Age-Dependent Electrocorticogram Dynamics and Epileptogenic Responsiveness in Rats Subjected to Prenatal Hypoxia

Abstract

Using electrocorticogram (ECoG) analysis, we compared age-related dynamics of general neuronal activity and convulsive epileptiform responsiveness induced by intracortical microinjections of 4-aminopyridine (4-AP) in control Wistar rats and those subjected to prenatal hypoxia (Hx; E14; 7% O2, 3 h). The studies were carried out in three age periods roughly corresponding to childhood (P20–27), adolescence (P30–45), and adulthood (P90–120). It was found that in the process of postnatal development of the control rats, the peak of the ECoG power spectrum density (PSD) of the theta rhythm during wakefulness shifted from the low to the higher frequency, while in the Hx rats this shift had the opposite direction. Moreover, the Hx rats had different frequency characteristics of the ECoG PSD and longer episodes of spike-and-wave discharges caused by 4-AP injections compared to the controls. The total ECoG PSD of slow-wave sleep (1–5 Hz) was also dramatically decreased in the process of development of the Hx rats. Such alterations in PSD could be explained by the changes in balance of the excitation and inhibition processes in the cortical networks. Analyzing protein levels of neurotransmitter transporters in the brain structures of the Hx rats, we found that the content of the glutamate transporter EAAT1 was higher in the parietal cortex in all age groups of Hx rats while in the hippocampus it decreased during postnatal development compared to controls. Furthermore, the content of the vesicular acetylcholine transporter in the parietal cortex, and of the inhibitory GABA transporter 1 in the hippocampus, was also affected by prenatal Hx. These data suggest that prenatal Hx results in a shift in the excitatory and inhibitory balance in the rat cortex towards excitation, making the rat’s brain more vulnerable to the effects of proconvulsant drugs and predisposing animals to epileptogenesis during postnatal life.

The Anti-Epileptic Effects of Carbenoxolone In Vitro and In Vivo

“…CBX is administered at doses up to 100 mg/kg in various epilepsy models [ 49 ]. As shown by our and other works [ 11 , 40 , 50 ], the latent period of seizure development with cortical administration of 4-AP is 20 to 30 min. In the present work, we were interested in whether CBX administration would prevent the development of seizures or significantly attenuate them.…”

“…For in vivo experiments,14 adult rats (Wistar male, 250–350 g, 3–5 months) were implanted with a block of electrodes for recording an electrocorticogram (ECoG) and a cannula for the intracortical introduction of substances [ 40 ]. The type of metal electrode block, as well as the electrode and cannula implantation procedure, was described previously [ 36 ].…”

“…Similar doses of 4-AP have been used by various researchers for intracortical administration in models of induced focal epilepsy, in vivo, and on neocortical slices [ 40 , 47 , 48 ]. CBX is administered at doses up to 100 mg/kg in various epilepsy models [ 49 ].…”

Maternal Hypoxia Increases the Excitability of Neurons in the Entorhinal Cortex and Dorsal Hippocampus of Rat Offspring

“…Hypoxia leads to cognitive impairments in animals ( Nyakas et al, 1996 ; Zhuravin et al, 2019 ), alters EEG rhythm carachteristic ( Kalinina et al, 2019 ), and increases vulnerability to proconvulsive drugs ( Sadaghiani and Saboory, 2010 ; Kalinina et al, 2019 ). However, to our knowledge, no reports have been published concerning the changes in biophysical properties of hippocampal and cortical neurons in animals subjected to hypoxia during embryogenesis.…”

“…Animals subjected to prenatal hypoxia exhibit alterations in subunit composition of NMDA receptors in the CA1 area of the hippocampus ( Zhuravin et al, 2019 ; Vetrovoy et al, 2021 ), and an upregulated glutamate uptake system ( Kalinina et al, 2019 ). The effect of prenatal hypoxia on the cholinergic system in brain cortical structures was also shown ( Kochkina et al, 2015 ; Morozova et al, 2020 ).…”