Finding that oxygen treatment restores neurological function lost by inflammation, in two models of MS. Such treatment also reduces demyelination (Amatruda et al, Neuropathol. Appl. Neurobiol., 2023).
Discovery that the significant CNS tissue hypoxia resulting from neuroinflammation is due to reduced blood flow. The hypoxia can be sufficiently severe to impair mitochondrial function, which, in turn, causes disability. Also the finding that restoring blood flow using nimodipine restores spinal oxygenation and can rapidly reduce disability. Further, that nimodipine therapy also reduces demyelination in both EAE, and a model of the early MS lesion (Desai et al, Ann. Neurol., 2020).
Finding that neuroinflammatory lesions can be severely hypoxic so that normal function is prevented, causing symptoms and demyelination. Also that oxygen therapy can alleviate the symptoms (Davies et al., Ann. Neurol., 2013; Desai et al, Ann. Neurol., 2016 (Awarded the Multiple Sclerosis Research Prize for 2017)).
Discovery in a model of diabetes that high dietary fat consumption impairs axonal mitochondrial function in vivo (Sajic et al., 2021, J Neurosci).
Introduction of a method to protect brain function during resuscitation after haemorrhagic shock (Ida et al., Brit. J. Anaesth., 2018).
Finding that the drug safinamide has strong neuroprotective effects in neuroinflammatory models of MS (Morsali et al., Brain, 2013) and Parkinson’s disease (Sadeghian et al., Neuropath. Appl. Neurobiol., 2016).
Neuroprotection achieved in a stroke model by blockade of the sodium calcium exchanger (Bei & Smith, Neuropharmacol., 2012).
The discovery that sodium channel blocking agents are very effective neuroprotective agents in a range of neuroinflammatory lesions (Kapoor et al., Ann. Neurol., 2003; Bechtold et al., Ann. Neurol., 2004; Bechtold and Smith 2005; Bechtold et al., J. Neurol. Sci., 2005; Bechtold et al., J. Neurol., 2006; Morsali et al., Brain, 2013).
The discovery that the inflammatory mediator nitric oxide can both block axonal conduction (Redford et al., Brain, 1997) and cause degeneration (Smith et al., Ann. Neurol., 2001), and that sodium channel blocking agents can provide protection (Kapoor et al., Ann. Neurol., 2003).
Introduction of the first experimental model of the primary, or Pattern III, MS lesion (Felts et al., Brain, 2005; Marik et al., Brain, 2007; Sharma et al., Acta Neuropath., 2010).
- A systematic approach to selecting licensed drugs for repurposing in the treatment of progressive multiple sclerosis (Cunniffe et al., 2021).
Role of the Perivascular Space in Cerebral Small Vessel Disease. Perivascular spaces in the brain: anatomy, physiology, and contributions to pathology of brain diseases (Wardlaw, et al., 2020).
Understanding the role of the perivascular space in cerebral small vessel disease (Brown et al., 2018).
Small vessels, dementia and chronic diseases – molecular mechanisms and pathophysiology (Horsburgh et al., 2018).
Experimental autoimmune encephalomyelitis from a tissue energy perspective (Desai & Smith, 2017).
Understanding a role for hypoxia in lesion formation and location in the deep and periventricular white matter in small vessel disease and multiple sclerosis. (Martinez Sosa & Smith, 2017).
Neuroprotection and repair in multiple sclerosis (Franklin et al., 2012).
Newly-lesioned tissue in multiple sclerosis - a role for oxidative damage? (Smith, 2011).
Sodium channels and multiple sclerosis: roles in symptom production, damage and therapy (Smith, 2007).
The conduction properties of demyelinated and remyelinated axons (Smith & Waxman, 2005).
The role of nitric oxide in multiple sclerosis (Smith & Lassmann, 2002).
Pathogenesis of Guillain-Barré syndrome (Hughes et al., 1999).
Demyelination: the role of reactive oxygen and nitrogen species (Smith, Kapoor & Felts, 1999).
Treatment of inflammatory neuropathy (Hughes et al., 1997).