Hippocampal High-Frequency Stimulation Inhibites the Progression of Rapid Kindling-Induced Seizure in Rats

Abstract

<p> <span style="font-family:Verdana;">Epilepsy is one of the most common serious neurological disorders. Pharmacoresistant epilepsy patients are poorly controlled or their seizures are refractory to drug treatment. Resective surgery is frequently a promising therapy in this population, however, not all the patients meet the eligibility criteria for the surgical treatment. Deep brain stimulation has been investigated in clinical studies and animal studies as an alternative treatment, but the optimal stimulation pa</span><span style="font-family:Verdana;">rameters remain an issue.</span><span style="font-family:Verdana;"> The present study was designed to investigate the effect of unilateral high</span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">frequency stimula</span><span style="font-family:Verdana;">tion (HFS) of hippocampus on seizure development by using the hippocampal rapid kindling method (hRK) in rats, and compared th</span><span style="font-family:Verdana;">e</span><span style="font-family:Verdana;"> results with those of low-frequency stimulation previously published by our group. We used male Wistar rats implanted with electrodes in the ventral hippocampus. All rats underwent hRK (biphasic square wave pulses, 20 Hz for 10 seconds) during three consecutive days (twelve stimulations per day). The control group (hRK; n</span><span> </span><span style="font-family:Verdana;">=</span><span> </span><span style="font-family:Verdana;">7) received only RK stimulus, while the treated group (HFS-hRK; n</span><span> </span><span style="font-family:Verdana;">=</span><span> </span><span style="font-family:Verdana;">9) received also HFS (biphasic square wave pulses, 130 Hz for 30 seconds) immediately before the RK stimulus, during three consecutive days. At the end of behavioral testing 78% (p</span><span> </span><span style="font-family:Verdana;"><</span><span> </span><span style="font-family:Verdana;">0.01) of the animals receiving HFS treatment were still not fully kindled staying in stages 0</span><span> </span><span style="font-family:Verdana;">-</span><span style="font-family:Verdana;">III (p</span><span> </span><span style="font-family:Verdana;"><</span><span> </span><span style="font-family:Verdana;">0.01). HFS group needed a higher number of stimulations to achieve stage III (p</span><span> </span><span style="font-family:Verdana;"><</span><span> </span><span style="font-family:Verdana;">0.05) with respect to control group. How</span><span style="font-family:Verdana;">ever, no significant differences in the cumulative daily afterdischarge duration were observed. HFS did not present sig</span><span style="font-family:Verdana;">nificant differences compared with LFS in any of studied parameters. Th</span><span style="font-family:Verdana;">e</span><span style="font-family:Verdana;"> findings suggest that unilateral HFS applied on hippocampus effectively inhibited the epileptogenic process induced by hippocampal rapid kindling. According to the comparative results about hippocam...

An Age Dependent Seizure Vulnerability of Hippocampal CA2: Finding the Targets to Rescue Seizure-Induced Social Recognition Memory Deficits

“…The basic mechanism of a hyper-excitable state can result from the delicate imbalance of excitation and inhibition in the brain. This imbalance has been associated with increased synaptic neurotransmission, decreased inhibitory inputs, increased synchronous excitatory stimuli (temporal summation in post-synaptic neurons) or an alteration of ion channels/ion concentrations effect (Gori et al, 2013;Vasilev et. al., 2018).…”

“…al., 2018). Seizure animal models, such as a single injection of pentylenetetrazol (PTZ), an antagonist of gamma-aminobutyric acid (GABA) type A receptor can evoke structural changes in brain tissue and rapid formation of 'dark neurons' in the hippocampal pyramidal layer and will last up to 1-week post seizure effect (Gori et al, 2013;Vasilev et. al., 2018).…”

“…When investigating at the neuronal level, the major excitatory neurotransmitter that initiates ionotropic receptors such as α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) and Nmethyl-D-aspartate (NMDA) is the amino acid glutamate. Studies have shown that the NMDA and AMPA receptor agonists can initiate seizure activity and that antagonists towards these receptors can suppress seizure activity (Gori et al, 2013;Vasilev et al, 2018), presenting a major clinical research target.…”