Changes in gene expression during delayed neuronal death after cerebral ischemia in the rat

Sammanfattning: After transient global cerebral ischemia, selected populations of neurons in the brain will die after a period of 2-3 days, a phenomenon termed delayed neuronal death. This is of clinical importance as delayed neuronal death has been found to occur in humans as well. The mechanism that kills a neuron 2-3 days after the initial insult is unclear, but transcriptional steps have been implicated. The aim of this thesis work was to study some of the changes in gene expression after transient global ischemia in the rat and to find a transcriptional pattern that correlated with neuronal death. The results show that: most changes in gene expression found to occur after ischemia, take place in neurons that survive the insult as well as neurons destined to die. This suggests that these changes are related to stress rather than a specific death mechanism. This included genes that have been shown to be important in neuronal death, e.g. p53. using differential display PCR we found the specific induction of an endogenous provirus in neurons destined to die. The expression of this retrovirus correlated exceptionally well with death, suggesting that the mechanisms that regulate the expression of the provirus may be involved in the regulation of neuronal death after ischemia.