Development of an ex vivo model for the study of cerebrovascular function utilizing isolated mouse olfactory artery

OBJECTIVE: Cerebral vessels, such as intracerebral perforating arterioles isolated from rat brain, have been widely used as an ex vivo model to study the cerebrovascular function associated with cerebrovascular disorders and the therapeutic effects of various pharmacological agents. These perforating arterioles, however, have demonstrated differences in the vascular architecture and reactivity compared with a larger leptomeningeal artery which has been commonly implicated in cerebrovascular disease. In this study, therefore, we developed the method for studying cerebrovascular function utilizing the olfactory artery isolated from the mouse brain. METHODS: The olfactory artery (OA) was isolated from the C57/BL6 wild-type mouse brain. After removing connective tissues, one side of the isolated vessel segment (approximately -500 µm in length) was cannulated and the opposite end of the vessel was completely sealed while being viewed with an inverted microscope. After verifying the absence of pressure leakage, we examined the vascular reactivity to various vasoactive agents under the fixed intravascular pressure (60 mm Hg). RESULTS: We found that the isolated mouse OAs were able to constrict in response to vasoconstrictors, including KCl, phenylephrine, endothelin-1, and prostaglandin PGH(2). Moreover, this isolated vessel demonstrated vasodilation in a dose-dependent manner when vasodilatory agents, acetylcholine and bradykinin, were applied. CONCLUSION: Our findings suggest that the isolated olfactory artery would provide as a useful ex vivo model to study the molecular and cellular mechanisms of vascular function underlying cerebrovascular disorders and the direct effects of such disease-modifying pathways on cerebrovascular function utilizing pharmacological agents and genetically modified mouse models

Recent Application of Bio-Alcohol: Bio-Jet Fuel

Recently, the biomass-based energy production has been actively studied as a research and development area for reducing carbon emissions as a solution to global warming caused by the increase of carbon dioxide emissions. Especially, as the energy consumption in the air transportation field increases, the carbon dioxide emissions increase simultaneously. Therefore, the bio-jet fuel production technology is being actively developed to solve this problem. The bio-jet fuel manufacturing process is a process of manufacturing biomass-derived jet fuel that can replace the existing petroleum-based jet fuel. It includes an alcohol-to-jet (ATJ) process using bio-alcohol such as bio-butanol and bio-ethanol, oil-to-jet (OTJ) process using vegetable oil, and an F-T process using syngas obtained from gasification of biomass-based raw materials

TrkB agonist antibody pretreatment enhances neuronal survival and long-term sensory motor function following hypoxic ischemic injury in neonatal rats

Perinatal hypoxic ischemia (H-I) causes brain damage and long-term neurological impairments, leading to motor dysfunctions and cerebral palsy. Many studies have demonstrated that the TrkB-ERK1/2 signaling pathway plays a key role in mediating the protective effect of brain-derived neurotrophic factor (BDNF) following perinatal H-I brain injury in experimental animals. In the present study, we explored the neuroprotective effects of the TrkB-specific agonist monoclonal antibody 29D7 on H-I brain injury in neonatal rats. First, we found that intracerebroventricular (icv) administration of 29D7 in normal P7 rats markedly increased the levels of phosphorylated ERK1/2 and phosphorylated AKT in neurons up to 24 h. Second, P7 rats received icv administration of 29D7 and subjected to H-I injury induced by unilateral carotid artery ligation and exposure to hypoxia (8% oxygen). We found that 29D7, to a similar extent to BDNF, significantly inhibited activation of caspase-3, a biochemical hallmark of apoptosis, following H-I injury. Third, we found that this 29D7-mediated neuroprotective action persisted at least up to 5 weeks post-H-I injury as assessed by brain tissue loss, implicating long-term neurotrophic effects rather than an acute delay of cell death. Moreover, the long-term neuroprotective effect of 29D7 was tightly correlated with sensorimotor functional recovery as assessed by a tape-removal test, while 29D7 did not significantly improve rotarod performance. Taken together, these findings demonstrate that pretreatment with the TrkB-selective agonist 29D7 significantly increases neuronal survival and behavioral recovery following neonatal hypoxic-ischemic brain injury

N-(2,5-Dimeth­oxy­phen­yl)-N′-(4-hy­droxy­pheneth­yl)urea

In the title compound, C17H20N2O4, the 2,5-dimeth­oxy­phenyl unit is almost planar, with an r.m.s. deviation of 0.015 Å. The dihedral angle between the 2,5-dimeth­oxy­phenyl ring and the urea plane is 20.95 (8)°. The H atoms of the urea NH groups are positioned syn to each other. The mol­ecular structure is stabilized by a short intra­molecular N—H⋯O hydrogen bond. In the crystal, inter­molecular N—H⋯O and O—H⋯O hydrogen bonds link the mol­ecules into a three-dimensional network

1-[3-(Hy­droxy­meth­yl)phen­yl]-3-phenyl­urea

In the title compound, C14H14N2O2, the dihedral angle between the benzene rings is 23.6 (1)°. The H atoms of the urea NH groups are positioned syn to each other. In the crystal, inter­molecular N—H⋯O and O—H⋯O hydrogen bonds link the mol­ecules into a three-dimensional network

Characterization of Mammalian Selenoprotein O: A Redox-Active Mitochondrial Protein

Selenoproteins exhibit diverse biological functions, most of which are associated with redox control. However, the functions of approximately half of mammalian selenoproteins are not known. One such protein is Selenoprotein O (SelO), the largest mammalian selenoprotein with orthologs found in a wide range of organisms, including bacteria and yeast. Here, we report characterization of mammalian SelO. Expression of this protein could be verified in HEK 293T cells by metabolic labeling of cells with 75Se, and it was abolished when selenocysteine was replaced with serine. A CxxU motif was identified in the C-terminal region of SelO. This protein was reversibly oxidized in a time- and concentration-dependent manner in HEK 293T cells when cells were treated with hydrogen peroxide. This treatment led to the formation of a transient 88 kDa SelO-containing complex. The formation of this complex was enhanced by replacing the CxxU motif with SxxC, but abolished when it was replaced with SxxS, suggesting a redox interaction of SelO with another protein through its Sec residue. SelO was localized to mitochondria and expressed across mouse tissues. Its expression was little affected by selenium deficiency, suggesting it has a high priority for selenium supply. Taken together, these results show that SelO is a redox-active mitochondrial selenoprotein