Neurotrauma reports最新文献

Traumatic brain injury (TBI) remains a significant public health concern, with no effective therapeutic interventions to ameliorate the enduring consequences. The prevailing understanding of TBI pathophysiology indicates a central role for vascular dysfunction. Transforming growth factor-β (TGF-β) is a multifunctional cytokine crucial for vascular development. Aberrant TGF-β signaling is implicated in vascular pathologies associated with various neurological conditions. We recently developed a novel small molecule drug, C381, a TGF-β activator with the ability to restore lysosomal function. Here we used a mouse model of repetitive mild TBI (mTBI) to examine whether C381 would attenuate vascular injury. We first employed RNA-seq analysis to investigate the gene expression patterns associated with mTBI and evaluated the therapeutic potential of C381 in mitigating these changes. Our results demonstrate distinct mTBI-related gene expression signatures, prominently implicating pathways related to vascular integrity and endothelial function. Notably, treatment with C381 reversed these mTBI-induced gene expression changes. Immunohistochemical analysis further corroborated these findings, revealing that C381 treatment attenuated vascular damage in mTBI-affected brain tissue. These findings strongly support the potential clinical usefulness of C381 as a novel therapeutic intervention for mTBI.

This study aimed to evaluate the predictive value and clinical impact of a clinically implemented artificial neural network software model. The software detects intracranial hemorrhage (ICH) from head computed tomography (CT) scans and artificial intelligence (AI)-identified positive cases are then annotated in the work list for early radiologist evaluation. The index test was AI detection by the program Zebra Medical Vision-HealthICH+. Radiologist-confirmed ICH was the reference standard. The study compared whether time benefits from using the AI model led to faster escalation of patient care or surgery within the first 24 h. A total of 2,306 patients were evaluated by the software, and 288 AI-positive cases were included. The AI tool had a positive predictive value of 0.823. There was, however, no significant time reduction when comparing the patients who required escalation of care and those who did not. There was also no significant time reduction in those who required acute surgery compared with those who did not. Among the individual patients with reduced time delay, no cases with evident clinical benefit were identified. Although the clinically implemented AI-based decision support system showed adequate predictive value in identifying ICH, there was no significant clinical benefit for the patients in our setting. While AI-assisted detection of ICH shows great promise from a technical perspective, there remains a need to evaluate the clinical impact and perform external validation across different settings.

After mild traumatic brain injury (mTBI), a subgroup of individuals experience persistent post-concussion symptoms (PPCS) that include headaches, cognitive difficulties, and fatigue. The aim of this preliminary study was to investigate possible effects associated with metacognitive therapy (MCT) on PPCS, maladaptive coping strategies, and positive and negative metacognitive beliefs following mTBI. A pre-post design supplemented with single-case A-B replication series to assess potential MCT mechanisms was used. Of the nine participants who received MCT, all experienced a decrease in PPCS, which constituted a reliable improvement for eight participants. For eight participants (we could calculate effect sizes for eight out of nine participants), moderate to very large decreases in maladaptive coping styles and positive and negative metacognitive beliefs were observed. However, based on visual analyses, participants 6, 8, and 9 show a downward baseline trend regarding MCT mechanisms that may have persisted into the intervention phase. No adverse events were reported. In conclusion, MCT was associated with improvements in PPCS and unhelpful psychological mechanisms, but caution is required in interpreting this association. Future research using formal single-case replication on symptom measures and randomized controlled trials appears to be justified.

The aging US population has altered the epidemiology of traumatic injury, but there are few studies examining changing patterns of traumatic intracranial hemorrhage (tICH). We examined temporal changes in incidence, demographics, severity, management, and outcomes of tICH among trauma admissions at six US Level I trauma centers over 6 years (July 1, 2016-June 30, 2022). Patients with tICH (subdural, epidural, subarachnoid, and intracerebral hemorrhage) were identified by 10th revision of the International Statistical Classification of Diseases diagnosis codes. Temporal trends were examined over 12 six-month intervals using joinpoint regression and reported as biannual percent change (BPC); models without joinpoints are described as linear trends over time. There were 67,514 trauma admissions over 6 years and 11,935 (17.7%) patients had a tICH. The proportion of tICH injuries significantly increased 2.6% biannually from July 2016 to July 2019 (BPC = 2.6, p = 0.04), then leveled off through June 2022 (BPC = -0.9, p = 0.19). Similarly, the proportion of geriatric patients (≥65 years old) increased 2.4% biannually from July 2016 to July 2019 (BPC = 2.4, p = 0.001) as did injuries due to falls (BPC = 2.2, p = 0.01). Three of the four most prevalent comorbidities significantly increased: hypertension linearly increased 2.1% biannually, functional dependence increased 25.5% biannually through June 2019, and chronic anticoagulant use increased 19.0% biannually through June 2019 and then 3.1% thereafter. There were no trends in the rates of neurosurgical intervention (BPC = -0.89, p = 0.40), ED Glasgow coma score 3-8 (BPC = -0.4, p = 0.77), or presence of severe extracranial injuries (BPC = -0.7, p = 0.45). In-hospital mortality linearly declined 2.6% biannually (BPC = 2.6, p = 0.05); however, there was a 10.3% biannual linear increase in discharge to hospice care (BPC = 10.3, p < 0.001). These results demonstrate the incidence of tICH admissions is temporally increasing, and the population is growing older with more comorbidities and injuries from falls. Yet, traumatic brain injury severity and neurosurgical management are unchanged. The shift from in-patient death to hospice care suggests an increased need for palliative care services.

Resilience is associated with the degree to which post-concussion symptoms (PCS) are experienced. However, the role of resilience in the recovery trajectory of minority women, who tend to have prolonged concussion recovery, is poorly characterized. We evaluated the association between resilience and PCS, to determine if the association differed by race. A secondary data analysis was performed. Resilience was assessed using the Resilience Scale and PCS with the Rivermead questionnaire. Both variables were evaluated 6-10 weeks post-injury. Baseline demographics, spearman correlation, and multivariable linear regression models were used to determine the association between resilience and PCS. Seventy-seven women (mean age 28 ± 7.6) were included, 57% were White, and 43% were Black or Hispanic. The overall cohort had a moderate association between resilience and PCS (R = -0.304, p = 0.007). The association was present in minorities (R = -0.486, p = 0.004), and was stronger for Blacks (R = -0.745, p < 0.001). After adjusting for religion as a covariate separately, resilience (β = -0.156, 95% confidence interval [CI]: -0.285, -0.026; p = 0.019) and mood (β = 1.082, 95% CI: 0.847, 1.317; p < 0.001), were both independent predictors of PCS. The adjusted associations were stronger for the minority subgroup for both resilience (β = -0.231, 95% CI: -0.413, -0.050; p = 0.014) and mood (β = 1.122, 95% CI: 0.753, 1.491; p < 0.001). Our findings show that compared with Whites, minority individuals with higher resilience have greater resolution of PCS. However, mood is also of importance in this association. Thus resilience-based interventions must also target mood. Interventions that strengthen resilience may have promise in promoting equitable recovery in the setting of female concussions.

Traumatic brain injury (TBI) is the leading cause of morbidity and mortality worldwide. Multiple injury models have been developed to study this neurological disorder. One such model is the lateral fluid percussion injury (LFPI) rodent model. The LFPI model can be generated with different surgical procedures that could affect the injury and be reflected in neurobehavioral dysfunction and acute electroencephalograph (EEG) changes. A craniectomy was performed either with a trephine hand drill or with a trephine electric drill that was centered over the left hemisphere of adult, male Sprague Dawley rats. Sham craniectomy groups were assessed by hand-drilled (Sham_HMRI) and electric-drilled (Sham_EMRI) to evaluate by magnetic resonance imaging (MRI). Then, TBI was induced in separate groups, (TBI_H) and (TBI_E), using a fluid-percussion device. Sham-injured rats (Sham_H/Sham_E) underwent the same surgical procedures as the TBI rats. During the same surgery session, rats were implanted with screw and microwire electrodes positioned in the neocortex and hippocampus and the EEG activity was recorded 24 h for the first 7 days after TBI for assessing the acute EEG seizure and gamma event coupling. The electric drilling craniectomy induced greater tissue damage and sensorimotor deficits compared with the hand drill. Analysis of the EEG revealed acute seizures in at least one animal from each group after the procedure. Both TBI and Sham rats from the electric drill groups had a significant greater total number of seizures than the animals that were craniectomized manually (p < 0.05). Similarly, EEG functional connectivity was lower in Sham_E compared with Sham_H rats. These results suggest that electrical versus hand-drilling craniectomies produce cortical injury in addition to the LFPI which increases the likelihood for acute post-traumatic seizures. Differences in the surgical approach could be one reason for the variability in the injury that makes it difficult to replicate results between preclinical TBI studies.

Following severe traumatic brain injury (TBI), elevated catecholamine levels are associated with worsened secondary brain injury and poorer clinical outcomes. The mechanisms are uncertain but may include cerebral ischemia and blood-brain barrier disruption, with consequent cerebral edema manifesting as intracranial hypertension. Early beta-blockade (EBB) may mitigate these detrimental hyperadrenergic effects. Therapy Intensity Level (TIL) is a validated score that quantifies intracranial pressure (ICP)-lowering interventions, with higher TIL being a surrogate for more severe intracranial hypertension. In this post hoc secondary analysis of a dose-finding study of EBB with esmolol in adults with TBI, we compared summary TIL (TIL24) and domain TIL between patients who received esmolol and those who did not. The primary outcome was TIL24 for each 24-h epoch of the esmolol intervention period of 96 h. Baseline characteristics were comparable in the esmolol (E) and non-esmolol (NE) groups. Mean TIL24 was similar in both groups up to 48 h but then diverged. The mean (standard deviation) TIL24 score between 48 and 72 h was 4.8 (1.5) in group E versus 6.6 (5.4) in group NE and at 72-96 h 4.5 (1.5) in group E versus 7.0 (4.0) in group NE. TIL domain scores were lower in group E for hyperosmolar therapy, targeted temperature management, and surgical management (cerebrospinal fluid drainage, evacuation, or decompressive craniectomy). The association between esmolol use after TBI and the reduction in ICP-directed interventions is consistent with an effect of beta-blockade on reduction of cerebral edema. Further research is necessary to determine causality and mechanism.

Spinal cord injury (SCI) is one of the most serious conditions of the central nervous system, causing motor and sensory deficits that lead to a significant impairment in the quality of life. Previous studies have indicated that inosine can promote regeneration after SCI. Here we investigated the effects of inosine on the behavioral and morphological recovery after a compressive injury. Adult female C57BL/6 mice were subjected to laminectomy and spinal cord compression using a vascular clip. Inosine or saline injections were administered intraperitoneally, with the first dose performed 24 h after injury and daily for 7 days after injury. The mice were evaluated using Basso Mouse Scale (BMS), locomotor rating scale, and pinprick test for 8 weeks. At the end, the animals were anesthetized and euthanized, and the spinal cords were collected for morphological evaluation. Inosine-treated animals presented better results in the immunostaining for oligodendrocytes and in the number of myelinated fibers through semithin sections compared to saline-treated animals, showing that there was a greater preservation of the white matter. Analysis of the immunoreactivity of astrocytes and evaluation of the inflammatory profile with macrophage labeling revealed that the animals of the inosine group had a lower immunoreactivity when compared to control, which suggests a reduction of the glial scar and less inflammation, respectively, leading to a more favorable microenvironment for spinal cord regeneration. Indeed, inosine-treated animals scored higher on the BMS scale and presented better results on the pinprick test, indicating that the treatment contributed to motor and sensory recovery. After the animals were sacrificed, we obtained the electroneuromyography, where the inosine group showed a greater amplitude of the compound muscle action potential. These results indicate that inosine contributed to the regeneration process in the spinal cord of mice submitted to compressive injury and should be further investigated as a candidate for SCI therapy.

This study aims to evaluate the potential benefits of treating spinal cord injury (SCI) patients with acidic fibroblast growth factor (aFGF), a potent neurotrophic factor that preserves neuronal survival. The study involved 12 tetraplegic patients with American Spinal Injury Association Impairment Scale (AIS) Grade A SCI who were randomly assigned to receive either a recombinant human aFGF or a placebo every 4 weeks for three doses. Participants underwent comprehensive evaluations of medical, neurological, and functional parameters at baseline and every 4 weeks after the first dose until the 48th week. The first dose was administered directly to the injury site during surgery within 6 weeks of the SCI, while the subsequent two doses were administered via lumbar puncture with a 4-week interval. The results revealed promising beneficial effects of aFGF on AIS Grade A SCI patients. The study report highlights aFGF's potential to expedite motor recovery in complete SCI patients and significantly increase the probability of a 10-point improvement when compared to the placebo group (odds ratio = 6.06, p = 0.0004). Furthermore, aFGF treatment exhibited a significant reduction (p < 0.01) in the incidence or exacerbation rate of myelomalacia, a known secondary complication following SCIs.

Neurointensive care primarily focuses on secondary injury reduction, utilizing a variety of guideline-based approaches (including administration of high-dose sedation) to reduce the injured state. However, titration of sedation is currently based on the Richmond Agitation Sedation Scale (RASS), a subjective clinical grading score of a patient's response to external physical stimuli, and not an objective measure. Therefore, it is likely that there exists substantial variation in objective sedation depth for a given clinical grade in these patients, leading to undesired sedation depths and cerebral physiological consequences. Improper sedation can impede cerebral autoregulation, emphasizing the critical need for optimal sedation in traumatic brain injury (TBI) patients. This study evaluates the relationship between RASS to an objective measure of depth of sedation (bispectral index, BIS) and cerebral physiological measures. Fifty-nine patients were assessed using Jonckheere-Terpstra testing to compare various key physiologies with RASS. RASS (-5 through 0 categories) showed no statistically significant relationship between BIS and cerebral physiological parameters, after adjusting for multiple comparisons. Furthermore, it is crucial to note that within each RASS value, the distribution of the physiological measures all had high variability. As an exemplar, for RASS values of -5 and -4, BIS ranged from near 0 (burst suppression levels) up to over 80 (near awake states). BIS and other cerebral physiologies displayed substantial variation across each RASS category. This suggests that RASS as a means to titrate sedative medication for the goal of neuroprotection is insufficient. More momentary, individualized determination of sedation depth is required for TBI patients.