Translational strategies in peripheral neuroinflammation and neurovascular repair

Academic Article

Abstract

  • Current therapies for immune-mediated inflammatory disorders in peripheral nerves are non-specific, and partly efficacious. Peripheral nerve regeneration following axonal degeneration or injury is suboptimal, with current therapies focused on modulating the underlying etiology and treating the consequences, such as neuropathic pain and weakness. Despite significant advances in understanding mechanisms of peripheral nerve inflammation, as well as axonal degeneration and regeneration, there has been limited translation into effective new drugs for these disorders. A major limitation in the field has been the unavailability of reliable disease models or research tools that mimic some key essential features of these human conditions. A relatively overlooked aspect of peripheral nerve regeneration has been neurovascular repair required to restore the homeostatic microenvironment necessary for normal function. Using Guillain-Barr√© syndrome (GBS) and chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) as examples of human acute and chronic immune-mediated peripheral neuroinflammatory disorders respectively, we have performed detailed studies in representative mouse models to demonstrate essential features of the human disorders. These models are important tools to develop and test treatment strategies using realistic outcomes measures applicable to affected patients. In vitro models of the human blood-nerve barrier using endothelial cells derived by endoneurial microvessels provide insights into pro-inflammatory leukocyte-endothelial cell interactions relevant to peripheral neuroinflammation, as well as potential mediators and signaling pathways required for vascular proliferation, angiogenesis, remodeling and tight junction specialization necessary to restore peripheral nerve function following injury. This review discusses some of the progress being made in translational peripheral neurobiology and some future directions. ¬© Versita Sp. z o.o.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Ubogu EE
  • Start Page

  • 373
  • End Page

  • 383
  • Volume

  • 3
  • Issue

  • 4