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Aberrant neurogenesis after stroke: a retroviral cell labeling study.

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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  • Authors

    Niv F, Keiner S, Krishna -, Witte OW, Lie DC, Redecker C

    Source

    Stroke; a journal of cerebral circulation 43:9 2012 Sep pg 2468-75

    MeSH

    Animals
    Brain Ischemia
    Cytoplasmic Granules
    Dendrites
    Dendritic Spines
    Dentate Gyrus
    Genetic Vectors
    Green Fluorescent Proteins
    Immunohistochemistry
    Infarction, Middle Cerebral Artery
    Intracranial Thrombosis
    Luminescent Proteins
    Male
    Neurogenesis
    Neuronal Plasticity
    Neurons
    Rats
    Rats, Wistar
    Retroviridae
    Stroke

    Pub Type(s)

    Journal Article
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    22738919