Project 4

Intracellular chloride and acidotic states influencing seizure activity

 

Supervisors  

Laura Alberio (laura.alberio@ncl.ac.uk)

Rob Forsyth (robert.forsyth@ncl.ac.uk)

 

Overview

The regulation of chloride and pH within neurons concentration is pivotal for brain function because it impacts directly upon how inhibitory restraints work.  Without these functional restraints, epileptic seizures are a perennial risk.  Acid-base balance is particularly interesting in this respect; several clinical anti-epileptic therapies (the carbonic anhydrase inhibitors, topiramate and acetazolamide) appear to work through this mechanism, including, but there may be simpler approaches, implemented through respiration.  This project will use the latest imaging technology, involving 2-photon imaging of Ca2+, Cl- and pH within neurons deep in the brain, in living animals, to investigate brain excitability in different anaesthetic states.  We will also examine the effect of switching from breathing pure O2 to breathing carbogen (95% O2 / 5% CO2), which is currently being trialled for treating status epilepticus in neurological intensive care units.  Status epilepticus is a time-sensitive medical emergency with significant morbidity and mortality for patients of all ages.  We aim to provide critical pre-clinical evidence to support the pathway for translating any findings into clinical practice.  The supervisory team includes a clinically trained bench scientist and a consultant neurologist with a scientific background, thus providing a wealth of experience and expertise to support this studentship. 

< Back