Academic Journal
Microglia as target for anti-inflammatory approaches to prevent secondary brain injury after subarachnoid hemorrhage (SAH)
| Title: | Microglia as target for anti-inflammatory approaches to prevent secondary brain injury after subarachnoid hemorrhage (SAH) |
|---|---|
| Authors: | Peter Vajkoczy, Irina Kremenetskaia, Susan Brandenburg, Philipp Boehm-Sturm, Melina Nieminen-Kelhä, Ulf C. Schneider, Rebecca Heinz |
| Source: | J Neuroinflammation Journal of Neuroinflammation, Vol 18, Iss 1, Pp 1-13 (2021) |
| Publisher Information: | Springer Science and Business Media LLC, 2021. |
| Publication Year: | 2021 |
| Subject Terms: | 0301 basic medicine, Anti-Inflammatory Agents, Aminopyridines, CSF1-Receptor, Mice, 03 medical and health sciences, 0302 clinical medicine, Animals, Pyrroles, Subarachnoid hemorrhage, Secondary brain injury, RC346-429, Ischemic Preconditioning, Inflammation, Subarachnoid hemorrhage, Inflammation, Microglia, Secondary brain injury, Inflammatory preconditioning, CSF1-Receptor, Research, Inflammatory preconditioning, Subarachnoid Hemorrhage, Pyrroles/administration, Brain Injuries/diagnostic imaging [MeSH], Mice, Inbred C57BL [MeSH], Subarachnoid Hemorrhage/metabolism [MeSH], Microglia/drug effects [MeSH], Aminopyridines/administration, Animals [MeSH], Subarachnoid Hemorrhage/diagnostic imaging [MeSH], Brain Injuries/metabolism [MeSH], Microglia/metabolism [MeSH], Mice [MeSH], Microglia/pathology [MeSH], Brain Injuries/prevention, Subarachnoid Hemorrhage/drug therapy [MeSH], Anti-Inflammatory Agents/administration, Ischemic Preconditioning/methods [MeSH], 3. Good health, Mice, Inbred C57BL, Brain Injuries, Neurology. Diseases of the nervous system, Microglia, 600 Technik, Medizin, angewandte Wissenschaften::610 Medizin und Gesundheit::610 Medizin und Gesundheit |
| Description: | BackgroundMicroglia-driven cerebral spreading inflammation is a key contributor to secondary brain injury after SAH. Genetic depletion or deactivation of microglia has been shown to ameliorate neuronal cell death. Therefore, clinically feasible anti-inflammatory approaches counteracting microglia accumulation or activation are interesting targets for SAH treatment. Here, we tested two different methods of interference with microglia-driven cerebral inflammation in a murine SAH model: (i) inflammatory preconditioning and (ii) pharmacological deactivation.Methods7T-MRI-controlled SAH was induced by endovascular perforation in four groups of C57Bl/6 mice: (i) Sham-operation, (ii) SAH naïve, (iii) SAH followed by inflammatory preconditioning (LPS intraperitoneally), and (iv) SAH followed by pharmacological microglia deactivation (colony-stimulating factor-1 receptor-antagonist PLX3397 intraperitoneally). Microglia accumulation and neuronal cell death (immuno-fluorescence), as well as activation status (RT-PCR for inflammation-associated molecules from isolated microglia) were recorded at day 4 and 14. Toll-like receptor4 (TLR4) status was analyzed using FACS.ResultsFollowing SAH, significant cerebral spreading inflammation occurred. Microglia accumulation and pro-inflammatory gene expression were accompanied by neuronal cell death with a maximum on day 14 after SAH. Inflammatory preconditioning as well as PLX3397-treatment resulted in significantly reduced microglia accumulation and activation as well as neuronal cell death. TLR4 surface expression in preconditioned animals was diminished as a sign for receptor activation and internalization.ConclusionsMicroglia-driven cerebral spreading inflammation following SAH contributes to secondary brain injury. Two microglia-focused treatment strategies, (i) inflammatory preconditioning with LPS and (ii) pharmacological deactivation with PLX3397, led to significant reduction of neuronal cell death. Increased internalization of inflammation-driving TLR4 after preconditioning leaves less receptor molecules on the cell surface, providing a probable explanation for significantly reduced microglia activation. Our findings support microglia-focused treatment strategies to overcome secondary brain injury after SAH. Delayed inflammation onset provides a valuable clinical window of opportunity. |
| Document Type: | Article Conference object Other literature type |
| Language: | English |
| ISSN: | 1742-2094 |
| DOI: | 10.1186/s12974-021-02085-3 |
| DOI: | 10.17169/refubium-38014 |
| Access URL: | https://jneuroinflammation.biomedcentral.com/track/pdf/10.1186/s12974-021-02085-3 https://pubmed.ncbi.nlm.nih.gov/33516246 https://doaj.org/article/7149eb6e698044fdaf4dcb7f0e7500de https://link.springer.com/content/pdf/10.1186/s12974-021-02085-3.pdf https://link.springer.com/article/10.1186/s12974-021-02085-3 https://www.ncbi.nlm.nih.gov/pubmed/33516246 https://pubmed.ncbi.nlm.nih.gov/33516246/ http://www.ncbi.nlm.nih.gov/pubmed/33516246 https://europepmc.org/article/PMC/PMC7847606 https://repository.publisso.de/resource/frl:6465786 |
| Rights: | CC BY |
| Accession Number: | edsair.doi.dedup.....cea6f6fb4fb7fdbe4a5b584616d522c2 |
| Database: | OpenAIRE |
Be the first to leave a comment!