BackgroundTGFβ is both neuroprotective and a key immune system modulator and is likely to be an important target for future stroke therapy. The precise function of increased TGF-β1 after stroke is unknown and its pleiotropic nature means that it may convey a neuroprotective signal, orchestrate glial scarring or function as an important immune system regulator. We therefore investigated the time course and cell-specificity of TGFβ signaling after stroke, and whether its signaling pattern is altered by gender and aging.MethodsWe performed distal middle cerebral artery occlusion strokes on 5 and 18 month old TGFβ reporter mice to get a readout of TGFβ responses after stroke in real time. To determine which cell type is the source of increased TGFβ production after stroke, brain sections were stained with an anti-TGFβ antibody, colocalized with markers for reactive astrocytes, neurons, and activated microglia. To determine which cells are responding to TGFβ after stroke, brain sections were double-labelled with anti-pSmad2, a marker of TGFβ signaling, and markers of neurons, oligodendrocytes, endothelial cells, astrocytes and microglia.ResultsTGFβ signaling increased 2 fold after stroke, beginning on day 1 and peaking on day 7. This pattern of increase was preserved in old animals and absolute TGFβ signaling in the brain increased with age. Activated microglia and macrophages were the predominant source of increased TGFβ after stroke and astrocytes and activated microglia and macrophages demonstrated dramatic upregulation of TGFβ signaling after stroke. TGFβ signaling in neurons and oligodendrocytes did not undergo marked changes.ConclusionsWe found that TGFβ signaling increases with age and that astrocytes and activated microglia and macrophages are the main cell types that undergo increased TGFβ signaling in response to post-stroke increases in TGFβ. Therefore increased TGFβ after stroke likely regulates glial scar formation and the immune response to stroke.

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Stroke is the most common cause of long-term disability, and there are no known drug therapies to improve recovery after stroke. To understand how successful recovery occurs, dissect candidate molecular pathways, and test new therapies, there is a need for multiple distinct mouse stroke models, in which the parameters of recovery after stroke are well defined. Hypoxic–ischemic stroke is a well-established stroke model, but behavioral recovery in this model is not well described. We therefore examined a panel of behavioral tests to see whether they could be used to quantify functional recovery after hypoxic–ischemic stroke. We found that in C57BL/6J mice this stroke model produces high mortality (approximately one-third) and variable stroke sizes, but is fast and easy to perform on a large number of mice. Horizontal ladder test performance on day 1 after stroke was highly and reproducibly correlated with stroke size (P < 0.0001, R2 = 0.7652), and allowed for functional stratification of mice into a group with >18% foot faults and 2.1-fold larger strokes. This group exhibited significant functional deficits for as long as 3 weeks on the horizontal ladder test and through the last day of testing on automated gait analysis (33 days), rotarod (30 days), and elevated body swing test (EBST) (36 days). No deficits were observed in an automated activity chamber. We conclude that stratification by horizontal ladder test performance on day 1 identifies a subset of mice in which functional recovery from hypoxic–ischemic stroke can be studied.

Introduction: Intracranial vascular imaging was rapidly incorporated into acute ischemic stroke guidelines after positive endovascular trials in 2015. Since then, indications for advanced neuroimaging have broadened as the time window for treatment of large vessel occlusion stroke expanded. Although neuroimaging has been added to national guidelines, there may be considerable lag in incorporating these practices into standard ED care based on regional practice. We sought to analyze regional changes and variation in advanced neuroimaging relevant to stroke. Methods: Longitudinal cohort study using adult encounters admitted to the same hospital in the National Emergency Department Sample (NEDS), an AHRQ dataset containing a weighted 20% sample of US ED encounters. Adult encounters from 2013 to 2018 were included in the analysis. CTA and CTP imaging acquired in the ED was determined from Common Procedural Terminology (CPT) codes. Imaging rates per 100k encounters were analyzed by predefined NEDS region (Northeast, Midwest, South, or West) and by year (2013 vs 2018). Descriptive statistics with t-test used for comparison. Results: All regions showed a significant increase in rate of CTA use over time (p<0.001) with the Midwest demonstrating the largest percentage change (542%). All regions showed substantial increases in rate of CTP use across the time period with the Northeast having the largest magnitude of increase (5,376%) followed by the Midwest (1,035%). See Table for detail. Conclusion: Dramatic increases in CTA and CTP use by region were identified both in absolute terms and relative to their use in 2013. The findings demonstrate approximate geographic parity in order of magnitude of use with the change in usage suggesting rapid dissemination of new technologies in stroke imaging and future potential increases. Further analysis will evaluate other hospital properties to better understand changes in imaging rates nationally.

Introduction: Prior data indicate inpatient disparities exist among patients with stroke associated with insurance status for degree of neurologic impairment, hospital length of stay and mortality. Patients presenting to the Emergency Department (ED) with acute neurologic symptoms often require evaluation for acute ischemic stroke and, in 2015, guidelines recommended CTA when LVO is considered. CTP was added in 2018 for select patients. In the ED, the Emergency Medical Treatment and Labor Act (EMTALA) requires anyone presenting to be stabilized and treated, regardless of insurance status and should limit variability in advanced neuroimaging use based on insurance status. We examined ED stroke assessment disparities by evaluating national variability in the use of advanced stroke imaging by primary payer (Private Insurance, Medicare, Medicaid, Self-Pay). Methods: Retrospective cohort study using adult encounters admitted to the same hospital in the 2018 National Emergency Department Sample (NEDS), an AHRQ dataset containing a weighted 20% sample of US ED encounters. CTA (head/neck) and CTP imaging use was determined from Common Procedural Terminology (CPT) codes and adjusted by age. Rate per 100,000 ED visits were compared across primary payers using ANOVA with Tukey adjustment. Results: Age-adjusted CTP rates varied by payer but did not research statistical significance. Rates of CTA acquisition were significantly different across payer groups (p<0.001). See Table. Conclusion: Variability in age-adjusted rates of advanced neuroimaging use in the ED was identified. The variability for CTP, a unique ED imaging modality for stroke, was not significant, however interpretation is limited by confidence interval size. Variability in CTA was significant between groups and will undergo further analysis to evaluate for confounding by other patient or hospital factors.