General Introduction

Rotation-mediated aggregating cultures constructed from single cell suspensions of foetal brain have so far proved extremely useful and informative in multi-disciplinary neurobiological and neuropharmacological studies. However they have not yet been as extensively used for neurotoxicological investigations as have monolayer and explant cultures. Brain reaggregates appear to restrict cellular division whilst enhancing biochemical and morphological differentiation (see Seeds et al, 1980) and more closely reflect the in vivo developmental process than primary monolayer cultures. In fact, in several instances they have been found to express systems found in vivo and not in surface culture such as some of the myelin-related enzymes.

In common with other tissue culture models there are several advantages over in vivo studies (see also section D), added advantages being firstly the high tissue yield for neurochemical analysis, and secondly their long survival in chemically-defined, serum-free media (Honegger & Lenoir, 1980; Atterwill et al, 1985) enabling detailed studies of hormone action to be carried out. Of interest is a report that the longevity of cells in brain aggregate cultures can be further enhancaed by the addition of vitamin E.

The cells within these organotypic cultures change from a population of completely undifferentiated neuroepithelial cells to an integrated population of neurones, astroglia and oligodendroglia. The brain cells are generally mechanically dissociated (this is preferable to trypsinization, giving more viable cells) from 15–16 day rat foetuses and the cultures remain viable for around one to two months.