Injury-specific factors in the cerebrospinal fluid regulate astrocyte plasticity in the human brain

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https://rdp.sfb274.de/ (Research Data Platform) https://gepris.dfg.de/gepris/projekt/408885537 (DFG Gepris entry) The central nervous system (CNS) is a terminally differentiated tissue, where any insult carries a heightened risk - yet the tissue response to these insults is variable and can range from irreversible destruction to almost complete recovery. The rules that instruct these divergent outcomes are still unknown. The aim of this CRC is therefore to understand the biology of the multicellular ...

Neuronal loss in acute or chronic brain disease could be treated by neuronal replacement strategies, such as transplantation of young neurons, if they integrate properly into the existing networks. Here we explore the cell-based and molecular mechanisms causing hyperinnervation and overshoot loss of input connectivity as well as the newly discovered hurdle in output connectivity, the lack of myelination. Candidate as well as unbiased approaches are pursued to identify the critical checkpoints and ...

The glial environment influences neurological disease progression, yet much of our knowledge still relies on preclinical animal studies, especially regarding astrocyte heterogeneity. In murine models of traumatic brain injury, beneficial functions of proliferating reactive astrocytes on disease outcome have been unraveled, but little is known regarding if and when they are present in human brain pathology. Here we examined a broad spectrum of pathologies with and without intracerebral hemorrhage ...

Total protein content of CSF samples was measured by Bradford assay (BioRad, Feldkirchen, Germany)and 10μg per sample were proteolysed by the commercially available in-StageTip-NHS kit (PreOmics GmbH, Martinsried, Germany) according to the manufacturer's protocol. Briefly, CSF was reduced and alkylated and incubated for 3 hrs at 37°C with Lys-C and trypsin. Resulting peptides were dried for short term storage at -80°C. Prior to measurement, peptides were resuspended in 2% acetonitrile and 0.5% ...