Epilepsy is the most common neurological disorder, affecting nearly 50 million people worldwide. The condition can be manifested either due to genetic predisposition or acquired from acute insult which leads to alteration of cellular and molecular mechanisms. Evaluating the latest and the current knowledge in regard to the mechanisms underlying molecular and cellular alteration, hyperexcitability is a consequence of an imbalanced state wherein enhance excitatory glutamatergic and reduced inhibitory GABAergic signaling is considered to be accountable for seizures associated damage. However, neurodegeneration contributing to epileptogenesis has become increasingly appreciated. The components at the helm of neurodegenerative alterations during epileptogenesis include GABAergic neuronal and receptor changes, neuroinflammation, alteration in axonal transport, oxidative stress, excitotoxicity, and other cellular as well as functional changes. Targeting neurodegeneration with vitamin E as an antioxidant, anti-inflammatory and neuroprotective may prove to be one of the therapeutic approaches useful in managing epilepsy. In this review, we discuss and converse about the seizure-induced episodes as a link for the development of neurodegenerative and pathological consequences of epilepsy. We also put forth a summary of the potential intervention with vitamin E therapy in the management of epilepsy.

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Stress induces emotional arousal causing anxiety, irritability, exaggerated startle behaviour, and hypervigilance observed in patients with trauma and stress-related mental disorders, including acute stress disorder and post-traumatic stress disorder. Central norepinephrine release promotes stress-induced emotional arousal. However, the regulator of emotional arousal remains unknown. Here, we show that the arachidonate-derived metabolite produced by stress-activated leukocyte 12/15-lipoxygenase is remarkably elevated in the plasma and upregulates the central norepinephrine release, resulting in the enhancement of the struggle behaviour (= escape behaviour) in the tail suspension test. Struggle behaviour is mimicking a symptom of emotional arousal. This stress-induced struggle behaviour was absent in 12/15-lipoxygenase deficient mice; however, intravenous administration of a 12/15-lipoxygenase metabolite to these mice after stress exposure rekindled the struggle behaviour. Furthermore, tocotrienols and geranylgeraniol reduced stress-induced 12/15-lipoxygenase metabolite production and suppressed the struggle behaviour. Our findings indicate that arachidonate-derived 12/15-lipoxygenase metabolite is involved in the regulation of stress-enhanced central norepinephrine release and struggle behaviour. In addition, we propose 12/15-lipoxygenase as a potential therapeutic target for the treatment of emotional arousal observed in stress-related mental disorders.

Neurodegenerative disorders, such as Parkinson’s and Alzheimer’s disease, are claimed to be of major concern causing a significant disease burden worldwide. Oxidative stress, mitochondrial dysfunction and nerve damage are the main reasons for the emergence of these diseases. The formation of reactive oxygen species (ROS) is the common chemical molecule that is formed from all these three interdependent mechanisms which is highly reactive toward the neuronal cells. For these reasons, the administration of tocotrienols (T3s), which is a potent antioxidant, is proven to cater to this problem, through in vitro and in vivo investigations. Interestingly, their therapeutic potentials are not only limited to antioxidant property but also to being able to reverse the neuronal damage and act as a shield for mitochondria dysfunction. Thereby, T3s prevents the damage to the neurons. In regards to this statement, in this review, we focused on summarizing and discussing the potential therapeutic role of T3s on Alzheimer’s and Parkinson’s diseases, and their protective mechanisms based on evidence from the in vitro and in vivo studies. However, there is no clinical trial conducted to prove the efficacy of T3s for Alzheimer’s and Parkinson’s subjects. As such, the therapeutic role of T3s for these neurodegenerative disorders is still under debate.

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