Supply-demand mismatch transients in susceptible peri-infarct hot zones explain the origins of spreading injury depolarizations

SummaryPeri-infarct depolarizations (PIDs) are seemingly spontaneous spreading depression-like waves that negatively impact tissue outcome in both experimental and human stroke. Factors triggering PIDs are unknown. Here, we show that somatosensory activation of peri-infarct cortex triggers PIDs when the activated cortex is within a critical range of ischemia. We show that the mechanism involves increased oxygen utilization within the activated cortex, worsening the supply-demand mismatch. We support the concept by clinical data showing that mismatch predisposes stroke patients to PIDs as well. Conversely, transient worsening of mismatch by episodic hypoxemia or hypotension also reproducibly triggers PIDs. Therefore, PIDs are triggered upon supply-demand mismatch transients in metastable peri-infarct hot zones due to increased demand or reduced supply. Based on the data, we propose that minimizing sensory stimulation and hypoxic or hypotensive transients in stroke and brain injury would reduce PID incidence and their adverse impact on outcome.Video Abstrac

Status report on the geology of the Oak Ridge Reservation

This report provides an introduction to the present state of knowledge of the geology of the Oak Ridge Reservation (ORR) and a cursory introduction to the hydrogeology. An important element of this work is the construction of a modern detailed geologic map of the ORR (Plate 1), which remains in progress. An understanding of the geologic framework of the ORR is essential to many current and proposed activities related to land-use planning, waste management, environmental restoration, and waste remediation. Therefore, this report is also intended to convey the present state of knowledge of the geologic and geohydrologic framework of the ORR and vicinity and to present some of the available data that provide the basic framework for additional geologic mapping, subsurface geologic, and geohydrologic studies. In addition, some recently completed, detailed work on soils and other surficial materials is included because of the close relationships to bedrock geology and the need to recognize the weathered products of bedrock units. Weathering processes also have some influence on hydrologic systems and processes at depth

Bone sialoprotein as a potential key factor implicated in the pathophysiology of osteoarthritis

SummaryObjectiveWe previously identified an association between bone sialoprotein (BSP) and osteoarthritic (OA) chondrocyte hypertrophy but the precise role of BSP in ostearthritis (OA) has not been extensively studied. This study aimed to confirm the association between BSP and OA chondrocyte hypertrophy, to define its effect on molecules produced by chondrocytes and to analyse its association with cartilage degradation and vascular density at the osteochondral junction.MethodHuman OA chondrocytes were cultivated in order to increase hypertrophic differentiation. The effect of parathyroid hormone-related peptide (PTHrP), interleukin (IL)-1β or tumour necrosis factor (TNF)-α on BSP was analysed by real-time reverse transcription polymerase chain reaction (RT-PCR) and western blot. The effects of BSP on OA chondrocytes production of inflammatory response mediators (IL-6, nitric oxide), major matrix molecule (aggrecan), matrix metalloprotease-3 and angiogenic factors (vascular endothelial growth factor, basic fibroblast growth factor, IL-8, and thrombospondin-1) were investigated. BSP was detected by immunohistochemistry and was associated with cartilage lesions severity and vascular density.ResultsPTHrP significantly decreased BSP, confirming its association with chondrocyte hypertrophy. In presence of IL-1β, BSP stimulated IL-8 synthesis, a pro-angiogenic cytokine but decreased the production of TSP-1, an angiogenesis inhibitor. The presence of BSP-immunoreactive chondrocytes in cartilage was associated with the severity of histological cartilage lesions and with vascular density at the osteochondral junction.ConclusionThis study supports the implication of BSP in the pathology of OA and suggests that it could be a key mediator of the hypertrophic chondrocytes-induced angiogenesis. To control chondrocyte hypertrophic differentiation is promising in the treatment of OA