Peripheral nerve injury: primary sensory neuronal death & regeneration after chronic nerve injury

After a defined unilateral sciatic nerve transection in the rat, a novel triple staining technique was employed in order to enable the detection of neuronal death in L4 & L5 dorsal root ganglia by light microscopic morphology, and TdT Uptake Nick-End Labelling (TUNEL). Optical dissection was then used to quantify neuronal loss from statistically unbiased estimates of the number of surviving neurons. Neuronal death was demonstrated to begin within 24 hours of injury and to peak 2 weeks later, while neuronal loss plateaued 2 months after axotomy, and 39.2% of neurons died overall. Thus the most relevant experimental timepoints at which to examine the effects of putative neuroprotective strategies are 2 weeks and 2 months after axotomy, until which time a window of opportunity exists for therapeutic intervention. The principal that sensory outcome might be related to the delay between injury and nerve repair was confined by the fact that although surgical nerve repair reduced neuronal death 2 weeks after axotomy, the neuroprotective benefit depended upon how soon after injury the nerve was repaired. Even immediate repair did not entirely eliminate neuronal loss, confirming the need for an adjuvent therapy. Hence the effect of two promising agents with established clinical safety records was examined. N-acetyl-cysteine (NAC) is a clinically proven glutathione substrate antioxidant, and anti-mitotic properties. Systemic treatment caused a dose-dependent improvement in neuronal morphology, a significant reduction in the number of TUNEL positive neurons 2 weeks after axotomy (p<0.05), and 2 months after axotomy it was found to have reduced neuronal loss from 35% to only 3% (p<0.001). L-acetyl-carnitine (LAC) is a physiological peptide integral to mitochondrial aerobic glycolysis that was found to be even more neuroprotective than NAC, since after LAC treatment no neuronal loss was detected 2 months after axotomy (no treatment 35% loss; high-dose LAC -4% loss, p<0.001)

Caspase-2 is upregulated after sciatic nerve transection and its inhibition protects dorsal root ganglion neurons from Apoptosis after serum withdrawal

Sciatic nerve (SN) transection-induced apoptosis of dorsal root ganglion neurons (DRGN) is one factor determining the efficacy of peripheral axonal regeneration and the return of sensation. Here, we tested the hypothesis that caspase-2(CASP2) orchestrates apoptosis of axotomised DRGN both in vivo and in vitro by disrupting the local neurotrophic supply to DRGN. We observed significantly elevated levels of cleaved CASP2 (C-CASP2), compared to cleaved caspase-3 (C-CASP3), within TUNEL+DRGN and DRG glia (satellite and Schwann cells) after SN transection. A serum withdrawal cell culture model, which induced 40% apoptotic death in DRGN and 60% in glia, was used to model DRGN loss after neurotrophic factor withdrawal. Elevated C-CASP2 and TUNEL were observed in both DRGN and DRG glia, with C-CASP2 localisation shifting from the cytosol to the nucleus, a required step for induction of direct CASP2-mediated apoptosis. Furthermore, siRNAmediated downregulation of CASP2 protected 50% of DRGN from apoptosis after serum withdrawal, while downregulation of CASP3 had no effect on DRGN or DRG glia survival. We conclude that CASP2 orchestrates the death of SN-axotomised DRGN directly and also indirectly through loss of DRG glia and their local neurotrophic factor support. Accordingly, inhibiting CASP2 expression is a potential therapy for improving both the SN regeneration response and peripheral sensory recovery

The pervasive nature of heterodox economic spaces at a time of neoliberal crisis: towards a “postneoliberal” anarchist future

Re-reading the economic landscape of the western world as a largely non-capitalist landscape composed of economic plurality, this paper demonstrates how economic relations in contemporary western society are often embedded in non-commodified practices such as mutual aid, reciprocity, co-operation and inclusion. By highlighting how the long-overlooked lived practices in the contemporary world of production, consumption and exchange are heavily grounded in the very types and essences of non-capitalist economic relations that have long been proposed by anarchistic visions of employment and organization, this paper displays that such visions are far from utopian: they are embedded firmly in the present. Through focusing on the pervasive nature of heterodox economic spaces in the UK in particular, some ideas about how to develop an anarchist future of work and organization will be proposed. The outcome is to begin to engage in the demonstrative construction of a future based on mutualism and autonomous modes of organization and representation. © 2012 The Authors. Antipode© 2012 Antipode Foundation Ltd.

Quantifying the Impact of Water Abstraction for Low Head ‘Run of the River’ Hydropower on Localized River Channel Hydraulics and Benthic Macroinvertebrates

‘Run of the river’ (ROR) hydropower schemes have undergone a recent resurgence in Europe, and with legislation requiring the protection and enhancement of the physical and ecological condition of European rivers, there is a need to understand the impacts of these schemes. This paper presents an assessment of the eco-hydraulic impact of a ROR hydropower scheme in the Peak District National Park, UK. Due to the ponded nature of the depleted stretch at the study site, this paper focuses on the characterization of the hydraulic impact of water abstraction for a ROR scheme at the hydropower outlet and samples microhabitats of benthic macroinvertebrates within the hydraulically affected zones. Measurement of hydraulic transects shows that the scheme's operation notably alters river channel hydraulics at 60% of water depth, whilst impacts are much less distinct in close proximity to the river bed. We identify eco-hydraulic relationships between benthic macroinvertebrate communities and localized near-bed velocity and turbulence conditions, thus indicating the potential for water abstraction by ROR schemes to impact lower trophic levels of riverine ecosystems. However, spatial patch-scale (10–100 m2) meso-habitat comparisons of invertebrate communities around the hydropower outlet showed only subtle differences, suggesting that in this case benthic communities are only minimally impacted by the ROR scheme

Target-dependence of sensory neurons: An ultrastructural comparison of axotomised dorsal root ganglion neurons with allowed or denied reinnervation of peripheral targets

Evidence is emerging for a role of rough endoplasmic reticulum (RER) in the form of stress granules, the unfolded protein response and protein bodies in the response of neurons to injury and in neurodegenerative diseases. Here, we have studied the role of the peripheral target in regulating the RER and polyribosomes of Nissl bodies in axotomised adult cat dorsal root ganglion (DRG) neurons where axonal regeneration and peripheral target reinnervation was either allowed or denied. Retrograde labelling with horseradish peroxidise was used as an independent marker to enable selection of only those DRG neuronal cell bodies with axons in the injured intercostal nerves. Indications of polyribosomal dispersal were seen by 6 h following axotomy, and by 24 h the normal orderly arrangement of lamellae of RER in Nissl bodies had become disorganised. These ultrastructural changes preceded light microscopical chromatolysis by 1–3 d. The retrograde response was maximal 8–32 d after axotomy. Clusters of debris-laden satellite cells/macrophages were present at this time but no ultrastructural evidence of neuronal apoptosis or necrosis was seen and there were no differences in the initial retrograde response according to the type of injury. By 64 d following axotomy with reinnervation, approximately half the labelled DRG neurons showed restoration of the orderly arrangement of RER and polyribosomes in their Nissl bodies. This was not seen after axotomy with reinnervation denied. We propose that the target-dependent changes in Nissl body ultrastructure described here are part of a continuum that can modify neuronal protein synthesis directed towards growth, maintenance or death of the neuron. This represents a possible structural basis for mediating the varied effects of neurotrophic interactions.I. P. Johnson and T. A. Sear

Beyond Remittance: Evading Uselessness and Seeking Personhood in Fouta Djallon, Guinea

Remittance networks built through transnational migration have transformed local economies as well as social lives in many parts of the world. In this article, I examine the relationship between transnational migration and local business practices for ethnic Fulɓe people from the Fouta Djallon highlands of Guinea. Although some Fouta Djallon residents have withstood poverty with the help of remittances from migrant relatives, many migrants fail to earn money abroad. But despite slim chances of success, migration remains a popular undertaking, especially for young men. Meanwhile, non-migrants engage in small business projects that yield little or no income. Analyzing informants’ critiques of “uselessness,” I argue that both near- impossible migration quests and seemingly irrational business practices are linked by a common desire to achieve social personhood under adverse structural conditions. Apparent striving for success mitigates failure to send or earn money, even while reproducing ideals of mobility and entrepreneurship in responsible personhood

Latitudinal variation in cold hardiness in introduced Tamarix and native Populus

To investigate the evolution of clinal variation in an invasive plant, we compared cold hardiness in the introduced saltcedar (Tamarix ramosissima, Tamarix chinensis, and hybrids) and the native plains cottonwood (Populus deltoides subsp. monilifera). In a shadehouse in Colorado (41°N), we grew plants collected along a latitudinal gradient in the central United States (29–48°N). On 17 occasions between September 2005 and June 2006, we determined killing temperatures using freeze-induced electrolyte leakage and direct observation. In midwinter, cottonwood survived cooling to −70°C, while saltcedar was killed at −33 to −47°C. Frost sensitivity, therefore, may limit northward expansion of saltcedar in North America. Both species demonstrated inherited latitudinal variation in cold hardiness. For example, from September through January killing temperatures for saltcedar from 29.18°N were 5–21°C higher than those for saltcedar from 47.60°N, and on September 26 and October 11, killing temperatures for cottonwood from 33.06°N were >43°C higher than those for cottonwood from 47.60°N. Analysis of nine microsatellite loci showed that southern saltcedars are more closely related to T. chinensis while northern plants are more closely related to T. ramosissima. Hybridization may have introduced the genetic variability necessary for rapid evolution of the cline in saltcedar cold hardiness

Relational economies, social embeddedness and valuing labour in Agrarian change: An example from the developing world.

A relatively neglected area of research on agrarian and economic change is the role of indigenous concepts of labour value in the transition from subsistence to market production. In West New Britain Province, Papua New Guinea, the presence of a migrant population on an oil palm land settlement scheme (LSS) in close proximity to village-based oil palm growers, provided an opportunity to examine changing notions of labour value through the lens of smallholder productivity. Voluntary settlers on the LSS are experiencing population pressure and are highly dependent on oil palm for their livelihoods. In contrast, customary landowners in village settings produce oil palm in a situation of relative land abundance. By examining differences in how these two groups practise and value commodity production, the paper makes four key points. First, concepts of labour value are not static and involve struggles over how labour value is defined. Second, the transition to market-based notions of labour value can undermine labour’s social value with a consequent weakening of social relationships within and between families. Third, Theories of Value developed in western contexts and used to frame development policies and projects in the developing world are often inappropriate and even harmful to the welfare of communities that have different registers of value. Fourth, in response to Point 3, and following Rigg (2007), there is a need for ‘theorising upwards’ using empirical data from the developing world to inform theory rather than applying to the developing world models of sociality and economy developed in western contexts

Expression of ATF3 and axonal outgrowth are impaired after delayed nerve repair

Background: A delay in surgical nerve repair results in impaired nerve function in humans, but mechanisms behind the weakened nerve regeneration are not known. Activating transcription factor 3 (ATF3) increases the intrinsic growth state of injured neurons early after injury, but the role of long-term changes and their relation to axonal outgrowth after a delayed nerve repair are not well understood. ATF3 expression was examined by immunohistochemistry in motor and sensory neurons and in Schwann cells in rat sciatic nerve and related to axonal outgrowth after transection and delayed nerve repair (repair 0, 30, 90 or 180 days post-injury). Expression of the neuronal cell adhesion molecule (NCAM), which is expressed in non-myelinating Schwann cells, was also examined. Results: The number of neurons and Schwann cells expressing ATF3 declined and the length of axonal outgrowth was impaired if the repair was delayed. The decline was more rapid in motor neurons than in sensory neurons and Schwann cells. Regeneration distances over time correlated to number of ATF3 stained neurons and Schwann cells. Many neurofilament stained axons grew along ATF3 stained Schwann cells. If nerve repair was delayed the majority of Schwann cells in the distal nerve segment stained for NCAM. Conclusion: Delayed nerve repair impairs nerve regeneration and length of axonal outgrowth correlates to ATF3 expression in both neurons and Schwann cells. Mainly non-myelinating Schwann cells (NCAM stained) are present in distal nerve segments after delayed nerve repair. These data provide a neurobiological basis for the poor outcomes associated with delayed nerve repair. Nerve trunks should, if possible, be promptly repaired