Microglial cell population dynamics in the injured adult central nervous system.
Reactive microgliosis is characteristic of trauma and stroke as well as inflammatory and chronic neurodegenerative disease. A conspicuous feature of the microglial reaction to acute neural injury is a massive expansion of the microglial cell population which peaks a few days following injury. New data based on the use of radiation bone marrow-chimeric mice suggest this expansion also involves recruitment of bone marrow-derived cells, which migrate into the neural parenchyma and differentiate into microglia. Here, we discuss the contribution of bone marrow-derived cells to the injury-induced expansion of the microglial cell population, seen in the dentate gyrus with ongoing anterograde axonal and terminal synaptic degeneration, subsequent to transection of the entorhino-dentate perforant path projection. In this paradigm of minor brain injury, the bone marrow-derived cells are grossly outnumbered by activated resident microglia, which express the stem cell antigen CD34 concurrent to a marked capacity for self-renewal. The observation of a mixed origin of lesion-reactive microglia, consisting of a smaller subpopulation of exogenous bone marrow-derived microglia, and a larger population of activated resident microglia, the majority of which express CD34 and undergo proliferation, suggests that lesion-reactive microglia consist of functionally distinct cell populations. The demonstration of an injury-enhanced recruitment of bone marrow-derived cells into the perforant path-denervated dentate gyrus, raises the possibility of using genetically manipulated cells as vectors for lesion-site-specific gene therapy even in minimally injured areas of the central nervous system.
Ladeby
Rune
R
Medical Biotechnology Center, University of Southern Denmark, Odense C.
Wirenfeldt
Martin
M
Garcia-Ovejero
Daniel
D
Fenger
Christina
C
Dissing-Olesen
Lasse
L
Dalmau
Ishar
I
Finsen
Bente
B
D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002452:Cell Count; D002490:Central Nervous System / Q000166:cytology* / Q000276:immunology; D002493:Central Nervous System Diseases / Q000150:complications / Q000276:immunology / Q000473:pathology*; D006801:Humans; D017628:Microglia / Q000502:physiology*; D008954:Models, Biological; D009410:Nerve Degeneration / Q000209:etiology / Q000276:immunology / Q000473:pathology*; D013997:Time Factors
D015415:Biomarkers