Phasic Treatment with XXXX Stimulates Release of Exosomes that Protect Against Spreading Depression.

@entity2795 @entity17 @entity308 @entity3692 @entity66 @entity8382 @entity2704 @entity35 @entity15
UNASSIGNED: The detrimental effects of T-cell-secreted @entity3692 (IFNy) on @entity66 ( @entity66 ) and @entity17 in @entity15 ( @entity15 ) are well recognized. Recently, we demonstrated that IFNy-mediated damage to myelin also increases susceptibility to @entity308 ( @entity308 ; the likely basis of @entity2795 ). However, before onset of @entity15 , induction of physiological levels of IFNy, like that produced by environmental enrichment (EE), protects against @entity17 and @entity66 . Accordingly, we focused on the potential for physiological levels of IFNy to protect against @entity308 . EE, which occurs with a moderate and phasic increase in proinflammatory cytokines, reduces @entity2704 frequency. Thus, we applied phasic or pulsed IFNy to brain slice cultures to emulate EE. This treatment reduced @entity66 , increased @entity8382 , a marker for myelin, and reduced susceptibility to @entity308 . Building on our research on exosomes in EE-based neuroprotection, we found that IFNy stimulation of slice cultures induced release of exosomes, likely from the microglia that produce the same protective effects as IFNy treatment when applied to naive cultures. Finally, nasal administration of IFNy to @entity35 recapitulated in vitro effects, reducing @entity66 , increasing myelin, and reducing @entity308 . These results support phasic IFNy signaling as a therapeutic target for prevention of @entity308 and, by extension, @entity2704 .
