Type 2 diabetes mellitus facilitates status epilepticus in adult rats: Seizure severity, neurodegeneration, and oxidative stress.

OBJECTIVE: The goal of this research was to evaluate the effect of DM type 2 (DM2) on SE severity, neurodegeneration, and brain oxidative stress (OS) secondary to seizures. METHODS: DM2 was induced in postnatal day (P) 3 male rat pups by injecting streptozocin (STZ) 100 mg/kg; control rats were injected with citrate buffer as vehicle. At P90, SE was induced by the lithium-pilocarpine administration and seizure latency, frequency, and severity were evaluated. Neurodegeneration was assessed 24 h after SE by Fluoro-Jade B (F-JB) staining, whereas OS was estimated by measuring lipid peroxidation and reactive oxygen species (ROS). RESULTS: DM2 rats showed an increase in latency to the first generalized seizure and SE onset, had a higher number and a longer duration of seizures, and displayed a larger neurodegeneration in the hippocampus (CA3, CA1, dentate gyrus, and hilus), the piriform cortex, the dorsomedial nucleus of the thalamus and the cortical amygdala. Our results also show that only SE, neither DM2 nor the combination of DM2 with SE, caused the increase in ROS and brain lipid peroxidation. SIGNIFICANCE: DM2 causes higher seizure severity and neurodegeneration but did not exacerbate SE-induced OS under these conditions. PLAIN LANGUAGE SUMMARY: Our research performed in animal models suggests that type 2 diabetes mellitus (DM2) may be a risk factor for causing higher seizure severity and seizure-induced neuron cell death. However, even when long-term seizures promote an imbalance between brain pro-oxidants and antioxidants, DM2 does not exacerbate that disproportion.

A modification to the Kuramoto model to simulate epileptic seizures as synchronization.

The Kuramoto model was developed to describe the coupling of oscillators, motivated by the natural synchronization phenomena. We are interested in modeling an epileptic seizure considering it as the synchronization of action potentials using and modifying this model. In this article, we propose to modify this model, changing the constant coupling force for a function with logistic growth to simulate the onset and epileptic seizure level in an adult male rat caused by the administration of lithium-pilocarpine. Later, we select some frequencies and their respective amplitude values using an algorithm based on the fast Fourier transform (FFT) from an electroencephalography signal when the rat is in basal conditions. Then, we take these values as the natural frequencies of the oscillators in the modified Kuramoto model, considering every oscillator as a single neuron to simulate the emergence of an epileptic seizure numerically by increasing the synchronization value in the coupling function. Finally, using Dynamic Time Warping algorithm, we compare the simulated signal by the Kuramoto model with an FFT approximation of the epileptic seizure.

Oxidative stress: a common imbalance in diabetes and epilepsy.

The brain requires a large amount of energy. Its function can be altered when energy demand exceeds supply or during metabolic disturbances such as diabetes mellitus. Diabetes, a chronic disease with a high incidence worldwide, is characterized by high glucose levels (hyperglycemia); however, hypoglycemic states may also occur due to insulin treatment or poor control of the disease. These alterations in glucose levels affect the brain and could cause epileptic seizures and status epilepticus. In addition, it is known that oxidative stress states emerge as diabetes progresses, contributing to the development of diseases secondary to diabetes, including retinopathy, nephropathy, cardiovascular alterations, and alterations in the central nervous system, such as epileptic seizures. Seizures are a complex of transient signs and symptoms resulting from abnormal, simultaneous, and excessive activity of a population of neurons, and they can be both a cause and a consequence of oxidative stress. This review aims to outline studies linking diabetes mellitus and seizures to oxidative stress, a condition that may be relevant to the development of severe seizures in diabetes mellitus patients.