Endothelin-1 exerts potent vasoconstrictor and vasodilatory effects through its actions on its receptors A (ETrA) and B (ETrB), respectively. While ETrA and B have classically been thought to be expressed on vascular cell types, more recent evidence suggests that, particularly following brain injury, their expression may be seen in other, non-vascular cell types. To date no studies have comprehensively studied the cellular location of endothelin receptors following traumatic brain injury (TBI). Therefore, this study investigates the cellular localization of ETrA and B in normal and traumatized brains using an impact acceleration device. Adult male Sprague-Dawley rats were subjected to TBI by weight drop (450 g) from either 1.5, a distance known to elicit mild TBI in the absence of changed in cerebral blood flow (CBF) or 2 m, a distance shown to cause a significant reduction in CBF. One set of impacted brains were processed for Western determination of ETrA and B expression. Another set were processed for immunofluorescence (IF). For IF, ETrA and ETrB antibodies were combined with cell markers for neurons, astrocytes, microglia, oligodendrocytes, smooth muscle cells and endothelial cells of blood vessels. While ETrA and B was upregulated after more moderate to severe injury (2 m) overall receptor expression was unchanged in response to mild trauma (1.5 m). Double labeling IF confirmed prominent ETrA and ETrB labeling in NeuN labeled pyramidal neurons and interneurons in sensorymotor cortex (smCx) and hippocampus (hipp) post TBI. ETrA rather than ETrB was preferentially co-localized in vascular smooth muscle cells. After injury, a subpopulation of astrocytes in white matter co-localized ETrA but not ETrB. Localization of either receptor in endothelial cells was sparse. No prominent IF was detected in microglia and oligodendrocytes. Taken together with previous findings in other pathological states that show an apparent shift in the localization of ETrA and B, the observed receptor shifts in this work may underlie the ET-1-mediated pathotrajectory of TBI including hypoperfusion.
"Endothelin-1 was higher in the hypoxia group. This peptide and its receptors are widely expressed in different cellular types in central nervous system, including endothelial cells (Kallakuri et al., 2010) and astrocytes (Blomstrand et al., 2004). White matter injury is associated with increase of endothelin-1 levels, with a possible role in the reactive gliosis (Castañeda et al., 2011). "
"It is the most potent vasoconstrictor and is essential for embryonic development, vascular remodeling, and wound healing (19,20). Excessive activation of the ET system can be detrimental, leading to multidimensional pathological conditions, including BBB or BSCB disruption following ischemic brain injury and traumatic SCI, as well as inflammation (20,21). For example, the ET system is found throughout the brain as its components are synthesized in vascular, neuronal, and glial cells. "
[Show abstract][Hide abstract] ABSTRACT: After spinal cord injury (SCI), the disruption of blood-spinal cord barrier by activation of the endothelin (ET) system is a critical event leading to leukocyte infiltration, inflammatory response and oxidative stress, contributing to neurological disability. In the present study, we showed that blockade of ET receptor A (ETAR) and/or ET receptor B (ETBR) prevented early inflammatory responses directly via the inhibition of neutrophil and monocyte diapedesis and inflammatory mediator production following traumatic SCI in mice. Long-term neurological improvement, based on a series of tests of locomotor performance, occurred only in the spinal cord‑injured mice following blockade of ETAR and ETBR. We also examined the post‑traumatic changes of the micro-environment within the injured spinal cord of mice following blockade of ET receptors. Oxidative stress reflects an imbalance between malondialdehyde and superoxide dismutase in spinal cord‑injured mice treated with vehicle, whereas blockade of ETAR and ETBR reversed the oxidation state imbalance. In addition, hemeoxygenase-1, a protective protease involved in early SCI, was increased in spinal cord‑injured mice following the blockade of ETAR and ETBR, or only ETBR. Matrix metalloproteinase-9, a tissue-destructive protease involved in early damage, was decreased in the injured spinal cord of mice following blockade of ETAR, ETBR or a combination thereof. The findings of the present study therefore suggested an association between ETAR and ETBR in regulating early pathogenesis of SCI and determining the outcomes of long‑term neurological recovery.
International Journal of Molecular Medicine 04/2014; 34(1). DOI:10.3892/ijmm.2014.1751 · 2.09 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Semiconductor manufacturers are continually working to reduce
time-to-market in an effort to improve serviceability while decreasing
operating costs. IBMs Microelectronics Division semiconductor
manufacturing facility in Essex Junction, Vermont, recently embarked
upon an initiative to accomplish this with a comprehensive operations
management system. Operations management is a system that groups wafer
processing operations into 24-hour segments, or ranges, incorporating
the raw process times of each processing operation with the required
cycle time of the fabricator. Each day, work in process (WIP) is moved
within each range of each manufacturing operation during a 24-hour
period, thereby creating a productivity flow through the entire line. By
reducing the variability of a lines operations, inventory and cycle time
can be reduced and customer demands met. This paper discusses the
philosophy, planning, and implementation of the operations management
system in this fabricator. It will also discuss traditional operations
management and the theory of constraint management, as well as how,
through a team-oriented effort, the process was modified to fit this
multi-flow, multi-technology process line. Results, challenges and the
learning derived as a result of implementing this management system will
also be shared
Advanced Semiconductor Manufacturing Conference and Workshop, 1997. IEEE/SEMI; 10/1997
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