The effect of melatonin on spinal cord after ischemia in rats

Abstract

Study design: Experimental animal model to assess ischemic spinal cord injury (SCI) following occlusion of the thoracoabdominal aorta. Objectives: In the present study, we aimed to investigate the role of melatonin on SCI induced by ischemia and following reperfusion. Setting: Animal Research Laboratory, Inonu University, Malatya, Turkey. Methods: We evaluated oxidative damage and caspase-3 activity. In total, 32 adult Wistar albino rats were divided into four groups: Group 1, control (n = 8); Group 2 (n = 8), those subjected to ischemia/reperfusion (IR) by clamping the thoraco-abdominal aorta; Group 3 (n = 8), melatonin (50 mg kg −1 ) treated; and Group 4 (n = 8), melatonin (50 mg kg −1 ) followed by ischemia. All animals were kept alive for 48 h, and then spinal cord samples were removed. We assayed oxidative damage by measuring malondialdehyde (MDA), apoptosis by measuring activated caspase-3 (using immunoblots) and intrinsic antioxidative capacity by measuring reduced glutathione (GSH) levels in the spinal cord. Results: The results indicated a significant decrease in activity of caspase-3 in SCI animals after treatment with melatonin, as it significantly decreased the formation of MDA and decelerated the loss of GSH. Conclusion: This study suggested that melatonin could be an effective neuroprotective agent for treatment of SCI.

Protective Effect of Combined Melatonin and α-Tocopherol Administration in Spinal Cord Ischemia-Reperfusion Injury in Rat

“…Indeed, in experimental animal models of SCI model, melatonin promoted full repair of the damaged blood-SC barrier (Wu et al, 2014). Also, pre-treatment with melatonin fully restored SC GSH levels but partially reduced the levels of malondialdehyde (MDA) and cleaved caspase-3 activity after 48 hours of SC-IRI induction (Aydemir et al, 2016). Similar results were obtained by other investigators (Aghazadeh et al, 2007).…”

Effects of melatonin on severe crush spinal cord injury–induced reactive astrocyte and scar formation

“…Spinal cord injury (SCI) can cause severe disability, sensory and/or motor impairment, and other neurologic deficits. Phenomena occurring immediately after SCI include neuronal fiber damage, neural cell necrosis and apoptosis, metabolic disturbances, destruction of microvasculature, inflammation, lipid peroxidation, free radical production, demyelination, and glial scar formation, leading to extensive secondary tissue damage (Bareyre and Schwab, ; Jones et al, ; Samantaray et al, ; Aydemir et al, ). Robust cell death in the injured region happens from seconds to weeks after SCI, resulting in the formation of the cavities or cysts, which will block the ascending and descending neurotransmission (Bareyre and Schwab, ).…”

“…Melatonin is currently under scrutiny as an emerging neuroprotective agent for trauma and diseases of the central and peripheral nervous system. In CNS lesions, melatonin was reported to promote antiapoptotic signals, neurogenesis, axonal regeneration, microvascular preservation, and recovery of function, but most importantly to reduce inflammation (Hong et al, ; Tsai et al, ; Jing et al, ; Aydemir et al, ). Hence, it could be considered a protective mediator because of its ability as an antioxidant and scavenger of free radicals by significantly reducing calpain expression and caspase‐3 activity in acute SCI rats.…”

Current Developments in Antioxidant Therapies for Spinal Cord Injury

“…Intravenously, it decreased the synthesis of MDA and increased the synthesis of GSH and angiopoietin 1, and in mice with severe lesion, it decreased the expression of interleukin 1 beta (IL-1β) and NG-2 (neuron/glial antigen 2) [30,32,33]. In a model with lesion with vascular clips, the administration of 30 mg/kg alleviated post-traumatic injury associated with SCI by binding the PPARα-receptor; the administration of 50 mg/kg in moderate lesion decreased the BSCB permeability modulating the expression of brainderived neurotrophic factor (BDNF), growth-associated protein 43 (GAP-43), and caspase-3 [33][34][35]. In combination therapy with dexamethasone (10-0.025 mg/kg), it showed significant anti-inflammatory effects, attenuating the synthesis of tumor necrosis factor alpha (TNF-α) and iNOS and the nitration of tyrosine residues, increasing tissue recovery and motor capacity in an experimental SCI model of mouse [36], while the combination with methylprednisolone favored neurological recovery and decreased LP; its administration with zinc activated the internal antioxidant system and also decreased the LP [37][38][39].…”