title: Clinical and neurobiological advances in promoting regeneration of the ventral root avulsion lesion.
abstract: Root avulsions due to traction to the brachial plexus causes complete and permanent loss of function. Until fairly recent, such lesions were considered impossible to repair. Here we review clinical repair strategies and current progress in experimental ventral root avulsion lesions. The current gold standard in patients with a root avulsion is nerve transfer, whereas reimplantation of the avulsed root into the spinal cord has been performed in a limited number of cases. These neurosurgical repair strategies have significant benefit for the patient but functional recovery remains incomplete. Developing new ways to improve the functional outcome of neurosurgical repair is therefore essential. In the laboratory, the molecular and cellular changes following ventral root avulsion and the efficacy of intervention strategies have been studied at the level of spinal motoneurons, the ventral spinal root and peripheral nerve, and the skeletal muscle. We present an overview of cell-based pharmacological and neurotrophic factor treatment approaches that have been applied in combination with surgical reimplantation. These interventions all demonstrate neuroprotective effects on avulsed motoneurons, often accompanied with various degrees of axonal regeneration. However, effects on survival are usually transient and robust axon regeneration over long distances has as yet not been achieved. Key future areas of research include finding ways to further extend the post-lesion survival period of motoneurons, the identification of neuron-intrinsic factors which can promote persistent and long-distance axon regeneration, and finally prolonging the pro-regenerative state of Schwann cells in the distal nerve.
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, the Netherlands.
authors.forename: Ruben
authors.initials: R
authors.lastname: Eggers
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, the Netherlands.|Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Martijn R
authors.initials: MR
authors.lastname: Tannemaat
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, the Netherlands.|Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Fred
authors.initials: F
authors.lastname: De Winter
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, the Netherlands.|Department of Neurosurgery, Leiden University Medical Center, Leiden, the Netherlands.
authors.forename: Martijn J A
authors.initials: MJ
authors.lastname: Malessy
authors.affiliation: Laboratory for Neuroregeneration, Netherlands Institute for Neuroscience, Meibergdreef 47, 1105 BA, Amsterdam, the Netherlands.|Department of Molecular and Cellular Neurobiology, Center for Neurogenomics and Cognition research, Vrije Universiteit Amsterdam, Amsterdam, the Netherlands.
authors.forename: Joost
authors.initials: J
authors.lastname: Verhaagen
mesh_terms: D000818:Animals; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D009416:Nerve Regeneration; D018696:Neuroprotective Agents / Q000627:therapeutic use; D011843:Radiculopathy / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D013126:Spinal Nerve Roots / Q000378:metabolism / Q000503:physiopathology*; D033581:Stem Cell Transplantation / Q000379:methods
chemical_list: D018696:Neuroprotective Agents
keywords: brachial plexus; chronic injury; motoneuron; peripheral nerve regeneration; spinal cord