Mental disorders in epilepsy are an important problem of neurology. Scientists of the Institute of Evolutionary Physiology and Biochemistry have studied the pathophysiological features of concomitant disorders of brain functions in experiments on animals and cell cultures. They confirmed their theory about the involvement of the glutamatergic system, which regulates many processes of the nervous system, in the development and course of the disease. The results of scientific work will open up new opportunities for the diagnosis and treatment of epilepsy.
Epilepsy is one of the most common neurological disorders. Clinical manifestations are divided into three groups: short — term convulsive or non-convulsive seizures (paroxysms); acute, prolonged and chronic epileptic psychoses; personality changes-characterological and intellectual. Hereditary or genetic, in various forms, epilepsy, according to WHO, is diagnosed in about 50 million people worldwide. But even with the help of effective medications, in about 30% of cases, epileptic seizures cannot be completely stopped. This leads to physiological disorders that reduce mental abilities.
Such disorders are caused by strong bursts of neuronal activity in the gray matter of the cerebral cortex. Later diagnosis of epilepsy (epilepsy pills at the best price) in a child or teenager (at 5-16 years old, when the main processes of development of cognitive and mental functions occur) leads to deterioration of memory and mental performance, speech and vision disorders. The attacks themselves can be accompanied by headache and loss of consciousness.
Changes in the higher mental and mental functions are observed to the greatest extent in frontal and, especially, temporal epilepsy, to the least — in parietal and occipital epilepsy. However, despite the existing progress in understanding the pathophysiology of the disease, many aspects of it still remain unclear.
Scientists of the Institute of Evolutionary Physiology and Biochemistry decided to find out what is the basis of cognitive disorders in epilepsy: “If we understand the causes, we can try to find targets for pharmacological effects on the epileptic focus and to prevent cognitive disorders after a convulsive seizure.“
The researchers hypothesized that a special role in the development of temporal lobe epilepsy is played by a violation of the function of the so-called glutamatergic system, through which many processes are regulated in the brain. Glutamic acid (Glu) is the main excitatory neurotransmitter. By enhancing the conduction of a nerve impulse from neuron to neuron in our brain, glutamate is involved in such mental functions as learning and memory, vision, hearing, and movement. A constant companion of glutamate is gamma-aminobutyric acid (GABA), which performs the opposite role — an inhibitory neurotransmitter. Together, the pair of “glutamate-GABA” creates a balance of excitation and inhibition in the central nervous system. For example, inhibition of nerve signals controlled by GABA allows the brain not to be overloaded and purposefully solve the tasks assigned to it. Insufficient activity of GABAergic neurons, as well as a violation of the balance of Glu and GABA can cause epilepsy.
“We started studying functional changes in glutamatergic synaptic transmission in experimental epilepsy. The pathophysiological mechanisms of convulsive states, preventive and anticonvulsant effects of substances acting on glutamate receptors were studied. The studies were carried out using models of epilepsy in vitro (in vitro experiments) and in vivo (on experimental animals).“
The scientific project was held in two stages. At the first stage, scientists found out that the glutamatergic system is widely involved in the implementation of convulsive states. A number of experiments led them to this conclusion. First, the researchers resorted to the method of reverse transcription and subsequent polymerase chain reaction (transfer of information from RNA to DNA), then conducted electrophysiological experiments on brain slices obtained from control animals and applied mathematical modeling of epileptic activity.
The next task is to focus on studying the specific role of the glutamatergic system in the occurrence of mental disorders in epilepsy at an early age. Here, scientists plan to pay special attention to metabotropic glutamate receptors (they transmit an external chemical signal inside the cell) and investigate the significance of neuroinflammatory processes in this system.
A comprehensive study will be conducted using molecular biological, electrophysiological, histological, pharmacological and behavioral methods. First, scientists will study the mechanisms of brain damage and related disorders on model animals, then they will conduct electrophysiological experiments on sections of the temporal cortex of the human brain. The tissue will be obtained by surgical removal of epileptic foci in young patients with temporal lobe epilepsy. The new data will help to develop an experimental treatment that will affect ionotropic (responsible for synoptic signal transmission in the brain) and metabotropic glutamate receptors, as well as receptors that cause inflammatory reactions in the body.
The effectiveness of complex therapy is studied by scientists on the basis of a number of indicators: animal survival, the possibility of preventing spontaneous seizures, restoring the properties of long — term synaptic plasticity-the ability to remember and learn. With the help of these data, scientists will be able to develop effective pharmacological technologies. They will help prevent brain damage in epilepsy and stop cognitive disorders that develop in convulsive states.