Microglia is one of the major resident immune cells in the central nervous system and is considered to be the key cellular mediator of neuroinflammatory processes. Identification of different Microglial states of activation by morphologic means has been one of the major challenges in the field of neurobiology of diseases. Therefore, microglial biology demands techniques to identify differing stages of microglia in different neuroanatomic locations as well as understanding the role of Microglia in different Neurological diseases. This present study is aimed towards summarizing the literature and for understanding the progress made in different Cytomorphological and Cytochemical techniques of identifying Microglia. This study also review recently used Immunohistochemistry techniques, along with Ultrastructural studies determining different morphological features of resting to activated phagocytic Microglia in a viral induced experimental animal model of neuroinflammation. Results revealed that chronic Microglial activation is considered to be an important component of neuronal dysfunction, injury, and loss (and hence to disease progression). Thus, Microglial research with special emphasis on identification of different activation states of Microglia has gradually become significant. 1. Introduction Microglia, the resident macrophages of the Central Nervous System (CNS), is known to support and sustain proper Neuronal functions. Existence of this Glial cell in CNS has been reported, a century ago [1]. Nissl was the first to recognize Microglia and name it as “stabchenzellen” (rod cells) and considered it as a reactive neuroglia. He also suggested that, Microglia has the capacity of migration and Phagocytosis [1]. Regarding the origin of Microglia, a complete framework was provided for defining this particular cell type by del Rio-Hortega in 1932, but still many of the features remained controversial [2]. Microglia transits through different stages of development to attain its maturity and functionality in the CNS. The first stage is of Ameboid Microglia, and it shares common Immunological, Histochemical and Morphological features with Macrophages outside the CNS [2]. Hence, it is also sometimes termed as the Macrophages of the Brain. The Ameboid microglia is considered to be round in shape or have short and broad processes. It is assumed that cells with Dendrite and elongated morphology also belong to this particular type of Microglia (Ameboid) [3]. In due course of time and under certain circumstances, some parts of the Embryonic Ameboid Microglia gets
References
[1]
K. D. Barron, “The microglial cell. A historical review,” Journal of the Neurological Sciences, vol. 134, no. 1, pp. 57–68, 1995.
[2]
M. A. Cuadros and J. Navascués, “The origin and differentiation of microglial cells during development,” Progress in Neurobiology, vol. 56, no. 2, pp. 173–189, 1998.
[3]
M. A. Cuadros, A. Moujahid, A. Quesada, and J. Navascues, “Development of microglia in the quail optic tectum,” Journal of Comparative Neurology, vol. 348, no. 2, pp. 207–224, 1994.
[4]
D. M. Reid, V. H. Perry, P.-B. Andersson, and S. Gordon, “Mitosis and apoptosis of microglia in vivo induced by an anti-CR3 antibody which crosses the blood-brain barrier,” Neuroscience, vol. 56, no. 3, pp. 529–533, 1993.
[5]
R. B. Rock, G. Gekker, S. Hu et al., “Role of microglia in central nervous system infections,” Clinical Microbiology Reviews, vol. 17, no. 4, pp. 942–964, 2004.
[6]
L. J. Lawson, V. H. Perry, and S. Gordon, “Turnover of resident microglia in the normal adult mouse brain,” Neuroscience, vol. 48, no. 2, pp. 405–415, 1992.
[7]
Y. Matsumoto, K. Ohmori, and M. Fujiwara, “Immune regulation by brain cells in the central nervous system: microglia but not astrocytes present myelin basic protein to encephalitogenic T cells under in vivo-mimicking conditions,” Immunology, vol. 76, no. 2, pp. 209–216, 1992.
[8]
E. Lavi, D. H. Gilden, and Z. Wroblewska, “Experimental demyelination produced by the A59 strain of mouse hepatitis virus,” Neurology, vol. 34, no. 5, pp. 597–603, 1984.
[9]
J. D. Sarma, L. Fu, S. T. Hingley, and E. Lavi, “Mouse hepatitis virus type-2 infection in mice: an experimental model system of acute meningitis and hepatitis,” Experimental and Molecular Pathology, vol. 71, no. 1, pp. 1–12, 2001.
[10]
J. Das Sarma, L. Fu, S. T. Hingley, M. M. C. Lai, and E. Lavi, “Sequence analysis of the S gene of recombinant MHV-2/A59 coronaviruses reveals three candidate mutations associated with demyelination and hepatitis,” Journal of NeuroVirology, vol. 7, no. 5, pp. 432–436, 2001.
[11]
D. Chatterjee, K. Biswas, S. Nag, S. G. Ramachandra, and J. D. Sarma, “Microglia play a major role in direct viral-induced demyelination,” Clinical and Developmental Immunology, vol. 2013, Article ID 510396, 12 pages, 2013.
[12]
J. Das Sarma, L. C. Kenyon, S. T. Hingley, and K. S. Shindler, “Mechanisms of primary axonal damage in a viral model of multiple sclerosis,” Journal of Neuroscience, vol. 29, no. 33, pp. 10272–10280, 2009.
[13]
W. Penfield, “A method of staining oligodendroglia and microglia (combined method),” The American Journal of Pathology, vol. 4, no. 2, pp. 153–157, 1928.
[14]
D. S. Russell, “Intravital staining of microglia with trypan blue,” The American Journal of Pathology, vol. 5, no. 5, pp. 451–458, 1929.
[15]
M. Gencic and M. Oehmichen, “A modification of microglia impregnation,” Microscopica Acta, vol. 82, no. 3, pp. 201–206, 1979.
[16]
T. Scott, “A silver impregnation method for reactive microglia in 1 μm epoxy sections,” Acta Neuropathologica, vol. 46, no. 1-2, pp. 155–158, 1979.
[17]
H. Kettenmann, U. K. Hanisch, M. Noda, and A. Verkhratsky, “Physiology of microglia,” Physiological Reviews, vol. 91, no. 2, pp. 461–553, 2011.
[18]
M. Oehmichen, H. Wiethoelter, and M. Gencic, “Cytochemical markers for mononuclear phagocytes as demonstrated in reactive microglia and globoid cells,” Acta Histochemica, vol. 66, no. 2, pp. 243–252, 1980.
[19]
K. S. Shindler, L. C. Kenyon, M. Dutt, S. T. Hingley, and J. Das Sarma, “Experimental optic neuritis induced by a demyelinating strain of mouse hepatitis virus,” Journal of Virology, vol. 82, no. 17, pp. 8882–8886, 2008.
[20]
K. S. Shindler, D. Chatterjee, K. Biswas et al., “Macrophage-mediated optic neuritis induced by retrograde axonal transport of spike gene recombinant mouse hepatitis virus,” Journal of Neuropathology and Experimental Neurology, vol. 70, no. 6, pp. 470–480, 2011.
[21]
H. Kanazawa, K. Ohsawa, Y. Sasaki, S. Kohsaka, and Y. Imai, “Macrophage/microglia-specific protein Iba1 enhances membrane ruffling and Rac activation via phospholipase C-γ-dependent pathway,” Journal of Biological Chemistry, vol. 277, no. 22, pp. 20026–20032, 2002.
[22]
G. W. Simmons, W. W. Pong, R. J. Emnett et al., “Neurofibromatosis-1 heterozygosity increases microglia in a spatially and temporally restricted pattern relevant to mouse optic glioma formation and growth,” Journal of Neuropathology and Experimental Neurology, vol. 70, no. 1, pp. 51–62, 2011.
[23]
P. Damier, E. C. Hirsch, P. Zhang, Y. Agid, and F. Javoy-Agid, “Glutathione peroxidase, glial cells and Parkinson's disease,” Neuroscience, vol. 52, no. 1, pp. 1–6, 1993.
[24]
A. Cagnin, D. J. Brooks, A. M. Kennedy et al., “In-vivo measurement of activated microglia in dementia,” The Lancet, vol. 358, no. 9280, pp. 461–467, 2001.
[25]
H. Akiyama, S. Barger, S. Barnum et al., “Inflammation and Alzheimer's disease,” Neurobiology of Aging, vol. 21, no. 3, pp. 383–421, 2000.
[26]
C. K. Glass, K. Saijo, B. Winner, M. C. Marchetto, and F. H. Gage, “Mechanisms Underlying Inflammation in Neurodegeneration,” Cell, vol. 140, no. 6, pp. 918–934, 2010.
[27]
T. Wyss-Coray, J. D. Loike, T. C. Brionne et al., “Adult mouse astrocytes degrade amyloid-β in vitro and in situ,” Nature Medicine, vol. 9, no. 4, pp. 453–457, 2003.
[28]
M. L. Block and J. S. Hong, “Chronic microglial activation and progressive dopaminergic neurotoxicity,” Biochemical Society Transactions, vol. 35, no. 5, pp. 1127–1132, 2007.
[29]
P. L. McGeer and E. G. McGeer, “Glial reactions in Parkinson's disease,” Movement Disorders, vol. 23, no. 4, pp. 474–483, 2008.
[30]
T. Nagatsu and M. Sawada, “Inflammatory process in Parkinson's disease: role for cytokines,” Current Pharmaceutical Design, vol. 11, no. 8, pp. 999–1016, 2005.
[31]
P. L. McGeer, S. Itagaki, B. E. Boyes, and E. G. McGeer, “Reactive microglia are positive for HLA-DR in the substantia nigra of Parkinson's and Alzheimer's disease brains,” Neurology, vol. 38, no. 8, pp. 1285–1291, 1988.
[32]
P. L. McGeer and E. G. McGeer, “Inflammatory processes in amyotrophic lateral sclerosis,” Muscle and Nerve, vol. 26, no. 4, pp. 459–470, 2002.
[33]
L. Cartier, O. Hartley, M. Dubois-Dauphin, and K.-H. Krause, “Chemokine receptors in the central nervous system: role in brain inflammation and neurodegenerative diseases,” Brain Research Reviews, vol. 48, no. 1, pp. 16–42, 2005.