Systemic Injection of Low-Dose Lipopolysaccharide Fails to Break down the Blood–Brain Barrier or Activate the TLR4-MyD88 Pathway in Neonatal Rat Brain
| Autor: | Yin-Jie Yang, Li-Xin Shang, Peng Wang, Ding-Jun Hao, Xiao-Yan Wei, Xin Wang, Ya-Zhou Wang, Si-Wei You, Fang Kuang |
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| Rok vydání: | 2014 |
| Předmět: |
Lipopolysaccharides
Male medicine.medical_specialty Lipopolysaccharide toll-like receptor 4 blood–brain barrier Blood–brain barrier Article Catalysis Injections Rats Sprague-Dawley neonatal lcsh:Chemistry Inorganic Chemistry chemistry.chemical_compound Internal medicine medicine Animals rat Physical and Theoretical Chemistry Receptor lcsh:QH301-705.5 Molecular Biology Spectroscopy Evans Blue Microglia business.industry Organic Chemistry General Medicine Extravasation Rats Computer Science Applications medicine.anatomical_structure Endocrinology Animals Newborn low-dose lipopolysaccharide lcsh:Biology (General) lcsh:QD1-999 chemistry Blood-Brain Barrier Myeloid Differentiation Factor 88 TLR4 Female lipids (amino acids peptides and proteins) Tumor necrosis factor alpha business Signal Transduction |
| Zdroj: | International Journal of Molecular Sciences, Vol 15, Iss 6, Pp 10101-10115 (2014) International Journal of Molecular Sciences Volume 15 Issue 6 Pages 10101-10115 |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms150610101 |
| Popis: | We aimed to investigate whether peripheral low-dose lipopolysaccharide (LPS) induces the breakdown of the blood–brain barrier (BBB) and/or the activation of toll-like receptor 4 (TLR4) in the neonatal rat brain. Neonatal rats received intraperitoneal injections of low-dose LPS (0.3 mg/kg∙bw), and the BBB compromise was detected by Evans Blue extravasation and electron microscopy. Meanwhile, TLR4, adaptin myeloid differentiation factor 88 (MyD88), nuclear transcription factor kappa-B (NF-κB) p50 and tumor necrosis factor alpha (TNFα) in the neonatal rat brain were determined by quantitative real-time polymerase chain reaction (PCR) and Western Blot. Immunohistochemistry was used to determine the distribution and activation of microglia in the brain after LPS administration. It was demonstrated that Evans Blue extravasation was not observed in the brain parenchyma, and that tight junctions of cerebral endothelial cells remained intact after systemic injections of LPS in neonatal rats. Although intracerebroventricular injections of LPS activated microglia and up-regulated the expression of TLR4, MyD88, NF-κB p50 and TNFα in the neonatal rat brain, systemic LPS did not induce these responses. These findings indicate that while the neonatal rat brain responds to the direct intra-cerebral administration of LPS through robust TLR4 activation, systemic low-dose LPS does not induce the innate immune reaction or compromise the BBB in neonatal rats. |
| Databáze: | OpenAIRE |
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