The impairment of cerebral blood flow during an ischaemic insult restricts the delivery of oxygen and glucose to the brain. The subsequent energy depletion triggers a cascade of events, including release of the excitotoxin, glutamate. In this thesis, the microglial response to pharmacological manipulation of energy metabolism, depletion of oxygen and glucose, and glutamate exposure was explored. Glucose deprivation did not compromise microglial viability. In contrast, glucose deprivation in the presence of the glycolytic inhibitor, 2-deoxyglucose triggered microglial death and induced cytoskeletal changes. Two-deoxyglucose treatment, even in the presence of glucose, strongly activated microglia, attenuated microglial proliferation and/or adhesion and triggered nuclear pyknosis. Microglia were relatively resistant to short exposure to the respiratory chain inhibitor, cyanide, compared with neurons. Oxygen-glucose deprivation was a milder insult for microglia than cyanide or 2-deoxyglucose treatment. It did not trigger cytoskeletal changes or induce nuclear pyknosis. However, both hypoxia and oxygen-glucose deprivation irreversibly compromised microglial proliferation and/or adhesion. Glutamate treatment triggered neuronal but not microglial nuclear pyknosis. Microglial conditioned medium containing soluble factors released from microglia was neuroprotective when added to neurons prior to neuronal exposure to glutamate. However, when microglial conditioned medium was added to untreated neurons, an increase in neuronal calcium levels was triggered, mediated by P2 purinergic- and NMDA- receptor activation. Taken together these results indicate that microglia are more able to tolerate energy deprivation or glutamate than neurons. Furthermore, the above results demonstrate that microglia may interact with neurons, releasing factors which modulate neuronal signalling and survival. Following a severe metabolic insult, as may occur in the ischaemic core, strong microglial activation is observed. This is associated with microglial death and may be a mechanism of down-regulating the microglial contribution to an inflammatory response, although removal of microglia by these processes may compromise brain repair.