The chronology of lesion repair in the developing rat brain: biological significance of the pre-existing extracellular space.

We observed the histological peculiarities of the repair process in a destructive lesion of the developing rat brain during neurogenesis. Degeneration was induced selectively in certain cells of the proliferating phase in the rat fetal neopallium on embryonic day 16 by transplacental administration of ethylnitrosourea. Successive elimination of necrotic cells and the restoration process were observed. The repair process was divided into the following steps: elimination of individually affected cells by phagocytes in the pre-existing extracellular space; successive restoration of the disintegrated area by cells which differentiated from remaining matrix cells. No reactive gliosis, fibrosis, abnormal vascularization or infiltration of granulocytes and lymphocytes was observed at any time. The thinned neopallium on postnatal day 21 revealed only a small number and abnormal distribution of the cortical neurons. It may be assumed that the fetal brain owes its unique repair features to the presence of a vast extracellular space under normal conditions. In this pre-existing extracellular space, every kind of cell seems to exist separately without the intracellular adhesions characteristic of the adult brain. When degeneration occurs in certain cells the phagocytes would be able to eliminate the degenerate cells completely in this space without having to break intercellular adhesions. As a result, after the completion of cell elimination, the injured brain is restored to its original state with no cell reaction, giving the appearance of a small brain with normal-looking histological architecture, save only for the sparseness of cells.