AI Article Synopsis
- Isoflurane induces higher levels of apoptosis in cerebrovascular endothelial cells compared to sevoflurane and midazolam, particularly after hypoxic conditions.
- The study utilized an in vitro model to assess the effects of various anesthetics on the blood-brain barrier, measuring apoptosis indicators such as the Bax and Bcl-2 ratio and TUNEL intensity.
- Results suggest that high doses of isoflurane significantly increase apoptosis markers, indicating a potential neurotoxic effect on the injured brain that may have been previously overlooked.
Article Abstract
Background: The effects of anesthetics on the injured brain continue to be the subject of controversial discussion. Since isoflurane has recently been shown to induce apoptosis of cerebral endothelial cells, this study compared different anesthetic compounds regarding their potential to induce cerebro-vascular apoptosis.
Methods: The in vitro model of the blood-brain barrier used in this study consisted of astrocyte-conditioned human umbilical vein endothelial cells (AC-HUVEC) has been used. After 24 h of deep hypoxia and reoxygenation or control treatment, AC-HUVEC were exposed to 0, 0.5, 1.0, or 2.0 times the minimum alveolar concentration of isoflurane or sevoflurane, or 0, 75, 150, or 300 nM of midazolam for 2 h. After 24 h, AC-HUVEC were harvested, and the degree of apoptosis was assessed by means of Western blots for the Bax and Bcl-2 ratio and, for controls and the highest concentration groups, terminal deoxynucleotidyl-mediated dUTP-biotin nick end labeling (TUNEL).
Results: Without hypoxic pretreatment, 2.0 MAC of isoflurane slightly increased TUNEL intensity compared to control and sevoflurane, but without any significant changes in the Bax and Bcl-2 ratio. After hypoxic pretreatment, exposure to isoflurane led to a multifold increase in the Bax and Bcl-2 ratio in a dose dependent manner, which was also significantly higher than the ratio observed in the 2 MAC sevoflurane group. TUNEL intensity in the post-hypoxic 2 MAC isoflurane group was increased by a factor of 11 vs. control and by 40 vs. sevoflurane. Sevoflurane and midazolam did not significantly alter these markers of apoptosis, when compared to the control group.
Conclusions: Isoflurane administered after hypoxia elevates markers of apoptosis in endothelial cells transdifferentiated to the cerebro-vascular endothelium. Endothelial apoptosis may be a previously underestimated mechanism of anesthetic neurotoxicity. Administration of high concentrations of isoflurane in experimental settings may have negative effects on the blood-brain barrier.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475016 | PMC |
| http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0130408 | PLOS |
Publication Analysis
Top Keywords
Similar Publications
Preventive effect of Tyr-Pro, a blood-brain barrier transportable dipeptide, on memory impairment in SAMP8 mice.
NPJ Sci Food
December 2024
Department of Bioscience and Biotechnology, Faculty of Agriculture, Graduate School of Kyushu University, Fukuoka, Japan.
In a series of studies on blood-brain barrier transportable peptides, a soybean dipeptide, Tyr-Pro, penetrated the mouse brain parenchyma after oral intake and improved short and long memory impairment in acute Alzheimer's model mice. Here, we aimed to clarify the anti-dementia effects of this peptide administered to SAMP8 mice prior to dementia onset. At the end of the 25-week protocol in 16-week-old SAMP8 mice, Tyr-Pro (10 mg/kg/day) significantly improved the reduced spatial learning ability compared with that in the control and amino acid (Tyr + Pro) groups as indicated by the results of Morris water maze tests conducted for five consecutive days.
View Article and Find Full Text PDFNET formation-mediated in situ protein delivery to the inflamed central nervous system.
Nat Commun
December 2024
College of Pharmacy and Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, Republic of Korea.
Delivering protein drugs to the central nervous system (CNS) is challenging due to the blood-brain and blood-spinal cord barrier. Here we show that neutrophils, which naturally migrate through these barriers to inflamed CNS sites and release neutrophil extracellular traps (NETs), can be leveraged for therapeutic delivery. Tannic acid nanoparticles tethered with anti-Ly6G antibody and interferon-β (aLy6G-IFNβ@TLP) are constructed for targeted neutrophil delivery.
View Article and Find Full Text PDFFerritin-Based Supramolecular Assembly Drug Delivery System for Aminated Fullerene Derivatives to Enhance Tumor-Targeted Therapy.
Adv Sci (Weinh)
December 2024
CAS Engineering Laboratory for Nanozyme, Key Laboratory of Protein and Peptide Pharmaceutical Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, P. R. China.
Owing to their attractive antitumor effects, aminated fullerene derivatives are emerging as promising therapeutic drugs for cancer. However, their in vivo applications are severely limited due to cation toxicity. To address this problem, human heavy chain ferritin (HFn), possessing natural biocompatibility is utilized, to develop a novel supramolecular assembly drug delivery system.
View Article and Find Full Text PDFBlood-brain barrier disruption and microglial activation during hypoxia and post-hypoxic recovery in aged mice.
Brain Commun
December 2024
San Diego Biomedical Research Institute, San Diego, CA 92121, USA.
Hypoxia triggers blood-brain barrier disruption and a strong microglial activation response around leaky cerebral blood vessels. These events are greatly amplified in aged mice which is translationally relevant because aged patients are far more likely to suffer hypoxic events from heart or lung disease, and because of the pathogenic role of blood-brain barrier breakdown in vascular dementia. Importantly, it is currently unclear if disrupted cerebral blood vessels spontaneously repair and if they do, whether surrounding microglia deactivates.
View Article and Find Full Text PDFEverolimus in pituitary tumor: a review of preclinical and clinical evidence.
Front Endocrinol (Lausanne)
December 2024
Department of Endocrinology and Metabolism, Lanzhou University Second Hospital, Lanzhou, Gansu, China.
Although pituitary tumors (PTs) are mostly benign, some PTs are characterized by low surgical resection rates, high recurrence rates, and poor response to conventional treatments and profoundly affect patients' quality of life. Everolimus (EVE) is the only FDA-approved mTOR inhibitor, which can be used for oral treatment. It effectively inhibits tumor cell proliferation and angiogenesis.
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!