Object
Following subarachnoid hemorrhage (SAH), cerebral arteries undergo morphologic and functional modifications. We aimed to study the perturbations of the expression of four smooth muscle cytoskeletal and contractile proteins and an extracellular protein, collagen-I, after SAH, and the possible preventive effects of an anti-inflammatory drug, dexamethasone.
Methods
Using a one-hemorrhage rabbit model (autologous blood injection into the cisterna magna), we studied, first, the effects of SAH on the expression of alpha-actin, h-caldesmon, vimentin, smoothelin-B, and collagen-I, and second, whether post-SAH systemic administration of dexamethasone (3 daily injections of 5.6 mg/kg i.m.) corrected the alterations induced by the SAH. Measurements were made at day 7 after SAH. The proteins were studied by indirect immunohistochemical staining of 20 μ frozen artery sections using a laser-scanning confocal microscope and attached software to determine the relative protein staining densities.
Results
Compared to sham arteries, the staining density of the media of SAH arteries was reduced for alpha-actin (11%, p = 0. 01) and for h-caldesmon (−15%, p = 0.06), but increased for vimentin (+15%, p = 0.04) and smoothelin-B (+53%, p = 0.04). Compared to arteries of the SAH group, those from the dexamethasone-treated SAH group showed higher values of density for alpha-actin (+13%, p = 0.05) and h-caldesmon (+20%, p = 0.01), and lower values for vimentin (−55%, p = 0.05) and non-significantly different values for smoothelin-B. The density of collagen-I in the adventitia decreased significantly after SAH (−45%, p = 0.01), but dexamethasone treatment was without effect on this decrease. These results are summarized in the figure.
Conclusions
Thus, SAH-induced alterations in the density of 3 out of 4 smooth muscle proteins were reversed by dexamethasone treatment; two of these are directly related to contraction. This drug may potentially be useful to prevent certain morphological and functional changes in cerebral arteries after SAH (See Figure 1).
Means and SD of immunostaining intensities expressed relative to values in sham animals. Coll-med=medial collagen; coll-adv=adventitial collagen. *p<0.05 between sham and sah groups (p=0.06 for h-cald). § p<0.05 between sah and sah dexa groups.