TOBeATPAIN Project 8: Impact of neuroinflammation and neurodegeneration on brain and spinal cord homeostasis: relevance to nociception
Early Stage Researcher 8 – Fátima Gimeno Ferrer
Individual Research Project 8
Project Title: Impact of neuroinflammation and neurodegeneration on brain and spinal cord homeostasis: relevance to nociception
Supervisor: Prof. Frank Richter (UKJ)
Co-supervisor(s): Prof. Michaela Kress (MUI) and Prof. S. Paulie (Mabtech)
Objectives
Tight regulation of homeostasis in brain and spinal cord is required for normal neuronal function. Maintenance of homeostasis involves control of changes in extracellular fluid volume, ion concentrations and pH, perfusion and vascular permeability, turnover of transmitters/mediators and energy supply. These changes can be measured by using ion selective electrodes, an approach that has provided evidence for brain extracellular volume changes in AD models. This observation leads to the following questions: i) are changes in the milieu in neurodegenerative disease restricted to the brain or do they also occur in spinal cord; ii) does neuroinflammation – during the course of chronic systemic inflammation – cause significant alterations of brain and spinal cord homeostasis; iii) are brain and spinal cord homeostatic responses to noxious stimuli different in neurodegeneration compared to healthy brain; and iv) are cytokines and neuropeptides major effectors.
Aims
ESR 8 will assess:
- Extracellular volume, ion concentrations and diffusion of mediators in brain and spinal cord in electrophysiological studies in vivo;
- Impact of such changes on neuronal excitability by measuring cortical spreading depression and field potentials in the spinal cord;
- Changes in perfusion and vascular permeability by using dyes and neuroimaging (functional MRI).
Summary of Findings
Expected results
Definition of functional importance of homeostatic changes in neurodegenerative diseases versus chronic peripheral inflammation.
Secondment(s): MUI (3 months). Assess the effect of cytokines on neuronal activity in cortical slices. KI (3 months). Calcium imaging in cortical slices. Mabtech (1 month). Measure cytokine in cerebrospinal fluid with multiplex technology, training on business management and patent process.
