Erythropoietin: a multimodal neuroprotective agent

The tissue protective functions of the hematopoietic growth factor erythropoietin (EPO) are independent of its action on erythropoiesis. EPO and its receptors (EPOR) are expressed in multiple brain cells during brain development and upregulated in the adult brain after injury. Peripherally administered EPO crosses the blood-brain barrier and activates in the brain anti-apoptotic, anti-oxidant and anti-inflammatory signaling in neurons, glial and cerebrovascular endothelial cells and stimulates angiogenesis and neurogenesis. These mechanisms underlie its potent tissue protective effects in experimental models of stroke, cerebral hemorrhage, traumatic brain injury, neuroinflammatory and neurodegenerative disease. The preclinical data in support of the use of EPO in brain disease have already been translated to first clinical pilot studies with encouraging results with the use of EPO as a neuroprotective agent

Restoration versus reconstruction: cellular mechanisms of skin, nerve and muscle regeneration compared

In tissues characterized by a high turnover or following acute injury, regeneration replaces damaged cells and is involved in adaptation to external cues, leading to homeostasis of many tissues during adult life. An understanding of the mechanics underlying tissue regeneration is highly relevant to regenerative medicine-based interventions. In order to investigate the existence a leitmotif of tissue regeneration, we compared the cellular aspects of regeneration of skin, nerve and skeletal muscle, three organs characterized by different types of anatomical and functional organization. Epidermis is a stratified squamous epithelium that migrates from the edge of the wound on the underlying dermis to rebuild lost tissue. Peripheral neurons are elongated cells whose neurites are organized in bundles, within an endoneurium of connective tissue; they either die upon injury or undergo remodeling and axon regrowth. Skeletal muscle is characterized by elongated syncytial cells, i.e. muscle fibers, that can temporarily survive in broken pieces; satellite cells residing along the fibers form new fibers, which ultimately fuse with the old ones as well as with each other to restore the previous organization. Satellite cell asymmetrical division grants a reservoir of undifferentiated cells, while other stem cell populations of muscle and non-muscle origin participate in muscle renewal. Following damage, all the tissues analyzed here go through three phases: inflammation, regeneration and maturation. Another common feature is the occurrence of cellular de-differentiation and/or differentiation events, including gene transcription, which are typical of embryonic development. Nonetheless, various strategies are used by different tissues to replace their lost parts. The epidermis regenerates ex novo, whereas neurons restore their missing parts; muscle fibers use a mixed strategy, based on the regrowth of missing parts through reconstruction by means of newborn fibers. The choice of either strategy is influenced by the anatomical, physical and chemical features of the cells as well as by the extracellular matrix typical of a given tissue, which points to the existence of differential, evolutionary-based mechanisms for specific tissue regeneration. The shared, ordered sequence of steps that characterize the regeneration processes examined suggests it may be possible to model this extremely important phenomenon to reproduce multicellular organisms

Effects of the carbamylated erythropoietin (CEPO) on the expression of aquaporin 4 in a model of cerebral edema following traumatic brain injury in the rat

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