Haessler, A. | Search bioRxiv

bioRxiv2025

Ischemic injury triggers a protective microglial phenotype in models of Aβ pathology

Microglia are highly plastic cells that are capable of integrating subsequent insults. As the majority of Alzheimers Disease (AD) patients also show cerebrovascular pathology, we here aimed to dissect the interactions between AD and ischemic brain injury on the microglial response to amyloid beta (A{beta}) pathology. Surprisingly, we find that ischemic stroke in the presence of cerebral {beta}-amyloidosis results in the generation of a novel neuroprotective microglial phenotype. These microglia drive a rapid accumulation of highly dense A{beta} plaques that exhibit a relatively benign nature and are strikingly similar to A{beta} plaques observed in patients that are resilient to AD pathology. Thus, our data do not only highlight the impact of a co-morbid state of brain ischemia and A{beta} pathology on the microglial phenotype but also identify novel molecular pathways that may serve to promote beneficial microglial functions in AD.

neuroscience↗

bioRxiv2025

Raman spectroscopy reveals growth phase-dependent molecular differences in bacterial membrane vesicles

Bacterial membrane vesicles (BMVs) have attracted significant attention as highly efficient transport vehicles for molecules crossing biological barriers and as key mediators in infection processes. As interest in BMVs increases, the need for standardized isolation protocols and comprehensive analytical approaches becomes apparent. This study introduces Raman spectroscopy as a novel, chemically selective monitoring approach for the analysis of subtle biochemical changes in BMVs across different bacterial growth phases. BMVs derived from Pseudomonas aeruginosa, a Gram-negative human pathogen responsible for severe nosocomial infections, were isolated at six different time points and analyzed via established physicochemical and functional assays, as well as Raman spectroscopy. While established analytics revealed growth phase-dependent variations in protein content, surface charge, and immunogenic effects on human immune cells, Raman spectroscopy enabled the comprehensive analysis of molecular-level changes between isolation time points. Significant shifts in protein-to-lipid ratios, higher lipid saturation, and changes in protein secondary structure were detected in BMVs isolated from later growth phases. Further, the absence of spectral markers for nucleic acids enabled the identification of BMVs as outer membrane vesicles. These findings emphasize the critical influence of the isolation time point on BMV properties and highlight Raman spectroscopy as a powerful tool for semi-quantitative chemical profiling, revealing minuscule yet biologically significant changes in BMVs depending on isolation time points.

cell biology↗