Journal of neurotrauma
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Journal of neurotrauma · Sep 2022
Multimodal Biomarkers of Repetitive Head Impacts and Traumatic Encephalopathy Syndrome: A Clinico-Pathological Case Series.
Traumatic encephalopathy syndrome (TES) criteria were developed to aid diagnosis of chronic traumatic encephalopathy (CTE) pathology during life. Interpreting clinical and biomarker findings in patients with TES during life necessitates autopsy-based determination of the neuropathological profile. We report a clinicopathological series of nine patients with previous repetitive head impacts (RHI) classified retrospectively using the recent TES research framework (100% male and white/Caucasian, age at death 49-84) who completed antemortem neuropsychological evaluations, T1-weighted magnetic resonance imaging, diffusion tensor imaging (n = 6), (18)F-fluorodeoxyglucose-positron emission tomography (n = 5), and plasma measurement of neurofilament light (NfL), glial fibrillary acidic protein (GFAP), and total tau (n = 8). ⋯ Memory and executive function decline, limbic system brain changes (atrophy, decreased white matter integrity, hypometabolism), and plasma biomarker alterations are common in RHI and TES but may reflect multiple neuropathologies. In particular, the neuropathological differential for patients with RHI or TES presenting with medial temporal atrophy and memory loss should include limbic TDP-43. Researchers and clinicians should be cautious in attributing cognitive, neuroimaging, or other biomarker changes solely to CTE tau pathology based on previous RHI or a TES diagnosis alone.
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Journal of neurotrauma · Sep 2022
Comparison of common outcome measures for assessing independence in patients diagnosed with disorders of consciousness: A Traumatic Brain Injury Model Systems Study.
Patients with disorders of consciousness (DoC) after traumatic brain injury (TBI) recover to varying degrees of functional dependency. Dependency is difficult to measure but critical for interpreting clinical trial outcomes and prognostic counseling. In participants with DoC (i.e., not following commands) enrolled in the TBI Model Systems National Database (TBIMS NDB), we used the Functional Independence Measure (FIM®) as the reference to evaluate how accurately the Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS) assess dependency. ⋯ The DRSDepend had a sensitivity of 83% and a specificity of 94% for classifying FIM-dependency, with a greater AUROC than the data-derived optimal GOSE (≤3, p = 0.01) and DRS (≥10, p = 0.008) cut-points. Commonly used GOSE and DRS cut-points have limited specificity or sensitivity for identifying functional dependency. The DRSDepend identifies FIM-dependency more accurately than the GOSE and DRS cut-points, but requires further validation.
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Journal of neurotrauma · Sep 2022
Interleukin-4 reduces lesion volume and improves neurological function in the acute phase after experimental traumatic brain injury in mice.
Little is known about the impact of interleukin-4 (IL-4) on secondary brain damage in the acute phase after experimental traumatic brain injury (TBI). Therefore, we evaluated the effect of IL-4-Knockout (IL-4-KO) on structural damage, as well as functional impairment, in the acute phase after experimental TBI in mice. A total of 28 C57Bl/6 wildtype and 20 C57BL/6-Il4tm1Nnt/J IL-4-KO mice were subjected to controlled cortical impact (CCI). ⋯ Gait impairment was significantly more pronounced in IL-4-KO mice throughout the first week after CCI (e.g., 0.07 ± 0.01 sec vs. 0.00 ± 0.01 sec, p = 0.047 for right hindpaw Swing on D1; -1.76 ± 1.34 U vs. 2.53 ± 0.90 U, p = 0.01 for right forepaw mean intensity on D3; -0.01 ± 0.01 cm2 vs. 0.05 ± 0.01 cm2, p = 0.015 for left forepaw mean area on D7). In conclusion, IL-4 reduces structural damage and improves functional outcome in the acute phase after CCI. Neurobehavioral outcome assessment in IL-4-related studies should focus on motor function on the first 3 days after trauma induction.
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Journal of neurotrauma · Sep 2022
Fluvoxamine confers neuroprotection via inhibiting infiltration of peripheral leukocytes and M1 polarization of microglia/macrophages in a mouse model of traumatic brain injury.
Neuroinflammation is an important mediator of secondary injury pathogenesis that exerts dual beneficial and detrimental effects on pathophysiology of the central nervous system (CNS) after traumatic brain injury (TBI). Fluvoxamine is a serotonin selective reuptake inhibitor (SSRI) and has been reported to have the anti-inflammatory properties. However, the mechanisms and therapeutic effects of fluvoxamine in neuroinflammation after TBI have not be defined. ⋯ Fluvoxamine treatment promoted microglial/macrophage phenotypic transformation from pro-inflammatory M1-phenotype to anti-inflammatory M2-phenotype in in vivo and in vitro experiments. In addition, fluvoxamine treatment attenuated neuronal apoptosis, blood-brain barrier (BBB) disruption, cerebrovascular damage, and post-traumatic edema formation, thereby improving neurological function of mice subjected to TBI. These findings support the clinical evaluation of fluvoxamine as a neuroprotective therapy for TBI.