MicroRNAs (miRNAs) regulate gene expression and have a critical role in many biologic and pathologic processes. We hypothesized that miRNA expression profiles in injured brain (hippocampus) would show common as well as unique profiles when compared with those of blood. Adult, untouched, control rats were compared with rats with sham surgeries, ischemic strokes, brain hemorrhage (lysed blood, fresh blood, or thrombin), and kainate-induced seizures. Brain and whole-blood miRNA expression profiles were assessed 24 h later using TaqMan rodent miRNA arrays. MicroRNA response profiles were different for each condition. Many miRNAs changed more than 1.5-fold in brain and blood after each experimental manipulation, and several miRNAs were upregulated or downregulated in both brain and blood after a given injury. A few miRNAs (e.g., miR-298, miR-155, and miR-362-3p) were upregulated or downregulated more than twofold in both brain and blood after several different injuries. The results show the possible use of blood miRNAs as biomarkers for brain injury; that selected blood miRNAs may correlate with miRNA changes in the brain; and that many of the mRNAs, previously shown to be regulated in brain and blood after brain injury, are likely accounted for by changes in miRNA expression.

Numerous studies have documented increases in matrix metalloproteinases (MMPs), specifically MMP-9 levels following stroke, with such perturbations associated with disruption of the blood brain barrier (BBB), increased risk of hemorrhagic complications, and worsened outcome. Despite this, controversy remains as to which cells release MMP-9 at the normal and pathological BBB, with even less clarity in the context of stroke. This may be further complicated by the influence of tissue plasminogen activator (tPA) treatment. The aim of the present review is to examine the relationship between neutrophils, MMP-9 and tPA following ischemic stroke to elucidate which cells are responsible for the increases in MMP-9 and resultant barrier changes and hemorrhage observed following stroke.

Background and Purpose-A blood-based biomarker of acute ischemic stroke would be of significant value in clinical practice. This study aimed to (1) replicate in a larger cohort our previous study using gene expression profiling to predict ischemic stroke; and (2) refine prediction of ischemic stroke by including control groups relevant to ischemic stroke. Methods-Patients with ischemic stroke (nϭ70, 199 samples) were compared with control subjects who were healthy (nϭ38), had vascular risk factors (nϭ52), and who had myocardial infarction (nϭ17). Whole blood was drawn Յ3 hours, 5 hours, and 24 hours after stroke onset and from control subjects. RNA was processed on whole genome microarrays. Genes differentially expressed in ischemic stroke were identified and analyzed for predictive ability to discriminate stroke from control subjects. Results-The 29 probe sets previously reported predicted a new set of ischemic strokes with 93.5% sensitivity and 89.5% specificity. Sixty-and 46-probe sets differentiated control groups from 3-hour and 24-hour ischemic stroke samples, respectively. A 97-probe set correctly classified 86% of ischemic strokes (3 hourϩ24 hour), 84% of healthy subjects, 96% of vascular risk factor subjects, and 75% with myocardial infarction. Conclusions-This study replicated our previously reported gene expression profile in a larger cohort and identified additional genes that discriminate ischemic stroke from relevant control groups. This multigene approach shows potential for a point-of-care test in acute ischemic stroke. The diagnosis of ischemic stroke (IS) is made with clinical assessment in combination with brain imaging. However, the diagnosis is not always straightforward, particularly in the acute setting where an accurate, inexpensive, and rapid diagnosis is critical to optimally treat patients.Extensive efforts have been directed toward identifying blood based biomarkers for IS. More than 58 proteins and 7 panels of proteins have been described as biomarkers of IS. 3-5 RNA expression profiles in the blood have also been described in IS. 6 -8 We previously reported a 29-probe set expression profile predictive of IS. 6 This profile required validation in a second cohort, which has been done in the current study. We also describe a 97-probe set expression profile that differentiates IS from control subjects who are healthy, have vascular risk factors, and who have myocardial infarction. These profiles represent further refinement of gene expression as a diagnostic tool in patients with acute IS, which could be used to aid in the diagnosis of stroke in the context of clinical information and evaluation. Materials and MethodsThe study had 2 objectives: (1) to demonstrate that the previously identified 29 probes distinguish IS from healthy control subjects 6 in a new cohort; and (2) to identify additional genes that discriminate IS from vascular risk factor (Sex, Age and Variation in Vascular functionalitY [SAVVY]) control subjects and myocardial infarction (MI) control subjects. Whole blood w...