Chemokines after human ischemic stroke: From neurovascular unit to blood using protein arrays

Chemokines have a dual role in neuroinflammation: protective and detrimental.Their association with the pathophysiology of stroke is not clear.LMD combined with an antibodies array has allowed us to study chemokines in the NVU.CCL17 and CCL22 are associated with severity, but are not useful as outcome biomarkers.Therapeutical immunomodulation seems promising although further studies are needed.

Chemokines act mainly in guiding leukocyte migration along the endothelium. Apart from angiogenesis or neuronal survival, chemokines are involved in damage and repair of brain tissue after ischemic stroke. We studied the presence of chemokines directly in neurons and brain blood vessels that were obtained by means of laser microdissection from human ischemic brains. Using multiple ELISA Searchlight® array we evaluated nine chemokines (CCL1−5, CCL11, CCL17, CCL22, and CXCL8) in microdissected samples. We found higher levels of CCL1 and CCL2 in neurons than in vessels; CCL5 and CCL22 were decreased in the infarcted areas.The same ELISA array was performed in plasma samples from stroke patients. We explored the temporal profile of circulating chemokines from admission to 90 days after the cerebrovascular event, and found that only CCL22 showed significant changes along time and that these changes negatively correlated with neurological severity. When neurological outcome was assessed in the hyperacute phase of stroke no associations were found.From our study, we can conclude that these chemokines do not perform a clear role of outcome biomarkers. Further studies are necessary to assess which mechanisms underlie the association of chemokines with the neurological state at distinct time points since the differences found here could be reflecting the dual role of chemokines in neuroinflammation.

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