ArticleJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism2017
Chronic depletion of gonadal testosterone leads to blood-brain barrier dysfunction and inflammation in male mice.
Article in Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers.
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53 citing papers in PubMed, 93 citations in OpenAlex.
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- Comparative Analysis of Regional Blood-Brain Barrier Permeability in Humans and Rodents: An Evolutionary Perspective.Research square · 2026Article
- The Multifaceted Role of Androgen Receptor Signaling in Immunity: Implications for Oncology.Molecular cancer research : MCR · 2026Review
- The dual-sensitive period gut-brain crosstalk, neuroinflammation, and the biological roots of adolescent depression.Frontiers in immunology · 2026Review
- Dynamic modulation of the blood-brain barrier in the healthy brain.Nature reviews. Neuroscience · 2025Review
- Neurovascular coupling abnormalities in first-episode drug-naïve major depressive disorder patients.BMC psychiatry · 2025Article
- Impacts of systemic milieu on cerebrovascular and brain aging: insights from heterochronic parabiosis, blood exchange, and plasma transfer experiments.GeroScience · 2025Review
- The Hypothalamic-Pituitary-Ovarian Axis, Ovarian Disorders, and Brain Aging.Endocrinology · 2025Review
- Sex- and age- differences in the expression of critical blood-brain barrier regulators: a physiological context.Biology of sex differences · 2025Article
- Cholesterol-modifying strategies for Alzheimer disease: promise or fallacy?Expert review of neurotherapeutics · 2025Review
- Testosterone Modulates Oxidative Stress in a Sexually Dimorphic Manner in CBA/Ca Mice Infected withInternational journal of molecular sciences · 2025Article
- Genetic effects of circulating hormone and proteome on amyotrophic lateral sclerosis identified by Mendelian randomization.Scientific reports · 2025Article
- Understanding the Blood-Brain Barrier: From Physiology to Pathology.Advances in experimental medicine and biology · 2025Review
- Regulation of the blood-brain barrier function by peripheral cues in health and disease.Metabolic brain disease · 2024Review
- Androgen deprivation therapy exacerbates Alzheimer's-associated cognitive decline via increased brain immune cell infiltration.Science advances · 2024Article
- Animal Models of Osteoarthritis: Updated Models and Outcome Measures 2016-2023.Regenerative engineering and translational medicine · 2024Article
- Activation of testosterone-androgen receptor mediates cerebrovascular protection by photobiomodulation treatment in photothrombosis-induced stroke rats.CNS neuroscience & therapeutics · 2024Article
- Review
- Sex, hormones and cerebrovascular function: from development to disorder.Fluids and barriers of the CNS · 2024Review
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Authors and funding
3 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A dysfunction in the blood-brain barrier (BBB) is associated with many neurological and metabolic disorders. Although sex steroid hormones have been shown to impact vascular tone, endothelial function, oxidative stress, and inflammatory responses, there are still no data on the role of testosterone in the regulation of BBB structure and function. In this context, we investigated the effects of gonadal testosterone depletion on the integrity of capillary BBB and the surrounding parenchyma in male mice. Our results show increased BBB permeability for different tracers and endogenous immunoglobulins in chronically testosterone-depleted male mice. These results were associated with disorganization of tight junction structures shown by electron tomography and a lower amount of tight junction proteins such as claudin-5 and ZO-1. BBB leakage was also accompanied by activation of astrocytes and microglia, and up-regulation of inflammatory molecules such as inducible nitric oxide synthase (iNOS), cyclooxygenase 2 (COX-2), interleukin 1 beta (IL-1β), and tumor necrosis factor (TNF). Supplementation of castrated male mice with testosterone restored BBB selective permeability, tight junction integrity, and almost completely abrogated the inflammatory features. The present demonstration that testosterone transiently impacts cerebrovascular physiology in adult male mice should help gain new insights into neurological and metabolic diseases linked to hypogonadism in men of all ages.
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