Methodological Approaches to Experimental Evaluation of Neuroprotective Action of Potential Drugs

Abstract

The authors propose a novel approach to a comprehensive evaluation of neuroprotective effects using both in vitro and in vivo methods. This approach allows for the initial screening of numerous newly synthesized chemical compounds and substances from plant and animal sources while saving animal life by reducing the number of animals used in research. In vitro techniques, including mitochondrial suspensions and neuronal cell cultures, enable the assessment of neuroprotective activity, which can be challenging in intact organisms. The preliminary methods help outline the neuroprotection mechanism depending on the neurodestruction agent. The authors have validated a model of acute cerebrovascular accident, which simulates key cerebrovascular phenomena such as reduced cerebral blood flow, energy deficit, glutamate–calcium excitotoxicity, oxidative stress, and early gene expression. A significant advantage of this model is its ability to reproduce the clinical picture of cerebral ischemia: impaired motor activity; signs of neurological deficits (paresis, paralysis, etc.); as well as disturbances in attention, learning, and memory. Crucial to this approach is the selection of biochemical, molecular, and cellular markers to evaluate nerve tissue damage and characterize potential neuroprotective agents. Additionally, a comprehensive set of molecular, biochemical, histological, and immunohistochemical methods is proposed for evaluating neuroprotective effects and underlying mechanisms of potential pharmaceutical compounds.