Blast traumatic brain injury (bTBI) affects both military and civilian populations, and often results in chronic deficits in cognition and memory. Chronic glial activation after bTBI has been linked with cognitive decline. Pharmacological inhibition of sulfonylurea receptor 1 (SUR1) with glibenclamide was shown previously to reduce glial activation and improve cognition in contusive models of CNS trauma, but has not been examined in bTBI. We postulated that glibenclamide would reduce chronic glial activation and improve long-term memory function after bTBI. Using a rat direct cranial model of bTBI (dc-bTBI), we evaluated the efficacy of two glibenclamide treatment paradigms: glibenclamide prophylaxis (pre-treatment), and treatment with glibenclamide starting after dc-bTBI (post-treatment). Our results show that dc-bTBI caused hippocampal astrocyte and microglial/macrophage activation that was associated with hippocampal memory dysfunction (rapid place learning paradigm) at 28days, and that glibenclamide pre-treatment, but not post-treatment, effectively protected against glial activation and memory dysfunction. We also report that a brief transient time-window of blood-brain barrier (BBB) disruption occurs after dc-bTBI, and we speculate that glibenclamide, which is mostly protein bound and does not normally traverse the intact BBB, can undergo CNS delivery only during this brief transient opening of the BBB. Together, our findings indicate that prophylactic glibenclamide treatment may help to protect against chronic cognitive sequelae of bTBI in warfighters and other at-risk populations.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bbr.2017.06.038 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Anti-neuroinflammatory and Neuroprotective Effects of T-006 on Alzheimer's Disease Models by Modulating TLR4-Mediated MyD88/ NF-κB Signaling.
CNS Neurol Disord Drug Targets
January 2025
School of Medicine, Foshan University, Foshan, 528000, China.
Introduction: Neuroinflammation derived from the activation of the microglia is considered a vital pathogenic factor of Alzheimer's Disease (AD). T-006, a tetramethylpyrazine derivative, has been found to alleviate cognitive deficits via inhibiting tau expression and phosphorylation in AD transgenic mouse models. Recently, T-006 has been proven to dramatically decrease the levels of total Amyloid β (Aβ) peptide and Glial Fibrillary Acidic Protein (GFAP) and suppress the expression of ionized calcium binding adaptor molecule-1 (Iba-1) in APP/PS1 mice.
View Article and Find Full Text PDFThe role and mechanism of HMGB1-mediated Notch1/Hes-1 pathway in anxiety and depression-like behaviors in mice with chronic rhinosinusitis.
Mol Med
January 2025
Department of Otorhinolaryngology Head and Neck Surgery, Affiliated Hospital of Guizhou Medical University, Guiyang, 550004, China.
Background: Chronic rhinosinusitis (CRS) is a global health issue, with some patients experiencing anxiety and depression-like symptoms. This study investigates the role of HMGB1 in anxiety and depression-like behaviors associated with the microglial Notch1/Hes-1 pathway in CRS mice.
Methods: A CRS mouse model was developed, and behavioral assessments were conducted to evaluate anxiety and depression-like behaviors.
Repeated sevoflurane exposure causes hypomyelination in the prefrontal cortex of adult male mice.
Sci Rep
January 2025
Department of Anesthesiology, Affiliated Hospital of Zunyi Medical University, Zunyi, 563000, China.
As one of the most commonly used general anesthetics (GAs) in surgery, numerous studies have demonstrated the detrimental effects of sevoflurane exposure on myelination in the developing and elderly brain. However, the impact of sevoflurane exposure on intact myelin structure in the adult brain is barely discovered. Here, we show that repeated sevoflurane exposure, but not single exposure, causes hypomyelination and abnormal ultrastructure of myelin sheath in the prefrontal cortex (PFC) of adult male mice, which is considered as a critical brain region for general anesthesia mediated consciousness change.
View Article and Find Full Text PDFMitochondria and astrocyte reactivity: Key mechanism behind neuronal injury.
Neuroscience
January 2025
Biochemistry Department and Centro de Investigaciones Biomédicas (CEINBIO), Facultad de Medicina, Universidad de la República, Montevideo, Uruguay.
In this special issue to celebrate the 30th anniversary of the Uruguayan Society for Neuroscience (SNU), we find it pertinent to highlight that research on glial cells in Uruguay began almost alongside the history of SNU and contributed to the understanding of neuron-glia interactions within the international scientific community. Glial cells, particularly astrocytes, traditionally regarded as supportive components in the central nervous system (CNS), undergo notable morphological and functional alterations in response to neuronal damage, a phenomenon referred to as glial reactivity. Among the myriad functions of astrocytes, metabolic support holds significant relevance for neuronal function, given the high energy demand of the nervous system.
View Article and Find Full Text PDFECM29/proteasome-mediated self-antigen generation by CNS-resident neuroglia promotes regulatory T cell activation.
Cell Rep
January 2025
Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan. Electronic address:
Proteasomes generate antigenic peptides presented on cell surfaces-a process that, in neuroglia, is highly responsive to external stimuli. However, the function of the self-antigens presented by CNS parenchymal cells remains unclear. Here, we report that the fidelity of neuroglial self-antigens is crucial to suppress encephalitogenic T cell responses by elevating regulatory T (Treg) cell populations.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!