Vascular disruption and blood–brain barrier dysfunction in intracerebral hemorrhage

Abstract This article reviews current knowledge of the mechanisms underlying the initial hemorrhage and secondary blood–brain barrier (BBB) dysfunction in primary spontaneous intracerebral hemorrhage (ICH) in adults. Multiple etiologies are associated with ICH, for example, hypertension, Alzheimer’s disease, vascular malformations and coagulopathies (genetic or drug-induced). After the initial bleed, there can be continued bleeding over the first 24 hours, so-called hematoma expansion, which is associated with adverse outcomes. A number of clinical trials are focused on trying to limit such expansion. Significant progress has been made on the causes of BBB dysfunction after ICH at the molecular and cell signaling level. Blood components (e.g. thrombin, hemoglobin, iron) and the inflammatory response to those components play a large role in ICH-induced BBB dysfunction. There are current clinical trials of minimally invasive hematoma removal and iron chelation which may limit such dysfunction. Understanding the mechanisms underlying the initial hemorrhage and secondary BBB dysfunction in ICH is vital for developing methods to prevent and treat this devastating form of stroke.http://deepblue.lib.umich.edu/bitstream/2027.42/134526/1/12987_2014_Article_103.pd

The loss of plant functional groups increased arthropod diversity in an alpine meadow on the Tibetan Plateau

Plant species loss, driven by global changes and human activities, can have cascading effects on other trophic levels, such as arthropods, and alter the multitrophic structure of ecosystems. While the relationship between plant diversity and arthropod communities has been well-documented, few studies have explored the effects of species composition variation or plant functional groups. In this study, we conducted a long-term plant removal experiment to investigate the impact of plant functional group loss (specifically targeting tall grasses and sedges, as well as tall or short forbs) on arthropod diversity and their functional groups. Our findings revealed that the removal of plant functional groups resulted in increased arthropod richness, abundance and the exponential of Shannon entropy, contrary to the commonly observed positive correlation between plant diversity and consumer diversity. Furthermore, the removal of different plant groups had varying impacts on arthropod trophic levels. The removal of forbs had a more pronounced impact on herbivores compared to graminoids, but this impact did not consistently cascade to higher-trophic arthropods. Notably, the removal of short forbs had a more significant impact on predators, as evidenced by the increased richness, abundance, the exponential of Shannon entropy, inverse Simpson index and inverse Berger-Parker index of carnivores and abundance of omnivores, likely attributable to distinct underlying mechanisms. Our results highlight the importance of plant species identity in shaping arthropod communities in alpine grasslands. This study emphasizes the crucial role of high plant species diversity in controlling arthropods in natural grasslands, particularly in the context of plant diversity loss caused by global changes and human activities

Vascular disruption and blood–brain barrier dysfunction in intracerebral hemorrhage

Abstract This article reviews current knowledge of the mechanisms underlying the initial hemorrhage and secondary blood–brain barrier (BBB) dysfunction in primary spontaneous intracerebral hemorrhage (ICH) in adults. Multiple etiologies are associated with ICH, for example, hypertension, Alzheimer’s disease, vascular malformations and coagulopathies (genetic or drug-induced). After the initial bleed, there can be continued bleeding over the first 24 hours, so-called hematoma expansion, which is associated with adverse outcomes. A number of clinical trials are focused on trying to limit such expansion. Significant progress has been made on the causes of BBB dysfunction after ICH at the molecular and cell signaling level. Blood components (e.g. thrombin, hemoglobin, iron) and the inflammatory response to those components play a large role in ICH-induced BBB dysfunction. There are current clinical trials of minimally invasive hematoma removal and iron chelation which may limit such dysfunction. Understanding the mechanisms underlying the initial hemorrhage and secondary BBB dysfunction in ICH is vital for developing methods to prevent and treat this devastating form of stroke.http://deepblue.lib.umich.edu/bitstream/2027.42/109551/1/12987_2014_Article_103.pd

Mitophagy involved the biological processes of hormones

Mitochondria fulfill vital functions in energy production, maintaining ion balance, and facilitating material metabolism. Mitochondria are sacrificed to protect cells or induce apoptosis when the body is under stress. The regulatory pathways of mitophagy include both ubiquitin-dependent and non-dependent pathways. The involvement of mitophagy has been demonstrated in the onset and progression of numerous diseases, highlighting its significant role. Endocrine hormones are chemical substances secreted by endocrine organs or endocrine cells, which participate in the regulation of physiological functions and internal environmental homeostasis of the body. Imbalances in endocrine hormones contribute to the development of various diseases. However, the precise impact of mitophagy on the physiological and pathological processes involving endocrine hormones remains unclear. This article aims to comprehensively overview recent advancements in understanding the mechanisms through which mitophagy regulates endocrine hormones

The Phenolic Components of Gastrodia elata improve Prognosis in Rats after Cerebral Ischemia/Reperfusion by Enhancing the Endogenous Antioxidant Mechanisms

Pharmacological or spontaneous thrombolysis in ischemic stroke triggers an outbreak of reactive oxygen species and results in neuron death. Nrf2-mediated antioxidation in cells has been proved as a pivotal target for neuroprotection. This research reports that phenolic components of Gastrodia elata Blume (PCGE), a traditional Chinese medicine, can alleviate the pathological lesions in the penumbra and hippocampus by increasing the survival of neurons and astrocytes and improve neurofunction and cognition after reperfusion in a rat model of middle cerebral artery occlusion. LDH assay indicated that pretreatment of cells with PCGE (25 μg/ml) for 24 h significantly reduced H2O2-induced cell death in astrocytes and SH-SY5Y cells. Western blot showed that the nucleus accumulation of Nrf2 and the expression of cellular HO-1 and NQO-1, two of Nrf2 downstream proteins, were increased in both cells. BDNF, an Nrf2-dependent neurotrophic factor, was also upregulated by PCGE in astrocytes. These results illustrated that PCGE can reduce the cerebral ischemia/reperfusion injury and improve prognosis by remedying the cell damage within affected tissues. The protective effects of PCGE seem to be via activation of a Nrf2-mediated cellular defense system. Therefore, PCGE could be a therapeutic candidate for ischemic stroke and other oxidative stress associated neurological disorders

Regulation of PKM2 and Nrf2-ARE pathway during benzoquinone induced oxidative stress in yolk sac hematopoietic stem cells.

Benzene is an occupational toxicant and an environmental pollutant that is able to induce the production of reactive oxygen species (ROS), causing oxidative stress and damages of the macromolecules in target cells, such as the hematopoietic stem cells. We had previously found that embryonic yolk sac hematopoietic stem cells (YS-HSCs) are more sensitive to benzene toxicity than the adult bone marrow hematopoietic stem cells, and that nuclear factor-erythroid-2-related factor 2 (Nrf2) is the major regulator of cytoprotective responses to oxidative stress. In the present report, we investigated the effect of PKM2 and Nrf2-ARE pathway on the cellular antioxidant response to oxidative stress induced by benzene metabolite benzoquinone (BQ) in YS-HSC isolated from embryonic yolk sac and enriched by magnetic-activated cell sorting (MACS). Treatment of the YS-HSC with various concentrations of BQ for 6 hours induces ROS generation in a dose-dependent manner. Additional tests showed that BQ is also capable of inducing expression of NADPH oxidase1 (NOX1), and several other antioxidant enzymes or drug-metabolizing enzymes, including heme oxygenase 1 (HMOX1), superoxide dismutase (SOD), catalase and NAD(P)H dehydrogenase quinone 1 (NQO1). Concomitantly, only the expression of PKM2 protein was decreased by the treatment of BQ but not the PKM2 mRNA, which suggested that BQ may induce PKM2 degradation. Pretreatment of the cells with antioxidant N-acetylcysteine (NAC) decreased ROS generation and prevented BQ-induced PKM2 degradation, suggesting involvement of ROS in the PKM2 protein degradation in cellular response to BQ. These findings suggest that BQ is a potent inducer of ROS generation and the subsequent antioxidant responses of the YS-HSC. The accumulated ROS may attenuate the expression of PKM2, a key regulator of the pyruvate metabolism and glycolysis