A Concomitant Muscle Injury Does Not Worsen Traumatic Brain Injury Outcomes in Mice

被引:9
作者
Sun, Mujun [1 ]
Brady, Rhys D. [2 ,3 ]
van der Poel, Chris [4 ]
Apted, Danielle [4 ]
Semple, Bridgette D. [1 ,2 ,3 ]
Church, Jarrod E. [4 ]
O'Brien, Terence J. [1 ,2 ,3 ]
McDonald, Stuart J. [4 ]
Shultz, Sandy R. [1 ,2 ,3 ]
机构
[1] Univ Melbourne, Royal Melbourne Hosp, Dept Med, Melbourne, Vic, Australia
[2] Monash Univ, Cent Clin Sch, Dept Neurosci, Melbourne, Vic, Australia
[3] Monash Univ, Cent Clin Sch, Dept Med, Melbourne, Vic, Australia
[4] La Trobe Univ, Dept Physiol Anat & Microbiol, Melbourne, Vic, Australia
基金
英国医学研究理事会;
关键词
polytrauma; weight-drop; cardiotoxin; neuroinflammation; cytokines; OXIDATIVE STRESS; SKELETAL-MUSCLE; RAT MODEL; ANIMAL-MODELS; BONE-FRACTURE; MOUSE MODEL; NEUROINFLAMMATION; PROTEIN; REGENERATION; INFLAMMATION;
D O I
10.3389/fneur.2018.01089
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Traumatic brain injury (TBI) often involves multitrauma in which concurrent extracranial injury occurs. We previously demonstrated that a long bone fracture exacerbates neuroinflammation and functional outcomes in mice given a TBI. Whether other forms of concomitant peripheral trauma that are common in the TBI setting, such as skeletal muscle injury, have similar effects is unknown. As such, here we developed a novel mouse multitrauma model by combining a closed-skull TBI with a cardiotoxin (CTX)-induced muscle injury to investigate whether muscle injury affects TBI outcomes. Adult male mice were assigned to four groups: sham-TBI + sham-muscle injury (SHAM); sham-TBI + CTX-muscle injury (CTX); TBI + sham-muscle injury (TBI); TBI + CTX-muscle injury (MULTI). Some mice were euthanized at 24 h post-injury to assess neuroinflammation and cerebral edema. The remaining mice underwent behavioral testing after a 30-day recovery period, and were euthanized at 35 days post-injury for post-mortem analysis. At 24 h post-injury, both TBI and MULTI mice had elevated edema, increased expression of GFAP (i.e., a marker for reactive astrocytes), and increased mRNA levels of inflammatory chemokines. There was also an effect of injury on cytokine levels at 35 days post-injury. However, the TBI and MULTI mice did not significantly differ on any of the measures assessed. These initial findings suggest that a concomitant muscle injury does not significantly affect preclinical TBI outcomes. Future studies should investigate the combination of different injury models, additional outcomes, and other post-injury time points.
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页数:11
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