Docosahexaenoic Acid Promotes Recovery of Motor Function by Neuroprotection and Neuroplasticity Mechanisms

The omega-3 polyunsaturated fatty acid, docosahexaenoic acid (DHA), has been shown to promote recovery of motor function after spinal cord injury. This is likely to be at least partly due to neuroprotective effects of DHA. However, recent studies have shown that DHA also supports neuroplasticity after injury, such as promoting sprouting of spared corticospinal tract (CST) axons. In this chapter, we review the published studies showing that DHA promotes recovery of motor function in rodent models of spinal cord injury (SCI), and consider the available data on the underlying mechanisms. This includes effects on inflammation and on neuronal and oligodendrocyte survival at the injury site, and effects on spared CST axons and serotonergic axons. Current data support the hypothesis that DHA promotes recovery of motor function by both neuroprotection and neuroplasticity mechanisms. The significance of this, and the implications of combining DHA with rehabilitation strategies, will be discussed

Comparative analysis of the time-dependent functional and molecular changes in spinal cord degeneration induced by the G93A SOD1 gene mutation and by mechanical compression

Peer reviewedPublisher PD

The human G93A-SOD1 mutation in a pre-symptomatic rat model of amyotrophic lateral sclerosis increases the vulnerability to a mild spinal cord compression

<p>Abstract</p> <p>Background</p> <p>Traumatic injuries can undermine neurological functions and act as risk factors for the development of irreversible and fatal neurodegenerative disorders like amyotrophic lateral sclerosis (ALS). In this study, we have investigated how a mutation of the superoxide dismutase 1 (SOD1) gene, linked to the development of ALS, modifies the acute response to a gentle mechanical compression of the spinal cord. In a 7-day post-injury time period, we have performed a comparative ontological analysis of the gene expression profiles of injured spinal cords obtained from pre-symptomatic rats over-expressing the G93A-SOD1 gene mutation and from wild type (WT) littermates.</p> <p>Results</p> <p>The steady post-injury functional recovery observed in WT rats was accompanied by the early activation at the epicenter of injury of several growth-promoting signals and by the down-regulation of intermediate neurofilaments and of genes involved in the regulation of ion currents at the 7 day post-injury time point. The poor functional recovery observed in G93A-SOD1 transgenic animals was accompanied by the induction of fewer pro-survival signals, by an early activation of inflammatory markers, of several pro-apoptotic genes involved in cytochrome-C release and by the persistent up-regulation of the heavy neurofilament subunits and of genes involved in membrane excitability. These molecular changes occurred along with a pronounced atrophy of spinal cord motor neurones in the G93A-SOD1 rats compared to WT littermates after compression injury.</p> <p>Conclusions</p> <p>In an experimental paradigm of mild mechanical trauma which causes no major tissue damage, the G93A-SOD1 gene mutation alters the balance between pro-apoptotic and pro-survival molecular signals in the spinal cord tissue from the pre-symptomatic rat, leading to a premature activation of molecular pathways implicated in the natural development of ALS.</p

The spatiotemporal localization of JAM-C following sciatic nerve crush in adult rats

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Working, travelling, and identity: J.B. Priestley’s English Journey (1934)

The motivation for travel is central to its form and content. This article addresses an under-represented area of travel writing: the travel text that results from a journey undertaken for work purposes. By considering J. B. Priestley’s English Journey as a case-study, it argues that the text’s critical reception, at first disorientated and confused, and later dominated by historical and political readings, has resulted from Priestley’s emphasis on work rather than leisure. In his text Priestley explores the relationship of work and identity, and his own position as writer and traveller is central to this, symbolised in his preoccupation with the figure of the travelling salesman

Brain phospholipid precursors administered post-injury reduce tissue damage and improve neurological outcome in experimental traumatic brain injury

Traumatic brain injury (TBI) leads to cellular loss, destabilisation of membranes, disruption of synapses and altered brain connectivity, and increased risk of neurodegenerative disease. A significant and long-lasting decrease in phospholipids (PL), essential membrane constituents, has recently been reported in plasma and brain tissue, in human and experimental TBI. We hypothesised that supporting PL synthesis post-injury could improve outcome after TBI. We tested this hypothesis using a multi-nutrient combination designed to support the biosynthesis of phospholipids and available for clinical use. The multi-nutrient Fortasyn® Connect (FC) contains polyunsaturated omega-3 fatty acids, choline, uridine, vitamins, co-factors required for PL biosynthesis, and has been shown to have significant beneficial effects in early Alzheimer's disease. Male C57BL/6 mice received a controlled cortical impact injury and then were fed a control diet or a diet enriched with FC for 70 days. FC led to a significantly improved sensorimotor outcome and cognition, reduced lesion size and oligodendrocyte loss, and it restored myelin. It reversed the loss of the synaptic protein synaptophysin and decreased levels of the axon growth inhibitor Nogo-A, thus creating a permissive environment. It decreased microglia activation and the rise in ß-amyloid precursor protein and restored the depressed neurogenesis. The effects of this medical multi-nutrient suggest that support of PL biosynthesis after TBI, a new treatment paradigm, has significant therapeutic potential in this neurological condition for which there is no satisfactory treatment. The multi-nutrient tested has been used in dementia patients, is safe and well-tolerated, which would enable rapid clinical exploration in TBI