The role of the substantia nigra pars reticulata in kindling resistance in rats with genetic absence epilepsy

Abstract

Summary Objective Genetic Absence Epilepsy Rats from Strasbourg (GAERS) show a resistance to secondary generalization of focal limbic seizures evoked by kindling. The substantia nigra pars reticulata (SNR) is involved in the propagation and modulation of seizures in kindling. We first examined the role of the SNRanterior and SNRposterior subregions in the resistance to the development of kindling in GAERS. Subsequently, to determine whether kindling resistance relates to differential sensitivity of GABAergic or dopaminergic SNR neurons to kindling, we studied the effects of kindling-inducing stimulations on parvalbumin (PRV; GABAergic neuron marker) or tyrosine hydroxylase (TH; dopaminergic neuron marker) immunoreactivity (ir) respectively in GAERS and in nonepileptic control (NEC) Wistar rats that lack kindling resistance. Methods Adult male GAERS were implanted with a stimulation electrode in the amygdala and bilateral injection cannulas for lidocaine or saline injection (30 min before each kindling stimulation until the animals reached three stage 5 seizures or the 22 stimulations) into the SNRanterior or SNRposterior. In another experiment, PRV-ir in SNRanterior and SNRposterior and TH-ir in SNRposterior only were densitometrically compared in GAERS-SHAM, NEC-SHAM GAERS-STIM and NEC-STIM animals (6 kindling stimulations). Results Bilateral SNRposterior infusions of lidocaine eliminated the kindling resistance and resulted in stage 5 generalized motor seizures in all kindled rats. Bilateral lidocaine infusions in the SNRanterior failed to alter the kindling resistance in GAERS. PRV-ir in the SNRposterior was unaltered in GAERS-STIM but increased in NEC-STIM group. Cellular TH-ir in the SNRposterior significantly increased by kindling stimulations in both NEC-STIM and GAERS-STIM groups. Significance The kindling resistance in GAERS is mediated by the SNRposterior in a lidocaine-sensitive manner. The insensitivity to kindling stimulation of PRV-ir in SNRposterior of GAERS but not NEC rats, implicate GABAergic SNRposterior neurons in kindling resistance. In contrast, the observed stimulation-specific increase in TH-ir in the SNRposterior is unrelated to kindling resistance.

Abnormalities of diffusional kurtosis imaging and regional homogeneity in idiopathic generalized epilepsy with generalized tonic‑clonic seizures

“…Furthermore, reduced dopamine transporter binding has been detected in the putamen of patients with IGE-GTCS, who primarily exhibited impairments in motor control and speed, which suggests that dopamine may be neuroprotective and may inhibit the onset of seizures (29). In addition, the substantia nigra may mediate the spread of epileptic activity (30). The imaging threshold set by SPM may result in brain areas appearing smaller than they actually are and may account for the absence in the results of the current study regarding small basal ganglia nuclei.…”

The Effect of Agmatine on Spike-and-Wave Discharges in a Genetic Model of Absence Epilepsy

“…Stereotaxic surgery was performed as previously reported (24). Briefly, rats were anesthetized with ketamine (100 mg/kg, ip) and xylazine (10 mg/kg, ip).…”

Managing epilepsy by modulating glia

“…IL-1β was found to be significantly induced in reactive astrocytes in the somatosensory cortex of GAERS, and was involved in SWD generation in an age-dependent manner as follows: partial at postnatal day 20 GAERS and fully in all adult GAERS when SWDs are completely developed. [59,60] The expression of the cytokine was associated with the development of SWDs. Both SWD number and duration were shown to reduce by inhibition of IL-1β biosynthesis in adult GAERS.…”