Decreased Secondary Lesion Growth and Attenuated Immune Response after Traumatic Brain Injury in Tlr2/4−/− Mice
Danger-associated molecular patterns are released by damaged cells and trigger neuroinflammation through activation of non-specific pattern recognition receptors, e.g., toll-like receptors (TLRs). Since the role of TLR2 and 4 after traumatic brain injury (TBI) is still unclear, we examined the outco...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2017-08-01
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| Series: | Frontiers in Neurology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fneur.2017.00455/full |
| _version_ | 1811261689621905408 |
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| author | Sandro M. Krieg Florian Voigt Florian Voigt Pascal Knuefermann Carsten Jürgen Kirschning Nikolaus Plesnila Nikolaus Plesnila Florian Ringel Florian Ringel |
| author_facet | Sandro M. Krieg Florian Voigt Florian Voigt Pascal Knuefermann Carsten Jürgen Kirschning Nikolaus Plesnila Nikolaus Plesnila Florian Ringel Florian Ringel |
| author_sort | Sandro M. Krieg |
| collection | DOAJ |
| description | Danger-associated molecular patterns are released by damaged cells and trigger neuroinflammation through activation of non-specific pattern recognition receptors, e.g., toll-like receptors (TLRs). Since the role of TLR2 and 4 after traumatic brain injury (TBI) is still unclear, we examined the outcome and the expression of pro-inflammatory mediators after experimental TBI in Tlr2/4−/− and wild-type (WT) mice. Tlr2/4−/− and WT mice were subjected to controlled cortical injury and contusion volume and brain edema formation were assessed 24 h thereafter. Expression of inflammatory markers in brain tissue was measured by quantitative PCR 15 min, 3 h, 6 h, 12 h, and 24 h after controlled cortical impact (CCI). Contusion volume was significantly attenuated in Tlr2/4−/− mice (29.7 ± 0.7 mm3 as compared to 33.5 ± 0.8 mm3 in WT; p < 0.05) after CCI while brain edema was not affected. Only interleukin (IL)-1β gene expression was increased after CCI in the Tlr2/4−/− relative to WT mice. Inducible nitric oxide synthetase, TNF, IL-6, and COX-2 were similar in injured WT and Tlr2/4−/− mice, while the increase in high-mobility group box 1 was attenuated at 6 h. TLR2 and 4 are consequently shown to potentially promote secondary brain injury after experimental CCI via neuroinflammation and may therefore represent a novel therapeutic target for the treatment of TBI. |
| first_indexed | 2024-04-12T19:08:55Z |
| format | Article |
| id | doaj.art-5f97d37d71af4cca90b7e4ae1a364836 |
| institution | Directory Open Access Journal |
| issn | 1664-2295 |
| language | English |
| last_indexed | 2024-04-12T19:08:55Z |
| publishDate | 2017-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neurology |
| spelling | doaj.art-5f97d37d71af4cca90b7e4ae1a3648362022-12-22T03:19:56ZengFrontiers Media S.A.Frontiers in Neurology1664-22952017-08-01810.3389/fneur.2017.00455292103Decreased Secondary Lesion Growth and Attenuated Immune Response after Traumatic Brain Injury in Tlr2/4−/− MiceSandro M. Krieg0Florian Voigt1Florian Voigt2Pascal Knuefermann3Carsten Jürgen Kirschning4Nikolaus Plesnila5Nikolaus Plesnila6Florian Ringel7Florian Ringel8Department of Neurosurgery, Technische Universität München, Munich, GermanyDepartment of Neurosurgery, Technische Universität München, Munich, GermanyInstitute for Surgical Research, University of Munich Medical Center, Ludwig-Maximilians-Universität München, Munich, GermanyDepartment of Anesthesiology and Intensive Care Medicine, University Hospital Bonn, Bonn, GermanyInstitute of Medical Microbiology, University of Duisburg-Essen, Essen, GermanyInstitute for Surgical Research, University of Munich Medical Center, Ludwig-Maximilians-Universität München, Munich, GermanyInstitute for Stroke and Dementia Research, University of Munich Medical Center, Ludwig-Maximilians-Universität München, Munich, GermanyDepartment of Neurosurgery, Technische Universität München, Munich, GermanyDepartment of Neurosurgery, University of Mainz, Mainz, GermanyDanger-associated molecular patterns are released by damaged cells and trigger neuroinflammation through activation of non-specific pattern recognition receptors, e.g., toll-like receptors (TLRs). Since the role of TLR2 and 4 after traumatic brain injury (TBI) is still unclear, we examined the outcome and the expression of pro-inflammatory mediators after experimental TBI in Tlr2/4−/− and wild-type (WT) mice. Tlr2/4−/− and WT mice were subjected to controlled cortical injury and contusion volume and brain edema formation were assessed 24 h thereafter. Expression of inflammatory markers in brain tissue was measured by quantitative PCR 15 min, 3 h, 6 h, 12 h, and 24 h after controlled cortical impact (CCI). Contusion volume was significantly attenuated in Tlr2/4−/− mice (29.7 ± 0.7 mm3 as compared to 33.5 ± 0.8 mm3 in WT; p < 0.05) after CCI while brain edema was not affected. Only interleukin (IL)-1β gene expression was increased after CCI in the Tlr2/4−/− relative to WT mice. Inducible nitric oxide synthetase, TNF, IL-6, and COX-2 were similar in injured WT and Tlr2/4−/− mice, while the increase in high-mobility group box 1 was attenuated at 6 h. TLR2 and 4 are consequently shown to potentially promote secondary brain injury after experimental CCI via neuroinflammation and may therefore represent a novel therapeutic target for the treatment of TBI.http://journal.frontiersin.org/article/10.3389/fneur.2017.00455/fulltoll-like receptorsbrain edemaintracranial pressuresecondary brain damagetraumatic brain injury |
| spellingShingle | Sandro M. Krieg Florian Voigt Florian Voigt Pascal Knuefermann Carsten Jürgen Kirschning Nikolaus Plesnila Nikolaus Plesnila Florian Ringel Florian Ringel Decreased Secondary Lesion Growth and Attenuated Immune Response after Traumatic Brain Injury in Tlr2/4−/− Mice Frontiers in Neurology toll-like receptors brain edema intracranial pressure secondary brain damage traumatic brain injury |
| title | Decreased Secondary Lesion Growth and Attenuated Immune Response after Traumatic Brain Injury in Tlr2/4−/− Mice |
| title_full | Decreased Secondary Lesion Growth and Attenuated Immune Response after Traumatic Brain Injury in Tlr2/4−/− Mice |
| title_fullStr | Decreased Secondary Lesion Growth and Attenuated Immune Response after Traumatic Brain Injury in Tlr2/4−/− Mice |
| title_full_unstemmed | Decreased Secondary Lesion Growth and Attenuated Immune Response after Traumatic Brain Injury in Tlr2/4−/− Mice |
| title_short | Decreased Secondary Lesion Growth and Attenuated Immune Response after Traumatic Brain Injury in Tlr2/4−/− Mice |
| title_sort | decreased secondary lesion growth and attenuated immune response after traumatic brain injury in tlr2 4 mice |
| topic | toll-like receptors brain edema intracranial pressure secondary brain damage traumatic brain injury |
| url | http://journal.frontiersin.org/article/10.3389/fneur.2017.00455/full |
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