A healthy blood-brain barrier (BBB) shields the brain from high concentrations of blood glutamate, which can cause neurotoxicity and neurodegeneration. It is believed that traumatic brain injury (TBI) causes long-term BBB disruption, subsequently increasing brain glutamate in the blood, in addition to increased glutamate resulting from the neuronal injury. Here, we investigate the relationship between blood and brain glutamate levels in the context of BBB permeability. Rats exposed to BBB disruption through an osmotic model or TBI and treated with intravenous glutamate or saline were compared to control rats with an intact BBB treated with intravenous glutamate or saline. After BBB disruption and glutamate administration, the concentrations of glutamate in the cerebrospinal fluid and blood and brain tissue were analyzed. The results showed a strong correlation between the brain and blood glutamate concentrations in the groups with BBB disruption. We conclude that a healthy BBB protects the brain from high levels of blood glutamate, and the permeability of the BBB is a vital component in regulating levels of glutamate in the brain. These findings bring a new approach to treating the consequences of TBI and other diseases where long-term disruption of the BBB is the central mechanism of their development.
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http://dx.doi.org/10.3390/ijms24065897 | DOI Listing |
CNS Neurosci Ther
December 2024
Department of Anesthesiology, Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
Aims: This study investigated the protective role of Annexin A1 (ANXA1) in sepsis-associated encephalopathy (SAE) by examining its effects on brain vascular endothelium and blood-brain barrier (BBB) integrity.
Methods: Mice were divided into four groups: wild type (WT), cecal ligation and puncture (CLP), ANXA1 knockout (ANXA1[-/-]), and ANXA1(-/-) with CLP. Neurobehavioral changes were assessed using the Y-maze test, while BBB integrity was evaluated through Evans blue dye (EBD) staining and permeability tests with fluorescein isothiocyanate (FITC)-dextran.
CPT Pharmacometrics Syst Pharmacol
December 2024
Department of Pharmaceutics and Brain Barriers Research Center, College of Pharmacy, University of Minnesota, Minneapolis, Minnesota, USA.
Type 2 diabetes mellitus (T2DM), characterized by insulin resistance, is closely associated with Alzheimer's disease (AD). Cerebrovascular dysfunction is manifested in both T2DM and AD, and is often considered as a pathological link between the two diseases. Insulin signaling regulates critical functions of the blood-brain barrier (BBB), and endothelial insulin resistance could lead to BBB dysfunction, aggravating AD pathology.
View Article and Find Full Text PDFJCI Insight
December 2024
Department of Neurological Surgery, Feinberg School of Medicine, Northwestern University, Chicago, United States of America.
Cerebral endothelial cell (EC) injury and blood-brain barrier (BBB) permeability contribute to neuronal injury in acute neurological disease states. Preclinical experiments have used animal models to study this phenomenon, yet the response of human cerebral ECs to BBB disruption remains unclear. In our Phase 1 clinical trial (NCT04528680), we used low-intensity pulsed ultrasound with microbubbles (LIPU/MB) to induce transient BBB disruption of peri-tumoral brain in patients with recurrent glioblastoma.
View Article and Find Full Text PDFFront Microbiol
December 2024
Department of Pathogen Biology, Guangdong Provincial Key Laboratory of Tropical Diseases Research, School of Public Health, Key Laboratory of Infectious Diseases Research in South China (Southern Medical University), Ministry of Education, Southern Medical University, Guangzhou, Guangdong, China.
is an intracellular opportunistic parasite that exists in a latent form within the human central nervous system (CNS), even in immune-competent hosts. During acute infection, traverses the blood-brain barrier (BBB). In the subsequent chronic infection phase, the infiltration of immune cells into the brain, driven by infection and the formation of parasitic cysts, leads to persistent activation and proliferation of astrocytes and microglia.
View Article and Find Full Text PDFBiomed Pharmacother
December 2024
Department of Radiology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, United States. Electronic address:
The technology of focused ultrasound-mediated disruption of the blood-brain barrier (FUS-BBB opening) has now been used in over 20 Phase 1 clinical trials to validate the safety and feasibility of BBB opening for drug delivery in patients with brain tumors and neurodegenerative diseases. The primary treatment parameters, FUS intensity and microbubble dose, are chosen to balance sufficient BBB disruption to achieve drug delivery against potential acute vessel damage leading to microhemorrhage. However, other safety considerations due to second order effects caused by BBB disruption, such as inflammation and alteration of neurovascular function, are only beginning to be understood.
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