How could (the molecular effects of) physical exercise be simulated in a microglial cell culture model?
Many cytokines are normally up- og down-regulated following physical exercise (e.g. IL-10 up, TNF-alpha down). However, the difficulty is that a number of pro-inflammatory cytokines are also up-regulated (e.g. IL-6), and applying them to your culture would hardly simulate the effect of physical exercise.
As our knowledge of what exactly exercise does is limited, it would probably be very hard to simulate this in a culture. In vivo, you microglia would be influenced by discrete changes in plasma proteins as well as neural activity, body temperature, blood flow etc., and simply applying some of these stimuli may have a very different effect in vitro.
However, if you want to give it a shot, I would take a closer look at cytokine changes, as it's reasonable to assume that microglia would respond to these.
I would not believe that an in vitro model of exercise would be valid. What you can do it validate the immunomodulatory potential of factors that you identify are altered by exercise in vivo. As Thomas rightly points out, we do not know how exercise 'works' in the brain, although neurotrophins certainly play a big role. I would consider what hypothesis you want to test with an in vitro system and decide with your 'reviewers hat' on, whether it can ever be convincingly achieved in vitro. Good luck !
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