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“microglia/macrophages” without further distinction polarization: tumor‑associated macrophages as a paradigm
of their real origin, thereby gaining only a single for polarized M2 mononuclear phagocytes. Trends Immunol
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Durafourt BA, Moore CS, Zammit DA, Johnson TA, Zaguia F,
most recent experimental data from brain injury models Guiot MC, Bar‑Or A, Antel JP. Comparison of polarization properties
even revealed that microglial cells did not transform to of human adult microglia and blood‑derived macrophages. Glia
classical M1 or M2 phenotypes under circumstances in 2012;60:717‑27.
which their blood-borne-derived counterparts do, thereby 7. Michelucci A, Heurtaux T, Grandbarbe L, Morga E, Heuschling P.
Characterization of the microglial phenotype under specific
suggesting another regulatory function subtype. [17] pro‑inflammatory and anti‑inflammatory conditions: effects
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Sudduth TL, Schmitt FA, Nelson PT, Wilcock DM. Neuroinflammatory
myeloid cells seem to exert more cytotoxic properties. phenotype in early Alzheimer’s disease. Neurobiol Aging
Because the pioneering authors of the M1-M2 concept 2013;34:1051‑9.
in macrophages stated that their proposed views of 9. Liao B, Zhao W, Beers DR, Henkel JS, Appel SH. Transformation
classifying macrophages in either a M1 or M2 polarized from a neuroprotective to a neurotoxic microglial phenotype in a
mouse model of ALS. Exp Neurol 2012;237:147‑52.
state might be an oversimplification, a fortiori is its 10. Kobayashi K, Imagama S, Ohgomori T, Hirano K, Uchimura K,
transfer to microglia cells. In CNS pathologies, Sakamoto K, Hirakawa A, Takeuchi H, Suzumura A, Ishiguro N,
[3]
microglial cells are nonclonal and show a high-degree Kadomatsu K. Minocycline selectively inhibits M1 polarization of
microglia. Cell Death Dis 2013;4:e525.
of plasticity, as well as intermixture with peripheral, 11. Selenica ML, Alvarez JA, Nash KR, Lee DC, Cao C, Lin X, Reid P,
blood-borne macrophages. Mouton PR, Morgan D, Gordon MN. Diverse activation of microglia
by chemokine (C‑C motif) ligand 2 overexpression in brain.
Deciphering the immunological properties of microglial J Neuroinflammation 2013;10:86.
cells under normal and pathological circumstances with 12. Xu Y, Qian L, Zong G, Ma K, Zhu X, Zhang H, Li N, Yang Q,
Bai H, Ben J, Li X, Xu Y, Chen Q. Class A scavenger receptor
regard to the M1/M2 concept requires more functional promotes cerebral ischemic injury by pivoting microglia/macrophage
studies, which will need to take into account the distinct polarization. Neuroscience 2012;218:35‑48.
microglial gene expression signature. 13. Kumar A, Stoica BA, Sabirzhanov B, Burns MP, Faden AI, Loane DJ.
Traumatic brain injury in aged animals increases lesion size and
chronically alters microglial/macrophage classical and alternative
More sophisticated scientific neuroimmunological activation states. Neurobiol Aging 2013;34:1397‑411.
and/or neuroinflammatory research approaches are 14. Sielska M, Przanowski P, Wylot B, Gabrusiewicz K, Maleszewska M,
necessary. Notably, sorting myeloid cell populations Kijewska M, Zawadzka M, Kucharska J, Vinnakota K, Kettenmann H,
Kotulska K, Grajkowska W, Kaminska B. Distinct roles of CSF
might pave the way for deeper insight into the family cytokines in macrophage infiltration and activation in glioma
applicability of the M1/M2 immune polarization concept progression and injury response. J Pathol 2013;230:310‑21.
for microglia, the resident immune cells of the CNS. [18] 15. Hirai T, Uchida K, Nakajima H, Guerrero AR, Takeura N, Watanabe S,
Such studies will impact and broaden the knowledge of Sugita D, Yoshida A, Johnson WE, Baba H. The prevalence and
phenotype of activated microglia/macrophages within the spinal cord
basic research and influence further treatment strategies of the hyperostotic mouse (twy/twy) changes in response to chronic
in traumatic, inflammatory, or neoplastic disorders of progressive spinal cord compression: implications for human cervical
the CNS. compressive myelopathy. PLoS One 2013;8:e64528.
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Allan SM. Microglia and macrophages differentially modulate cell
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