Abstract
Posttraumatic epilepsy (PTE) is a prevalent type of acquired epilepsy secondary to traumatic brain injury, and is characterized by repeated seizures. Traditional antiepileptic drugs have minimal response in preventing posttraumatic epileptic seizures. It is essential for the development of new therapeutic strategy. Our previous work disclosed a potent neuroprotective role of baicalein, a flavonoid extracted from Scutellaria baicalensis Georgi, against inherited epilepsy in rats. Whether baicalein has protective potential in posttraumatic epileptic seizures and the possible molecular mechanism remain elusive. Additionally, the brain is vulnerable to lipid peroxidation-induced damage due to high consumption of oxygen and abundant polyunsaturated fatty acids in neuronal membranes. Our present investigation aimed to elucidate whether baicalein exerts neuroprotective effects on posttraumatic epileptic seizures by inhibiting ferroptosis, a newly discovered lipid peroxidation-dependent cell death modality. We found that baicalein significantly reduced seizure score, number of seizures, and average seizure duration in an iron chloride (FeCl3)-induced PTE mouse model. The neuroprotective effect of baicalein was also validated in a ferric ammonium citrate (FAC)-induced HT22 hippocampal neuron damage model. Moreover, in vitro, baicalein could remarkably decrease ferroptotic indices (lipid reactive oxygen species, 4-hydroxynonenal, and prostaglandin endoperoxide synthase 2) and inhibit the expression of 12/15-lipoxygenase (12/15-LOX) in an iron-induced HT22 cell damage model. These findings were also validated in a mouse PTE model. It was concluded that baicalein exerted neuroprotective effects against posttraumatic epileptic seizures via suppressing ferroptosis and 12/15-LOX was likely to be involved in baicalein’s neuroprotection.
Highlights
Posttraumatic epilepsy (PTE), a recurrent seizure disorder, is the consequence of traumatic brain injury (TBI) (Agrawal et al, 2006; Kharatishvili and Pitkänen, 2010; Lamar et al, 2014; Pitkanen et al, 2014)
The data showed that preadministration of 100 mg/kg baicalein significantly reduced the seizure score, number of seizures, and seizure duration compared to the iron chloride (FeCl3)-induced posttraumatic epileptic seizure group (Figure 1D–F)
Our study showed that pretreatment with baicalein in FeCl3induced epileptic seizure mice significantly improved the epileptic seizure behavior and exhibited great neuroprotection in PTE mice
Summary
Posttraumatic epilepsy (PTE), a recurrent seizure disorder, is the consequence of traumatic brain injury (TBI) (Agrawal et al, 2006; Kharatishvili and Pitkänen, 2010; Lamar et al, 2014; Pitkanen et al, 2014). It is estimated that nearly 80% of patients suffer from seizures within 1 year post-TBI (Volavka, 2011). Epidemiological studies have shown that more than 3 million people have PTE globally, comprising approximately 5–6% of all epilepsy patients (Pi et al, 2014; Szaflarski et al, 2014; Singh and Trevick, 2016; Chartrain et al, 2017). It is hoped that effective treatment could be administered at some point within this latency to stop the process, so that posttraumatic epileptic seizures will not occur. Identification of potential compounds or methods that provide neuroprotective effects on posttraumatic epileptic seizures is important
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