Dynamic Responses of Microglia in Animal Models of Multiple Sclerosis

Abstract

Microglia play an essential role in maintaining central nervous system (CNS) homeostasis, as well as responding to injury and disease. Most neurological disorders feature microglial activation, a process whereby microglia undergo profound morphological and transcriptional changes aimed at containing CNS damage and promoting repair, but often resulting in overt inflammation that sustains and propagates the neurodegenerative process. This is especially evident in multiple sclerosis (MS), were microglial activation and microglia-driven neuroinflammation are considered key events in the onset, progression, and resolution of the disease. Our understanding of microglial functions in MS has widened exponentially in the last decade by way of new tools and

TNFR2 Signaling Regulates the Immunomodulatory Function of Oligodendrocyte Precursor Cells

“…To parse out the specific contribution of OPCs in this process, we established primary cultures of OPCs from WT and TNFR2 −/− mice and assessed their response to an inflammatory environment by exposing them to a combination of Th1 cytokines (TNF, IL1β, and IFNγ) known to be highly upregulated in the CNS following EAE and MS ( Figure 1 A) [ 27 , 28 ]. In naïve conditions, WT OPCs expressed low levels of Tnfrsf1b (gene name for TNFR2) and, in comparison, markedly higher levels of Tnfrsf1a (gene name for TNFR1) ( Figure 1 B, 1.0 ± 0.2 versus 957.3 ± 109.8).…”

Increased risk for cerebral small vessel disease is associated with quantitative susceptibility mapping in HIV infected and uninfected individuals

“…In the early stages of MS lesions, microglia form nodules in the normal appearing white matter (NAWM) without any signs of demyelination nor BBB alterations. As MS progresses, the roles of microglia change from increased activation to eventual hypocellular lesions with small amounts of microglia ( Plastini et al, 2020 ). Throughout the MS lesion progression, QSM changes in response to the amount and roles of microglia and thus iron deposition ( Li et al, 2016 , Zhang et al, 2019a , Zhang et al, 2016 ).…”

The DMT and Psilocin Treatment Changes CD11b+ Activated Microglia Immunological Phenotype

“…Parkinson Disease (Lull and Block, 2010), Multiple Sclerosis (Plastini et al, 2020) and TBI (Loane and Kumar, 2016). Moreover, stem cell grafts are often proposed as cell therapy for neurodegeneration and brain damage; however, host vs. graft immune response can be a severe limitation (Piquet et al, 2012).…”

“…The inflammatory environment which limits brain regeneration can be caused by hyperactive microglial cells as often seen in neurodegenerative disorders and brain damage, such as ALS (Geloso et al, 2017), Alzheimer Disease (Hemonnot et al, 2019), and Parkinson Disease (Lull and Block, 2010), Multiple Sclerosis (Plastini et al, 2020) and TBI (Loane and Kumar, 2016). Moreover, stem cell grafts are often proposed as cell therapy for neurodegeneration and brain damage; however, host vs. graft immune response can be a severe limitation (Piquet et al, 2012).…”