REVIEW ARTICLE: Melatonin plus exercise-based neurorehabilitative therapy for spinal cord injury

Abstract

: Spinal cord injury (SCI) is damage to the spinal cord caused by the trauma or disease that results in compromised or loss of body function. Subsequent to SCI in humans, many individuals have residual motor and sensory deficits that impair functional performance and quality of life. The available treatments for SCI are rehabilitation therapy, activity‐based therapies, and pharmacological treatment using antioxidants and their agonists. Among pharmacological treatments, the most efficient and commonly used antioxidant for experimental SCI treatment is melatonin, an indolamine secreted by pineal gland at night. Melatonin’s receptor‐independent free radical scavenging action and its broad‐spectrum antioxidant activity makes it an ideal antioxidant to protect tissue from oxidative stress‐induced secondary damage after SCI. Owing to the limitations of an activity‐based therapy and antioxidant treatment singly on the functional recovery and oxidative stress‐induced secondary damages after SCI, a melatonin plus exercise treatment may be a more effective therapy for SCI. As suggested herein, supplementation with melatonin in conjunction with exercise not only would improve the functional recovery by enhancing the beneficial effects of exercise but would reduce the secondary tissue damage simultaneously. Finally, melatonin may protect against exercise‐induced fatigue and impairments. In this review, based on the documented evidence regarding the beneficial effects of melatonin, activity‐based therapy and the combination of both on functional recovery, as well as reduction of secondary damage caused by oxidative stress after SCI, we suggest the melatonin combined with exercise would be a novel neurorehabilitative strategy for the faster recovery after SCI.

Gene regulation by melatonin linked to epigenetic phenomena

“…It has long been known and well established that melatonin induces apoptosis in cancer cells (Joo and Yoo, 2009;Leja-Szpak et al, 2010;Sainz et al, 2003) but not in normal cells it prevents apoptosis (Gonca Akbulut et al, in press;Hong et al, 2010;Sainz et al, 2003;Wang, 2009). Melatonin is effective in inducing apoptosis in both animal and human cancer cells (Casado-Zapico et al, 2011).…”

Melatonin as an Interventional Novel Candidate for the Individual with Autistic Fragile X Syndrome in Human

“…Recently, melatonin has been reported that could act as neuroprotective agent against neurological injury [104][105][106][107]. In experimental study, rodents injected with melatonin plus dexamethasone that has a neurotoxic action on hippocampus has been demonstrated the neuroprotective effect of melatonin.…”

Melatonin protection from chronic, low-level ionizing radiation

“…The most reactive and, therefore, destructive of the ROS is the hydroxyl radical ( OH). Melatonin has repeatedly been shown, using a wide variety of techniques, to rapidly scavenge this reactant when and where it is intracellularly generated; this deprives the OH of the opportunity to destroy critical neighboring molecules [17][18][19][20][21][22]. Melatonin, however, does not restrict itself to scavenging only the OH; rather, it also interacts with and neutralizes with varying degrees of efficiency, singlet oxygen, the superoxide anion radical, hydrogen peroxide and the peroxynitrite anion [23][24][25][26][27].…”

“…This has been amply documented in studies where melatonin was shown to protect against tissue damage and cellular death resulting from free radicals generated as a result of processes that either involve exposure to radioactivity or other toxins that stimulate free radical production. Thus, melatonin has been repeatedly shown to reduce free radical-mediated damage in the gastrointestinal tract [87], lungs [68], liver [69,88], kidney [89], testis [54], urinary bladder [90], pancreas [91], bone marrow [92], brain [38,93] and spinal cord [20], skeletal muscle [19], and other organs as well. These ubiquitous actions of melatonin show that its distribution in the body is not limited to only some organs.…”