Extrinsic and intrinsic determinants of nerve regeneration

After central nervous system (CNS) injury axons fail to regenerate often leading to persistent neurologic deficit although injured peripheral nervous system (PNS) axons mount a robust regenerative response that may lead to functional recovery. Some of the failures of CNS regeneration arise from the many glial-based inhibitory molecules found in the injured CNS, whereas the intrinsic regenerative potential of some CNS neurons is actively curtailed during CNS maturation and limited after injury. In this review, the molecular basis for extrinsic and intrinsic modulation of axon regeneration within the nervous system is evaluated. A more complete understanding of the factors limiting axonal regeneration will provide a rational basis, which is used to develop improved treatments for nervous system injury

Sustained Delivery of Activated Rho GTPases and BDNF Promotes Axon Growth in CSPG-Rich Regions Following Spinal Cord Injury

Background: Spinal cord injury (SCI) often results in permanent functional loss. This physical trauma leads to secondary events, such as the deposition of inhibitory chondroitin sulfate proteoglycan (CSPG) within astroglial scar tissue at the lesion. Methodology/Principal Findings: We examined whether local delivery of constitutively active (CA) Rho GTPases, Cdc42 and Rac1 to the lesion site alleviated CSPG-mediated inhibition of regenerating axons. A dorsal over-hemisection lesion was created in the rat spinal cord and the resulting cavity was conformally filled with an in situ gelling hydrogel combined with lipid microtubes that slowly released constitutively active (CA) Cdc42, Rac1, or Brain-derived neurotrophic factor (BDNF). Treatment with BDNF, CA-Cdc42, or CA-Rac1 reduced the number of GFAP-positive astrocytes, as well as CSPG deposition, at the interface of the implanted hydrogel and host tissue. Neurofilament 160kDa positively stained axons traversed the glial scar extensively, entering the hydrogel-filled cavity in the treatments with BDNF and CA-Rho GTPases. The treated animals had a higher percentage of axons from the corticospinal tract that traversed the CSPG-rich regions located proximal to the lesion site. Conclusion: Local delivery of CA-Cdc42, CA-Rac1, and BDNF may have a significant therapeutic role in overcoming CSPGmediate

ccdc80-l1 Is Involved in Axon Pathfinding of Zebrafish Motoneurons

Axon pathfinding is a subfield of neural development by which neurons send out axons to reach the correct targets. In particular, motoneurons extend their axons toward skeletal muscles, leading to spontaneous motor activity. In this study, we identified the zebrafish Ccdc80 and Ccdc80-like1 (Ccdc80-l1) proteins in silico on the basis of their high aminoacidic sequence identity with the human CCDC80 (Coiled-Coil Domain Containing 80). We focused on ccdc80-l1 gene that is expressed in nervous and non-nervous tissues, in particular in territories correlated with axonal migration, such as adaxial cells and muscle pioneers. Loss of ccdc80-l1 in zebrafish embryos induced motility issues, although somitogenesis and myogenesis were not impaired. Our results strongly suggest that ccdc80-l1 is involved in axon guidance of primary and secondary motoneurons populations, but not in their proper formation. ccdc80-l1 has a differential role as regards the development of ventral and dorsal motoneurons, and this is consistent with the asymmetric distribution of the transcript. The axonal migration defects observed in ccdc80-l1 loss-of-function embryos are similar to the phenotype of several mutants with altered Hedgehog activity. Indeed, we reported that ccdc80-l1 expression is positively regulated by the Hedgehog pathway in adaxial cells and muscle pioneers. These findings strongly indicate ccdc80-l1 as a down-stream effector of the Hedgehog pathway

Inflammogenesis of Secondary Spinal Cord Injury

Spinal cord injury (SCI) and spinal infarction lead to neurological complications and eventually to paraplegia or quadriplegia. These extremely debilitating conditions are major contributors to morbidity. Our understanding of SCI has certainly increased during the last decade, but remains far from clear. SCI consists of two defined phases: the initial impact causes primary injury, which is followed by a prolonged secondary injury consisting of evolving sub-phases that may last for years. The underlying pathophysiological mechanisms driving this condition are complex. Derangement of the vasculature is a notable feature of the pathology of SCI. In particular, an important component of SCI is the ischemia-reperfusion injury (IRI) that leads to endothelial dysfunction and changes in vascular permeability. Indeed, together with endothelial cell damage and failure in homeostasis, ischemia reperfusion injury triggers full-blown inflammatory cascades arising from activation of residential innate immune cells (microglia and astrocytes) and infiltrating leukocytes (neutrophils and macrophages). These inflammatory cells release neurotoxins (proinflammatory cytokines and chemokines, free radicals, excitotoxic amino acids, nitric oxide (NO)), all of which partake in axonal and neuronal deficit. Therefore, our review considers the recent advances in SCI mechanisms, whereby it becomes clear that SCI is a heterogeneous condition. Hence, this leads towards evidence of a restorative approach based on monotherapy with multiple targets or combinatorial treatment. Moreover, from evaluation of the existing literature, it appears that there is an urgent requirement for multi-centered, randomized trials for a large patient population. These clinical studies would offer an opportunity in stratifying SCI patients at high risk and selecting appropriate, optimal therapeutic regimens for personalized medicine.Grant #NPRP 4-571-3-171 from the Qatar National Research Fund(a member of Qatar Foundation)

Dosimetry tools and techniques for IMRT

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98734/1/MPH001313.pd

Anglo-Saxon crops and weeds: a case study in quantitative archaeobotany

There is a growing recognition within Anglo-Saxon archaeology that farming practices underwent momentous transformations in the Mid Saxon period, between the seventh and ninth centuries AD: transformations which underpinned the growth of the Anglo-Saxon kingdoms and, arguably, set the trajectory for English agricultural development for centuries to come. Meanwhile, in the field of archaeobotany, a growing set of quantitative methods has been developed to facilitate the systematic investigation of agricultural change through the study of charred plant remains. This study applies a standardised set of repeatable quantitative analyses to the charred remains of Anglo-Saxon crops and weeds, to shed light on crucial developments in crop husbandry between the seventh and ninth centuries. The analyses demonstrate the significance of the Anglo-Saxon archaeobotanical record in elucidating how greater crop surpluses were attained through ecologically-sensitive diversification and specialisation strategies in this period. At the same time, assumptions, variables and key parameters are presented fully and explicitly to facilitate repetition of the work, thus also enabling the book to be used as a source of comparative data and a methodological handbook for similar research in other periods and places. It constitutes a specialist, data-driven companion volume to the author’s more general narrative account published as Farming Transformed in Anglo-Saxon England (Windgather, 2018). </p

Anglo-Saxon crops and weeds: a case study in quantitative archaeobotany

There is a growing recognition within Anglo-Saxon archaeology that farming practices underwent momentous transformations in the Mid Saxon period, between the seventh and ninth centuries AD: transformations which underpinned the growth of the Anglo-Saxon kingdoms and, arguably, set the trajectory for English agricultural development for centuries to come. Meanwhile, in the field of archaeobotany, a growing set of quantitative methods has been developed to facilitate the systematic investigation of agricultural change through the study of charred plant remains. This study applies a standardised set of repeatable quantitative analyses to the charred remains of Anglo-Saxon crops and weeds, to shed light on crucial developments in crop husbandry between the seventh and ninth centuries. The analyses demonstrate the significance of the Anglo-Saxon archaeobotanical record in elucidating how greater crop surpluses were attained through ecologically-sensitive diversification and specialisation strategies in this period. At the same time, assumptions, variables and key parameters are presented fully and explicitly to facilitate repetition of the work, thus also enabling the book to be used as a source of comparative data and a methodological handbook for similar research in other periods and places. It constitutes a specialist, data-driven companion volume to the author’s more general narrative account published as Farming Transformed in Anglo-Saxon England (Windgather, 2018). </p

Archaeology and agriculture: insights from an Essex farmer

Following the publication of his book Farming Transformed in Anglo-Saxon England (Windgather, 2018), an archaeological study of agricultural development in seventh- to ninth-century England, Mark McKerracher heard from a number of readers