In recent years, the need for sophisticated human in vitro models for integrative biology has motivated the development of organ-on-a-chip platforms. Organ-on-a-chip devices are engineered to mimic the mechanical, biochemical and physiological properties of human organs; however, there are many important considerations when selecting or designing an appropriate device for investigating a specific scientific question. Building microfluidic Brain-on-a-Chip (BoC) models from the ground-up will allow for research questions to be answered more thoroughly in the brain research field, but the design of these devices requires several choices to be made throughout the design development phase. These considerations include the cell types, extracellular matrix (ECM) material(s), and perfusion/flow considerations. Choices made early in the design cycle will dictate the limitations of the device and influence the end-point results such as the permeability of the endothelial cell monolayer, and the expression of cell type-specific markers. To better understand why the engineering aspects of a microfluidic BoC need to be influenced by the desired biological environment, recent progress in microfluidic BoC technology is compared. This review focuses on perfusable blood–brain barrier (BBB) and neurovascular unit (NVU) models with discussions about the chip architecture, the ECM used, and how they relate to the in vivo human brain. With increased knowledge on how to make informed choices when selecting or designing BoC models, the scientific community will benefit from shorter development phases and platforms curated for their application.

The first Vascular Contributions to Cognitive Impairment and Dementia (VCID) Workshop, held on May12-16, 2025 at The Jackson Laboratory, provided scientific content and career development training in the latest developments in VCID and Alzheimer’s Disease (AD) and related dementia (ADRD). The Workshop aimed to foster interdisciplinary collaborations and empower the next generation of diverse scientists to advance ADRD research from mechanism to intervention. The meeting placed a strong emphasis on neurovascular pathology, its central role in ADRD pathogenesis, its modulation by both central and peripheral factors, and the critical need to dissect the mechanistic basis of VCID through experimental models. The workshop included talks from both faculty and trainees and was bookended by two keynote addresses by Drs. Donna Wilcock and Costantino Iadecola, leaders and pioneers in the VCID field. The second VCID workshop is planned for April 28-May 1, 2026, to be held at Washington University in St. Louis.

Traumatic brain injury (TBI) is an established risk factor for neurodegenerative diseases. In this study, we used the Closed Head Injury Model of Engineered Rotational Acceleration (CHIMERA) to investigate the effects of a single high-energy TBI in rTg4510 mice, a mouse model of tauopathy. Fifteen male rTg4510 mice (4 mo) were impacted at 4.0 J using interfaced CHIMERA and were compared to sham controls. Immediately after injury, the TBI mice showed significant mortality (7/15; 47%) and a prolonged duration of loss of the righting reflex. At 2 mo post-injury, surviving mice displayed significant microgliosis (Iba1) and axonal injury (Neurosilver). Western blotting indicated a reduced p-GSK-3β (S9):GSK-3β ratio in TBI mice, suggesting chronic activation of tau kinase. Although longitudinal analysis of plasma total tau suggested that TBI accelerates the appearance of tau in the circulation, there were no significant differences in brain total or p-tau levels, nor did we observe evidence of enhanced neurodegeneration in TBI mice compared to sham mice. In summary, we showed that a single high-energy head impact induces chronic white matter injury and altered GSK-3β activity without an apparent change in post-injury tauopathy in rTg4510 mice.

Objectives: Obesity in children can lead to morbidity and mortality due to metabolic and inflammatory comorbidities. Aims: The objective of the study was to investigate the alterations in acute inflammatory markers, serum amyloid P (SAP) and cortisol, and endocrine markers, leptin and insulin, in obese children. Materials and Methods: Serum leptin, insulin, cortisol, and amyloid P concentrations were measured in obese (BMI percentile >85, n = 17) and nonobese (BMI percentile < 75, n = 20) children using ELISA and Bio-Plex Bead-based assay. Statistical Analysis Used: Serum concentrations of analytes were compared between normal and obese groups using 2-tailed student's t-test. Results: Mean leptin, insulin, and SAP serum concentrations were significantly higher in obese children as compared to the controls (97.19 vs. 4.06, P < 0.05; 21.31 vs 3.56, P < 0.05; 46.77 vs. 17.89, P < 0.05; respectively). No difference was found in mean serum cortisol levels of the two groups. However, cortisol values were higher in obese subjects compared to the control group (7.89 vs 6.30, P = 0.15). Leptin corelated with insulin (r = 0.42, P = 0.043) and cortisol (r = 0.48, P = 0.025) levels in the obese group. Furthermore, leptin, insulin, and SAP levels were corelated with BMI (r = 0.80, P < 0.000; r = 0.67, P = 0.015, respectively) and body weight (r = 0.52, P = 0.01; r = 0.52, P = 0.002; r = 0.54, P = 0.01, respectively) in the obese group but did not demonstrate a significant relationship in the nonobese group. Conclusion: Elevated SAP levels and increase in leptin and insulin indicated a preeminent disposition of morbidly obese children to the development of low-grade inflammation and metabolic syndrome.

Background: Traumatic brain injury (TBI) results in multifaceted neuropathology including neuroinflammation, neuronal loss, axonal damage and blood brain barrier damage, which can lead to cognitive impairment and dementia including Alzheimer’s disease (AD) and related dementias (ADRDs). Detailed analysis of the molecular and cellular changes that occur in injured brain is crucial to understand TBI’s contributions to dementia and AD. The Closed Head Impact Model of Engineered Rotational Acceleration (CHIMERA) is a non‐surgical model of impact‐acceleration injury that mimics the biomechanics and pathophysiology of human TBI. Methods: Adult male mice received a mild CHIMERA injury (2.1J) and acute neurological deficits were assessed as compared to sham group. At 7 days post‐TBI, cardiac blood was collected for biomarker analysis and brain was harvested for 10x genomics Visium spatial transcriptomic and multiplexed fluorescence in situ hybridization (mFISH) analysis. Results: Injured mice showed delayed righting reflex recovery and poor performance on neurological tests. Increased plasma glial fibrillary acidic protein (GFAP) and neurofilament light levels (NfL) were found in TBI compared to sham mice. We identified widespread (6614 DEGs: 82% downregulated, 18% upregulated) as well as regional cell type specific gene dysregulation in several clusters. We cross‐referenced our dataset with genes identified in human genome wide association studies in AD and TBI and found conserved genes in all three datasets ( Ace, AdamTS4, AdamTS1, Trem2, ApoE, Cacna1a, RbFox1, Clu, Apoc1, Mapt ). In the optic tract cluster, we identified that the astrocytic marker Gfap , microglial marker Aif1 and several disease‐associated microglia (DAMs) genes including Apoe, Ctsd, Trem2 were upregulated. GFAP immunolabelling confirmed astrogliosis in optic tract and hippocampus. In the neocortical cluster, we found downregulation of Itm2c , a negative regulator of amyloid‐beta peptide production, and Scg5 , a chaperone protein that prevent aggregation of secreted proteins associated with neurodegeneration, which may contribute to TBI‐associated susceptibility to AD. mFISH labelling validated downregulation of these genes in cortex. Conclusions: Our data‐rich spatial transcriptomics approach identified molecular and cellular substrates crucial to TBI pathology and its comorbidities including AD and ADRD. Together, this work will provide spatial molecular maps of diffuse brain injury and novel insights into TBI’s contributions to dementia.