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Influence of interleukin-4 on secondary brain damage after experimental traumatic brain injury in mice
Einfluss von Interleukin-4 auf den sekundären Hirnschaden nach experimentellem Schädel-Hirn-Trauma im Mausmodell
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Published: | June 26, 2020 |
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Objective: Recent focus of experimental research in traumatic brain injury has been directed towards the role of inflammatory processes. Proinflammatory pathways have become the focus of interest; however, in models of ischemic stroke and spinal cord injury it has been shown that anti-inflammatory pathways, especially the interleukin-4 (IL-4) pathway, play an important role in the evolution of secondary brain injury as well. Therefore, we aimed to assess the role of the interleukin-4 pathway on secondary brain damage following experimental traumatic brain injury.
Methods: C57/Bl6 wildtype as well as C57BL/6-Il4tm1Nnt/J interleukin-4 knockout mice were subjected to controlled cortical impact (CCI) injury (tip diameter 2mm, impact depth 1mm, velocity 8m/s, contact time 150ms). Neurological function was assessed using hole board, video open field and CatWalk XT gait analysis tests 24 hours as well as three and seven days after CCI. In addition, contusion volume was determined by Nissl staining and pericontusional distribution of IL-4 and IL-4 receptor assessed by immunohistochemistry at the same timepoints.
Results: Exploration (33.9 +/- 2.4 vs. 24.8 +/- 3.7 hole board explorations per 10 minutes on day 3, p= 0.008), locomotion (154.1 +/- 18.6 seconds vs. 100.9 +/- 15.3 seconds to visit all open field sections on day 1, p=0.033) and motor function (i.e. difference in left hindpaw print area on day 3: -0.017 +/- 0.012 cm2 vs. -0.050 +/- 0.015 cm2, p=0.04) was significantly more impaired in interleukin-4 knockout mice. Contusion volume was significantly higher (81.0 +/- 7.8 vs. 123.3 +/- 7.7 on day 3, p=0.04) and pericontusional distribution of IL-4 and IL-4 receptor significantly lower in IL-4 knockout mice.
Conclusion: Interleukin-4 plays an important role in the evolution of secondary brain damage after experimental traumatic brain injury as lack of interleukin-4 in the pericontusional area leads to larger contusion volumes and to deterioration in neurological outcome. The current results provide the basis for future studies examining a potential positive therapeutic effect of interleukin-4 in CCI.