Stroke and in this case cerebral infarction affects 20 million people each year and five million of them die. In Sweden 30-35000 people will be affected and one of three of them will be severely disabled. In addition, one of six will suffer a new stroke within six years. The cause of stroke is usually a vessel in the brain that is blocked, resulting in massive neuronal cell death. Since treatment of stroke in the acute phase is still very limited, more research will be needed.
Today it is known that there is a constant formation of new cells in the SubVentricular Zone (SVZ), which is adjacent to the lateral ventricles in the brain and in the SubGranular Zone (SGZ) of the hippocampus. Here the formation of immature neurons (neuroblasts) takes place and then wander through the "front footpath" (Rostral Migratory Stream (RMS) to the Olfactory Bulb (OB), in order to mature into nerve cells (neurons). In connection with medical conditions such as stroke, neuroblasts wander out of the SVZ to the damaged tissue in which a small fraction of them develop into neurons and replace their predecessors. We now know that this process continues long after a stroke. Furthermore, it is known that similar medical conditions often are associated with inflammation and the involvement of microglia. These inflammatory conditions affect the formation of new nerve cells in several ways.
In this thesis our goal has been to determine the effect of stroke on neurogenesis in aged brain, to determine the effects of TNF-α antibody infusion on the survival of the new striatal and hippocampal neurons formed after stroke, to characterize the inflammatory profile following stroke in the SVZ and striatum and try to evaluate the effect on neurogenesis after manipulation of microglia in intact brain and following stroke. We showed that even aging animals have good potential mechanisms for self-repair after stroke. Similarly, cytokines as TNF-α and its receptors influence neurogenesis after stroke, depending on the receptor that is expressed, the concentration and duration of expression, and the environment. We also showed that the long-term accumulation of microglia with proneurogenic phenotype in the SVZ implies a supportive role of these cells for the continuous neurogenesis after stroke. However, when we depleted the subpopulation Mac-1-saporin in the SVZ, there were no alterations in the numbers of newly formed neuroblasts in the striatum or the migratory distance. We therefore suggest that microglia may have a supportive proneurogenic role but that the microglia population is a heterogeneous group with different forms of activation-pathways.
- Lindvall, Olle, Supervisor
- Ekdahl Clementson, Christine, Supervisor
|Award date||2010 Dec 3|
|Publication status||Published - 2010|
Place: Belfrage salen, Biomedicinskt Centrum, Lund
Name: Nilsson, Michael
Affiliation: Sahlgrenska Universitet Sjuhus, GÖTEBORG