http://stroke.ahajournals.org/content/early/2012/06/26/STROKEAHA.112.660977.abstract
Abstract
Background and Purpose—Adult
neurogenesis in the dentate gyrus is a unique form of brain plasticity
that is strongly stimulated after stroke. We
investigate the morphological properties of
new granule cells, which are born and develop after the ischemic insult,
and query
whether these adult-born neurons properly
integrate into the pre-existing hippocampal circuitries.
Methods—Two
well-established models were used to induce either small cortical
infarcts (photothrombosis model) or large territorial
infarcts (transient middle cerebral artery
occlusion model). New granule cells were labeled 4 days after the
initial insult
by intrahippocampal injection of a retroviral
vector encoding green fluorescent protein and newborn neurons were
morphologically
analyzed using a semiautomatic Neurolucida
system and confocal laser scanning microscopy at 6 weeks.
Results—Approximately
5% to 10% of newborn granule cells displayed significant morphological
abnormalities comprising additional basal
dendrites and, after middle cerebral artery
occlusion, also ectopic cell position. The extent of morphological
abnormalities
was higher after large territorial infarcts
and seems to depend on the severity of ischemic damage. An increased
portion of
mushroom spines in aberrant neurons suggests
stable synaptic integration. However, poststroke generated granule cells
with
regular appearance also demonstrate
alterations in dendritic complexity and spine morphology.
Conclusions—The
remarkable stimulation of dentate neurogenesis after stroke coincides
with an increased rate of aberrantly integrated
neurons, which may contribute to functional
impairments and, hypothetically, favor pathogenesis of adjustment
disorders, cognitive
deficits, or epilepsy often seen in stroke
patients.
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