Neuroprotective Activity of Thioctic Acid in Central Nervous System Lesions Consequent to Peripheral Nerve Injury

Abstract

Peripheral neuropathies are heterogeneous disorders presenting often with hyperalgesia and allodynia. This 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. Thioctic 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 neurofilament were observed in SHR. This phenomenon was more pronounced after CCI. Thioctic acid countered astrogliosis and neuronal damage, (+)-thioctic acid being more active than (+/−)- or (−)-enantiomers. These findings 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.

Effect of treatment with the antioxidant alpha-lipoic (thioctic) acid on heart and kidney microvasculature in spontaneously hypertensive rats

“…In fact, in a model of increased oxidative stress, in vitro, alpha-lipoic acid countered the ROS production (11,44,45). In addition, in SHR, alpha-lipoic acid reduced the oxidative stress decreasing the plasmatic malondyaldeyde levels and oxidative status of plasmatic protein (12).…”

“…The antioxidant activity of alpha-lipoic was investigated in an animal model of hypertension such as spontaneously hypertensive rats (SHR) (11,12). SHR has specific and uniform genetic predisposition to develop arterial hypertension (13), allowing to study causes, mechanisms, pathology and behavioral consequences of the disease.…”

Strategic Design and Fabrication of Nerve Guidance Conduits for Peripheral Nerve Regeneration

“…Peripheral nerve injuries occur through traumatic, non‐traumatic, and iatrogenic events, and cause painful neuropathies and neuromas, poor sensation, and weakness and paralysis for patients due to the loss of function in damaged motor and sensory axons . Successful regeneration of injured nerves is important for improving patient quality of life, and preventing complications that can result from the repair process gone wrong.…”

Effects of alpha lipoic acid on motor function and antioxidant enzyme activity of nerve tissue after sciatic nerve crush injury in rats

“…ALA is a strong antioxidant and neuroprotective agent naturally occurring in the body, and is also present in some foods (27,40). It is routinely used for the treatment of some pain disorders such as diabetic neuropathy (10).…”

“…These actions contribute to reduced oxidative stress (28). Many experimental results show that both ALA and dihydrolipoic acid (DHLA), its reduced form, can improve the antioxidant capacity of tissue against different forms of oxidative stress (37,40). Hydroxyl radicals, singlet oxygen, peroxynitrite, and hypochlorous acid are scavenged by ALA, and hydroxyl radicals, superoxide, peroxyl radical, peroxynitrite, nitric oxide, and hypochlorous acid are scavenged by DHLA (10).…”