Stroke/Cerebral Vasospasm

Re^2: Spasmogens and cerebral vasospasm

Marilyn J. Cipolla

On Tue Dec 8, John Zhang wrote
>On Mon Dec 7, Marilyn J. Cipolla wrote
>>I commend you on your wonderful study of cerebral spasmogens.  It is intesting that there was a dissociation between those factors that caused an increase in intracellular calcium in cultured smooth muscle cells, and those that caused vasospasm in vivo.  I can think of several possibilities for this:  cultured cells are not structurally positioned the same as those in whole arteries, which are exposed to mechanical forces such as pressure or shear stress.  These mechanical forces have been shown to be important for mediating intracellular structures such as the polymerization state of actin.  Actin filaments are not only important for cross-bridge formation, but are also linked to ion channels that may control intracellular calcium.  It may be that the effect that you see on intracellular calcium is an artifact of cell culture, since the actin filaments would likely not be in an appropriate position or polymerization state.  Do you know if calcium is required for vasospasm?  The spasmogen that mediates vasospasm during SAH may be calcium-independent.  There have been many substances that cause contraction without a change in intracellular calcium, mostly linked to protein kinase C. I find this very interesting and an important work.  

>thank you for your comments. Even though we used fresh isolated smooth muscle cells from rat basilar artery and used cells within 4 hrs, I agree that isolated cells are different from these in the vessel wall. Another side of the issue is cerebral vasospasm takes days to develop and calcium studies are done in several min. The acute effect may not be the true response leads to a prolonged contraction. Incubating arteries in hemoglobin for days may produce contraction not reproducible by in vitro conditions. The calcium dependence of vasospasm is another issue people disagree. Some in vivo studies showed that the resting calcium during spasm was actually lower than normal arteries, even though all studies using cultures or fresh isolation demonstrate a calcium response to spasmgenes. PKC is an aspect people interested and some of PKC-induced contraction is calcium independent. As you know that PKC leads to the activation of tyrosine kinasesa and further MAPK. These two "new" fields are our current interests. Tyrosine and MAP kinase play roles in proliferation as well as contraction (by caldesmon), and proliferation is another aspect of vasospasm.


I think that the time course of vasospasm, being several days, is really interesting and probably key to discovering what factors play a role.  I wonder how the cells within the vascular wall are altered phenotypically during this time period.  I guess if you knew that then your work would be complete!

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