Enhancing Models of Age-Related Neuroinflammation and Neurodegeneration: Bridging Translational Gaps Using Rodents and Zebrafish

Age-related neuroinflammation is increasingly recognized as a central driver and modulator of neurodegenerative change, yet many preclinical studies continue to rely on young or middle-aged animals, limiting their ability to reflect the biology of the aging central nervous system. Aging profoundly alters neuroimmune signaling, glial function, blood–brain barrier integrity, vascular coupling, and mitochondrial homeostasis, reshaping vulnerability to conditions such as Alzheimer’s disease, Parkinson’s disease, and vascular cognitive impairment and dementia. As a result, preclinical models often diverge from the human disease context, contributing to enduring translational gaps between experimental findings and clinical outcomes.This Research Topic aims to advance the development and refinement of age-appropriate rodent and zebrafish models that better capture the neuroinflammatory mechanisms driving neurodegeneration in the aging brain. The emphasis is on studies that dissect cellular and molecular mechanisms, enhance model validity, and improve translational alignment with human aging trajectories. Comparative and cross-species studies are encouraged where they offer mechanistic or translational insight, while high-quality investigations using either rodents or zebrafish are equally welcome.The Topic is centered on neuroinflammation in aging-related neurodegeneration, encompassing glial reactivity and immune-brain–vascular interactions, barrier dysfunction, and inflammatory contributions to synaptic and circuit impairment. It also invites studies on design, phenotyping, or validation approaches when directly linked to aging-associated neuroinflammatory pathways. By prioritizing mechanistic depth and translational rigor, this collection aims to foster more reproducible preclinical research and strengthen the bridge between experimental systems and human brain aging.This Research Topic welcomes original research, methods, brief reports, and reviews within the following focused themes:- Development and validation of age-appropriate rodent and zebrafish models of neuroinflammation in aging-related neurodegeneration- Cellular and molecular neuroimmune mechanisms in the aging CNS, including glial plasticity, immune crosstalk, and barrier dysfunction- Cross-species and translational studies integrating behavioral, imaging, omic, or biomarker-linked readouts to clarify neuroinflammatory mechanisms in aging- Model validation, reproducibility, and experimental design strategies that enhance translational relevance in aging neuroinflammation research----Topic Editor Dr. Kizil is the co-founder, shareholder, and scientific advisor of Neuron-D GmbH. Dr. Kizil has also received research funding from the National Institutes of Health and the European Union. Dr. Tokay, Dr. Trofimov, and Dr. Cosacak declare no competing interests. Topic editors: Tursonjan Tokay, Alexander Trofimov, Caghan Kizil, Mehmet Ilyas Cosacak Source: https://www.frontiersin.org/research-topics/80583/enhancing-models-of-age-related-neuroinflammation-and-neurodegeneration-bridging-translational-gaps-using-rodents-and-zebrafish