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Remote Neurodegeneration: Multiple Actors for One Play

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Abstract

Remote neurodegeneration significantly influences the clinical outcome in many central nervous system (CNS) pathologies, such as stroke, multiple sclerosis, and traumatic brain and spinal cord injuries. Because these processes develop days or months after injury, they are accompanied by a therapeutic window of opportunity. The complexity and clinical significance of remote damage is prompting many groups to examine the factors of remote degeneration. This research is providing insights into key unanswered questions, opening new avenues for innovative neuroprotective therapies. In this review, we evaluate data from various remote degeneration models to describe the complexity of the systems that are involved and the importance of their interactions in reducing damage and promoting recovery after brain lesions. Specifically, we recapitulate the current data on remote neuronal degeneration, focusing on molecular and cellular events, as studied in stroke and brain and spinal cord injury models. Remote damage is a multifactorial phenomenon in which many components become active in specific time frames. Days, weeks, or months after injury onset, the interplay between key effectors differentially affects neuronal survival and functional outcomes. In particular, we discuss apoptosis, inflammation, oxidative damage, and autophagy—all of which mediate remote degeneration at specific times. We also review current findings on the pharmacological manipulation of remote degeneration mechanisms in reducing damage and sustaining outcomes. These novel treatments differ from those that have been proposed to limit primary lesion site damage, representing new perspectives on neuroprotection.

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Acknowledgments

This work was supported by the Italian Ministry of Health (Ricerca Corrente - MM), by the Wings for Life Spinal Cord Research Foundation (M.T.V.), by the International Foundation for Research in Paraplegia (IFP) (M.T.V.), and by the program Young Researchers of Italian Ministry of Health (GR10.184; M.T.V.). We thank Prof. G. Bernardi for his continuous support and encouragement. The professional editorial work of Blue Pencil Science is also acknowledged.

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The authors declare that they have no conflict of interest.

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  1. Experimental Neurorehabilitation Laboratory, Santa Lucia Foundation I.R.C.C.S., Via del Fosso di Fiorano 65, 00143, Rome, Italy

    Maria Teresa Viscomi & Marco Molinari

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  1. Maria Teresa Viscomi
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Correspondence to Maria Teresa Viscomi.

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Viscomi, M.T., Molinari, M. Remote Neurodegeneration: Multiple Actors for One Play. Mol Neurobiol 50, 368–389 (2014). https://doi.org/10.1007/s12035-013-8629-x

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