Ischemic stroke is one of the leading causes of death, and even timely treatment can result in severe disabilities. Reperfusion of the ischemic stroke region and restoration of the blood supply often lead to a series of cellular and biochemical consequences, including generation of reactive oxygen species (ROS), expression of inflammatory cytokines, inflammation, and cerebral cell damage, which is collectively called cerebral ischemia-reperfusion (IR) injury. Since ROS and inflammatory cytokines are involved in cerebral IR injury, injury could involve cellular senescence. Thus, we investigated whether senolytic therapy that eliminates senescent cells could be an effective treatment for cerebral IR injury. To determine whether IR induces neural cell senescence in vitro, astrocytes were subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). OGD/R induced astrocyte senescence and senescent cells in OGD/R-injured astrocytes were effectively eliminated in vitro by ABT263, a senolytic agent. IR in rats with intraluminal middle cerebral artery occlusion induced cellular senescence in the ischemic region. The senescent cells in IR-injured rats were effectively eliminated by intravenous injections of ABT263. Importantly, ABT263 treatment significantly reduced the infarct volume and improved neurological function in behavioral tests. This study demonstrated, for the first time, that senolytic therapy has therapeutic potential for cerebral IR injury.

Marked protein catabolism is common in critically ill patients. We hypothesized that optimal protein supplementation using nitrogen balance might be associated with better outcomes in the neurointensive care unit (NICU) patients. A total of 175 patients admitted to the NICU between July 2017 and December 2018 were included. Nitrogen balance was measured after NICU admission and measurements were repeated in 77 patients. The outcomes were compared according to initial nitrogen balance results and improvement of nitrogen balance on follow-up measurements. A total of 140 (80.0%) patients had a negative nitrogen balance on initial assessments. The negative balance group had more events of in-hospital mortality and poor functional outcome at three months. In follow-up measurement patients, 39 (50.6%) showed an improvement in nitrogen balance. The improvement group had fewer events of in-hospital mortality (p = 0.047) and poor functional outcomes (p = 0.046). Moreover, improvement of nitrogen balance was associated with a lower risk of poor functional outcomes (Odds ratio, 0.247; 95% confidence interval, 0.066–0.925, p = 0.038). This study demonstrated that a significant proportion of patients in the NICU were under protein hypercatabolism. Moreover, an improvement in protein balance was related to improved outcomes in neurocritically ill patients. Further studies are needed to confirm the relationship between protein balance and outcomes.

This study evaluated the potential of iron oxide nanoparticle-loaded human embryonic stem cell (ESC)-derived spherical neural masses (SNMs) to improve the transportation of stem cells to the brain, ameliorate brain damage from intracerebral hemorrhage (ICH), and recover the functional status after ICH under an external magnetic field of a magnet attached to a helmet. At 24 h after induction of ICH, rats were randomly separated into three experimental groups: ICH with injection of phosphate-buffered saline (PBS group), ICH with intravenous injection of magnetosome-like ferrimagnetic iron oxide nanocubes (FION)-labeled SNMs (SNMs* group), and ICH with intravenous injection of FION-labeled SNMs followed by three days of external magnetic field exposure for targeted delivery by a magnet-embedded helmet (SNMs*+Helmet group). On day 3 after ICH induction, an increased Prussian blue-stained area and decreased swelling volume were observed in the SNMs*+Helmet group compared with that of the other groups. A significantly decreased recruitment of macrophages and neutrophils and a downregulation of pro-inflammatory cytokines followed by improved neurological function three days after ICH were observed in the SNMs*+Helmet group. Hemispheric atrophy at six weeks after ICH was significantly decreased in the SNMs*+Helmet group compared with that of the PBS group. In conclusion, we have developed a targeted delivery system using FION tagged to stem cells and a magnet-embedded helmet. The targeted delivery of SNMs might have the potential for developing novel therapeutic strategies for ICH.

Background: Optimal antithrombotic regimens to prevent recurrent stroke in patients with ischemic stroke due to atrial fibrillation (AF) and atherosclerotic large-vessel stenosis remain unknown. Aims: This study aimed to evaluate the effect of multiple antithrombotic therapies on outcomes at 1 year after ischemic stroke due to two or more causes. Methods: We identified 862 patients with ischemic stroke due to AF and large artery atherosclerosis from the linked data. These patients were categorized into three groups according to antithrombotic therapies at discharge: (1) antiplatelets, (2) oral anticoagulants (OAC), and (3) antiplatelets plus OAC. The study outcomes were recurrent ischemic stroke, composite outcomes for cardiovascular events, and major bleeding after 1 year. Inverse probability of treatment weighting (IPTW) was used to balance the three groups using propensity scores. Results: Among 862 patients, 169 (19.6%) were treated with antiplatelets, 405 (47.0%) were treated with OAC, and 288 (33.4%) were treated with antiplatelets and OAC. After applying IPTW, only OAC had a significant beneficial effect on the 1-year composite outcome (hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.23–0.60, p < 0.001) and death (HR: 0.35, 95% CI: (0.19–0.63), p < 0.001). The combination of antiplatelet agents and OAC group had an increased risk of major bleeding complications (HR: 5.27, 95% CI: (1.31–21.16), p = 0.019). However, there was no significant difference in 1-year recurrent stroke events among the three groups. Conclusion: This study demonstrated that OAC monotherapy was associated with lower risks of composite outcome and death in patients at 1 year after ischemic stroke due to AF and atherosclerotic stenosis. In addition, the combination of an antiplatelet and OAC had a high risk of major bleeding.

Cerebral vasospasm and delayed cerebral ischemia are common complications associated with subarachnoid hemorrhage (SAH) outcomes. Various modalities can be used to evaluate and detect cerebral vasospasm after SAH. Transcranial Doppler (TCD) ultrasonography can be used as an appropriate bedside dynamic monitoring tool to screen for the presence and progression of cerebral vasospasm in patients with SAH. This article briefly reviewed the severity of SAH and pathophysiology of vasospasm. In addition, information regarding the use of TCD for monitoring cerebral vasospasm, several variables measured by TCD to monitor vasospasm detection, and differentiating vasospasm from physiological conditions in the clinical setting following SAH were presented in this article.