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Microglia in the human fetal spinal cord--patterns of distribution, morphology and phenotype
1Department of Neuropathology, Institute of Psychiatry, De Crespigny Park, London SE5 8JN, UK. p.rezaie@iop.kcl.ac.uk
Abstract:
Microglia, the intrinsic macrophages of the nervous system, colonise the cerebrum around the second trimester in man. In order to determine the extent of microglial influx into the nervous system, we have examined their distribution within the human fetal spinal cord in relation to astrocytic and vascular development between 9 and 16 weeks of gestation, using conventional immunohistochemistry [CD11b; CD45; CD64; CD68; ICAM-1; ICAM-2; VCAM-1; PECAM; GFAP; vimentin] and lectin histochemistry [RCA-1]. Microglia are identifiable by 9 weeks, within the ventricular/sub-ventricular zones. Human fetal microglia display heterogeneity in phenotype and are more readily identified by CD68 in the spinal cord. There is a marked influx of cells dorsal and ventral to the neural cavity, from the marginal layer [meninges/connective tissue] with advancing gestational age, with greatest cell densities towards the end of the time period in this study. This inward migration is associated with progressive vascularisation, ICAM-2 expression and co-localises with GFAP and vimentin positive radial glia. The patterns of microglial migration in human fetal cord differ from that within the cerebrum, but generally conform to a route following white to gray matter.
Insights
Human fetal microglia migrate into the spinal cord starting at 9 weeks gestation, with increasing density and specific migration patterns related to vascular and glial development. This study details their distribution and phenotype heterogeneity.
Area of Science:
- Neuroscience
- Developmental Biology
- Immunology
Background:
- Microglia are the resident immune cells of the central nervous system.
- Their development and migration patterns in the human fetal spinal cord are not fully understood.
- Previous studies have focused on microglial colonization of the cerebrum.
Purpose of the Study:
- To investigate the distribution and migration of microglia within the human fetal spinal cord.
- To correlate microglial development with astrocytic and vascular development.
- To characterize microglial phenotypes during early gestation.
Main Methods:
- Immunohistochemistry using markers such as CD68, GFAP, vimentin, and PECAM.
- Lectin histochemistry with RCA-1.
- Examination of human fetal spinal cord tissue from 9 to 16 weeks of gestation.
Main Results:
- Microglia are present by 9 weeks gestation in the ventricular/sub-ventricular zones.
- A significant influx of microglia occurs dorsally and ventrally from the marginal layer with increasing gestational age.
- Microglial migration is associated with vascularization, ICAM-2 expression, and radial glia (GFAP/vimentin positive).
- Human fetal microglia exhibit phenotypic heterogeneity, with CD68 being a reliable marker in the spinal cord.
Conclusions:
- Microglial colonization of the human fetal spinal cord begins early in development.
- Microglial migration follows specific routes, generally from white to gray matter, and is influenced by vascular and glial development.
- The patterns observed in the spinal cord differ from those in the cerebrum.