Progesterone and Ischaemia

After reading the NO, ischaemia and brain inflammation article from last Monday's discussion, I was interested in the effects of progesterone following ischaemia. The article talked about how progesterone can decrease lesion volume and enhance the functionality of both male and female rodent subjects. Estrogen is thought to be neuroprotective because it blocks NOS-2 expression.

I found an interesting article from the American Heart Association, which studied the effects of progesterone on ovariectomized rats. These rats were given hormone treatments before MCAO. The study showed that the progesterone treatment did not improve brain injury in the ovariectomized rats. It also showed that chronic progesterone levels worsened the lesion volume.
It seems as though progesterone is neuroprotective in males and pre-menopausal women. It is known that pre-menopausal women have a much lower risk for stoke than men. But stroke risk in post-menopausal women increases greatly.

In the study of ovariectomized rats, it is suggested that lower levels of progesterone may be beneficial, and that progesterone exposure duration may also play an important role. Progesterone withdrawal could also have some effect on the rats. Rats going through progesterone withdrawal were more prone to seizure-activity. The article makes an important point about the interaction of progesterone and estrogen; progesterone is not needed for estrogen to reduce stroke injury, but estrogen needs to be primed for progesterone to be effective. Combination these hormones could produce beneficial effects. Estrogen is thought to be neuroprotective even in ovariectomized rats.

This study did not talk about nitric oxide (NO) at all, but it's possible that NO plays no role in progesterone's effect on ischaemia. I would guess that it does play a role though, because NOS-2 expression can be blocked by estrogen, and estrogen and progesterone are similar hormones. I think that when combined with estrogen, progesterone could also block NOS-2 expression, which would decrease lesion volume in ovariectomized rats.

References:
Murphy, S., C.L. Gibson. "Nitric oxide, ischaemia and brain inflammation."
Biochemical Society Transactions 35.5 (2007): 1133-1137. Web. 20 Feb 2011.

Murphy, Stephanie J., VMD, PhD, Richard J. Traystman, PhD, Patricia D. Hurn, PhD. "Progesterone Exacerbates Striatal Stroke Injury in Progesterone-Deficient Female Animals."
Stroke 31 (2000): 1173-1178. Web 27 Feb 2011.
http://stroke.ahajournals.org/cgi/content/full/strokeaha;31/5/1173.

Gibson, Claire L., Laura J. Gray, Philip M. W. Bath, and Sean P. Murphy. "Progesterone for the treatment of experimental brain injury; a systematic review."
Brain A Journal of Neurology 131.2 (2007): 318-328. Web. 27 Feb 2011.
http://brain.oxfordjournals.org/content/131/2/318.full