Effect of Lacosamide and Ethosuximide Chronic Treatment on Neural Precursor Cells and Cognitive Functions after Pilocarpine Induced Status Epilepticus in Mice

Abstract

Seizures in about 40% of patients with epilepsy fail to respond to anti-seizure medication (ASM) and may lead to uncontrolled and prolonged seizures often inducing status epilepticus (SE). The aim of the study was to evaluate the impact of a long-term treatment with two different generation ASMs: ethosuximide (ETS, a classic ASM) and lacosamide (LCM, a 3rd generation ASM) on neural stem cells’ (NSCs’) proliferation and learning and memory functions after pilocarpine (PILO)-induced SE in mice. The following drugs were used: LCM (10 mg/kg), ETS (20 mg/kg), and PILO (300 mg/kg). Cell counting was done using confocal microscope and ImageJ software. Cognitive functions were evaluated with the Morris water maze (MWM) test. The level of several selected neurometabolites was measured with magnetic resonance spectroscopy (MRS). Obtained results indicated no significant impact of ETS treatment on the neurogenesis process in PILO mice. Interestingly, LCM significantly decreased the total amount of newborn neurons. The MWM test indicated no significant changes in the time and distance traveled by the ETS and LCM groups compared to PILO control mice, although all measured parameters were more favorable for the PILO mice treated with ASM. Conclusions: The presented results show that long term treatment with LCM and ETS seems to be safe for the cognitive functions and the proper course of neurogenesis in the mouse PILO-induced SE model, although one should remember that LCM administered chronically may act to reduce new neurons’ formation.

VEGF Modulates Neurogenesis and Microvascular Remodeling in Epileptogenesis After Status Epilepticus in Immature Rats

“…The axons of mature neurons in the MoDG follow the pathway of moss fibers of granular cells in the hippocampal DG into the CA3 region after SE, forming abnormal synaptic connections with CA3 neurons (34). The synapses formed by moss fibers exhibit high excitability and low inhibition and are prone to abnormal synchronous discharges; thus, they increase excitability, lead to SRS, form abnormal excitatory neural circuits associated with epilepsy and are the pathological basis of refractory temporal lobe epilepsy (35,36).…”

The Effect of a Diet Enriched with Jerusalem artichoke, Inulin, and Fluoxetine on Cognitive Functions, Neurogenesis, and the Composition of the Intestinal Microbiota in Mice

“…Animals underwent a behavioral MWM test 24 h after the last administration of TPB, INU, FLU, and water for injections (for the control group), according to the methods described earlier [ 45 , 46 , 47 ]. The MWM is the one of the most commonly used behavioral tests to assess learning and memory processes.…”

“…For determining the influence of TPB, INU, and FLU on the process of neurogenesis, 50 μm free-floating sections (stored at 4 °C) were immunohistochemically stained to visualize BrdU/NeuN and BrdU/GFAP positive cells according to the methods described previously [ 45 , 46 , 47 , 55 , 56 ].…”

“…To further establish the phenotype of BrdU labeled cells, we performed a double/triple confocal immunofluorescence staining with BrdU, neuronal nuclei (NeuN), and glial acid fibrillar protein (GFAP) in the granular cell layer (GCL) and subgranular zone (SGZ) of dentate gyrus (DG) using the methods described earlier [ 45 , 46 , 47 , 55 , 56 ] five mice in each group ( n = 5).The exact area of DG of the hippocampus designated for the quantitative analysis of neurogenesis is presented in Figure 2 . Confocal imaging was performed using a Nikon A1R confocal microscope (Tokyo, Japan).…”

Differential effects of antiseizure medications on neurogenesis: Evidence from cells to animals

“…Szewczyk et al showed that long-term exposure to ESM (20 mg/kg, 10 days) did not induce any cognitive deficits in the pilocarpine (300 mg/kg, i.p) mouse model of status epilepticus. Moreover, ESM had no negative effects on neurogenesis and the level of BrdU + /NeuN + cells in the pilocarpine-treated mice [ 47 ].…”