Melatonin attenuated early brain injury induced by subarachnoid hemorrhage via regulating NLRP3 inflammasome and apoptosis signaling

Abstract

Subarachnoid hemorrhage (SAH) is a devastating condition with high morbidity and mortality rates due to the lack of effective therapy. Nucleotide-binding oligomerization domain-like receptor family pyrin domain-containing 3 (NLRP3) inflammasome activation associated with the upregulation of apoptotic signaling pathway has been implicated in various inflammatory diseases including hemorrhagic insults. Melatonin is reported to possess substantial anti-inflammatory properties, which is beneficial for early brain injury (EBI) after SAH. However, the molecular mechanisms have not been clearly identified. This study was designed to investigate the protective effects of melatonin against EBI induced by SAH and to elucidate the potential mechanisms. The adult mice were subjected to SAH. Melatonin or vehicle was injected intraperitoneally 2 hr after SAH. Melatonin was neuroprotective, as shown by increased survival rate, as well as elevated neurological score, greater survival of neurons, preserved brain glutathione levels, and reduced brain edema, malondialdehyde concentrations, apoptotic ratio, and blood-brain barrier (BBB) disruption. Melatonin also attenuated the expressions of NLRP3, apoptosis-associated speck-like protein containing a caspase recruitment domain (ASC), cleaved caspase-1, interleukin-1β (IL-1β), and interleukin-6 (IL-6); these changes were also associated with an increase in the anti-apoptotic factor (Bcl2) and reduction in the pro-apoptotic factor (Bim). In summary, our results demonstrate that melatonin treatment attenuates the EBI following SAH by inhibiting NLRP3 inflammasome-associated apoptosis.

Rett Syndrome: Treatment with IGF-I, Melatonin, Blackcurrant Extracts, and Rehabilitation

“…MT exerts potent scavenging effects on toxic reactive oxygen species [74,75]. In addition, this hormone has anti-inflammatory properties, and it is a mitochondrial protector, besides playing multiple important functions in the human body [76][77][78][79][80][81].…”

Is the Use of Growth hormone and Melatonin Justified in Spinal Cord Injuries?

“…For instance, it is a highly effective hormone for reducing oxidative stress, via direct detoxification of reactive oxygen and reactive nitrogen species, stimulates antioxidant enzymes and suppress the activity of pro-oxidant enzymes, chelates several transition metals [33]. MT is also an important neuroprotective hormone reducing the effects of hemorrhagic stroke in several experimental models, acting as an antioxidant, anti-apoptosis and antiinflammatory agent [34]. MT plays an important role as an agent protective of mitochondria and regulates the electron transport chain responsible of the mitochondrial production of energy [35].…”

A Rare Case of Aicardi-Goutières Syndrome Who Showed a Positive Evolution after Being Treated with Growth Hormone, High Doses of Melatonin and Neurorehabilitation

“…In turn, MT was given, preventively, because of its potent scavenging effects on the toxic reactive oxygen species (ROS) [33,34], to which the brain is particularly sensitive, most likely elevated because of the clinical situation of the patient and the work carried out in his neurorehabilitation. Moreover, the clinical history indicated that neopterin, a marker of inflammatory-immune processes [35], had been detected to be elevated in a CSF sample of the patient; therefore, given the anti-inflammatory effects of MT [36,37], we thought that the administration of this indolamine could add more beneficial effects to the patient.…”

“…Apart of the high number of beneficial effects that MT plays in the human organism, this hormone has anti-inflammatory properties and it is a mitochondrial protector [36,37,52]; in addition, it has been shown that, in rats, melatonin protects the liver against ischemia/reperfusion injury by inducing heme-oxygenase-1 overexpression, which, in turn, suprresses the type 1 IFN signaling pathway dowstream of Toll-like receptor 4 [53], a transmembrane receptor whose activation leads to the induction of a type 1 IFN response in Trex1 null mice [54], one of the genes whose mutations lead to AGS [44].…”