Journal of neurotrauma
-
Journal of neurotrauma · Jul 2023
Cerebrospinal fluid levels of lysophosphatidic acids can provide suitable biomarkers of blast-induced traumatic brain injury.
Blast-induced traumatic brain injury (bTBI) has been identified as the signature injury of Operation Iraqi Freedom and Operation Enduring Freedom. Although the incidence of bTBI increased significantly after the introduction of improvised explosive devices, the mechanism of the injury is still uncertain, which is negatively impacting the development of suitable countermeasures. Identification of suitable biomarkers that could aid in the proper diagnosis of and prognosis for both acute and chronic bTBI is essential since bTBI frequently is occult and may not be associated with overtly detectable injuries to the head. ⋯ In the plasma, several LPA species increased acutely, returned to normal levels by 24 h, and were significantly decreased at 1 year post-blast overpressure exposures. These decreases in LPA species in the plasma were associated with decreased levels of lysophosphatidyl choline, suggesting a defective upstream biosynthetic pathway of LPAs in the plasma. Notably, the changes in LPA levels in the CSF (but not plasma) negatively correlated with neurobehavioral functions in these rats, suggesting that CSF levels of LPAs may provide a suitable biomarker of bTBI that reflects severity of injury.
-
Journal of neurotrauma · Jul 2023
ADAM17 aggravates the inflammatory response by modulating microglia polarization through the TGF-β1/Smad pathway following experimental traumatic brain injury.
Microglia-mediated neuroinflammatory responses play important roles in secondary neurological injury after traumatic brain injury (TBI). The TGF-β pathway participates in the regulation of M1/M2 phenotype transformation of microglia. TGF-β can activate the Smad pathway by binding to TGF-βRs, which is regulated by the cleavage function of A disintegrin and metalloproteinase 17 (ADAM17). ⋯ The neuroprotective effect of ADAM17 inhibition was related to a shift from the M1 microglial phenotype to the M2 microglial phenotype, thus reducing TBI-induced neuroinflammation. ADAM17 inhibition increased expression of TGF-βRs on the microglia membrane, promoted formation of TGF-β1/TGF-βRII complexes, and induced intranuclear translocation of Smads, which activated the TGF-β/Smad pathway. In conclusion, our study suggested that ADAM17 inhibition regulated microglia M1/M2 phenotype polarization through the TGF-β1/Smad pathway and influenced the neuroinflammatory response after TBI.
-
Journal of neurotrauma · Jul 2023
Observational StudyWithdrawal of life sustaining therapies in children with severe traumatic brain injury.
Neuroprognostication in severe traumatic brain injury (sTBI) is challenging and occurs in critical care settings to determine withdrawal of life-sustaining therapies (WLST). However, formal pediatric sTBI neuroprognostication guidelines are lacking, brain death criteria vary, and dilemmas regarding WLST persist, which lead to institutional differences. We studied WLST practice and outcome in pediatric sTBI to provide insight into WLST-associated factors and survivor recovery trajectory ≥1 year post-sTBI. ⋯ Median survivor PCPC score improved from 4 to 2 with no vegetative patients 1 year post-sTBI. Our findings show the WLST decision process was multi-disciplinary and guided by specific clinical features at presentation, clinical course, and (serial) neurological diagnostic modalities, of which the testing combination was determined by case-to-case variation. This stresses the need for international guidelines to provide accurate neuroprognostication within an appropriate timeframe whereby overall survivor outcome data provides valuable context and guidance in the acute phase decision process.
-
Journal of neurotrauma · Jul 2023
ReviewPutting the mind to rest: a historical foundation for rest as a treatment for traumatic brain injury.
Rest after traumatic brain injury (TBI) has been a part of clinical practice for more than a century but the use of rest as a treatment has ancient roots. In contemporary practice, rest recommendations have been significantly reduced but are still present. This advice to brain injured patients, on the face of it makes some logical sense but was not historically anchored in either theory or empirical data. ⋯ The goals and theoretical explanations for this approach have evolved and in modern conception include avoiding reinjury and reducing the metabolic demands on injured tissue. Moreover, as cellular and molecular understanding of the physiology of TBI developed, scientists and clinicians sometimes retroactively cited these new data in support of rest recommendations. Here, we trace the history of this approach and how it has been shaped by new understanding of the underlying pathology associated with brain injury.
-
Journal of neurotrauma · Jul 2023
Use of support vector machines approach via ComBat harmonized diffusion tensor imaging for the diagnosis and prognosis of mild traumatic brain injury: a CENTER-TBI study.
The prediction of functional outcome after mild traumatic brain injury (mTBI) is challenging. Conventional magnetic resonance imaging (MRI) does not do a good job of explaining the variance in outcome, as many patients with incomplete recovery will have normal-appearing clinical neuroimaging. More advanced quantitative techniques such as diffusion MRI (dMRI), can detect microstructural changes not otherwise visible, and so may offer a way to improve outcome prediction. ⋯ Similar to the analysis between mTBI patients and controls, the three-category-harmonized ComBat FA and MD maps voxelwise approach yields statistically significant prediction scores between mTBI patients with complete and those with incomplete recovery (71.8% specificity, 66.2% F1-score and 0.71 AUC, p < 0.05), which provided a modest increase in the classification score (accuracy: 66.4%) compared with the classification based on age and sex only and ROI-wise approaches (accuracy: 61.4% and 64.7%, respectively). This study showed that ComBat harmonized FA and MD may provide additional information for diagnosis and prognosis of mTBI in a multi-modal machine learning approach. These findings demonstrate that dMRI may assist in the early detection of patients at risk of incomplete recovery from mTBI.