemical analysis. In the spinal cord an increase of oxidative stress marker were observed in rats after sciatic nerve ligation accompanied with an phenomena of astrogliosis and neuronal damage in particular in the posterior dorsal horn without activation of apoptotic process. Treatment with the antioxidant reduced oxidative stress and astrogliosis in spinal cord, in particular (+)-thioctic acid was more active than (+/-)- or (-)-enantiomers. The above results demonstrated a damage in the spinal cord after peripheral nerve injury and neuroprotective effect elicited by thioctic acid. The demonstration of an activity of thioctic acid suggests that appropriate antioxidant strategies may represent a therapeutic approach in the treatment of compressive neuropathies.