The Per2 polymorphism rs10462023 is associated with the risk of stroke in a Chinese population

The key clock protein Period2 (Per2) has been suggested to play an essential role in regulating endothelial function. It also regulates the expression of plasminogen activator inhibitor-1, but its role in stroke development has not been studied. To explore the possible association between Per2 and ischemic stroke (IS), 479 Chinese IS patients and 306 healthy controls were recruited, and five tag single nucleotide polymorphisms representing the Per2 locus were genotyped using the Sequenom MassARRAY system. A significant difference was observed in the genotypic distribution (p = 0.014) and allele frequency (p = 0.005) of rs10462023, with carriers of the G allele being more prone to developing IS. After adjusting for possible risk factors including smoking, alcohol use, and history of hypertension and diabetes, a significant association was still apparent. Haplotype analysis also supported the association between Per2 and IS. This study suggests that Per2 variations are associated with IS and may represent genetic risk factors for IS in a Chinese population.     

Extremes of human heat tolerance: life at the precipice of thermoregulatory failure

1. Human life is sustainable only below an internal temperature of roughly 42–44 °C. Yet our ability to survive at severe environmental extremes is testimony to the marvels of integrative human physiology.

2. One approach to understanding human thermoregulatory capacity is to examine the upper limits of thermal balance between man and the air environment, i.e. the maximal environmental conditions under which humans can maintain a steady-state core temperature. Heat acclimation expands the zone of thermal balance.

3. Human beings can and do, often willingly, tolerate extreme heat stresses well above these thermal balance limits. Survival in all such cases is limited to abbreviated exposure times, which in turn are limited by the robustness of the thermoregulatory response.

4. Figures are provided that relate tolerance time and the rate of change in core temperature to environmental characteristics based on data compiled from the literature.     

Functional coupling of TRPM2 and extrasynaptic NMDARs exacerbates excitotoxicity in ischemic brain injury

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Diffuse optical detection of global cerebral ischemia in an adult porcine model

Rapid screening for ischemic strokes in prehospital settings may improve patient outcomes by allowing early deployment of vascular recanalization therapies. However, there are no low-cost and convenient methods that can assess ischemic strokes in such a setting. Diffuse correlation spectroscopy (DCS) is a promising method for continuous, noninvasive transcranial monitoring of cerebral blood flow. In this study, we used a DCS system to detect cerebral hemodynamics before and after acute ischemic stroke in pigs. Seven adult porcines were chosen to establish ischemic stroke models via bilateral common carotid artery ligation (n = 5) or air emboli (n = 2). The results showed a significant difference in blood flow index (BFI) between the normal and ischemic groups. Relative blood flow index (rBFI) exhibited excellent results. Therefore, the diffuse optical method can assess the hemodynamic changes in acute cerebral ischemic stroke onset in pigs, and rBFI may be a promising biomarker for identifying cerebral ischemic stroke.     

Efficacy and Safety of Analog Insulin in Comparison With Human Insulin for Hyperglycemia in Hospitalized Patients With Acute Stroke: A Randomized,Open-Label,Single-Center Trial

ObjectiveTo assess the efficacy and safety of analog insulins in comparison with human insulins for hyperglycemia in hospitalized patients with acute stroke.MethodsIn this single-center, open-label, randomized trial, 102 patients (age 59.4 ± 11.7 years, 54 women) admitted with acute stroke (52 ischemic, 50 hemorrhagic) and hyperglycemia were assigned to analog insulin (n = 52) or human insulin (n = 50) group during February to June 2021. Insulin was initiated and titrated according to the predefined standard protocol. The capillary blood glucose (BG) level was monitored by standardized glucometers. The primary outcomes were mean daily BG and the number of hypoglycemic events.ResultsBetween the 2 treatment groups, there was no significant difference in the mean daily BG (P >.05 for all days) or in the frequency of hypoglycemic episodes (P =.727). Four participants experienced severe hypoglycemia; all were receiving human insulin (P =.054). In the analog insulin group, there was a tendency toward lower daily total requirement for insulin (P =.053). The difference in bolus insulin dose was significantly lower in the analog insulin group (P =.029), but the difference in basal insulin dose was similar (P =.167). Between the 2 groups, there were no significant differences in the hospital mortality rate, modified Rankin Scale score on outcome, or length of hospital stay (P =.729,.658, and.918, respectively).ConclusionHospitalized patients acute stroke and hyperglycemia exhibited similar mean BG but a trend of lower incidence of severe hypoglycemia when treated with analog insulins in comparison with human insulin.     

Microglia drive transient insult-induced brain injury by chemotactic recruitment of CD8+ T lymphocytes

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基于自噬溶酶体形成机制调控缺血性脑卒中后神经元自噬流

脑卒中是由脑血管阻塞或出血引发的急性脑血管病，约84%的临床脑卒中患者由脑缺血引起。研究表明，自噬广泛参与并显著影响脑卒中病理生理进程。自噬是一个将陈旧蛋白质、损伤细胞器及多余胞质组分等呈递给溶酶体进行降解的代谢过程，其包括自噬的激活、自噬体的形成和成熟、自噬体与溶酶体融合、自噬产物在自噬溶酶体内消化和降解等过程。自噬流通常被定义为自噬/溶酶体信号机制。最近发现，自噬流障碍是导致缺血性脑卒中后神经元损伤的重要原因，而在自噬过程中任一步骤发生障碍均可导致自噬流损伤。本文重点对自噬体-溶酶体融合的机制，以及该机制在缺血性脑卒中后发生障碍的致病机理进行详细阐述，以期基于自噬体-溶酶体融合机制对神经元自噬流进行调节，进而诱导缺血性脑卒中后的神经保护。本文可为脑卒中病理机制研究指明方向，为脑卒中治疗探寻新的线索。     

Resolvin D1 reprograms energy metabolism to promote microglia to phagocytize neutrophils after ischemic stroke

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