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UCL Queen Square Institute of Neurology

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Experimental Neuroinflammation Group

Head of Group: Prof. Kenneth Smith

Email: k.smith@ucl.ac.uk  Tel: 020 7679 4013

 

Highlights

Milestone and recent findings in neuroinflammation and neuroprotection:

  • Discovery that neuroinflammatory lesions can be severely hypoxic so that normal function is prevented, causing symptoms.  Also that oxygen therapy can alleviate the symptoms (Davies et al. 2013).
  • Finding that the drug safinamide has strong neuroprotective effects in neuroinflammatory models of MS (Morsali et al. 2013) and Parkinson’s disease (in preparation).
  • Neuroprotection achieved in a stroke model by blockade of the sodium calcium exchanger (Bei and Smith 2012).
  • The discovery that sodium channel blocking agents are very effective neuroprotective agents in a range of neuroinflammatory lesions (Kapoor et al. 2003; Bechtold et al. 2004; Bechtold and Smith 2005; Bechtold et al. 2005; Bechtold et al. 2006; Morsali et al. 2013)).
  • The discovery that the inflammatory mediator nitric oxide can both block axonal conduction (Redford et al. 1997) and cause degeneration (Smith et al. 2001), and that sodium channel blocking agents can provide protection (Kapoor et al. 2003) (reviewed in (Smith 2007)).
  • Introduction of the first experimental model of the primary, or Pattern III, MS lesion (Felts et al. 2005; Marik et al. 2007; Sharma et al. 2010).

Other recent findings in the lab:

  • Realisation that mitochondrial trafficking along axons is profoundly influenced by the level of impulse activity (Sajic et al. 2013).
  • Discovery that sustained impulse activity causes substantial but reversible morphological changes at nodes of Ranvier, including a remarkable herniation of the nodal axoplasm.  The changes may reveal the return pathway for sodium ions (submitted).  
  • Evidence that the MS therapy 4-aminopyridine (Ampyra, Fampyra) may work mainly on synapses rather than demyelinated axons (Smith et al. 2000).

Further reading:

  • Bechtold DA, Kapoor R, Smith KJ.  Ann Neurol. 2004;55:607-616. 
  • Bechtold DA, Miller SJ, Dawson AC et al.  J Neurol. 2006;253:1542-51. 
  • Bechtold DA, Smith KJ.  J Neurol Sci. 2005;233:27-35. 
  • Bechtold DA, Yue X, Evans RM, Davies M, Gregson NA, Smith KJ.  Brain. 2005;128:18-28. 
  • Bei F, Smith KJ.  Neuropharmacology. 2012;63:405-414. 
  • Davies AL, Desai RA, Bloomfield PS et al.  Ann Neurol. 2013;74:815-825. 
  • Felts PA, Woolston AM, Fernando HB et al.  Brain. 2005;128:1649-1666. 
  • Kapoor R, Davies M, Blaker PA, Hall SM, Smith KJ.  Ann Neurol. 2003;53:174-180.
  • Marik C, Felts PA, Bauer J, Lassmann H, Smith KJ.  Brain. 2007;130:2800-2815.
  • Morsali D, Bechtold D, Lee W et al.  Brain. 2013;136:1067-1082. 
  • Redford EJ, Kapoor R, Smith KJ.  Brain. 1997;120:2149-2157. 
  • Sajic M, Mastrolia V, Lee CY et al.  PLoS Biol. 2013;11:e1001754.
  • Sharma R, Fischer MT, Bauer J et al.  Acta Neuropathologica. 2010;120:223-236.
  • Smith KJ.  Brain Pathol. 2007;17:230-242. 
  • Smith KJ, Felts PA, John GR.  Brain. 2000;123:171-184.
  • Smith KJ, Kapoor R, Hall SM, Davies M.  Ann Neurol. 2001;49:470-476.