Acute ischemic stroke is a common cause of morbidity and mortality worldwide. Thrombolysis with recombinant tissue plasminogen activator and endovascular thrombectomy are the main revascularization therapies for acute ischemic stroke. However, ischemia-reperfusion injury after revascularization therapy can result in worsening outcomes. Among all possible pathological mechanisms of ischemia-reperfusion injury, free radical damage (mainly oxidative/nitrosative stress injury) has been found to play a key role in the process. Free radicals lead to protein dysfunction, DNA damage, and lipid peroxidation, resulting in cell death. Additionally, free radical damage has a strong connection with inducing hemorrhagic transformation and cerebral edema, which are the major complications of revascularization therapy, and mainly influencing neurological outcomes due to the disruption of the blood-brain barrier. In order to get a better clinical prognosis, more and more studies focus on the pharmaceutical and nonpharmaceutical neuroprotective therapies against free radical damage. This review discusses the pathological mechanisms of free radicals in ischemia-reperfusion injury and adjunctive neuroprotective therapies combined with revascularization therapy against free radical damage.

In China, stroke is a major cause of mortality, and long-term physical and cognitive impairment. To meet this challenge, the Ministry of Health China Stroke Prevention Project Committee (CSPPC) was established in April 2011. This committee actively promotes stroke prevention and control in China. With government financial support of 838.4 million CNY, 8.352 million people from 536 screening points in 31 provinces have received stroke screening and follow-up over the last seven years (2012–2018). In 2016, the CSPPC issued a plan to establish stroke centers. To shorten the pre-hospital period, the CSPPC established a stroke center network, stroke map, and stroke “Green Channel” to create three 1-h gold rescue circles, abbreviated as “1-1-1” (onset to call time <1 h; pre-hospital transfer time < 1 h, and door-to-needle time < 1 h). From 2017 to 2018, the median door-to-needle time dropped by 4.0% (95% confidence interval (CI), 1.4–9.4) from 50 min to 48 min, and the median onset-to-needle time dropped by 2.8% (95% CI, 0.4–5.2) from 180 min to 175 min. As of 31 December 2018, the CSPPC has established 380 stroke centers in mainland China. From 1 November 2018, the CSPPC has monitored the quality of stroke care in stroke center hospitals through the China Stroke Data Center Data Reporting Platform. The CSPPC Stroke program has led to a significant improvement in stroke care. This program needs to be further promoted nationwide.

Reports of dCA in patients with ICH group are scarce, yet diverse. In a case-control study, a higher gain was observed within 3 days of ICH onset when compared with the healthy controls, indicating a less effective dCA during the acute stage. 7 In a recent study, researchers obtained serial measurements and stated that a higher bilateral gain could last 5 days Background and Purpose-Cerebral autoregulation is crucial in patients with intracerebral hemorrhage. Dynamic cerebral autoregulation is probably altered in acute intracerebral hemorrhage; however, the temporal course of dynamic cerebral autoregulation and its correlation with clinical factors and outcomes are poorly understood. Methods-Forty-three acute supratentorial intracerebral hemorrhage patients (53.7±10.0 years old, 30 men) were enrolled for serial measurements performed on days 1 to 2, 4 to 6, 10 to 12, and 30 days after ictus. Noninvasive continuous cerebral blood flow velocity and arterial blood pressure were recorded simultaneously using transcranial Doppler and a servocontrolled plethysmograph, respectively. Transfer function analysis was used to derive the autoregulatory parameters, including phase difference (PD), gain, and the rate of recovery of cerebral blood flow velocity. Results were compared with healthy controls and correlated with clinical factors and the 90-day outcome. Results-PD did not differ between affected and unaffected hemispheres over time. A significant lower PD (indicating dynamic cerebral autoregulation impaired) was found in bilateral hemispheres on days 1 to 2, 4 to 6, and 10 to 12, followed by later recovery on day 30. Lower bilateral PD on days 1 to 2 was associated with poorer Glasgow Coma Scale score at that time. Lower affected-side PD on days 4 to 6 was an independent predictive value for a poorer modified Rankin Scale at 90 days. Conclusions-In patients with supratentorial intracerebral hemorrhage, dynamic cerebral autoregulation is bilaterally impaired lasting at least 10 to 12 days and recovers within a month. Individual PD value is associated with clinical status at acute stage and affected-side PD on days 4 to 6 can be an independent predictor for clinical outcome. after ictus, whereas a higher gain value was not associated with any clinical factors or outcome. 14 Serial index Mx (reflecting both static and dynamic CA) was also derived within 5 days after ICH onset. Although it was not generally impaired on the first day, a secondary decline between days 3 and 5 could possibly occur mainly on the affected side, and this may be associated with poorer clinical status and outcomes.15 Yet, the above studies all garnered attention toward the early stage after ICH, while ignoring the subacute and recovery stages. This left unresolved whether, when, and to what extent could the altered dCA be restored.Thus, in the present study, we sought to (1) investigate the time course of dCA in ICH patients with serial follow-ups, including 1 to 2 days after ictus and 3 additional time points within a month, and (2) explore th...

Cerebral autoregulation (CA) is a protective mechanism that maintains cerebral blood flow at a relatively constant level despite fluctuations of cerebral perfusion pressure or arterial blood pressure. It is a universal physiological mechanism that may involve myogenic, neural control as well as metabolic regulations of cerebral vasculature in response to changes in pressure or cerebral blood flow. Traditionally, CA has been represented by a sigmoid curve with a wide plateau between about 50 mm Hg and 170 mm Hg of steady-state changes in mean arterial pressure, defined as static CA. With the advent of transcranial Doppler, measurement of cerebral blood flow in response to transient changes in arterial pressure has been used to assess dynamic CA. However, a gold standard for measuring CA is not currently available. Stroke has been the leading cause of long-term adult disability throughout the world. A better understanding of CA and its response to pathological derangements can help assess the severity of stroke, guide management decisions, assess response to interventions and provide prognostic information. The objective of this review is to provide a comprehensive insight about physiology of autoregulation, measurement methodologies and clinical applications in stroke to help build a consensus for what should be included in an internationally agreed protocol for CA testing and monitoring, and to promote its translation into clinical bedside practice for stroke management.

BackgroundEpidemiological studies have shown that ambient air pollution is closely associated with increased respiratory inflammation and decreased lung function. Particulate matters (PMs) are major components of air pollution that damages lung cells. However, the mechanisms remain to be elucidated. This study examines the effects of PMs on intercellular adhesion molecule-1 (ICAM-1) expression and the related mechanisms in vitro and in vivo.ResultThe cytotoxicity, reactive oxygen species (ROS) generation, and monocyte adherence to A549 cells were more severely affected by treatment with O-PMs (organic solvent-extractable fraction of SRM1649b) than with W-PMs (water-soluble fraction of SRM1649b). We observed a significant increase in ICAM-1 expression by O-PMs, but not W-PMs. O-PMs also induced the phosphorylation of AKT, p65, and STAT3. Pretreating A549 cells with N-acetyl cysteine (NAC), an antioxidant, attenuated O-PMs-induced ROS generation, the phosphorylation of the mentioned kinases, and the expression of ICAM-1. Furthermore, an AKT inhibitor (LY294002), NF-κB inhibitor (BAY11–7082), and STAT3 inhibitor (Stattic) significantly down-regulated O-PMs-induced ICAM-1 expression as well as the adhesion of U937 cells to epithelial cells. Interleukin-6 (IL-6) was the most significantly changed cytokine in O-PMs-treated A549 cells according to the analysis of the cytokine antibody array. The IL-6 receptor inhibitor tocilizumab (TCZ) and small interfering RNA for IL-6 significantly reduced ICAM-1 secretion and expression as well as the reduction of the AKT, p65, and STAT3 phosphorylation in O-PMs-treated A549 cells. In addition, the intratracheal instillation of PMs significantly increased the levels of the ICAM-1 and IL-6 in lung tissues and plasma in WT mice, but not in IL-6 knockout mice. Pre-administration of NAC attenuated those PMs-induced adverse effects in WT mice. Furthermore, patients with chronic obstructive pulmonary disease (COPD) had higher plasma levels of ICAM-1 and IL-6 compared to healthy subjects.ConclusionThese results suggest that PMs increase ICAM-1 expression in pulmonary epithelial cells in vitro and in vivo through the IL-6/AKT/STAT3/NF-κB signaling pathway.Electronic supplementary materialThe online version of this article (10.1186/s12989-018-0240-x) contains supplementary material, which is available to authorized users.