skip to content

Neurochemistry Research Group

Division of Neurosurgery
 

SUSTAIN BRAIN PROJECT- ongoing

Oral succinate administration

We are recruiting patients with TBI requiring neurocritical care and multimodal monitoring, and utilised a tiered management protocol targeting LPR. Identified patients with persistent raised LPR despite adequate cerebral glucose and oxygen provision, we clinically classified as cerebral ‘mitochondrial dysfunction’ (MD). In patients with TBI and MD, we administer disodium succinate orally, recovering metabolites in blood serum and microdialysis and utilised nuclear magnetic resonance spectroscopy (NMR) for identification and quantification.
 

This is complimented by oral ongoing oral succinate pharmokinetics studies in healthy volunteers. 

 

Previous succinate studies by our group include, most recently, administered disodium 2,3-13C2 succinate (12 mmol/L) by retrodialysis into the monitored region of the brain.

In 5 patients with multimodality-defined MD, succinate administration resulted in reduced LPR(−12%) and raised brain glucose(+17%). NMR of microdialysates demonstrated that the exogenous 13C-labelled succinate was metabolised intracellularly via the tricarboxylic acid cycle. By targeting LPR using a tiered clinical algorithm incorporating intracranial pressure, brain tissue oxygenation and microdialysis parameters, we identified MD in TBI patients requiring neurointensive care. In these, focal succinate administration improved energy metabolism, evidenced by reduction in LPR. Succinate merits further investigation for TBI therapy.

Neurochem_logo_large

Updates: 12/05/2021
- New paper Front page- link

Updates: 20/12/2021
- New paper Front page- link

Updates: 04/11/2021
- New PhD Opportunity Front page- link
- New Team Photo

Updates: 14/10/2021
- New Papers in Recent Publications
- Updated Team members and Our Research
- New Media/Outreach video
- New Funding page