The brain is a highly dynamic organ that requires a constant energy source to function normally. This energy is mostly supplied by glucose, a simple sugar that serves as the brain’s principal fuel source. Glucose transport across the blood–brain barrier (BBB) is primarily controlled via sodium-independent facilitated glucose transport, such as by glucose transporter 1 (GLUT1) and 3 (GLUT3). However, other glucose transporters, including GLUT4 and the sodium-dependent transporters SGLT1 and SGLT6, have been reported in vitro and in vivo. When the BBB endothelial layer is crossed, neurons and astrocytes can absorb the glucose using their GLUT1 and GLUT3 transporters. Glucose then enters the glycolytic pathway and is metabolized into adenosine triphosphate (ATP), which supplies the energy to support cellular functions. The transport and metabolism of glucose in the brain are impacted by several medical conditions, which can cause neurological and neuropsychiatric symptoms. Alzheimer’s disease (AD), Parkinson’s disease (PD), epilepsy, traumatic brain injury (TBI), schizophrenia, etc., are a few of the most prevalent disorders, characterized by a decline in brain metabolism or hypometabolism early in the course of the disease. Indeed, AD is considered a metabolic disorder related to decreased brain glucose metabolism, involving brain insulin resistance and age-dependent mitochondrial dysfunction. Although the conventional view is that reduced cerebral metabolism is an effect of neuronal loss and consequent brain atrophy, a growing body of evidence points to the opposite, where hypometabolism is prodromal or at least precedes the onset of brain atrophy and the manifestation of clinical symptoms. The underlying processes responsible for these glucose transport and metabolic abnormalities are complicated and remain poorly understood. This review article provides a comprehensive overview of the current understanding of hypometabolism in AD and potential therapeutic targets.

Microfluidics-based organ-on-a-chip technology allows for developing a new class of in-vitro blood-brain barrier (BBB) models that recapitulate many hemodynamic and architectural features of the brain microvasculature not attainable with conventional two-dimensional platforms. Herein, we describe and validate a novel microfluidic BBB model that closely mimics the one in situ. Induced pluripotent stem cell (iPSC)-derived brain microvascular endothelial cells (BMECs) were juxtaposed with primary human pericytes and astrocytes in a co-culture to enable BBB-specific characteristics, such as low paracellular permeability, efflux activity, and osmotic responses. The permeability coefficients of [¹³C₁₂] sucrose and [¹³C₆] mannitol were assessed using a highly sensitive LC-MS/MS procedure. The resulting BBB displayed continuous tight-junction patterns, low permeability to mannitol and sucrose, and quasi-physiological responses to hyperosmolar opening and p-glycoprotein inhibitor treatment, as demonstrated by decreased BBB integrity and increased permeability of rhodamine 123, respectively. Astrocytes and pericytes on the abluminal side of the vascular channel provided the environmental cues necessary to form a tight barrier and extend the model’s long-term viability for time-course studies. In conclusion, our novel multi-culture microfluidic platform showcased the ability to replicate a quasi-physiological brain microvascular, thus enabling the development of a highly predictive and translationally relevant BBB model.

As the number of confirmed cases and deaths occurring from Coronavirus disease 2019 (COVID-19) surges worldwide, health experts are striving hard to fully comprehend the extent of damage caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Although COVID-19 primarily manifests itself in the form of severe respiratory distress, it is also known to cause systemic damage to almost all major organs and organ systems within the body. In this review, we discuss the molecular mechanisms leading to multi-organ failure seen in COVID-19 patients. We also examine the potential of stem cell therapy in treating COVID-19 multi-organ failure cases.

Neurological disorders and cardiovascular disease (CVD) remain leading causes of global morbidity and mortality and often coexist, in part through shared mechanisms of chronic inflammation and oxidative stress. Neuroinflammatory signaling, including microglial activation, cytokine release, and impaired autonomic regulation, contributes to endothelial dysfunction, atherosclerosis, hypertension, and stroke, while cardiac and metabolic disturbances can reciprocally exacerbate brain pathology. Increasing evidence shows that several antidiabetic agents exert pleiotropic anti-inflammatory and antioxidant effects that extend beyond glycemic control. Metformin, SGLT2 inhibitors, DPP-4 inhibitors, and GLP-1 receptor agonists modulate key pathways such as AMPK, NF-κB, Nrf2 activation, and NLRP3 inflammasome suppression, with demonstrated vascular and neuroprotective actions in preclinical models. Clinically, GLP-1 receptor agonists and SGLT2 inhibitors reduce major cardiovascular events, improve systemic inflammatory markers, and show emerging signals for cognitive benefit, while metformin and DPP-4 inhibitors exhibit supportive but less robust evidence. This review synthesizes molecular, preclinical, and clinical data across drug classes, with particular emphasis on GLP-1 receptor agonists, and highlights outstanding translational questions including blood–brain barrier penetration, biomarker development, optimal patient selection, and timing of intervention. We propose a unified framework to guide future trials aimed at leveraging antidiabetic therapies such as DDP-4 anti-inflammatory and antioxidant interventions for neurological and cardiovascular diseases.