Animal models of early brain disorders : behavioural and electrophysiological approaches
Year: 2016
Type: dissertation
Abstract: This Thesis addresses fundamental mechanisms of brain disorders that occur in preterm infants or during early childhood. To this end, we have developed animal models to mimic disorder-specific pathological conditions in the brain. During critical periods of development of the mammalian brain, cell migration and synapse formation are crucially important to set up newly developed neuronal circuits that will support complex network activity. A particular set of cells, the subplate neurons, is the first to mature during the earliest stages of cortical development. These neurons act as transient relay and processing station for signals coming from subcortical structures to the cortex. Their high dependence on oxygen supply makes them vulnerable to injuries that take place during pregnancy. In the present work, conditions of this kind were mimicked by specific toxin-based ablation of subplate neurons. At a more advanced stage of brain development, a very common type of brain disorder is febrile seizures (FS). They represent convulsive events in humans that are promoted by respiratory alkalosis during febrile illness. The global incidence of FS is estimated from 2 to 14 % (depending on ethnicity) of all children in the age of 6 months to 5 years. Using an animal based on 13-14 day old rats exposed to hyperthermia, we show that a pro-excitatory action of GABA based on the neuron-specific carbonic anhydrase (CA) isoform VII is crucially involved in the generation of these seizures. Finally, while it is widely assumed that FS are limbic in origin, this Thesis provides new evidence that the brainstem can have an independent and prominent role in the generation of FS, and also of convulsions induced by kainic acid, which so far, have been considered prototypical in studies of limbic seizures. As a whole, this work demonstrates the high utility and heuristic value of custom-designed animal models in studies of basic mechanisms and consequences of disorders in the developing brain.
Source: Työväentutkimus Vuosikirja
Author: Yukin, Alexey
Language: English
Subfield: Clinical Neurology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W2345999867