Post-stroke treatment with argon preserved neurons and attenuated microglia/macrophage activation long-termly in a rat model of transient middle cerebral artery occlusion (tMCAO)

In a previous study from our group, argon has shown to significantly attenuate brain injury, reduce brain inflammation and enhance M2 microglia/macrophage polarization until 7 days after ischemic stroke. However, the long-term effects of argon have not been reported thus far. In the present study, we analyzed the underlying neuroprotective effects and potential mechanisms of argon, up to 30 days after ischemic stroke. Argon administration with a 3 h delay after stroke onset and 1 h after reperfusion demonstrated long-term neuroprotective effect by preserving the neurons at the ischemic boundary zone 30 days after stroke. Furthermore, the excessive microglia/macrophage activation in rat brain was reduced by argon treatment 30 days after ischemic insult. However, long-lasting neurological improvement was not detectable. More sensorimotor functional measures, age- and disease-related models, as well as further histological and molecular biological analyses will be needed to extend the understanding of argon’s neuroprotective effects and mechanism of action after ischemic stroke.

Comparison of transcranial doppler ultrasound indices in large and small vessel disease cerebral infarction

Background: Atherosclerotic involvement of large and small cerebral arteries leading to infarction is among the most prevalent subtypes of stroke worldwide. The hemodynamic changes due to these arterial pathologies can be studied non-invasively and in real-time by using transcranial Doppler (TCD) techniques. TCD indices of the studied arteries may guide the clinician in differentiating these two underlying arterial pathologies. Methods: A cross-sectional study of patients with small and large vessel types of cerebral infraction based on the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) stroke classification was undertaken in the inpatient population of neurology service of Razi Hospital, Tabriz, Iran, from October 2018 to October 2019. After clinical diagnosis, all cases underwent TCD studies, brain magnetic resonance imaging (MRI), and brain and cervical four-vessel magnetic resonance angiography (MRA). The results of TCD indices related to major arteries of the circle of Willis were tabulated and compared between large and small vessel subtypes of cerebral infarction. Results: A statistically significant difference between right middle cerebral artery (MCA) pulsatility index (PI), left MCA PI, right internal carotid artery (ICA) PI, end-diastolic velocity (EDV), left ICA PI, left ICA EDV, left anterior cerebral artery (ACA) PI, and right vertebral artery (VA) PI measures of the two groups was seen (P < 0.05). In comparison to the large vessel group, left ACA, right VA, and bilateral MCAs and ICAs in the small-vessel stroke group demonstrated an elevated PI. Conclusion: A significant increase of PI occurs in the majority of intracranial arteries of patients with small vessel stroke. This makes PI a valuable marker for differentiating strokes with different underlying pathophysiologies.

Factor VII activating protease (FSAP) inhibits the outcome of ischemic stroke in mouse models.

Factor VII activating protease (FSAP) is a circulating serine protease, and individuals with the Marburg I (MI) single nucleotide polymorphism (SNP), which results in an inactive enzyme, have an increased risk of stroke. The outcome of ischemic stroke is more marked in FSAP-deficient mice compared to their wild-type (WT) counterparts. Plasma FSAP levels are raised in patients as well as mice after stroke. In vitro, FSAP promotes fibrinolysis by cleavage of fibrinogen, activates protease-activated receptors and decreases the cellular cytotoxicity of histones. Since these are desirable properties in stroke treatment, we tested the effect of recombinant serine protease domain of FSAP (FSAP-SPD) on ischemic stroke in mice. A combination of tissue plasminogen activator (tPA) and FSAP-SPD enhanced clot lysis, improved microvascular perfusion and neurological outcome and reduced infarct volumes in a mouse model of thromboembolic stroke. In the tail bleeding model FSAP-SPD treatment provoked a faster clotting time indicating that it has a pro-coagulant effect that is described before. FSAP-SPD improved stroke outcome and diminished the negative effects of co-treatment with tPA in the transient middle cerebral artery occlusion model. The inactive MI-isoform of FSAP did not have any effects in either model. In mice with FSAP deficiency there were minor differences in the outcomes of stroke but the treatment with FSAP-SPD was equally effective. Thus, FSAP represents a promising novel therapeutic strategy in the treatment of ischemic stroke that requires further evaluation.

Potential Role of Exosomes in Ischemic Stroke Treatment

Ischemic stroke is a life-threatening cerebral vascular disease and accounts for high disability and mortality worldwide. Currently, no efficient therapeutic strategies are available for promoting neurological recovery in clinical practice, except rehabilitation. The majority of neuroprotective drugs showed positive impact in pre-clinical studies but failed in clinical trials. Therefore, there is an urgent demand for new promising therapeutic approaches for ischemic stroke treatment. Emerging evidence suggests that exosomes mediate communication between cells in both physiological and pathological conditions. Exosomes have received extensive attention for therapy following a stroke, because of their unique characteristics, such as the ability to cross the blood brain–barrier, low immunogenicity, and low toxicity. An increasing number of studies have demonstrated positively neurorestorative effects of exosome-based therapy, which are largely mediated by the microRNA cargo. Herein, we review the current knowledge of exosomes, the relationships between exosomes and stroke, and the therapeutic effects of exosome-based treatments in neurovascular remodeling processes after stroke. Exosomes provide a viable and prospective treatment strategy for ischemic stroke patients.

Can competition improve hospital quality of care? A difference-in-differences approach to evaluate the effect of increasing quality transparency on hospital quality

Public reporting on the quality of care is intended to guide patients to the provider with the highest quality and to stimulate a fair competition on quality. We apply a difference-in-differences design to test whether hospital quality has improved more in markets that are more competitive after the first public release of performance data in Germany in 2008. Panel data from 947 hospitals from 2006 to 2010 are used. Due to the high complexity of the treatment of stroke patients, we approximate general hospital quality by the 30-day risk-adjusted mortality rate for stroke treatment. Market structure is measured (comparatively) by the Herfindahl–Hirschman index (HHI) and by the number of hospitals in the relevant market. Predicted market shares based on exogenous variables only are used to compute the HHI to allow a causal interpretation of the reform effect. A homogenous positive effect of competition on quality of care is found. This effect is mainly driven by the response of non-profit hospitals that have a narrow range of services and private for-profit hospitals with a medium range of services. The results highlight the relevance of outcome transparency to enhance hospital quality competition.

Work of a stroke team: experience of transferring ischemic stroke patients from district hospitals to Krasnoyarsk Regional Vascular Center for thrombectomy

Modern high-technology methods for ischemic stroke treatment (systemic thrombolysis, mechanical thrombectomy, thrombaspiration, stenting of cerebral arteries) can improve the rehabilitation potential and survival of patients. Important tasks here are selection for reperfusion and its performance on the greatest possible number of peracute patients. Mechanical thrombectomy combined with systemic thrombolysis is the most effective reperfusion strategy in the therapeutic window, but the availability of endovascular methods is limited to highly specialized centres. One way to solve this problem is to organize effective logistics with stroke patients, which will provide high-tech care for patients living far from large treatment centers due to regulated interaction between institutions at different levels.The aim of the study was to improve emergency interaction related to transfer of peracute stroke patients from primary vascular units and district hospitals of the Krasnoyarsk region to Krasnoyarsk Regional Vascular Center for thrombectomy.

Transcarotid access for remote robotic endovascular neurointerventions: a cadaveric proof-of-concept study

OBJECTIVE The purpose of this proof-of-concept study was to demonstrate the setup and feasibility of transcarotid access for remote robotic neurointerventions in a cadaveric model. METHODS The interventional procedures were performed in a fresh-frozen cadaveric model using an endovascular robotic system and a robotic angiography imaging system. A prototype remote, robotic-drive system with an ethernet-based network connectivity and audio-video communication system was used to drive the robotic system remotely. After surgical exposure of the common carotid artery in a cadaveric model, an 8-Fr arterial was inserted and anchored. A telescopic guiding sheath and catheter/microcatheter combination was modified to account for the “workable” length with the CorPath GRX robotic system using transcarotid access. RESULTS To simulate a carotid stenting procedure, a 0.014-inch wire was advanced robotically to the extracranial internal carotid artery. After confirming the wire position and anatomy by angiography, a self-expandable rapid exchange nitinol stent was loaded into the robotic cassette, advanced, and then deployed robotically across the carotid bifurcation. To simulate an endovascular stroke recanalization procedure, a 0.014-inch wire was advanced into the proximal middle cerebral artery with robotic assistance. A modified 2.95-Fr delivery microcatheter (Velocity, Penumbra Inc.) was loaded into the robotic cassette and positioned. After robotic retraction of the wire, it was switched manually to a mechanical thrombectomy device (Solitaire X, Medtronic). The stentriever was then advanced robotically into the end of the microcatheter. After robotic unfolding and short microcatheter retraction, the microcatheter was manually removed and the stent retriever was extracted using robotic assistance. During intravascular navigation, the device position was guided by 2D angiography and confirmed by 3D cone-beam CT angiography. CONCLUSIONS In this proof-of-concept cadaver study, the authors demonstrated the setup and technical feasibility of transcarotid access for remote robot-assisted neurointerventions such as carotid artery stenting and mechanical thrombectomy. Using transcarotid access, catheter length modifications were necessary to achieve “working length” compatibility with the current-generation CorPath GRX robotic system. While further improvements in dedicated robotic solutions for neurointerventions and next-generation thrombectomy devices are necessary, the transcarotid approach provides a direct, relatively rapid access route to the brain for delivering remote stroke treatment.

Nationwide Acute Stroke Care Quality and Disparity in Korea: Focusing on the Type of Healthcare Facilities and the Socioeconomic Status of Patients

Background: The quality ofstroke care has a significantimpact onmortality and complications. The purpose ofthisstudy wasto investigate the difference in the quality of acute stroke treatment according to the type of healthcare facility and the socioeconomic status of patients.Methods: Thisstudy used Health Insurance Review and Assessment Service’s Healthcare Quality Assessment for Stroke 2013 data and included 10,399 cases from 201 healthcare facilities. Quality of care was categorized from grade 1 (best group) to grade 5 (worst group) according to performance scores using 10 processindicators.Results: The mean performance score was 91.5. Only 31% of all patients received treatment at grade 1 hospitals while 10% received treatment at grade 3 or lower hospitals. The difference in performance score by the type of healthcare facility existed (tertiary hospitals: 94.3, general hospitals: 88.7).Ofthe 159 general hospitals, 66 hospitals provided grade 3 orlower quality care.NHI patients used more tertiary hospitalsthan MA patients(51% vs. 38%), and MA patientswere more likely to use general hospitals providing grade 3 or lower quality care (11% vs. 21%).Conclusions: This study showed that some general hospitals provided low quality stroke care, and MA patients were more likely to use those hospitals. In order to increase the quality and equity of stroke treatment, a strategy to gather patients at healthcare facilitiesthat provide appropriate medicalservices will be needed.