Severe Brain Injury Research Articles

Trauma in Neonatal Acute Brain Slices Alters Calcium and Network Dynamics and Causes Calpain-Mediated Cell Death.

Preparing acute brain slices produces trauma that mimics severe penetrating brain injury. In neonatal acute brain slices, the spatiotemporal characteristics of trauma-induced calcium dynamics in neurons and its effect on network activity are relatively unknown. Using multiphoton laser scanning microscopy of the somatosensory neocortex in acute neonatal mouse brain slices (P8-12), we simultaneously imaged neuronal Ca2+ dynamics (GCaMP6s) and cytotoxicity (propidium iodide or PI) to determine the relationship between cytotoxic Ca2+ loaded neurons (GCaMP-filled) and cell viability at different depths and incubation times. PI+ cells and GCaMP-filled neurons were abundant at the surface of the slices, with an exponential decrease with depth. Regions with high PI+ cells correlated with elevated neuronal and neuropil Ca2+ The number of PI+ cells and GCaMP-filled neurons increased with prolonged incubation. GCaMP-filled neurons did not participate in stimulus-evoked or seizure-evoked network activity. Significantly, the superficial tissue, with a higher degree of trauma-induced injury, showed attenuated seizure-related neuronal Ca2+ responses. Calpain inhibition prevented the increase in PI+ cells and GCaMP-filled neurons in the deep tissue and during prolonged incubation times. Isoform-specific pharmacological inhibition implicated calpain-2 as a significant contributor to trauma-induced injury in acute slices. Our results show a calpain-mediated spatiotemporal relationship between cell death and aberrant neuronal Ca2+ load in acute neonatal brain slices. Also, we demonstrate that neurons in acute brain slices exhibit altered physiology depending on the degree of trauma-induced injury. Blocking calpains may be a therapeutic option to prevent acute neuronal death during traumatic brain injury in the young brain.

Perception of diagnosis by family caregivers in severe brain injury patients in China

ObjectivesSurrogate decision-making by family caregivers for patients with severe brain injury is influenced by the availability and understanding of relevant information and expectations for future rehabilitation. We aimed to compare the consistency of family caregivers’ perceptions with clinical diagnoses and to inform their expectation of prognosis in the future.MethodsThe Coma Recovery Scale-Revised was used to assess the diagnosis of inpatients with severe brain injury between February 2019 and February 2020. A main family caregiver was included per patient. The family caregiver’s perception of the patient’s consciousness and expectations of future recovery were collected through questionnaires and compared consistently with the clinical diagnosis.ResultsThe final sample included 101 main family caregivers of patients (57 UWS, unresponsive wakefulness syndrome, 37 MCS, minimally conscious state, 7 EMCS, emergence from MCS) with severe brain injury. Only 57 family caregivers correctly assessed the level of consciousness as indicated by the CRS-R, showing weak consistency (Kappa = 0.217, P = 0.002). Family caregivers’ demographic characteristics and CRS-R diagnosis influenced the consistency between perception and clinical diagnosis. Family caregivers who provided hands-on care to patients showed higher levels of consistent perception (AOR = 12.24, 95% CI = 2.06-73.00, P = 0.006). Compared to UWS, the family caregivers of MCS patients were more likely to have a correct perception (OR = 7.68, 95% CI = 1.34–44.06). Family caregivers had positive expectations for patients’ recovery in terms of both communication and returning to normal life.ConclusionNearly half of family caregivers have inadequate understanding of their relative’s level of consciousness, and most of them report overly optimistic expectations that do not align with clinical diagnosis. Providing more medical information to family caregivers to support their surrogate decision-making process is essential.

Accuracy of acute hyperglycemia as a biomarker of severe brain damage in children with traumatic brain injury.

Biomarkers are substances measured at the systemic level to evaluate organic responses in certain situations, establishing diagnoses, disease staging, and prognosis. Blood glucose is a biomarker recognized as a predictor of prognosis in children victims of traumatic brain injury (TBI). The scope of this study was to identify the accuracy of blood glucose as a biomarker of severe brain injury. A retrospective analytical study was conducted through the consecutive review of medical records of children and teenage victims of TBI who underwent neurological surgery between 2016 and 2023 in a level 1 trauma center. Two groups were compared: children with Glasgow Coma Scale (GCS) score ≤ 8 and children with GCS > 8. We calculated the predictive values to define the accuracy of blood glucose as a biomarker of brain injury. Ninety-two medical records were included for analysis. Hyperglycemia predominated in cases with GCS ≤ 8 (48% vs 3%; p < 0.0001; OR, 30; 95% CI, 5.9902-150.2448). The glycemic measurement considering the cutoff point of 200 mg/dL or 11.1 mmol/L showed a specificity of 97%, a positive predictive value of 86%, an accuracy of 84%, and a likelihood ratio for a positive test of 16. Victims with GCS ≤ 8 are 16 times more likely to develop acute hyperglycemia after TBI when compared to those with GCS > 8. Blood glucose is a biomarker with an accuracy of 84% to predict severe brain injury, considering the cutoff point of 200 mg/dL or 11.1 mmol/L.

Severe course of leptospirosis: A case report

This study describes a clinical case of severe leptospirosis. Patient K., was admitted to the neurosurgical department on November 26, 2023, with a diagnosis of “Closed craniocerebral injury dated 22.11.2023. Severe brain injury. Linear fracture of the occipital bone. Eyelid hematoma. An abrasion of the upper eyelid on the right.” On November 29, 2023, an objective examination drew attention to an increase in body temperature to 39.5°C, subictericity of the sclera and skin, and conjunctival injections. Hemorrhagic rash appeared on the skin of the trunk and limbs. The hemodynamics was unstable, with episodes of arterial hypotension. Laboratory examination revealed mild anemia, signs of hepatic–renal insufficiency, hyperbilirubinemia, and increased concentrations of creatine phosphokinase, C-reactive protein, and procalcitonin. Fluctuations in hepatic–renal insufficiency and levels of creatine phosphokinase and procalcitonin increased. In addition, the differential diagnostic search aimed at identifying the following infectious diseases: hemorrhagic fever with renal syndrome, leptospirosis, malaria, and viral hepatitis. IgM to Leptospira interrogans were detected (December 11, 2023). The patient received antibacterial therapy, extracorporeal detoxification, artificial ventilation, infusion therapy, and correction of the hemostasis system. With the complex treatment, the patient’s condition stabilized, and the patient was discharged from the hospital on the 61st day with restoration of health.

Cerebral Gray Matter May Not Explain Sleep Slow-Wave Characteristics after Severe Brain Injury.

Sleep slow waves are the hallmark of deeper non-rapid eye movement sleep. It is generally assumed that gray matter properties predict slow-wave density, morphology, and spectral power in healthy adults. Here, we tested the association between gray matter volume (GMV) and slow-wave characteristics in 27 patients with moderate-to-severe traumatic brain injury (TBI, 32.0 ± 12.2 years old, eight women) and compared that with 32 healthy controls (29.2 ± 11.5 years old, nine women). Participants underwent overnight polysomnography and cerebral MRI with a 3 Tesla scanner. A whole-brain voxel-wise analysis was performed to compare GMV between groups. Slow-wave density, morphology, and spectral power (0.4-6 Hz) were computed, and GMV was extracted from the thalamus, cingulate, insula, precuneus, and orbitofrontal cortex to test the relationship between slow waves and gray matter in regions implicated in the generation and/or propagation of slow waves. Compared with controls, TBI patients had significantly lower frontal and temporal GMV and exhibited a subtle decrease in slow-wave frequency. Moreover, higher GMV in the orbitofrontal cortex, insula, cingulate cortex, and precuneus was associated with higher slow-wave frequency and slope, but only in healthy controls. Higher orbitofrontal GMV was also associated with higher slow-wave density in healthy participants. While we observed the expected associations between GMV and slow-wave characteristics in healthy controls, no such associations were observed in the TBI group despite lower GMV. This finding challenges the presumed role of GMV in slow-wave generation and morphology.

Factors affecting severity and prognosis of traumatic brain injury among Bangladeshi patients: An institution based cross-sectional study

Objective Traumatic brain injury (TBI) proves to be an obstacle for Bangladeshi patients due to the lack of facilities and specialist doctors in regional sections of the country. This study aimed to record different attributes of Bangladeshi TBI patients over a year i.e., their injury characteristics, treatments received and understand their impacts on the severity of TBI. Method This cross-sectional study was carried out among 280 TBI patients treated in a tertiary care hospital in Dhaka. The physicians determined TBI's severity and prognosis as per the Glasgow Coma Scale (GCS) and Glasgow Outcome Score (GOS) respectively. Results Most TBI patients were male (76.1%) and aged between 18 and 50 years (52.2%), as in previous studies in South Asian countries. However, the prevalence of TBI due to road traffic accidents (RTAs) was much higher (67.9%) than in the earlier studies in South Asia. Additionally, more patients suffered from severe TBI (29.3%) and moderate TBI (35.7%), and a higher percentage of patients went through surgery (56.8%) compared to previous studies. A significant association of demographic (residence) and clinical characteristics (consciousness after injury, CT scan findings and treatment type) with the severity of TBI was found in bivariate analysis. It also revealed the significant dependence of clinical characteristics (TBI etiology, post-injury consciousness, treatment type and TBI severity) on TBI prognosis. Multivariate analysis showed that patients who were unconscious after TBI and with evident brain injury observed in CT scans have a substantially higher risk of having moderate or severe TBI than mild TBI. Moreover, patients with TBI due to RTAs or falls, evident brain injury in CT scans, post-surgical seizure, and moderate or severe TBI have a significantly higher risk of getting a more unfavorable TBI prognosis than moderate disability. Conclusions In this study, RTAs were found to be the major cause of TBI. Additionally, some variables were identified as possible determinants of TBI severity and prognosis among Bangladeshi patients. The correlation of these variables with TBI should be further studied with the hopes that steps will be taken to reduce TBI incidents and improve its management to reduce the overall burden.

Characterizing Intimate Partner Violence-Caused Brain Injury in a Sample of Survivors in the Two Spirit, Lesbian, Gay, Bisexual, Transgender, Queer or Questioning Community.

Research in the field of intimate partner violence-caused brain injury (IPV-BI) has predominantly focused on heterosexual women, ignoring the unique needs of the Two Spirit, Lesbian, Gay, Bisexual, Transgender, Queer or Questioning (2S/LGBTQ) community. The purpose of this exploratory research was to better understand the prevalence of IPV and IPV-BI in 2S/LGBTQ relationships where IPV was defined as physical, psychological, financial, sexual, and/or identity-based abuse from a current of former intimate partner. This study used a cross sectional internet-based survey that ran from September to December of 2022. In addition to descriptive statistics, prevalence rates and their corresponding Wilson Score confidence intervals are reported to estimate the proportion of individuals who experienced IPV and IPV-BI. Finally, for both gender identity and sexual orientation, we tested whether participants with each identity had differing levels of brain injury severity compared to participants who did not hold that identity using Mann-Whitney U tests. In total, 170 2S/LGBTQ+ adults responded to the survey. Among the respondents, 54% identified as Two-Spirit, 24% identified as gay, 17% identified as queer, 14% identified as bisexual, and 8% identified as lesbian or pansexual, respectively. Respondents were predominantly multiracial, post-secondary educated, full-time employed, cisgender women (35%) or cisgender men (19%). The overwhelming majority reported lifetime prevalence of IPV at 98% (n = 166, 95% CI [94.11, 99.08]). Additionally, 68% (n = 115, 95% CI [60.29, 74.22]) of participants reported symptoms consistent with an IPV-BI. These results are consistent with the findings that the 2S/LGBTQ community are at heightened risk of experiencing physical IPV. These findings are the first to our knowledge to report a high rate of symptoms consistent with an IPV-BI in the 2S/LGBTQ population.

Safety and Feasibility of Electrocardiogram-Guided Tip Positioning Combined with Ultrasound-Guided Placement of Peripherally Inserted Central Catheter Performed in Severe Brain Injury Patients

ObjectiveTo explore the safety and feasibility of using electrocardiogram (ECG)-guided tip positioning combined with ultrasound-guided placement of peripherally inserted central catheters (PICC) in patients with severe brain injury in a neurosurgery intensive care unit.MethodsWe retrospectively analyzed 400 patients who underwent PICC catheterization in a neurosurgery intensive care unit from January 2017 to January 2021. Of those, a group of 157 patients received only ultrasound-guided PICC placement. The second group (243 patients) received ECG-guided tip positioning combined with ultrasound-guided PICC placement. A logistic regression analysis was conducted on gender, arm circumference, and ECG usage based on whether the results were in place. The positioning accuracy, success rate of primary catheterization, incidence of ectopic catheters, average catheterization depth, and incidence of catheterization complications were observed.ResultsLogistic regression analysis showed that only ECG guidance helps to achieve accurate PICC (OD, 4.541; 95CI, 2.224–9.271; p < 0.001). The correct placement rate of the PICC tip was significantly higher in ECG-guided tip positioning combined with the ultrasound guidance group (90.73%) compared to the ultrasound-only group (79.00%, P < 0.001). There was no significant difference between the two groups in terms of difficult catheter delivery and replace the punctured vessel, and the incidences of blocked blood return in the ECG-plus-ultrasound group was significantly better than the ultrasound group (9.55%) (χ2 = 14.402, P < 0.001).ConclusionIn patients with severe brain injury, ECG-guided tip positioning combined with ultrasound guidance in PICC catheterization can significantly increase the rate of correct tip placement without increasing the difficulty of catheterization.

Enhanced Survival of 22-25 Week Preterm Infants After Proactive Care Implementation: A Comparative Analysis of Two Time Periods.

To investigate the impact of proactive perinatal care on periviable preterm infants before and after its implementation. This retrospective cohort study was conducted over a period of 10 y, from 2013 to 2019, referred to as Phase I, and from 2020 to 2022, referred to as Phase II. A total of 162 eligible infants born between 220/7 and 256/7 wk of gestation were included in this analysis. A total of 125 infants were born in phase I, and 37 infants in phase II received proactive care with minimal handling. The mortality decreased from 54.4% to 24.3% (P = 0.001). The composite outcomes of severe brain injury or death, sepsis or death and necrotizing enterocolitis or death were also improved with proactive care. Gestational age [adjusted odds ratio (aOR) 0.900; 95% confidence interval (CI), 0.836-0.970], air leak syndrome (aOR 4.958; 95% CI, 1.681-14.624), massive pulmonary hemorrhage (aOR 4.944; 95% CI, 2.055-11.893), and birth in phase II (aOR 0.324; 95% CI, 0.115-0.912) were independently associated with mortality. The implementation of proactive care with minimal handling resulted in an increased survival rate and a reduction in the combined morbidities between the two time periods. The provision of proactive perinatal care with minimal handling is crucial for improving both the survival rates and clinical outcomes of these vulnerable infants.

Survival and predictive factors of clinical outcome in patients with severe acquired brain injury.

Despite the many tools available to modern medicine, predicting the neurological and functional status of patients after severe brain injury remains difficult. This analysis evaluates the outcomes of patients with the most severe degree of cerebral function impairment. Retrospective cohort study. Patients hospitalized in the long-term Intensive Care Unit (ICU) department in the Military University Hospital in Prague between 2015-2022. We analyzed patients with severe acquired brain damage from five distinct etiologies whose initial Glasgow Coma Scale (GCS) score was eight or less upon admission to ICU due to neurological damage. Several parameters reflecting the patients' clinical status were evaluated. Overall survival after discharge from the ICU was calculated according to the Kaplan-Meier model with comparison between traumatic (TR) and non-traumatic (non-TR) etiologies. The analyzed cohort of 221 patients consisted of 116 patients of TR and 105 of non-TR etiology. There was no significant difference in overall survival between TR and non-TR groups. The length of hospitalization in the ICU was similar in both groups with a median of 94 days. The majority of patients had an improvement of GCS during the hospitalization with a median improvement of five points. GCS improvement occurred in the vast majority of patients regardless of TR or non-TR etiology. We did not observe a statistically significant difference in mortality or log-term neurological status between patients with severe brain injury of traumatic or non-traumatic etiology for the duration of our follow-up. The majority of patients had improved GCS, were successfully decannulated, but remained disabled with severe limitations of functional independence. The return of the patient to normal life is a rehabilitation challenge, regardless of the etiology of brain injury, and is extremely influenced by the level of development of neurorehabilitation programs in individual institutions, the severity of brain injury, and the individual motivation of the patient.

Short-term outcomes of early intensive neurorehabilitation for prolonged disorders of consciousness: A prospective cohort study

BackgroundAdvances in medical care have increased survival in people with severe brain injuries and with that the number of survivors with prolonged disorders of consciousness (PDOC) has increased. In the literature, early intensive neurorehabilitation (EIN) for people with PDOC is recommended to achieve the best possible outcomes. ObjectivesTo evaluate the frequency and extent of recovery of consciousness, mortality, complications, pain and discomfort, and medication during a nationwide EIN programme in people with PDOC after acquired brain injury. We hypothesized that level of consciousness would improve in half of people with PDOC. MethodsProspective cohort study. People with PDOC aged 16 years and older admitted to the EIN department centralized in a single rehabilitation centre in the Netherlands (Libra Rehabilitation & Audiology) were included. The EIN delivers a subacute medical level of care and rehabilitation for a maximum duration of 14 weeks. The outcome measures were level of consciousness (CRS-R), mortality, number of complications, medication and pain/discomfort (NCS-R). ResultsOf the 104 people included, 68 % emerged to a minimal conscious state with command-following or higher during EIN and 44 % regained consciousness. Mortality during EIN was 6 %, and 50 % of deaths followed a non-treatment decision or withdrawal of life-sustaining treatment. Almost all participants had at least 1 medical complication, leading to hospital readmission for 30 %. 73 % showed no pain or discomfort. During EIN, cardiovascular medication and analgesics were reduced by 15 %. ConclusionsDuring the EIN programme, a large percentage of people with PDOC regained at least a minimal conscious state or even consciousness. These outcomes and the frequent medical complications in these people suggest that intensive specialized care should be offered to all people with PDOC. The outcomes of this study might help health professionals to better inform the families of people with PDOC about the short-term prognosis of PDOC. Protocol registration numberThe Dutch Trial Register, NL 8138.

Post-Intensive Care Syndrome in Neurocritical Care Patients.

Post-intensive care syndrome (PICS) refers to unintended consequences of critical care that manifest as new or worsening impairments in physical functioning, cognitive ability, or mental health. As intensive care unit (ICU) survival continues to improve, PICS is becoming increasingly recognized as a public health problem. Studies that focus on PICS have typically excluded patients with acute brain injuries and chronic neurodegenerative problems. However, patients who require neurocritical care undoubtedly suffer from impairments that overlap substantially with those encompassed by PICS. A major challenge is to distinguish between impairments related to brain injury and those that occur as a consequence of critical care. The general principles for the prevention and management of PICS and multidomain impairments in patients with moderate and severe neurological injuries are similar including the ICU liberation bundle, multidisciplinary team-based care throughout the continuum of care, and increasing awareness regarding the challenges of critical care survivorship among patients, families, and multidisciplinary team members. An extension of this concept, PICS-Family (PICS-F) refers to the mental health consequences of the intensive care experience for families and loved ones of ICU survivors. A dyadic approach to ICU survivorship with an emphasis on recognizing families and caregivers that may be at risk of developing PICS-F after neurocritical care illness can help improve outcomes for ICU survivors. In this review, we will summarize our current understanding of PICS and PICS-F, emerging literature on PICS in severe acute brain injury, strategies for preventing and treating PICS, and share our recommendations for future directions.

Prognostication in Neurocritical Care.

This article synthesizes the current literature on prognostication in neurocritical care, identifies existing challenges, and proposes future research directions to reduce variability and enhance scientific and patient-centered approaches to neuroprognostication. Patients with severe acute brain injury often lack the capacity to make their own medical decisions, leaving surrogate decision makers responsible for life-or-death choices. These decisions heavily rely on clinicians' prognostication, which is still considered an art because of the previous lack of specific guidelines. Consequently, there is significant variability in neuroprognostication practices. This article examines various aspects of neuroprognostication. It explores the cognitive approach to prognostication, highlights the use of statistical modeling such as Bayesian models and machine learning, emphasizes the importance of clinician-family communication during prognostic disclosures, and proposes shared decision making for more patient-centered care. This article identifies ongoing challenges in the field and emphasizes the need for future research to ameliorate variability in neuroprognostication. By focusing on scientific methodologies and patient-centered approaches, this research aims to provide guidance and tools that may enhance neuroprognostication in neurocritical care.

Swallowing Assessment in Post-Comatose Patients: A Feasibility Study on the SWADOC Tool.

Background: After a severe brain injury and a coma, patients may develop disorders of consciousness (DoC), frequently accompanied by severe dysphagia. The evaluation and therapy of swallowing are therefore essential aspects of their management. Objectives: This study aims to evaluate the SWallowing Assessment in Disorders of Consciousness (SWADOC) tool in the assessment of swallowing in post-comatose patients. Here, we validate its quantitative items, describe preliminary results and identify limitations. Methods: Fourteen post-comatose patients were repeatedly evaluated with the Simplified Evaluation of CONsciousness Disorders (SECONDs) and with the SWADOC. Results: The internal consistency of the oral and pharyngeal subscales of the SWADOC was good. The test-retest reliability showed that all items, all subscores and the total score were stable except for two items (endo-buccal secretions and bronchial congestion). A comparison to the Facial Oral Tract Therapy Swallowing Assessment of Saliva (F.O.T.T-SAS) confirmed that scoring with the SWADOC offers a greater potential for quantitative observations in assessing swallowing abilities among patients with DoC. The SECONDs scores and SWADOC total scores showed a significant positive correlation (τ = 0.78, p < 0.001). Conclusions: This study provides preliminary but encouraging results on the psychometric properties of the SWADOC tool. It shows that this tool is relevant and feasible as a bedside assessment of dysphagia in patients with DoC.

Novel biomarkers of preterm brain injury from blood transcriptome in sheep model of intrauterine asphyxia.

Infants born preterm have a higher incidence of neurological deficits. A key step in finding effective treatments is to identify biomarkers that reliably predict outcome. Following umbilical cord occlusion (UCO) in pregnant sheep, whole fetal blood RNA was sequenced pre- and post-UCO, brain injury outcome was determined by battery of neuropathology scoring and the transcriptome signature correlated to the degree of brain injury. Additionally, we developed a novel analytical procedure to deduce cell blood composition over time. Sixty-one genes were identified with significant altered expression after UCO. In pre-UCO blood, the level of three mRNAs (Trex2, Znf280b, novel miRNA) and in post-UCO, four mRNAs (Fam184a, Angptl2, novel lincRNA and an unknown protein-coding gene) were associated to brain injury (FDR < 0.01). Several of these mRNAs are related to inflammation and angiogenesis. Pathway analysis highlighted genes playing a role in perinatal death and growth failure. Results also indicate that several leukocyte populations undergo significant changes after UCO. We have used a whole transcriptomic approach to uncover novel biomarkers in fetal blood that correlate to neuropathology in the preterm sheep brain. The current data forms a basis for future studies to investigate mechanisms of these mRNAs in the injury progression. Trend analysis of genes following asphyxia reveal a group of genes associated with perinatal death and growth failure. Several pre-asphyxia transcripts were associated to brain injury severity suggesting genomic susceptibility to injury. Several post-asphyxia transcripts were correlated to brain injury severity, thus, serve as potential novel biomarkers of injury outcome. Successfully adaptation of cell profiling algorithms suggests significant changes in blood cell composition following asphyxia.

Serum NfL and GFAP as biomarkers of progressive neurodegeneration in TBI.

We examined spatial patterns of brain atrophy after mild, moderate, and severe traumatic brain injury (TBI), the relationship between progression of brain atrophy with initial traumatic axonal injury (TAI), cognitive outcome, and with serum biomarkers of brain injury. A total of 143 patients with TBI and 43 controls were studied cross-sectionally and longitudinally up to 5 years with multiple assessments, which included brain magnetic resonance imaging, cognitive testing, and serum biomarkers. TBI patients showed progressive volume loss regardless of injury severity over several years, andTAI was independently associated with accelerated brain atrophy. Cognitive performance improved over time. Higher baseline serum neurofilament light (NfL) and glial fibrillary acidic protein (GFAP) were associated with greater rate of brain atrophy over 5 years. Spatial patterns of atrophy differ by injury severity and TAI is associated with the progression of brain atrophy. Serum NfL and GFAP show promise as non-invasive prognostic biomarkers of progressive neurodegeneration in TBI. In this longitudinal study of patient with mild, moderate, and severe traumatic brain injury (TBI) who were assessed with paired magnetic resonance imaging (MRI), blood biomarkers, and cognitive assessments, we found that brain atrophy after TBI is progressive and continues for many years even after a mild head trauma without signs of brain injury on conventional MRI. We found that spatial pattern of brain atrophy differs between mild, moderate, and severe TBI, where in patients with mild TBI , atrophy is mainly seen in the gray matter, while in those with moderate to severe brain injury atrophy is predominantly seen in the subcortical gray matter and whiter matter. Cognitive performance improves over time after a TBI. Serum measures of neurofilament light or glial fibrillary acidic protein are associated with progression of brain atrophy after TBI.

Influence of cerebrospinal fluid drainage in the first days after aneurysm rupture on the severity of early brain injury following aneurysmal subarachnoid hemorrhage

PurposeProgressive cerebral edema with refractory intracranial hypertension (ICP) requiring decompressive hemicraniectomy (DHC) is a severe manifestation of early brain injury (EBI) after aneurysmal subarachnoid hemorrhage (aSAH). The purpose of the study was to investigate whether a more pronounced cerebrospinal fluid (CSF) drainage has an influence on cerebral perfusion pressure (CPP) and the extent of EBI after aSAH.MethodsPatients with aSAH and indication for ICP-monitoring admitted to our center between 2012 and 2020 were retrospectively included. EBI was categorized based on intracranial blood burden, persistent loss of consciousness, and SEBES (Subarachnoid Hemorrhage Early Brain Edema Score) score on the third day after ictus. The draining CSF and vital signs such as ICP and CPP were documented daily.Results90 out of 324 eligible aSAH patients (28%) were included. The mean age was 54.2 ± 11.9 years. DHC was performed in 24% (22/90) of patients. Mean CSF drainage within 72 h after ictus was 168.5 ± 78.5 ml. A higher CSF drainage within 72 h after ictus correlated with a less severe EBI and a less frequent need for DHC (r=-0.33, p = 0.001) and with a higher mean CPP on day 3 after ictus (r = 0.2351, p = 0.02).ConclusionA more pronounced CSF drainage in the first 3 days of aSAH was associated with higher CPP and a less severe course of EBI and required less frequently a DHC. These results support the hypothesis that an early and pronounced CSF drainage may facilitate blood clearance and positively influence the course of EBI.

Traumatic brain injury heterogeneity affects cell death and autophagy.

Traumatic brain injury (TBI) mechanism and severity are heterogenous clinically, resulting in a multitude of physical, cognitive, and behavioral deficits. Impact variability influences the origin, spread, and classification of molecular dysfunction which limits strategies for comprehensive clinical intervention. Indeed, there are currently no clinically approved therapeutics for treating the secondary consequences associated with TBI. Thus, examining pathophysiological changes from heterogeneous impacts is imperative for improving clinical translation and evaluating the efficacy of potential therapeutic strategies. Here we utilized TBI models that varied in both injury mechanism and severity including severe traditional controlled cortical impact (CCI), modified mild CCI (MTBI), and multiple severities of closed-head diffuse TBI (DTBI), and assessed pathophysiological changes. Severe CCI induced cortical lesions and necrosis, while both MTBI and DTBI lacked lesions or significant necrotic damage. Autophagy was activated in the ipsilateral cortex following CCI, but acutely impaired in the ipsilateral hippocampus. Additionally, autophagy was activated in the cortex following DTBI, and autophagic impairment was observed in either the cortex or hippocampus following impact from each DTBI severity. Thus, we provide evidence that autophagy is a therapeutic target for both mild and severe TBI. However, dramatic increases in necrosis following CCI may negatively impact the clinical translatability of therapeutics designed to treat acute dysfunction in TBI. Overall, these results provide evidence that injury sequalae affiliated with TBI heterogeneity is linked through autophagy activation and/or impaired autophagic flux. Thus, therapeutic strategies designed to intervene in autophagy may alleviate pathophysiological consequences, in addition to the cognitive and behavioral deficits observed in TBI.

Xanthoangelol alleviates ischemic stroke injury by inhibiting the inflammatory activation of microglia

BackgroundLocal inflammation induced by microglial activation plays a significant role in the pathological process of cerebral ischemia. Angelica keiskei (Miq.) Koidz., a traditional botanical drug, can be used as a diuretic, laxative or galactagogue. Xanthoangelol (XA), an active chalcone compound from the aerial part of Angelica keiskei, has anti-inflammatory effects in the peripheral tissues. However, its effect against neuroinflammation is yet unclear. ObjectiveThe present study aims to investigate whether XA could mitigate ischemic stroke damage through attenuating neuroinflammation due to microglia activation. MethodsMiddle cerebral artery occlusion/reperfusion (MCAO/R) induced cerebral ischemia and oxygen-glucose deprivation/reperfusion (OGD/R) or lipopolysaccharide (LPS)-stimulated BV2 microglia cells were utilized to evaluate XA's protection against ischemic injury and neuroinflammation. The severity of brain injury was assessed using 2, 3, 5-triphenyltetrazolium chloride (TTC) staining and neurological assessment. The expressions of inflammatory cytokines were quantified by enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). Reactive oxygen species (ROS) were assessed using dichlorodihydrofluorescein diacetate (DCF-DA) staining. NF-κB p65 nuclear translocation was confirmed by immunofluorescence (IF) staining. The expressions of proteins were quantified by Western blotting. ResultsXA was efficacious in reducing infarct size and improving neurological function in MCAO/R mice. In ischemic brain tissue, XA reduced microglial activation and proinflammatory cytokine expression. In lipopolysaccharide (LPS) and OGD/R-induced cell models, XA suppressed the production of ROS and decreased the secretion of inflammatory cytokines. Additionally, XA suppressed the nuclear translocation and phosphorylation of NF-κB p65 and blocked the activation of NLR family pyrin domain containing 3 (NLRP3) inflammasome. The protection of XA against MCAO/R-induced damages was not attenuated in TLR4−/− and MD2−/− mice. Mito-TEMPO treatment reversed XA's anti-inflammatory properties in OGD/R-induced BV2 cells. ConclusionXA attenuates ischemic stroke injury by suppressing microglial inflammatory responses. This efficacy is tied to its antioxidant activity and is independent of Toll-like receptor 4 (TLR4) or myeloid differentiation protein 2 (MD2).

Neurosurgical Injuries Associated with Recreational Horseback Riding: A 6-year Retrospective Analysis

Horseback riding can cause severe brain and spinal injuries. This study aimed to identify the spectrum of neurosurgical injuries related to recreational horseback riding. A retrospective study was performed utilizing the University of Puerto Rico neurosurgery database to identify patients who were consulted to the neurosurgery service between 2018 and 2023 after a horse fall during recreational activities. The outcome upon discharge using the modified Rankin scale (mRS) was documented. Descriptive statistics were used to report frequency and median values. The neurosurgery service evaluated and managed 112 patients with a horseback riding fall-related injury during six years. Ninety-eight (87.5%) patients were male. The patients' median age was 31.5 (IQR 22-40). There were 89 head injuries (79.5%), 19 spinal injuries(17%), and four combined head/spine injuries (3.5%). Forty percent of the patients were admitted to inpatient care with a median length of stay of seven days (IQR 3-17). Twenty-four patients (21%) required surgery. Upon discharge, 86.6% of the patients had a mRS grade of 0-2, 3.6 % had a grade of 3, 1.8% had a grade of 4, and 1.8% had a grade of 5. Seven patients (6%) died (mRS grade 6). Most neurological injuries involve isolated trauma to the head. Fifteen percent of the riders' falls were caused after the horse was impacted by a motor vehicle. Forty percent of the patients require admission and 21% undergo surgery. Ten percent of the patients had a poor mRS grade of 4-6 when discharged.