Microglial Activation

Microglial Activation

 

Activated Microglia

Microglia are increasingly being considered as a therapeutic target across a range of CNS diseases (Multiple Sclerosis, Pain, Alzheimer’s disease, Spinal Cord injury). Microglia are the primary immune cell residing with the central nervous system (CNS) and can activated by diverse stimuli which define their polarization status.

Microglia can be polarised to the proinflammatory M1 phenotype by IFN-γ and LPS, whilst the anti-inflammatory M2 status can occur in the presence of IL-4 and IL-13. M1 microglia can present antigen and release cytokines which may affect differentiation of pathogenic T-cells, whereas M2 microglia play an immunoregulatory role and can phagocytosis of myelin debris, which is important for promoting remyelination. Furthermore, data have shown that M2 microglia have capacity to improve the remyelination efficiency of OPCs.

Altering the balance either to reduce M1 function to dampen the pro-inflammatory response or through boosting the M2 effector function can be utilised to therapeutic effect in a variety of different disease models.

M1 Methodology

  • Mixed glial cultures prepared specific to therapeutic protocol
  • M1 phenotype activated through culture with LPS and IFN-ƴ
  • Culture purity can be determined using flow cytometry
  • Cytokine production by ELISA (TNFα, IL-1β, IL-6. Others on request)
  • Nitric Oxide (NO) assessed by Greiss Test

M2 Methodology in development

  • Mixed glial cultures prepared specific to therapeutic protocol
  • M2 phenotype activated through culture with IL-4 and IL-13
  • Culture purity can be determined using flow cytometry
  • Cytokine production by ELISA (IL-10. Others on request)
  • Mannose receptor, CD206 as measured by flow cytometry

Depending on the nature of the compound, studies are designed with either M1 or M2 polarisations or can include a combination of both assessments to investigate the M1 to M2 switch.

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Edinburgh
EH16 4UX
UK

Tel: +44 (0) 131 658 5164
Email: info@aquila-bm.com

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