Longer / open ended questions Flashcards
You look at androgen having hyperinflammatory role, what if estrogen is protective?
Could this be an effect of estradiol, since you are not preventing conversion of T into E?
Could be, estradiol seen to inhibit IL1 production in response to stimulation by LPS
How are A exacerbating the IR, what mechanism?
See a difference in proinflammatory response, but what if females have higher IL-10 (antiinflammatory response)
Looked at IL-10 in this same model and there was not difference detected BUT IL1Ra was increased in females,
Are GBS bacteria affecting the BB directly and the developing brain?
Are fetal cytokines affecting the BBB and triggering brain injuries?
Characteristics of an ASD brain?
Increased astrocyte, activated microglia
Neuroinflammation
How do you know IL1b is a key player?
Tested using IL1ra, blockade, alienates the specific role of IL-1, shown decreased inflammation in placenta correlating to less severe neurobehavioral deficits in offspring
Does this model replicate in clinic GBS transmission?
No, does not replicate ascending route, by GBS colonising genital tract
A group developed a mouse model of GBS colonisation, but there were limitations
- differential exposure of fetuses closer to genital tract
- high litter variation
What is the mechanism, how are androgens regulating IR?
modulate the innate IR through cell proliferation, cytokine secretion, toll like receptor expression
AR important for development of PMN precursor cells (AR KO mice- neutropenic, more susceptible to acute bacterial infection), AR important for development of PMN precusor cells impacts their proilferation activity
AR/androgen enhance granulocyte colony stimulating factor - activation of extracellular signal-regulated kinase 1/2 and through maintaing signal transducer and activator or transcription (STAT3) activity
