Stress-induced blood brain barrier disruption: Molecular mechanisms and signaling pathways
Abstract
Stress is a nonspecific response to a threat or noxious stimuli with resultant damaging consequences. Stress is believed to be an underlying process that can trigger central nervous system disorders such as depression, anxiety, and post-traumatic stress disorder. Though the pathophysiological basis is not completely understood, data have consistently shown a pivotal role of inflammatory mediators and hypothalamo-pituitary-adrenal (HPA) axis activation in stress induced disorders. Indeed emerging experimental evidences indicate a concurrent activation of inflammatory signaling pathways and not only the HPA axis, but also, peripheral and central renin-angiotensin system (RAS). Furthermore, recent experimental data indicate that the HPA and RAS are coupled to the signaling of a range of central neuro-transmitter, -mediator and -peptide molecules that are also regulated, at least in part, by inflammatory signaling cascades and vice versa. More recently, experimental evidences suggest a critical role of stress in disruption of the blood brain barrier (BBB), a neurovascular unit that regulates the movement of substances and blood-borne immune cells into the brain parenchyma, and prevents peripheral injury to the brain substance. However, the mechanisms underlying stress-induced BBB disruption are not exactly known. In this review, we summarize studies conducted on the effects of stress on the BBB and integrate recent data that suggest possible molecular mechanisms and signaling pathways underlying stress-induced BBB disruption. Key molecular targets and pharmacological candidates for treatment of stress and related illnesses are also summarized.
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Rudge, J. D. (2022) · Journal of Alzheimer's Disease Reports · doi:10.3233/adr-210299 · Cited by 58 · see citing works
- Authors
- Welcome, M. O., & Mastorakis, N. E.
- Affiliations
- Nile University of Nigeria (NG)
- Technical University of Sofia (BG)
- Corresponding author
- Welcome, Menizibeya O.
- Venue
- Pharmacological Research
- Publisher
- Elsevier BV
- Published
- 2020-07
- Volume
- 157
- Pages
- 104769
- ISSN
- 1043-6618 (ISSN-L)
- OpenAlex
- W3015939805
- Semantic Scholar
- ef8143aeed6958182584eb8c3395e7a594708c10
- Cited by
- 139
- References
- 271
- Citations by year
- 2026: 21 · 2025: 38 · 2024: 22 · 2023: 27 · 2022: 17 · 2021: 12 · 2020: 2
- FWCI
- 4.74
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Pharmacological Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Keywords
- stress, blood-brain barrier disruption, neuroinflammation, hypothalamic-pituitary-adrenal axis, renin-angiotensin system, inflammatory signaling, neurovascular unit, depression, anxiety, post-traumatic stress disorder, neurotransmitters
- MeSH terms
- Animals, Blood-Brain Barrier, Capillary Permeability, Humans, Renin-Angiotensin System, Stress, Physiological, Stress, Psychological, Signal Transduction, Reactive Oxygen Species, Neurotransmitter Agents, Oxidative Stress, Inflammation Mediators
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