Hindawi Publishing Corporation BioMed Research International Volume 2013, Article ID 985093, 14 pages http://dx.doi.org/10.1155/2013/985093 Research Article Neuroprotective Activity of Thioctic Acid in Central Nervous System Lesions Consequent to Peripheral Nerve Injury Daniele Tomassoni, 1 Francesco Amenta, 2 Lorenzo Di Cesare Mannelli, 3 Carla Ghelardini, 3 Innocent E. Nwankwo, 2 Alessandra Pacini, 4 and Seyed Khosrow Tayebati 2 1 School of Bioscience and Biotechnology, University of Camerino, Via Gentile III da Varano, 62032 Camerino, Italy 2 School of Medicinal and Health Products Sciences, University of Camerino, Via Madonna delle Carceri, 9, 62032 Camerino, Italy 3 Department of Clinical and Preclinical Pharmacology, University of Florence, Viale Pieraccini, 6, 50134 Florence, Italy 4 Department of Anatomy, Histology and Forensic Medicine, University of Florence, Largo Brambilla, 1, 50134 Florence, Italy Correspondence should be addressed to Daniele Tomassoni; daniele.tomassoni@unicam.it Received 7 August 2013; Revised 25 November 2013; Accepted 25 November 2013 Academic Editor: Swaran J. S. Flora Copyright © 2013 Daniele Tomassoni et al. Tis is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Peripheral neuropathies are heterogeneous disorders presenting ofen with hyperalgesia and allodynia. Tis study has assessed if chronic constriction injury (CCI) of sciatic nerve is accompanied by increased oxidative stress and central nervous system (CNS) changes and if these changes are sensitive to treatment with thioctic acid. Tioctic acid is a naturally occurring antioxidant existing in two optical isomers (+)- and (−)-thioctic acid and in the racemic form. It has been proposed for treating disorders associated with increased oxidative stress. Sciatic nerve CCI was made in spontaneously hypertensive rats (SHRs) and in normotensive reference cohorts. Rats were untreated or treated intraperitoneally for 14 days with (+/−)-, (+)-, or (−)-thioctic acid. Oxidative stress, astrogliosis, myelin sheets status, and neuronal injury in motor and sensory cerebrocortical areas were assessed. Increase of oxidative stress markers, astrogliosis, and neuronal damage accompanied by a decreased expression of neuroflament were observed in SHR. Tis phenomenon was more pronounced afer CCI. Tioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/−)- or (−)-enantiomers. Tese fndings suggest a neuroprotective activity of thioctic acid on CNS lesions consequent to CCI and that the compound may represent a therapeutic option for entrapment neuropathies. 1. Introduction Lesions of the nervous system can induce dysfunctional pain signalling and altered sensory mechanisms identifying a heterogeneous category of diseases defned neuropathies. Tese pathologies are difcult to treat. In general, drugs avail- able counter hyperalgesic symptomatology of neuropathy, but do not afect the course of these diseases. Neuroprotective and/or neurorestorative efects elicited by pharmacological treatments were reported only rarely [1]. Chronic constriction injury (CCI) is an animal model of peripheral neuropathy induced by the loose ligation of the sciatic nerve [2]. CCI mimics an entrapment mononeu- ropathy and is characterized by a painful syndrome with hyperalgesia. Painful symptomatology starts approximately from the 3rd day afer nerve injury, reaches a plateau between 7 and 15 days, and then decreases [3]. In CCI, hyperalgesia is accompanied by the occurrence of apoptosis phenomena in the nerve starting from the second week afer ligation [4]. Treatment of neuropathic pain, initiated or caused by central nervous system (CNS) primary lesions/dysfunctions or by peripheral nervous system (nerves outside the brain and spinal cord) damage is problematic because of sever- ity, chronicity, and resistance to common analgesics [5]. Reactive oxygen species (ROS) have been implicated in the development of persistent pain states resulting from nerve injury or infammatory phenomena [6–10]. Several studies have shown that antioxidants are efective in alleviating hyperalgesia in spinal nerve-ligated neuropathic rats [11, 12] and capsaicin-induced secondary mechanical hyperalgesia