scholarly journals CD93 regulates central nervous system inflammation in two mouse models of autoimmune encephalomyelitis

Immunology ◽  
2018 ◽  
Vol 155 (3) ◽  
pp. 346-355 ◽  
Author(s):  
Mark R. Griffiths ◽  
Marina Botto ◽  
Bryan Paul Morgan ◽  
James W. Neal ◽  
Philippe Gasque
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Mouse Models ◽  
Autoimmune Encephalomyelitis ◽  
Central Nervous System Inflammation

scholarly journals Central nervous system infusion of TrkB agonist, 7,8-dihydroxyflavone, is ineffective in promoting myelin repair in cuprizone and experimental autoimmune encephalomyelitis mouse models of multiple sclerosis

2021 ◽  
Author(s):  
Jessica Louise Fletcher ◽  
Rhiannon J Wood ◽  
Alexa R Prawdiuk ◽  
Ryan O'Rafferty ◽  
Ophelia Ehrlich ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Central Nervous System ◽  
Nervous System ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Mouse Models ◽  
Clinical Signs ◽  
Autoimmune Encephalomyelitis ◽  
Myelin Repair ◽  
Intracerebroventricular Infusion ◽  
Experimental Autoimmune

Small molecular weight functional mimetics of brain-derived neurotrophic factor (BDNF) which act via the TrkB receptor have been developed to overcome the pharmacokinetic limitations of BDNF as a therapeutic agent for neurological disease. Activation of TrkB signalling on oligodendrocytes has been identified as a potential strategy for promoting myelin repair in demyelinating conditions such as Multiple Sclerosis (MS). Here, we tested the efficacy of intracerebroventricular infusion of TrkB agonist 7,8-dihydroxyflavone (DHF) to promote myelin repair in the cuprizone model of de- and remyelination and alter the course of experimental autoimmune encephalomyelitis (EAE), after the onset of clinical signs. In these two distinct, but common mouse models used for the preclinical testing of MS therapeutics, we found that DHF infusion increased the percentage of myelin basic protein and density of oligodendrocyte progenitor cells (OPCs) in the corpus callosum of female C57BL/6 mice after cuprizone demyelination. However, DHF did not alter the percentage of axons myelinated or increase the density of post-mitotic oligodendrocytes in this model. Direct central nervous system infusion of DHF infusion also had no effect on the clinical course of EAE in male and female C57BL/6 mice, and examination of the lumbar spinal cord after 21 days of treatment revealed extensive demyelination, with active phagocytosis of myelin debris by Iba1+ macrophages/microglia. These results indicate that direct central nervous system infusion of DHF is ineffective at promoting myelin repair in toxin-induced and inflammatory models of demyelination.

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