Region-specific protective effects of monomethyl fumarate in cerebellar and hippocampal organotypic slice cultures following oxygen-glucose deprivation.
Oliver AlthausNico Ter JungSarah StahlkeCarsten TheissJennifer Herzog-NiesceryHeike VogelsangThomas WeberPhilipp GudeVeronika MatschkePublished in: PloS one (2024)
To date, apart from moderate hypothermia, there are almost no adequate interventions available for neuroprotection in cases of brain damage due to cardiac arrest. Affected persons often have severe limitations in their quality of life. The aim of this study was to investigate protective properties of the active compound of dimethyl fumarate, monomethyl fumarate (MMF), on distinct regions of the central nervous system after ischemic events. Dimethyl fumarate is an already established drug in neurology with known anti-inflammatory and antioxidant properties. In this study, we chose organotypic slice cultures of rat cerebellum and hippocampus as an ex vivo model. To simulate cardiac arrest and return of spontaneous circulation we performed oxygen-glucose-deprivation (OGD) followed by treatments with different concentrations of MMF (1-30 μM in cerebellum and 5-30 μM in hippocampus). Immunofluorescence staining with propidium iodide (PI) and 4',6-diamidine-2-phenylindole (DAPI) was performed to analyze PI/DAPI ratio after imaging with a spinning disc confocal microscope. In the statistical analysis, the relative cell death of the different groups was compared. In both, the cerebellum and hippocampus, the MMF-treated group showed a significantly lower PI/DAPI ratio compared to the non-treated group after OGD. Thus, we showed for the first time that both cerebellar and hippocampal slice cultures treated with MMF after OGD are significantly less affected by cell death.
Keyphrases
- cardiac arrest
- cerebral ischemia
- cell death
- cardiopulmonary resuscitation
- anti inflammatory
- oxidative stress
- subarachnoid hemorrhage
- brain injury
- blood brain barrier
- magnetic resonance imaging
- type diabetes
- high resolution
- physical activity
- cognitive impairment
- computed tomography
- image quality
- blood pressure
- ischemia reperfusion injury
- magnetic resonance
- early onset
- emergency department
- cell proliferation
- high intensity
- mass spectrometry
- cerebrospinal fluid
- cell cycle arrest
- electronic health record
- signaling pathway
- functional connectivity
- dual energy