Neurotrauma reports最新文献

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.

Decompressive craniectomy (DC) primarily aims at decreasing intracranial pressure (ICP) by allowing for the brain tissue to expand. However, it is uncertain to what extent DC impacts the transmission of vasogenic slow waves and thus the validity and utility of the pressure reactivity index (PRx). The purpose of this systematically performed scoping review is to assess the current knowledge of the impact of DC on ICP waveforms and measures of vascular reactivity. This scoping review considered studies including patients over 18 years old suffering from acute brain injuries (ABIs), who underwent secondary DC and had a perioperative (pre/post-DC) recording of ICP or waveform analysis. A search was conducted in EMBASE, PubMed, Web of Science, Scopus, and Medline from November 2023 till January 2024, yielding 787 studies. Duplicated studies were automatically removed, and two researchers independently screened the remaining studies. After examining 586 titles and abstracts, 38 full-text studies were assessed for eligibility, and 4 studies were included in the final review. The review suggests that cerebrovascular reactivity and slow waves are altered after DC, with positive PRx values and reduced slow power. One study suggested that the nature of slow waves and interactions is on the whole largely preserved. However, the findings should be interpreted with caution due to methodological limitations and the low number of studies.

The Glasgow Coma Scale (GCS) is the most commonly used consciousness rating scale worldwide. Although it is a sensitive and accurate way of assessing a patient's level of consciousness, it is time-consuming and requires training. We designed the Simple Coma Scale (SCS) as a simplified version of the GCS. In this study, we examined whether the SCS could predict favorable neurogenic outcomes at discharge, survival, and GCS scores in patients with traumatic brain injury (TBI). We analyzed the data of 1,230 patients registered in the Japan Neurotrauma Data Bank (Project 2015) between April 2015 and March 2017. In the SCS, eye, verbal, and motor scores are given based on a 3-point scoring system, with similar wording ("Normal," "Something Wrong," and "None") used for all scores. The SCS is based on a 7-point scale. The Glasgow Outcome Scale was used to assess the outcomes. For the receiver operating characteristic (ROC) curves with the objective variable of good prognosis at discharge in the SCS and GCS, the area under the curve (AUC) for the SCS was 0.740 (95% confidence interval [CI]: 0.711-0.769), and that of the GCS was 0.757 (95% CI: 0.729-0.786). For ROC curves with survival as the objective variable, the AUC of the SCS was 0.751 (95% CI: 0.724-0.778), and that of the GCS was 0.764 (95% CI: 0.737-0.791). The SCS, similar to the GCS, may predict good prognosis and survival at discharge. Further analyses will continue to examine the usefulness and practicality of the SCS.

Surgical site infections (SSIs) remain a major cause of life-threatening morbidity following surgery for depressed skull fractures (DSFs) among patients with traumatic brain injury (TBI). The timing of the surgery for DSF has been questioned as a risk of SSI without a clear cutoff. We aimed to compare the risk of SSI within 3 months between surgery done before versus after 48 h of injury and with its preoperative predictors. We conducted a prospective cohort study at Mulago Hospital, Uganda. Patients with mild-to-moderate TBI with DSF were followed up perioperatively from the operating time up to 3 months. The outcome variables were the incidence risk of SSI, types of SSI, microbial culture patterns of wound isolates, and hospital length of stay. We enrolled 127 patients with DSF, median age = 24 (interquartile range [IQR] = 17-31 years), 88.2% (112/127) male, and assault victims = 53.5%. The frontal bone involved 59%, while 50.4% had a dural tear. The incidence of SSI was 18.9%, mainly superficial incisional infection; Gram-negative microorganisms were the most common isolates (64.7%). The group of surgical intervention >48 h had an increased incidence of SSI (57.3% vs. 42.7%, p = 0.006), a longer median of postoperative hospital stay (8[IQR = 6-12] days versus 5 [IQR = 4-9], [p < 0.001]), and a higher rate of reoperation (71.4% vs. 28.6%, p = 0.05) in comparison with the group of ≤48 h. In multivariate analysis between the group of SSI and no SSI, surgical timing >48 h (95% confidence interval [CI], 1.25-6.22), pneumocranium on computed tomography [CT] scan (95% CI: 1.50-5.36), and involvement of air sinus (95% CI: 1.55-5.47) were associated with a >2.5-fold increase in the rate of SSI. The SSI group had a longer median hospital stay (p value <0.001). The SSI risk in DSF is high following a surgical intervention >48 h of injury, with predictors such as the frontal location of DSF, pneumocranium on a CT scan, and involvement of the air sinus. We recommend early surgical intervention within 48 h of injury.

The objective of this study was to understand whether exposure to adverse childhood experiences (ACEs) before 18 years of age predicts increased neurobehavioral symptom reporting in adults presenting for treatment secondary to persistent symptoms after mild traumatic brain injury (mTBI). This cross-sectional study identified 78 individuals with mTBI from 2014 to 2018 presenting for treatment to an outpatient multidisciplinary rehabilitation clinic. Neurobehavioral symptom inventory (NSI-22) scores were collected on admission, and ACEs for each patient were abstracted by medical record review. A linear regression model was used to assess if an individual who experienced at least one ACE before age 18 resulted in significantly different neurobehavioral scores compared with those not reporting any history of an ACE before age 18. Participants who reported at least one ACE before age 18 had significantly increased NSI-22 scores on admission to the rehabilitation clinic compared with patients without history of ACEs (mean difference 10.1, p = 0.011), adjusted for age and gender. For individuals presenting for treatment after mTBI, a history of ACEs before age 18 was associated with increased neurobehavioral symptoms.

Spinal cord transcutaneous stimulation (scTS) offers a promising approach to enhance cardiovascular regulation in individuals with a high-level spinal cord injury (SCI), addressing the challenges of unstable blood pressure (BP) and the accompanying hypo- and hypertensive events. While scTS offers flexibility in stimulation locations, it also leads to significant variability and lack of validation in stimulation sites utilized by studies. Our study presents findings from a case series involving eight individuals with chronic cervical SCI, examining the hemodynamic effects of scTS applied in different vertebral locations, spanning from high cervical to sacral regions. Stimulation of the lumbosacral vertebrae region (L1/2, S1/2, and also including T11/12) significantly elevated BP, unlike cervical or upper thoracic stimulation. The observed trend, which remained consistent across different participants, highlights the promising role of lumbosacral stimulation in neuromodulating BP.