Perinatal hypoxic-ischemic (HI) brain injury is a major cause of permanent neurological dysfunction in children. An approach to study the treatment of neonatal HI encephalopathy that allows for neuroprotection is to investigate the states of tolerance to HI. Twenty-four-hour carotid-artery ligation preconditioning established by delaying the onset of hypoxia for 24 hours after permanent unilateral carotid ligation rats markedly diminished the cerebral injury, however, the signaling mechanisms of this carotid-artery ligation preconditioning in neonatal rats remain unknown. Ligation of the carotid artery 24 hours before hypoxia provided complete neuroprotection and produced improved performance on the Morris water maze compared with ligation performed 1 hour before hypoxia. Carotid artery ligation 6 hours before hypoxia produced intermediate benefit. The 24-hour carotid-artery ligation preconditioning was associated with a robust and sustained activation of a transcription factor, the cAMP response element-binding protein (CREB), on its phosphorylation site on Ser133. Intracerebroventricular infusions of antisense CREB oligodeoxynucleotides significantly reduced the 24-hour carotid-artery ligation-induced neuroprotection effects by decreasing CREB expressions. Pharmacological activation of the cAMP-CREB signaling with rolipram 24 hours before hypoxia protected rat pups at behavioral and pathological levels by sustained increased CREB phosphorylation. This study suggests that 24-hour carotid-artery ligation preconditioning provides important mechanisms for potential pharmacological preconditioning against neonatal HI brain injury.

BackgroundIn very preterm infants, white matter injury is a prominent brain injury, and hypoxic ischemia (HI) and infection are the two primary pathogenic factors of this injury. Microglia and microvascular endothelial cells closely interact; therefore, a common signaling pathway may cause neuroinflammation and blood–brain barrier (BBB) damage after injury to the immature brain. CXC chemokine ligand 5 (CXCL5) is produced in inflammatory and endothelial cells by various organs in response to insults. CXCL5 levels markedly increased in the amniotic cavity in response to intrauterine infection and preterm birth in clinical studies. The objective of this study is to determine whether CXCL5 signaling is a shared pathway of neuroinflammation and BBB injury that contributes to white matter injury in the immature brain.MethodsPostpartum day 2 (P2) rat pups received lipopolysaccharide (LPS) followed by 90-min HI. Immunohistochemical analyses were performed to determine microglial activation, neutrophil infiltration, BBB damage, and myelin basic protein and glial fibrillary acidic protein expression. Immunofluorescence experiments were performed to determine the cellular distribution of CXCL5. Pharmacological tests were performed to inhibit or enhance CXCL5 activity.ResultsOn P2, predominant increases in microglial activation and BBB damage were observed 24 h after LPS-sensitized HI induction, and white matter injury (decreased myelination and increased astrogliosis) was observed on P12 compared with controls. Immunohistochemical analyses revealed increased CXCL5 expression in the white matter 6 and 24 h after insult. Immunofluorescence experiments revealed upregulated CXCL5 expression in the activated microglia and endothelial cells 24 h after insult. CXCL5 inhibition by SB225002, a selective nonpeptide inhibitor of CXCR2, significantly attenuated microglial activation and BBB damage, increased myelination, and reduced astrogliosis in the white matter after LPS-sensitized HI. In addition, CXCL5-sensitized HI or CXCL5 alone significantly induced BBB damage and white matter injury in association with different neuroinflammation mechanisms. CXCL5-sensitized HI-induced microglial activation and neutrophil infiltration, whereas CXCL5 alone predominately caused neutrophil infiltration.ConclusionsCXCL5 is a potential biomarker for white matter injury in preterm infants. Pharmacological blockade of CXCL5 signaling that attenuates dysregulated neuroinflammation can be used a therapeutic strategy against white matter injury in the immature brain.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-015-0474-6) contains supplementary material, which is available to authorized users.

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Cancers are generally recognized as the leading cause of death and a predominant barrier to prolonging life expectancy in both developed and developing countries. Emodin is a typical anthraquinone derivative from various plants that exhibits a wide spectrum of biological activities, such as anticancer, antibacterial, hepatoprotective and anti-inflammatory activities. Much previous preclinical evidence has demonstrated that emodin exhibits reliable effects on several cancer types, including lung cancer, liver cancer, colon cancer, breast cancer, pancreatic cancer, leukemia, cervical cancer, and ovarian cancer, etc . The related molecular mechanisms corresponding to the anticancer activities of emodin are involved in the induction of apoptosis, inhibition of cell proliferation, enhanced reactive oxygen species (ROS) accumulation, and induction of autophagy, etc . In the present review, we summarized the sources, anticancer properties in vitro and in vivo , molecular mechanisms, metabolic transformation and toxicities of emodin. In addition, we also discussed the limitations of the present investigations of emodin against cancers and gave some perspectives for them, which would be beneficial for the further exploration and development of this natural compound as a clinical cancer drug.

We report complete chloroplast genome of the Tibetan hulless barely using IIlumina Hiseq 2000 sequencing technology (IIlumina Inc., San Diego, CA). The chloroplast genome size is 136 462 bp in length that includes two inverted repeats (IRs) of 10 528 bp, which are separated by the large single copy (LSC 101 375 bp) and small single copy (SSC 14 030 bp). Hulless barely chloroplast genome encodes 76 protein-coding genes, four rRNA genes, and 29 tRNA genes. The maximum-likelihood (ML) phylogenetic tree of the nine complete chloroplast genomes was selected from Poaceae family using Oryza sativa japonica as the out-group, supporting that hulless barely is closely related to the Hordeum vulgare subsp. vulgare.