RESUMEN
Traumatic brain injury (TBI) is a debilitating acquired neurological disorder that afflicts nearly 74 million people worldwide annually. TBI has been classified as more than just a single insult because of its associated risk toward various long-term neurological and neurodegenerative disorders. This risk may be triggered by a series of postinjury secondary molecular and cellular pathology, which may be dependent on the severity of the TBI. Among the secondary injury mechanisms, neuroinflammation may be the most crucial as it may exacerbate brain damage and lead to fatal consequences when prolonged. This Review aimed to elucidate the influence of neuroinflammatory mediators on the TBI functional and pathological outcomes, particularly focusing on inflammatory cytokines which were associated with neuronal dysfunctions in the acute and chronic stages of TBI. These cytokines include interleukins (IL) such as IL-1(beta)ß, IL-4, IL-6, IL8, IL-10, IL-18, IL-33 and tumor necrosis factor alpha (TNF-α), which have been extensively studied. Apart from these, IL-2, interferon gamma (IFN-γ), and transforming growth factor-beta (TGF-ß) may also play a significant role in the pathogenesis of TBI. These neuroinflammatory mediators may trigger a series of pathological events such as cell death, microglial suppression, and increased catecholaminergic activity. Interestingly, in the acute phase of TBI, most of these mediators may also play a neuroprotective role by displaying anti-inflammatory properties, which may convert to a pro-inflammatory action in the chronic stages post TBI. Early identification and treatment of these mediators may help the development of more effective treatment options for TBI.
Asunto(s)
Lesiones Traumáticas del Encéfalo , Lesiones Encefálicas , Animales , Lesiones Encefálicas/patología , Lesiones Traumáticas del Encéfalo/complicaciones , Citocinas/metabolismo , Modelos Animales de Enfermedad , Humanos , Microglía/metabolismoRESUMEN
Epilepsy is a devastating neurological disorder characterized by the repeated occurrence of epileptic seizures. Epilepsy stands as a global health concern affecting around 70 million people worldwide. The mainstream antiepileptic drugs (AEDs) only exert symptomatic relief and drug-resistant epilepsy occurs in up to 33 percent of patients. Hence, the investigation of novel therapeutic strategies against epileptic seizures that could exert disease modifying effects is of paramount importance. In this context, compounds of natural origin with potential antiepileptic properties have recently gained increasing attention. Quercetin is a plant-derived flavonoid with several pharmacological activities. Emerging evidence has demonstrated the antiepileptic potential of quercetin as well. Herein, based on the available evidence, we discuss the neuroprotective effects of quercetin against epileptic seizures and further analyze the plausible underlying molecular mechanisms. Our review suggests that quercetin might be a potential therapeutic candidate against epilepsy that deserves further investigation, and paves the way for the development of plant-derived antiepileptic treatment approaches.
Asunto(s)
Epilepsia , Fármacos Neuroprotectores , Anticonvulsivantes/uso terapéutico , Epilepsia/tratamiento farmacológico , Humanos , Fármacos Neuroprotectores/uso terapéutico , Quercetina/uso terapéutico , Convulsiones/tratamiento farmacológicoRESUMEN
Epilepsy is a neurologicaldisorder characterized by persistent predisposition to recurrent seizurescaused by abnormal neuronal activity in the brain. Epileptic seizures maydevelop due to a relative imbalance of excitatory and inhibitory neurotransmitters. Expressional alterations of receptors and ion channelsactivated by neurotransmitters can lead to epilepsy pathogenesis. AIMS: In this updated comprehensive review, we discuss the emerging implication of mutations in neurotransmitter-mediated receptors and ion channels. We aim to provide critical findings of the current literature about the role of neurotransmitters in epilepsy. MATERIALS AND METHODS: A comprehensive literature review was conducted to identify and critically evaluate studies analyzing the possible relationship between epilepsy and neurotransmitters. The PubMed database was searched for related research articles. KEY FINDINGS: Glutamate and gamma-aminobutyric acid (GABA) are the main neurotransmitters playing a critical role in the pathophysiology of this balance, and irreversible neuronal damage may occur as a result of abnormal changes in these molecules. Acetylcholine (ACh), the main stimulant of the autonomic nervous system, mediates signal transmission through cholinergic and nicotinic receptors. Accumulating evidence indicates that dysfunction of nicotinic ACh receptors, which are widely expressed in hippocampal and cortical neurons, may be significantly implicated in the pathogenesis of epilepsy. The dopamine-norepinephrine-epinephrine cycle activates hormonal and neuronal pathways; serotonin, norepinephrine, histamine, and melatonin can act as both hormones and neurotransmitters. Recent reports have demonstrated that nitric oxide mediates cognitive and memory-related functions via stimulating neuronal transmission. SIGNIFICANCE: The elucidation of the role of the main mediators and receptors in epilepsy is crucial for developing new diagnostic and therapeutic approaches.