ABSTRACT
Two basic, but distinct, issues come to mind when considering a role of microglia in neurotoxicity. First, microglia respond rapidly to neuron injury whether it is induced by a neurotoxic agent, physical trauma, or by some other means. The microglial response to neuronal damage is characterized by a number of different events, which include mitosis/proliferation, changes in microglial morphology and phenotype, and increased production of growth factors and cytokines. All of these changes are collectively referred to as microglial activation, and they reflect an acute tissue response to injury. The biological significance of a microglial reaction to neuron injury is likely to be the same as in other tissues, namely, the engagement of cellular mechanisms that initiate the woundhealing process. The second issue concerns the possibility that microglia themselves may exert some type of cellular cytotoxicity that could be detrimental to neurons. The key questions here are, when do microglia become neurotoxic, what are the triggers, and how is microglial cytotoxicity
regulated? Obviously, if microglia were neurotoxic constitutively, or could be easily induced to become neurotoxic, given their ubiquitous presence throughout the CNS all neurons would be in constant danger of falling victim to microglia-mediated cytotoxicity. Therefore, microglial neurotoxicity in vivo likely represents a process that is under strict control and becomes unleashed only when the need for it arises, or when control mechanisms go awry.
