Absence of striatal newborn neurons with mature phenotype following defined striatal and cortical excitotoxic brain injuries.
Experimental stroke and excitotoxic brain lesion to the striatum increase the proliferation of cells residing within the ventricular wall and cause subsequent migration of newborn neuroblasts into the lesioned brain parenchyma. In this study, we clarify the different events of neurogenesis following striatal or cortical excitotoxic brain lesions in adult rats. Newborn cells were labeled by intraperitoneal injection of bromo-deoxy-uridine (BrdU), or by green fluorescent protein (GFP)-expressing lentiviral vectors injected into the subventricular zone (SVZ). We show that only neural progenitors born the first 5 days in the SVZ reside and expand within this neurogenic niche over time, and that these early labeled cells are more prone to migrate towards the striatum as neuroblasts. However, these neuroblasts could not mature into NeuN+ neurons in the striatum. Furthermore, we found that cortical lesions, close or distant from the SVZ, could not upregulate SVZ cell proliferation nor promote neurogenesis. Our study demonstrates that both the time window for labeling proliferating cells and the site of lesion are crucial when assessing neurogenesis following brain injury.
Neuronal Survival Unit, BMC A10, Dept of Experimental Medical Science, Wallenberg Neuroscience Center, 221 84 Lund, Sweden. tomas.deierborg@med.lu.se
Tomas
T
Deierborg
Karin
K
Staflin
Jelena
J
Pesic
Laurent
L
Roybon
Patrik
P
Brundin
Cecilia
C
Lundberg
D000818:Animals; D015415:Biomarkers; D020208:Brain Injury, Chronic / Q000139:chemically induced / Q000503:physiopathology*; D001973:Bromodeoxyuridine; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology; D049109:Cell Proliferation; D002540:Cerebral Cortex / Q000187:drug effects / Q000503:physiopathology; D003342:Corpus Striatum / Q000166:cytology / Q000187:drug effects / Q000503:physiopathology*; D004195:Disease Models, Animal; D049452:Green Fluorescent Proteins; D009410:Nerve Degeneration / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D055495:Neurogenesis / Q000502:physiology*; D009474:Neurons / Q000166:cytology / Q000502:physiology*; D009498:Neurotoxins / Q000633:toxicity*; D010641:Phenotype; D051381:Rats; D020127:Recovery of Function / Q000502:physiology; D012038:Regeneration / Q000502:physiology; D013234:Stem Cells / Q000166:cytology / Q000502:physiology*; D013997:Time Factors; D015854:Up-Regulation / Q000502:physiology
D015415:Biomarkers; D009498:Neurotoxins; D049452:Green Fluorescent Proteins; D001973:Bromodeoxyuridine