Among age-related diseases, cardiovascular and cerebrovascular diseases are major causes of death. Vascular dysfunction is a key characteristic of these diseases wherein age is an independent and essential risk factor. The present work will review morphological alterations of aging vessels in-depth, which includes the discussion of age-related microvessel loss and changes to vasculature involving the capillary basement membrane, intima, media, and adventitia as well as the accompanying vascular dysfunctions arising from these alterations.

Hydroxyapatite (HA) is an attractive bioceramic for hard tissue repair and regeneration due to its physicochemical similarities to natural apatite. However, its low fracture toughness, poor tensile strength and weak wear resistance become major obstacles for potential clinical applications. One promising method to tackle with these problems is exploiting graphene and its derivatives (graphene oxide and reduced graphene oxide) as nanoscale reinforcement fillers to fabricate graphene-based hydroxyapatite composites in the form of powders, coatings and scaffolds. The last few years witnessed increasing numbers of studies on the preparation, mechanical and biological evaluations of these novel materials. Herein, various preparation techniques, mechanical behaviors and toughen mechanism, the in vitro/in vivo biocompatible analysis, antibacterial properties of the graphene-based HA composites are presented in this review.

Sublethal hypoxic or ischemic events can improve the tolerance of tissues, organs, and even organisms from subsequent lethal injury caused by hypoxia or ischemia. This phenomenon has been termed hypoxic or ischemic preconditioning (HPC or IPC) and is well established in the heart and the brain. This review aims to discuss HPC and IPC with respect to their historical development and advancements in our understanding of the neurochemical basis for their neuroprotective role. Through decades of collaborative research and studies of HPC and IPC in other organ systems, our understanding of HPC and IPC-induced neuroprotection has expanded to include: early- (phosphorylation targets, transporter regulation, interfering RNA) and late- (regulation of genes like EPO, VEGF, and iNOS) phase changes, regulators of programmed cell death, members of metabolic pathways, receptor modulators, and many other novel targets. The rapid acceleration in our understanding of HPC and IPC will help facilitate transition into the clinical setting.

A rapid and reliable diagnostic test to distinguish ischemic from hemorrhagic stroke in patients presenting with stroke-like symptoms is essential to optimize management and triage for thrombolytic therapy. The present study measured serum concentrations of ubiquitin C-terminal hydrolase (UCH-L1) and glial fibrillary astrocytic protein (GFAP) in acute stroke patients and healthy controls and investigated their relation to stroke severity and patient characteristics. We also assessed the diagnostic performance of these markers for the differentiation of intracerebral hemorrhage (ICH) from ischemic stroke (IS). Both UCH-L1 and GFAP concentrations were significantly greater in ICH patients than in controls (p < 0.0001). However, exclusively GFAP differed in ICH compared with IS (p < 0.0001). GFAP yielded an AUC of 0.86 for differentiating between ICH and IS within 4.5hrs of symptom onset with a sensitivity of 61% and a specificity of 96% using a cut-off of 0.34ng/ml. Higher GFAP levels were associated with stroke severity and history of prior stroke. Our results demonstrate that blood UCH-L1 and GFAP are increased early after stroke and distinct biomarker-specific release profiles are associated with stroke characteristics and type. We also confirmed the potential of GFAP as a tool for early rule-in of ICH, while UCH-L1 was not clinically useful.

ObjectiveRemote ischemic conditioning (RIC) has been demonstrated to be safe and feasible for patients with acute ischemic stroke (AIS), as well as for those receiving intravenous thrombolysis. We assessed the safety and feasibility of RIC for AIS patients undergoing endovascular treatment (ET).MethodsWe conducted a pilot study with patients with AIS who were suspected of having an emergent large‐vessel occlusion in the anterior circulation and who were scheduled for ET within 6 hours of ictus. Four cycles of RIC were performed before recanalization, immediately following recanalization, and once daily for the subsequent 7 days. The primary outcome was any serious RIC‐related adverse events.ResultsTwenty subjects, aged 66.1 ± 12.1 years, were recruited. No subject experienced serious RIC‐related adverse events. The intracranial pressure, cranial perfusion pressure, mean arterial pressure, heart rate, middle cerebral artery peak systolic flow velocity, and pulsatility index did not change significantly before, during, or after the limb ischemia (P > 0.1 for all). Of 80 cycles, 71 (89%) were completed before recanalization and 80 (100%) were completed immediately after recanalization; 444 of 560 cycles (78%) were completed within 7 days posttreatment. No patients had to stop RIC because it affected routine clinical managements. Six subjects (30%) experienced intracerebral hemorrhage, which was symptomatic in one case (5%). At the 3‐month follow‐up, 11 subjects (55%) had achieved functional independence, and two subjects (10%) died.Interpretation RIC appears to be safe and feasible for patients with AIS undergoing ET. Investigations are urgently needed to determine the efficacy of RIC in this patient population.

Purpose: Limb remote ischemic per-conditioning or post-conditioning has been shown to be neuroprotective after cerebral ischemic stroke. However, the effect of combining remote per-conditioning with post-conditioning on ischemic/reperfusion injury as well as the underlying mechanisms are largely unexplored. Methods: Here, adult male Sprague Dawley rats were subjected to middle cerebral artery occlusion (MCAO). The limb ischemic stimulus was immediately applied after onset of focal ischemia (per-conditioning), followed by repeated short episodes of remote ischemia 24 hr after reperfusion (post-conditioning). The infarct volume, motor function, and the expression of neuroglobin (Ngb) were measured at different durations after reperfusion. Results: We found that a single episode of limb remote per-conditioning afforded short-term protection, but combining repeated remote post-conditioning during the 14 days after reperfusion significantly ameliorated cerebral ischemia/reperfusion injury. Interestingly, we also found that ischemic per- and post-conditioning significantly increased expression of Ngb, an oxygen-binding globin protein that has been demonstrated to be neuroprotective against stroke, at peri-infarct regions from day 1 to day 14 following ischemia/reperfusion.Conclusion: Our results suggest that the conventional per-conditioning combined with post-conditioning may be used as a novel neuroprotective strategy against ischemia-reperfusion injury, and Ngb seems to be one of the important players in limb remote ischemia-mediated neuroprotection.

Recent studies have demonstrated that the depletion of Regulatory T cells (Tregs) inhibits neural progenitor cell migration after brain ischemia. However, whether Tregs affect neural stem/progenitor cell proliferation is unclear. We explored the effect of Tregs on neurogenesis in the subventricular zone (SVZ) after ischemia. Tregs were isolated and activated in vitro. Adult male C57BL/6 mice underwent 60 min transient middle cerebral artery occlusion (tMCAO). Then Tregs (1 × 105) were injected into the left lateral ventricle (LV) of normal and ischemic mouse brain. Neurogenesis was determined by immunostaining. The mechanism was examined by inhibiting interleukin 10 (IL-10) and transforming growth factor (TGF-β) signaling. We found that the number of BrdU+ cells in the SVZ was significantly increased in the activated Tregs-treated mice. Double immunostaining showed that these BrdU+ cells expressed Mash1. Blocking IL-10 reduced the number of Mash1+/BrdU+ cells, but increased the amount of GFAP+/BrdU+ cells. Here, we conclude that activated Tregs enhanced neural stem cell (NSC) proliferation in the SVZ of normal and ischemic mice; blockage of IL-10 abolished Tregs-mediated NSC proliferation in vivo and in vitro. Our results suggest that activated Tregs promoted NSC proliferation via IL-10, which provides a new therapeutic approach for ischemic stroke.

No abstract