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Impact of prenatal immune challenge on the demyelination injury during adulthood.


ABSTRACT:

Aim

Brain inflammation is associated with several brain diseases such as multiple sclerosis (MS), a disease characterized by demyelination. Whether prenatal immune challenge affects demyelination-induced inflammation in the white matter during adulthood is unclear. In the present study, we used a well-established experimental model of focal demyelination to assess whether prenatal immune challenge affects demyelination-induced inflammation.

Methods

Pregnant rats were injected with either lipopolysaccharide (100 ?g/kg, ip) or pyrogen-free saline. A 2 ?L solution of the gliotoxin ethidium bromide (0.04%) was stereotaxically infused into the corpus callosum of adult male offspring. The extent of demyelination lesion was assessed using Luxol fast blue (LFB) staining. Oligodendrocyte precursor cells, mature oligodendrocytes, markers of cellular gliosis, and inflammation were monitored in the vicinity of the demyelination lesion area.

Results

Prenatal lipopolysaccharide reduced the size of the demyelination lesion during adulthood. This reduced lesion was associated with enhanced density of mature oligodendrocytes and reduced density of microglial cells in the vicinity of the demyelination lesion. Such reduction in microglial cell density was accompanied by a reduced activation of the nuclear factor ?B signaling pathway.

Conclusion

These data strongly suggest that prenatal immune challenge dampens the extent of demyelination during adulthood likely by reprogramming the local brain inflammatory response to demyelinating insults.

SUBMITTER: Mouihate A 

PROVIDER: S-EPMC6492747 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Publications

Impact of prenatal immune challenge on the demyelination injury during adulthood.

Mouihate Abdeslam A   Al-Hashash Hessah H   Rakhshani-Moghadam Sarah S   Kalakh Samah S  

CNS neuroscience & therapeutics 20170717 9


<h4>Aim</h4>Brain inflammation is associated with several brain diseases such as multiple sclerosis (MS), a disease characterized by demyelination. Whether prenatal immune challenge affects demyelination-induced inflammation in the white matter during adulthood is unclear. In the present study, we used a well-established experimental model of focal demyelination to assess whether prenatal immune challenge affects demyelination-induced inflammation.<h4>Methods</h4>Pregnant rats were injected with  ...[more]

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