Brain maldevelopment and delayed neuro-behavioural deviations, induced by perinatal insults, and possibilities of their prevention.

Noxious insults interfering perinatally lead to disorganization of normal perinatal brain development characterized by growth acceleration and intensive histogenesis and known as a sensitive "vulnerable" period of CNS development. Thus induced abnormities, sometimes very discrete, give rise to functional pathology which becomes apparent gradually during maturation as neurobehavioural deviations. For the study of these pathogenetic processes, two experimental models were established. Rat was chosen as an advantageous model animal since the "brain growth spurt" occurring in man in the third trimester of gravidity is shifted postnatally in this altricial species. Prolonged neonatal malnutrition (days 1-40) lead in adult rats to behavioural abnormities (hyperactivity, stereotypy, decreased adaptability, aggressivity) associated with biochemical and electrophysiological alterations in the brain. But this multifactorial and long-term insult was not suitable for more precise analysis. Therefore short-term inhibition of protein synthesis was induced in 7-day-old rats by cycloheximide which resulted in delayed behavioural deviations (hyperactivity, decreased habituation, learning deficit, motor incoordination) connected with permanent morphological, biochemical and endocrinological alterations. These models were used for testing brain maldevelopment-regulatory action of nootropics. Pyritinol administered for 7-10 days following the noxious intervention prevented the brain maldevelopment and functional disturbances in both experimental models. Favourable effects of early and long-term pyritinol treatment on neuro-psycho-pathological sequels of perinatal distress were confirmed in clinical controlled prospective study of 128 high-risk newborns.