Neuroprotection versus neurotoxicity

Abstract

Several original concepts concerning microglia have changed in the last decade. Ramified microglia are no longer seen to be resting cells and it also is very obvious today that microglia responses are by no means stereotypic, but manifold and targeted. Moreover, there is good evidence that microglia are not only important in brain pathology, but that they also play important roles in the healthy brain. One long-standing aspect of microglia biology, however, was never questioned: their involvement in brain disease. Based on morphological changes (retraction of processes and amoeboid shape) that inevitably occur in these cells in case of damage to the central nervous system, microglia in the diseased brain were called activated. Because activated microglia were always found in direct neighbourhood to dead or dying neurons, and since it is known now for more than 20 years that cultured microglia release numerous factors that are able to kill neurons, microglia activation was often seen as neurotoxic. From an evolutionary point of view, however, it is difficult to understand why an important, mostly post-mitotic and highly vulnerable organ like the brain would host numerous toxic cells. How microglia can protect the nervous tissue and what might go awry when microglia turn neurotoxic will be discussed in this chapter.