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Neurogenic and inflammatory response in the rodent brain following stroke

Heldmann, Ursula LU (2010) In Lund University, Faculty of Medicine Doctoral Dissertation Series 2010:114.
Abstract
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... (More)
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. (Less)
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author
supervisor
opponent
  • Professor Nilsson, Michael, Sahlgrenska Universitet Sjuhus, GÖTEBORG
organization
publishing date
type
Thesis
publication status
published
subject
keywords
inflammation, Mac-1-saporin, TNF-a, Neurogenesis, Microglia, stroke, aging
in
Lund University, Faculty of Medicine Doctoral Dissertation Series
volume
2010:114
pages
135 pages
publisher
Institutionen för kliniska vetenskaper, Lunds universitet
defense location
Belfrage salen, Biomedicinskt Centrum, Lund
defense date
2010-12-03 09:00
ISSN
1652-8220
ISBN
978-91-86671-30-3
language
English
LU publication?
yes
id
de683d5c-e445-4cae-9410-4faeda78fd76 (old id 1712560)
date added to LUP
2010-11-12 13:22:55
date last changed
2018-05-29 09:48:23
@phdthesis{de683d5c-e445-4cae-9410-4faeda78fd76,
  abstract     = {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. <br/><br>
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. <br/><br>
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.},
  author       = {Heldmann, Ursula},
  isbn         = {978-91-86671-30-3},
  issn         = {1652-8220},
  keyword      = {inflammation,Mac-1-saporin,TNF-a,Neurogenesis,Microglia,stroke,aging},
  language     = {eng},
  pages        = {135},
  publisher    = {Institutionen för kliniska vetenskaper, Lunds universitet},
  school       = {Lund University},
  series       = {Lund University, Faculty of Medicine Doctoral Dissertation Series},
  title        = {Neurogenic and inflammatory response in the rodent brain following stroke},
  volume       = {2010:114},
  year         = {2010},
}