46 research outputs found
Virus-mediated EpoR76E gene therapy preserves vision in a glaucoma model by modulating neuroinflammation and decreasing oxidative stress
A Novel Closed-Head Model of Mild Traumatic Brain Injury Caused by Primary Overpressure Blast to the Cranium Produces Sustained Emotional Deficits in Mice
Emotional disorders are a common outcome from mild traumatic brain injury (TBI) in humans, but their pathophysiological basis is poorly understood. We have developed a mouse model of closed-head blast injury using an air pressure wave delivered to a small area on one side of the cranium, to create mild TBI. We found that 20-psi blasts in 3-month-old C57BL/6 male mice yielded no obvious behavioral or histological evidence of brain injury, while 25ā40āpsi blasts produced transient anxiety in an open field arena but little histological evidence of brain damage. By contrast, 50ā60āpsi blasts resulted in anxiety-like behavior in an open field arena that became more evident with time after blast. In additional behavioral tests conducted 2ā8āweeks after blast, 50ā60āpsi mice also demonstrated increased acoustic startle, perseverance of learned fear, and enhanced contextual fear, as well as depression-like behavior and diminished prepulse inhibition. We found no evident cerebral pathology, but did observe scattered axonal degeneration in brain sections from 50 to 60āpsi mice 3ā8āweeks after blast. Thus, the TBI caused by single 50ā60āpsi blasts in mice exhibits the minimal neuronal loss coupled to ādiffuseā axonal injury characteristic of human mild TBI. A reduction in the abundance of a subpopulation of excitatory projection neurons in basolateral amygdala enriched in Thy1 was, however, observed. The reported link of this neuronal population to fear suppression suggests their damage by mild TBI may contribute to the heightened anxiety and fearfulness observed after blast in our mice. Our overpressure air blast model of concussion in mice will enable further studies of the mechanisms underlying the diverse emotional deficits seen after mild TBI
Systemic but not intraocular Epo Gene Transfer Protects the Retina from Light-and Genetic-Induced Degeneration
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Virus-mediated EpoR76E gene therapy preserves vision in a glaucoma model by modulating neuroinflammation and decreasing oxidative stress
Evidence that erythropoietin modulates neuroinflammation through differential action on neurons, astrocytes, and microglia
Neuroinflammation is a normal and healthy response to neuronal damage. However, excessive or chronic neuroinflammation exacerbates neurodegeneration after trauma and in progressive diseases such as Alzheimerās, Parkinsonās, age-related macular degeneration, and glaucoma. Therefore, molecules that modulate neuroinflammation are candidates as neuroprotective agents. Erythropoietin (EPO) is a known neuroprotective agent that indirectly attenuates neuroinflammation, in part, by inhibiting neuronal apoptosis. In this review, we provide evidence that EPO also modulates neuroinflammation upstream of apoptosis by acting directly on glia. Further, the signaling induced by EPO may differ depending on cell type and context possibly as a result of activation of different receptors. While significant progress has been made in our understanding of EPO signaling, this review also identifies areas for future study in terms of the role of EPO in modulating neuroinflammation
Correction: Neurodegeneration and Vision Loss after Mild Blunt Trauma in the C57Bl/6 and DBA/2J Mouse.
[This corrects the article DOI: 10.1371/journal.pone.0131921.]