scholarly journals Early Reciprocal Effects in a Murine Model of Traumatic Brain Injury and Femoral Fracture

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Katharina Ritter ◽  
Kirsten Jung ◽  
Christopher Dolderer ◽  
Dominik Appel ◽  
Christine C. Oswald ◽  
...  

Traumatic brain injury (TBI) represents a major cause of death and disability in early adulthood. Concomitant extracranial injury such as long bone fracture was reported to exacerbate TBI pathology. However, early reciprocal effects and mechanisms have been barely investigated. To address this issue, C57BL/6N mice were subjected to either the controlled cortical impact (CCI) model of TBI, fracture of the left femur (FF), combined injury (CCI+FF), or sham procedure. Behavioral alterations were monitored until 5 days post injury (dpi), followed by (immuno-)histology, gene and protein expression analyses using quantitative PCR, western blot, and ELISA. We found that CCI+FF mice exhibited increased neurological impairments, reduced recovery, and altered anxiety-related behavior compared to single injury groups. At 5 dpi, cerebral lesion size was not affected by combined injury but exaggerated hippocampal substance loss and increased perilesional astrogliosis were observed in CCI+FF mice compared to isolated CCI. Bone gene expression of the osteogenic markers Runx2, osteocalcin, alkaline phosphatase, and bone sialoprotein was induced by fracture injury but attenuated by concomitant TBI. Plasma concentrations of the biomarkers osteopontin and progranulin were elevated in CCI+FF mice compared to other experimental groups. Taken together, using a murine model of TBI and femoral fracture, we report early reciprocal impairments of brain tissue maintenance, behavioral recovery, and bone repair gene expression. Increased circulating levels of the biomarkers osteopontin and progranulin indicate ongoing tissue inflammation and repair. Our results may have implications for future therapeutic approaches to interfere with the pathological crosstalk between TBI and concomitant bone fracture.

2008 ◽  
Vol 9 (1) ◽  
pp. 62 ◽  
Author(s):  
Hervé Rhinn ◽  
Catherine Marchand-Leroux ◽  
Nicole Croci ◽  
Michel Plotkine ◽  
Daniel Scherman ◽  
...  

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ellen Otto ◽  
Paul Köhli ◽  
Jessika Appelt ◽  
Stefanie Menzel ◽  
Melanie Fuchs ◽  
...  

Abstract Systemic and local posttraumatic responses are often monitored on mRNA expression level using quantitative real-time PCR (qRT-PCR), which requires normalisation to adjust for confounding sources of variability. Normalisation requests reference (housekeeping) genes stable throughout time and divergent experimental conditions in the tissue of interest, which are crucial for a reliable and reproducible gene expression analysis. Although previous animal studies analysed reference genes following isolated trauma, this multiple-trauma gene expression analysis provides a notable study analysing reference genes in primarily affected (i.e. bone/fracture callus and hypothalamus) and secondarily affected organs (i.e. white adipose tissue, liver, muscle and spleen), following experimental long bone fracture and traumatic brain injury. We considered tissue-specific and commonly used top-ranked reference candidates from different functional groups that were evaluated applying the established expression stability analysis tools NormFinder, GeNorm, BestKeeper and RefFinder. In conclusion, reference gene expression in primary organs is highly time point as well as tissue-specific, and therefore requires careful evaluation for qRT-PCR analysis. Furthermore, the general application of Ppia, particularly in combination with a second reference gene, is strongly recommended for the analysis of systemic effects in the case of indirect trauma affecting secondary organs through local and systemic pathophysiological responses.


2005 ◽  
Vol 12 (3) ◽  
pp. 284-290 ◽  
Author(s):  
Daniel B. Michael ◽  
Donna M. Byers ◽  
Louis N. Irwin

2021 ◽  
Vol 28 ◽  
pp. 39-46
Author(s):  
Ina Lackner ◽  
Birte Weber ◽  
Melanie Haffner-Luntzer ◽  
Simona Hristova ◽  
Florian Gebhard ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rani Matuk ◽  
Mandy Pereira ◽  
Janette Baird ◽  
Mark Dooner ◽  
Yan Cheng ◽  
...  

AbstractTraumatic brain injury (TBI) is of significant concern in the realm of high impact contact sports, including mixed martial arts (MMA). Extracellular vesicles (EVs) travel between the brain and oral cavity and may be isolated from salivary samples as a noninvasive biomarker of TBI. Salivary EVs may highlight acute neurocognitive or neuropathological changes, which may be particularly useful as a biomarker in high impact sports. Pre and post-fight samples of saliva were isolated from 8 MMA fighters and 7 from controls. Real-time PCR of salivary EVs was done using the TaqMan Human Inflammatory array. Gene expression profiles were compared pre-fight to post-fight as well as pre-fight to controls. Largest signals were noted for fighters sustaining a loss by technical knockout (higher impact mechanism of injury) or a full match culminating in referee decision (longer length of fight), while smaller signals were noted for fighters winning by joint or choke submission (lower impact mechanism as well as less time). A correlation was observed between absolute gene information signals and fight related markers of head injury severity. Gene expression was also significantly different in MMA fighters pre-fight compared to controls. Our findings suggest that salivary EVs as a potential biomarker in the acute period following head injury to identify injury severity and can help elucidate pathophysiological processes involved in TBI.


2021 ◽  
Vol 9 (1) ◽  
Author(s):  
Amer Toutonji ◽  
Mamatha Mandava ◽  
Silvia Guglietta ◽  
Stephen Tomlinson

AbstractActivation of the complement system propagates neuroinflammation and brain damage early and chronically after traumatic brain injury (TBI). The complement system is complex and comprises more than 50 components, many of which remain to be characterized in the normal and injured brain. Moreover, complement therapeutic studies have focused on a limited number of histopathological outcomes, which while informative, do not assess the effect of complement inhibition on neuroprotection and inflammation in a comprehensive manner. Using high throughput gene expression technology (NanoString), we simultaneously analyzed complement gene expression profiles with other neuroinflammatory pathway genes at different time points after TBI. We additionally assessed the effects of complement inhibition on neuropathological processes. Analyses of neuroinflammatory genes were performed at days 3, 7, and 28 post injury in male C57BL/6 mice following a controlled cortical impact injury. We also characterized the expression of 59 complement genes at similar time points, and also at 1- and 2-years post injury. Overall, TBI upregulated the expression of markers of astrogliosis, immune cell activation, and cellular stress, and downregulated the expression of neuronal and synaptic markers from day 3 through 28 post injury. Moreover, TBI upregulated gene expression across most complement activation and effector pathways, with an early emphasis on classical pathway genes and with continued upregulation of C2, C3 and C4 expression 2 years post injury. Treatment using the targeted complement inhibitor, CR2-Crry, significantly ameliorated TBI-induced transcriptomic changes at all time points. Nevertheless, some immune and synaptic genes remained dysregulated with CR2-Crry treatment, suggesting adjuvant anti-inflammatory and neurotropic therapy may confer additional neuroprotection. In addition to characterizing complement gene expression in the normal and aging brain, our results demonstrate broad and chronic dysregulation of the complement system after TBI, and strengthen the view that the complement system is an attractive target for TBI therapy.


PLoS ONE ◽  
2017 ◽  
Vol 12 (10) ◽  
pp. e0185943 ◽  
Author(s):  
Deborah R. Boone ◽  
Jeanna M. Leek ◽  
Michael T. Falduto ◽  
Karen E. O. Torres ◽  
Stacy L. Sell ◽  
...  

2021 ◽  
Author(s):  
Aijun Zhang ◽  
Youming Lu ◽  
Lei Yuan ◽  
Pengqi Zhang ◽  
Dongdong Zou ◽  
...  

Abstract Blood-brain barrier (BBB) dysfunction is presented during traumatic brain injury (TBI) and is dependent upon the activation of the NLRP3/Caspase-1 inflammasome pathway. MicroRNA (miRNA) was proved to inhibit signaling pathway activation by targeting gene expression and we predicated in the database that miR-29a targets to NLRP3. Herein, this study aims to define the regulating role of miR-29a in NLRP3 expression and NLRP3/Caspase-1 inflammasome activation in TBI-induced BBB dysfunction. Our results indicated that miR-29a-5p alleviates TBI-induced the increased permeability of endothelial cell and BBB via suppressing NLRP3 expression and NLRP3/Caspase-1 inflammasome activation, providing a promising strategy for relieving TBI via inhibiting NLRP3/Caspase-1 inflammasome activation.


2021 ◽  
Vol 104 (2) ◽  
pp. 185-190

Background: Maxillofacial injuries are commonly associated with brain injuries, with the major etiological factors being traffic collision, violence, and fall from height. The incidence and etiology are important for the development of treatment and for the improvement of patient care in the future. Objective: To analyze the incidence of patterns of maxillofacial fractures with traumatic brain injuries and to measure the incidence of cause of injury, age, gender distribution, and length of stay in hospital. Materials and Methods: The present study was a retrospective study in Songklanagarind Hospital. The authors evaluated the patients that presented with a concomitant maxillofacial and traumatic brain injury in Songklanagarind Hospital between 2007 and 2016. The data were assessed using multiple logistic modeling and reported in term of percentage and corresponding 95% confidence intervals. Results: Eight hundred fifty-nine patients were studied, consisting of 73.3% male and 22.7% female. The mean age was 39.5 years. The severity of the traumatic brain injury was mild and 70.15% with associated alcohol consumption. The maxilla bone fracture was common in 49.9%. The patients with mild to moderate traumatic brain injury were related to the coronoid process of mandible and severe traumatic brain injury was related to Le Fort fracture type II and III. Conclusion: In the present study, the maxilla bone fracture was the most frequent site involved. In addition, there was an association between the severity of the head injury and the type of maxillofacial injury. Keywords: Traumatic brain injury, Maxillofacial fracture


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