Efficacy of N-acetyl cysteine in traumatic brain injury

In this study, using two different injury models in two different species, we found that early post-injury treatment with NAcetyl Cysteine (NAC) reversed the behavioral deficits associated with the TBI. These data suggest generalization of a protocol similar to our recent clinical trial with NAC in blast-induced mTBI in a battlefield setting [1], to mild concussion from blunt trauma. This study used both weight drop in mice and fluid percussion injury in rats. These were chosen to simulate either mild or moderate traumatic brain injury (TBI). For mice, we used novel object recognition and the Y maze. For rats, we used the Morris water maze. NAC was administered beginning 30-60 minutes after injury. Behavioral deficits due to injury in both species were significantly reversed by NAC treatment. We thus conclude NAC produces significant behavioral recovery after injury. Future preclinical studies are needed to define the mechanism of action, perhaps leading to more effective therapies in man

Delayed administration of a matrix metalloproteinase inhibitor limits progressive brain injury after hypoxia-ischemia in the neonatal rat

<p>Abstract</p> <p>Background</p> <p>Hypoxia-ischemia (H-I) can produce widespread neurodegeneration and deep cerebral white matter injury in the neonate. Resident microglia and invading leukocytes promote lesion progression by releasing reactive oxygen species, proteases and other pro-inflammatory mediators. After injury, expression of the gelatin-degrading matrix metalloproteinases (MMPs), MMP-2 and MMP-9, are thought to result in the proteolysis of extracellular matrix (ECM), activation of cytokines/chemokines, and the loss of vascular integrity. Thus, therapies targeting ECM degradation and progressive neuroinflammation may be beneficial in reducing H-I – induced neuropathy. Minocycline has MMP-inhibitory properties and is both anti-inflammatory and neuroprotective. AG3340 (prinomastat) is an MMP inhibitor with high selectivity for the gelatinases. The purpose of this study was to determine whether these compounds could limit H-I – induced injury when administered at a delayed time point.</p> <p>Methods</p> <p>Sprague-Dawley rats were exposed to H-I at postnatal day 7 (P7), consisting of unilateral carotid artery ligation followed by 90 min exposure to 8% O₂. Minocycline, AG3340, or vehicle were administered once daily for 6 days, beginning 24 hours after insult. Animals were sacrificed at P14 for neurohistological assessments. Immunohistochemistry was performed to determine the degree of reactive astrogliosis and immune cell activation/recruitment. Neural injury was detected using the Fluoro-Jade stain, a marker that identifies degenerating cells.</p> <p>Results</p> <p>CD11b and glial fibrillary acidic protein (GFAP) immunopositive cells increased in ipsilateral cortex after treatment with vehicle alone, demonstrating microglia/macrophage recruitment and reactive astrogliosis, respectively. Fluoro-Jade staining was markedly increased throughout the fronto-parietal cortex, striatum and hippocampus. Treatment with minocycline or AG3340 inhibited microglia/macrophage recruitment, attenuated astrogliosis and reduced Fluoro-Jade staining when compared to vehicle alone.</p> <p>Conclusion</p> <p>The selective gelatinase inhibitor AG3340 showed equal efficacy in reducing neural injury and dampening neuroinflammation when compared to the anti-inflammatory compound minocycline. Thus, MMP-2 and MMP-9 may be viable therapeutic targets to treat neonatal brain injury.</p

Internal deformation of the subducted Nazca slab inferred from seismic anisotropy

Within oceanic lithosphere a fossilized fabric is often preserved originating from the time of plate formation. Such fabric is thought to form at the mid-ocean ridge when olivine crystals align with the direction of plate spreading1, 2. It is unclear, however, whether this fossil fabric is preserved within slabs during subduction or overprinted by subduction-induced deformation. The alignment of olivine crystals, such as within fossil fabrics, can generate anisotropy that is sensed by passing seismic waves. Seismic anisotropy is therefore a useful tool for investigating the dynamics of subduction zones, but it has so far proved difficult to observe the anisotropic properties of the subducted slab itself. Here we analyse seismic anisotropy in the subducted Nazca slab beneath Peru and find that the fast direction of seismic wave propagation aligns with the contours of the slab. We use numerical modelling to simulate the olivine fabric created at the mid-ocean ridge, but find it is inconsistent with our observations of seismic anisotropy in the subducted Nazca slab. Instead we find that an orientation of the olivine crystal fast axes aligned parallel to the strike of the slab provides the best fit, consistent with along-strike extension induced by flattening of the slab during subduction (A. Kumar et al., manuscript in preparation). We conclude that the fossil fabric has been overprinted during subduction and that the Nazca slab must therefore be sufficiently weak to undergo internal deformation

Public Sector Reform and Governance for Adaptation: Implications of New Public Management for Adaptive Capacity in Mexico and Norway

Although many governments are assuming the responsibility of initiating adaptation policy in relation to climate change, the compatibility of “governance-for-adaptation” with the current paradigms of public administration has generally been overlooked. Over the last several decades, countries around the globe have embraced variants of the philosophy of administration broadly called “New Public Management” (NPM) in an effort to improve administrative efficiencies and the provision of public services. Using evidence from a case study of reforms in the building sector in Norway, and a case study of water and flood risk management in central Mexico, we analyze the implications of the adoption of the tenets of NPM for adaptive capacity. Our cases illustrate that some of the key attributes associated with governance for adaptation—namely, technical and financial capacities; institutional memory, learning and knowledge; and participation and accountability—have been eroded by NPM reforms. Despite improvements in specific operational tasks of the public sector in each case, we show that the success of NPM reforms presumes the existence of core elements of governance that have often been found lacking, including solid institutional frameworks and accountability. Our analysis illustrates the importance of considering both longer-term adaptive capacities and short-term efficiency goals in public sector administration reform

Changing geo-ecological functions of coral reefs in the Anthropocene

This is the author accepted manuscript. The final version is available from Wiley via the DOI in this record The ecology of many coral reefs has changed markedly over recent decades in response to various combinations of local and global stressors. These ecological changes have important implications for the abundance of taxa that regulate the production and erosion of skeletal carbonates, and thus for many of the geo-ecological functions that coral reefs provide, including reef framework production and sediment generation, the maintenance of reef habitat complexity and reef growth potential. These functional attributes underpin many of the ecosystem goods and services that reefs provide to society. Rapidly changing conditions of reefs in the Anthropocene are likely to significantly impact the capacity of reefs to sustain these geo-ecological functions. Although the Anthropocene footprint of disturbance will be expressed differently across ecoregions and habitats, the end point for many reefs may be broadly similar: (a) progressively shifting towards net neutral or negative carbonate budget states; (b) becoming structurally flatter; and (c) having lower vertical growth rates. It is also likely that a progressive depth-homogenisation will occur in terms of these processes. The Anthropocene is likely to be defined by an increasing disconnect between the ecological processes that drive carbonate production on the reef surface, and the net geological outcome of that production, that is, the accumulation of the underlying reef structure. Reef structures are thus likely to become increasingly relict or senescent features, which will reduce reef habitat complexity and sediment generation rates, and limit reef potential to accrete vertically at rates that can track rising sea levels. In the absence of pervasive stressors, recovery of degraded coral communities has been observed, resulting in high net-positive budgets being regained. However, the frequency and intensity of climate-driven bleaching events are predicted to increase over the next decades. This would increase the spatial footprint of disturbances and exacerbate the magnitude of the changes described here, limiting the capacity of many reefs to maintain their geo-ecological functions. The enforcement of effective marine protection or the benefits of geographic isolation or of favourable environmental conditions (“refugia” sites) may offer the hope of more optimistic futures in some locations. A plain language summary is available for this article.Royal Societ

High-resolution Sr/Ca ratios in a Porites lutea coral from Lakshadweep Archipelago, southeast Arabian Sea: An example from a region experiencing steady rise in the reef temperature

Here we present the first record of Sr/Ca variability in a massive Porites lutea coral from the Lakshadweep Archipelago, Arabian Sea. The annual mean sea surface temperature (SST) in this region and the surrounding areas has increased steadily in the recent past. During some major El Nino events, SSTs are even higher, imposing additional thermal-stress on corals, episodically leading to coral bleaching. We infer from the coral-Sr/Ca record (1981-2008) that during some of these events high and persistent SSTs lead to a dampening of the temperature signal in coral-Sr/Ca, impairing the coral's ability to record full scale warming. Thus, coral-Sr/Ca may provide a history of past El Nino Southern-Oscillation (ENSO) induced thermal-stress episodes, which are a recurrent feature also seen in cross-spectral analysis between coral-Sr/Ca and the Nino3.4 index. Despite the impact of episodical thermal-stress during major El Nino events, our coral proxy faithfully records the seasonal monsoon-induced summer cooling on the order of approximate to 2.3 degrees C. Calibration of coral-Sr/Ca with instrumental grid-SST data shows significant correlation to regional SST and monsoon variability. Hence, massive Porites corals of this region are highly valuable archives for reconstructing long-term changes in SST, strongly influenced by monsoon variability on seasonal scales. More importantly, our data show that this site with increasing SST is an ideal location for testing the future effects of the projected anthropogenic SST increase on coral reefs that are already under thermal-stress worldwide

Opinion: Urban Resilience Efforts Must Consider Social And Political Forces

Environmental disasters, ranging from catastrophic floods to extreme temperatures, have caused more than 30,000 deaths per year and more than US$ 250–300 billion a year in economic losses, globally, between 1995 and 2015. Improved infrastructure and planning for extreme events is essential in urban areas, where an increasingly greater fraction of the world’s inhabitants reside. In response, international governmental and private initiatives have placed the goal of resilience at the center stage of urban planning. [For example, The 100 Resilient Cities Initiative (www.100resilientcities.org/); the Global Covenant of Mayors (https://www.compactofmayors.org/globalcovenantofmayors/); and the recent UN Habitat III (https://habitat3.org/the-new-urban-agenda)]. In addition, scientific and policy communities alike now recognize the need for “safe-to-fail” infrastructural design, and the potential role of green and blue infrastructure in mediating hydrological and climatic risks in cities