A murine model of inflammation-induced cerebral microbleeds
| العنوان: | A murine model of inflammation-induced cerebral microbleeds |
|---|---|
| المؤلفون: | Rachita K. Sumbria, Ronald C. Kim, Tatiana B. Krasieva, David H. Cribbs, Mher Mahoney Grigoryan, Alexandra K. Dvornikova, Vitaly Vasilevko, Mark Fisher, Miriam Scadeng, Annlia Paganini-Hill |
| المصدر: | Sumbria, RK; Grigoryan, MM; Vasilevko, V; Krasieva, TB; Scadeng, M; Dvornikova, AK; et al.(2016). A murine model of inflammation-induced cerebral microbleeds. JOURNAL OF NEUROINFLAMMATION, 13. doi: 10.1186/s12974-016-0693-5. UC Irvine: Retrieved from: http://www.escholarship.org/uc/item/0rj1b3vbTest Journal of neuroinflammation, vol 13, iss 1 Journal of Neuroinflammation |
| بيانات النشر: | Springer Nature |
| مصطلحات موضوعية: | Lipopolysaccharides, Male, 0301 basic medicine, Pathology, Lipopolysaccharide, subcortex, blood brain barrier, Normal aging, Neurodegenerative, Inbred C57BL, Systemic inflammation, fluorescence microscopy, Mice, immunoglobulin G, chemistry.chemical_compound, 0302 clinical medicine, nervous system inflammation, 2.1 Biological and endogenous factors, animal, Aetiology, nuclear magnetic resonance imaging, C57BL mouse, adult, General Neuroscience, lipopolysaccharide, Brain, Hematology, respiratory system, intercellular adhesion molecule 1, unclassified drug, cell activation, 3. Good health, Animal models, female, Neurology, Blood-Brain Barrier, glial fibrillary acidic protein, Neurological, immunohistochemistry, brain hemorrhage, chemically induced, Female, medicine.symptom, Cerebral microbleeds, microvasculature, medicine.medical_specialty, diagnostic imaging, animal experiment, Clinical Sciences, Immunology, Inflammation, Hemosiderin, Article, animal tissue, brain cortex, Sepsis, 03 medical and health sciences, Cellular and Molecular Neuroscience, Cerebral microhemorrhage, medicine, Animals, Hypoxic brain injury, controlled study, Pathological, mouse, Cerebral Hemorrhage, nonhuman, Neurology & Neurosurgery, business.industry, Research, animal model, disease model, Neurosciences, medicine.disease, Brain Disorders, Mice, Inbred C57BL, Disease Models, Animal, 030104 developmental biology, protein Iba1, chemistry, Murine model, drug effects, Disease Models, Microvessels, business, metabolism, 030217 neurology & neurosurgery, adaptor protein |
| الوصف: | BackgroundCerebral microhemorrhages (CMH) are tiny deposits of blood degradation products in the brain and are pathological substrates of cerebral microbleeds. The existing CMH animal models are β-amyloid-, hypoxic brain injury-, or hypertension-induced. Recent evidence shows that CMH develop independently of hypoxic brain injury, hypertension, or amyloid deposition and CMH are associated with normal aging, sepsis, and neurodegenerative conditions. One common factor among the above pathologies is inflammation, and recent clinical studies show a link between systemic inflammation and CMH. Hence, we hypothesize that inflammation induces CMH development and thus, lipopolysaccharide (LPS)-induced CMH may be an appropriate model to study cerebral microbleeds.MethodsAdult C57BL/6 mice were injected with LPS (3 or 1mg/kg, i.p.) or saline at 0, 6, and 24h. At 2 or 7days after the first injection, brains were harvested. Hematoxylin and eosin (H&E) and Prussian blue (PB) were used to stain fresh (acute) hemorrhages and hemosiderin (sub-acute) hemorrhages, respectively. Brain tissue ICAM-1, IgG, Iba1, and GFAP immunohistochemistry were used to examine endothelium activation, blood-brain barrier (BBB) disruption, and neuroinflammation. MRI and fluorescence microscopy were used to further confirm CMH development in this model.ResultsLPS-treated mice developed H&E-positive (at 2days) and PB-positive (at 7days) CMH. No surface and negligible H&E-positive CMH were observed in saline-treated mice (n = 12). LPS (3mg/kg; n = 10) produced significantly higher number, size, and area of H&E-positive CMH at 2days. LPS (1mg/kg; n = 9) produced robust development of PB-positive CMH at 7days, with significantly higher number and area compared with saline (n = 9)-treated mice. CMH showed the highest distribution in the cerebellum followed by the sub-cortex and cortex. LPS-induced CMH were predominantly adjacent to cerebral capillaries, and CMH load was associated with indices of brain endothelium activation, BBB disruption, and neuroinflammation. Fluorescence microscopy confirmed the extravasation of red blood cells into the brain parenchyma, and MRI demonstrated the presence of cerebral microbleeds.ConclusionsLPS produced rapid and robust development of H&E-positive (at 2days) and PB-positive (at 7days) CMH. The ease of development of both H&E- and PB-positive CMH makes the LPS-induced mouse model suitable to study inflammation-induced CMH. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1742-2094 |
| DOI: | 10.1186/s12974-016-0693-5 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d51232de327c4b9bb709b6247d17d5dcTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d51232de327c4b9bb709b6247d17d5dc |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 17422094 |
|---|---|
| DOI: | 10.1186/s12974-016-0693-5 |