Comment from Dr. Mladenoff
IL-6 increases on Day 1 and Day 4 after mTBI and causes spontaneous neuroinflammation leading to long term brain damage. It is imperative to begin down regulating IL-6 as soon as possible after head trauma.
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Research More Info 12
Spontaneous Neuro Inflammation After mTBI
Effect of astrocyte-targeted production of IL-6 on traumatic brain injury and its impact on the cortical transcriptome
Article in Developmental Neurobiology 68(2):195-208 · February 2008 with 38 ReadsDOI: 10.1002/dneu.20584 · Source: PubMed
Article in Developmental Neurobiology 68(2):195-208 · February 2008 with 38 ReadsDOI: 10.1002/dneu.20584 · Source: PubMed
Abstract:
Interleukin-6 (IL-6) is one of the key players in the response of the brain cortex to injury. We have described previously that astrocyte-driven production of IL-6 (GFAP-IL6) in transgenic mice, although causing spontaneous neuroinflammation and long term damage, is beneficial after an acute (freeze) injury in the cortex, increasing healing and decreasing oxidative stress and apoptosis. To determine the transcriptional basis for these responses here we analyzed the global gene expression profile of the cortex, at 0 (unlesioned), 1 or 4 days post lesion (dpl), in both GFAP-IL6 mice and their control littermates. GFAP-IL6 mice showed an increase in genes associated with the inflammatory response both at 1 dpl (Iftm1, Endod1) and 4 dpl (Gfap, C4b), decreased expression of proapoptotic genes (i.e. Gadd45b, Clic4, p21) as well as reduced expression of genes involved in the control of oxidative stress (Atf4). Furthermore, the presence of IL-6 altered the expression of genes involved in hemostasis (Vwf), cell migration and proliferation (Cap2), and synaptic activity (Vamp2). All these changes in gene expression could underlie the phenotype of the GFAP-IL6 mice after injury, but many other possible factors were also identified in this study, highlighting the utility of this approach for deciphering new pathways orchestrated by IL-6.
... Corresponding to the results seen in IL-6 knockout mice, GFAP-IL-6 mice, which overexpress IL-6 in the CNS, showed faster recovery and healing after TBI [215,216]. Transcriptome analyses of IL-6 knockout ver- sus wildtype [217] and GFAP-IL-6 mice [218] post-TBI via cryoinjury, showed that multiple pathways involving inflammation, apoptosis and oxidative stress were affected by IL-6. For example, IL-6 knockouts had lower expression of the gene producing suppressor of cyto- kine signaling (SOCS), an inhibitory protein transcribed by the JAK/STAT pathway after IL-6 activation [217]. ...
... brain-derived neurotrophic factor, early growth response 1) post-injury [217]. Injured GFAP-IL-6 mice expressed higher levels of complement component 4 and other inflammatory mediator genes in addition to lower levels of select pro-apoptotic genes and oxidative stress-related genes in comparison to injured wildtype mice [218]. ...
... brain-derived neurotrophic factor, early growth response 1) post-injury [217]. Injured GFAP-IL-6 mice expressed higher levels of complement component 4 and other inflammatory mediator genes in addition to lower levels of select pro-apoptotic genes and oxidative stress-related genes in comparison to injured wildtype mice [218]. ...
Effect of astrocyte-targeted production of IL-6 on traumatic brain injury and its impact on the cortical transcriptome |
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