Aberrant neurogenesis after stroke: a retroviral cell labeling study.
OBJECTIVE
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.
Hans Berger Department of Neurology, Jena University Hospital, Erlanger Allee 101, 07747 Jena, Germany.
Fanny
F
Niv
Silke
S
Keiner
-K
-
Krishna
Otto W
OW
Witte
Dieter Chichung
DC
Lie
Christoph
C
Redecker
D000818:Animals; D002545:Brain Ischemia / Q000473:pathology; D003594:Cytoplasmic Granules / Q000473:pathology / Q000648:ultrastructure; D003712:Dendrites / Q000473:pathology / Q000648:ultrastructure; D049229:Dendritic Spines / Q000473:pathology / Q000648:ultrastructure; D018891:Dentate Gyrus / Q000473:pathology; D005822:Genetic Vectors; D049452:Green Fluorescent Proteins / Q000235:genetics; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D020767:Intracranial Thrombosis / Q000473:pathology; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D055495:Neurogenesis / Q000502:physiology*; D009473:Neuronal Plasticity / Q000502:physiology; D009474:Neurons / Q000473:pathology / Q000648:ultrastructure; D051381:Rats; D017208:Rats, Wistar; D012190:Retroviridae / Q000235:genetics*; D020521:Stroke / Q000473:pathology*; D000097573:Red Fluorescent Protein
D049452:Green Fluorescent Proteins; D008164:Luminescent Proteins; D000097573:Red Fluorescent Protein