Abstract
Anterior nucleus of thalamus (ANT) stimulation has been proved to be effective in the treatment of refractory epilepsy, but the underlying mechanisms remain to be elucidated. We examined the role of ANT stimulation on hippocampal neuron death after seizures induced by kainic acid (KA). Our data showed that ANT stimulation could significantly rescue neurons from death induced by seizures, by reducing the release of cytochrome c (cyto c) and also via apoptosis-inducing factor (AIF) induced by seizures through inhibiting the activated caspase-9 and caspase-3. Our data suggest that ANT stimulation may protect against neuronal loss and reduce neuronal injury in the ipsilateral CA3 region of the hippocampus in the KA-induced epileptic rats, and the underlying mechanism may be mediated by inhibiting mitochondrial caspase-dependent (cyto c release and the subsequent cleavage of caspase-) and caspase-independent (nuclear translocation of AIF) apoptosis pathways.
Highlights
Epilepsy is a progressive neurodegenerative disorder characterized by an enduring predisposition to generate seizures [1]
These results demonstrated that Kainic acid (KA)-induced seizures caused prominent neuronal loss in the hippocampus and anterior nucleus of thalamus (ANT) stimulation could rescue neurons from death induced by seizures
Our results illustrated that ANT stimulation could significantly decrease the numbers of TUNEL positive cells and increase the number of surviving cells, indicating that ANT stimulation could rescue neurons from death induced by seizures and has a protective effect on hippocampal neuronals in KA-induced
Summary
Epilepsy is a progressive neurodegenerative disorder characterized by an enduring predisposition to generate seizures [1]. The resection of mesial temporal structures can lead to the absence of seizures in more than 70% of patients [3]. We have proposed hypotheses that ANT-DBS could have neuroprotective effects in epilepsy patients by regulating the metabolism of amino acids [8]. It is still unclear whether ANT stimulation has protection on hippocampal neurons. Intra-hippocampal KA injection in rats has been widely used a model to study the mechanisms of seizure-induced neuronal cell death in the hippocampus [11,12]. In the present study, we examined the protective effects and potential mechanisms of ANT stimulation on hippocampal neurons in kainic acid epilepsy rats
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