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Osteopontin Attenuates Changes in Cerebrovascular Structure‐Function Relations Induced by Subarachnoid Hemorrhage in Rat Brain
Author(s) -
Kim Dahlim,
Doan Coleen,
Carreon Desirelys,
Budbazar Enkhjargal,
Zhang John H,
Pearce William J
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.1275.2
Subject(s) - subarachnoid hemorrhage , osteopontin , medicine , colocalization , cerebral arteries , endocrinology , anesthesia , cardiology , neuroscience , biology
Subarachnoid hemorrhage (SAH) is a common injury involving a complex and incompletely understood etiology. The present study explores the hypothesis that brain injury caused by SAH involves major changes in the structure and function of small cerebral arteries, in addition to its well‐known effects on neurons, glia and capillary endothelium. To evaluate this hypothesis, we studied the effects of SAH via endovascular perforation of the bifurcation of the anterior and middle cerebral arteries (MCA) in the adult rat brain. Artery samples were harvested 24 hours post‐injury for assessment of vascular structure and function. To test if the 44 kDa extracellular matrix protein Osteopontin (OPN) could serve as a vasoprotectant, some animals were treated with OPN via intranasal administration (5 μg in 50 μl PBS) at 1 hour post‐injury. As indicated by MLCK‐MLC20 colocalization quantified via confocal microscopy, SAH caused a significant 32% increase in contractile differentiation. This effect of SAH was attenuated by 66% (11% increase) following treatment with OPN. Simultaneously, SAH decreased the magnitude of the cytosolic calcium response to potassium depolarization by 28 nM (19%), and this effect was reversed to an increase of 41nM (49%) after OPN treatment. Additionally, SAH caused a passive dilation of 13 μM compared to untreated Sham control arteries, and after OPN treatment, this dilation was reduced to only 4 μM (69% reduction). Together, these results illustrate that SAH induces vascular injury that is largely prevented by intranasal treatment with OPN. Specifically, SAH promotes passive dilation and increased contractile differentiation, but compromises regulation of cytosolic calcium; these effects are consistent with the development of cerebral vasospasm and/or loss of cerebral autoregulation, both of which are well‐known consequences of SAH. Interestingly, OPN can bind and activate multiple integrin receptors, can promote inflammation via neutrophil recruitment, and can interact with other vasotrophic growth factors such as VEGF. It is not clear which, if any or all of these factors contribute to its neuroprotective profile. The present study strongly suggests that OPN is also vasoprotective within the context of SAH, which may contribute significantly to its neuroprotective efficacy. Support or Funding Information These studies were supported by an NIH Program Project grant from NINDS (NS082184), and an NIH R01 grant also from NINDS (NS076945).