EFFECT OF CHLORAL HYDRATE ON MORPHOLOGICAL CHANGES IN THE NEOCORTEX AND FUNCTIONAL STATE OF OLD MALE RATS

Abstract

In order to avoid obtaining distorted results at the stage of preclinical study of new pharmaceutical substances and therapeutic strategies, it is necessary to take into account the features and possible influence of the age of the animal and the anesthesia used on the outcome of the experiment. We studied the effect of chloral hydrate on morphological changes in neurons and the reaction of neocortical microglia and the functional state of old male Wistar rats (24 months). Differences were assessed in control rats and in the group using chloral hydrate at the dose required to achieve anesthesia (400 mg/kg animal weight) after 48hours. After the application of chloral hydrate, the surviving animals (mortality rate 37.5%) showed a significant increase in the signs of neurological deficit in the form of motor, sensory and behavioral disorders compared to the rats of the control group. In the fronto-parietal region of the neocortex of the surviving animals, the expression level of the Iba-1 protein was significantly higher than in the control, neurons and microgliocytes with pronounced morphological changes were noted, while their number did not significantly differ from that in the control group. The obtained results suggest that the adverse effect in the early period after anesthesia with chloral hydrate without model surgical intervention in old rats, which manifests itself in the form of a deterioration in the functional state and mortality, can be realized due to the activation of microglia in the fronto-parietal region of the neocortex. However, the process of determining the specific structure of the brain, the activation of microglia in which is more responsible for the formation of neurological disorders, is quite complex and needs further study. In fundamental and preclinical studies of neuroprotective effects, in which old rats are used as the object of study and chloral hydrate is used as an anesthetic, these features must be taken into account.