Abstract
Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide. Acquired epilepsy is initiated by neurological insults, such as status epilepticus, which can result in the generation of ROS and induction of oxidative stress. Suppressing oxidative stress by upregulation of the transcription factor, nuclear factor erythroid 2-related factor 2 (Nrf2) has been shown to be an effective strategy to increase endogenous antioxidant defences, including in brain diseases, and can ameliorate neuronal damage and seizure occurrence in epilepsy. Here, we aim to test the neuroprotective potential of a naturally occurring Nrf2 activator sulforaphane, in in vitro epileptiform activity model and a temporal lobe epilepsy rat model. Sulforaphane significantly decreased ROS generation during epileptiform activity, restored glutathione levels, and prevented seizure-like activity-induced neuronal cell death. When given to rats after 2 h of kainic acid-induced status epilepticus, sulforaphane significantly increased the expression of Nrf2 and related antioxidant genes, improved oxidative stress markers, and increased the total antioxidant capacity in both the plasma and hippocampus. In addition, sulforaphane significantly decreased status epilepticus-induced neuronal cell death. Our results demonstrate that Nrf2 activation following an insult to the brain exerts a neuroprotective effect by reducing neuronal death, increasing the antioxidant capacity, and thus may also modify epilepsy development.
Highlights
In keeping with previous studies, we found that induction of seizure-like activity by omitting magnesium from the medium induced 350% and 600% increase in the rate of reactive oxygen species (ROS) production, 10 and 15 min after exposure to low Mg2+, respectively (Figure 1A)
Cocultures exposed to low Mg2+ show an almost 50% decrease in GSH levels, which was almost completely restored by SFN (5 μM, pre-treatment for 24 h); (F (2, 15) = 18.62, p < 0.0001, Figure 1B and Figure S3)
We presented data on the antioxidant properties and neuroprotective effects of SFN, a naturally occurring nuclear factor erythroid 2-related factor 2 (Nrf2) activator, as monotherapy following kainic acid (KA)-induced status epilepticus (SE) in rats
Summary
Epilepsy is a chronic disease of the brain that affects over 65 million people worldwide [1], representing 1–2% of the population, making it one of the most common neurological diseases globally. It is common in all age groups and is associated with a burden of socio-economical, behavioural, psychiatric, and other medical issues for patients, their caregivers, and society [2]. There are over 27 FDA approved anti-epileptic drugs (AEDs) Even though these AEDs medications are used to treat the symptoms of the disease (i.e., control the seizures), the disease is not adequately controlled in a third of epileptic patients [3], and the core of the illness remains intact and perplexing dilemma
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