Computational modeling and uncertainty prediction of hyperelastic constitutive responses of damaged brain tissue under different temperature and strain rates.

The effect of strain rate and temperature on the hyperelastic material stress-strain characteristics of the damaged porcine brain tissue is evaluated in this present work. The desired constitutive responses are obtained using the commercially available finite element (FE) tool ABAQUS, utilizing 8-noded brick elements. The model's accuracy has been verified by comparing the results from the previously published literature. Further, the stress-strain behavior of the brain tissue is evaluated by varying the damages at various strain rates and temperatures (13, 20, 27, and 37°C) under compression test. Additionally, the sensitivity analysis of the model is computed to check the effect of input parameters, that is, the temperature, strain rate, and damages on the material properties (shear modulus). The modeling and discussion sections enumerate the inclusive features and model capabilities.

Understanding the barriers and facilitators of healthcare services for brain injury and concurrent mental health and substance use issues: a qualitative study.

BACKGROUND: People with acquired brain injury (ABI) may experience concurrent conditions such as, mental health and substance use concerns, that require specialized care. There are services that aim to support people with ABI and these conditions separately; however, little is known about the facilitators and barriers of these services. Therefore, the purpose of this study was to engage stakeholders to investigate the facilitators and barriers of healthcare services for ABI and concurrent issues. METHODS: Semi-structured focus groups were conducted in-person and virtually with people with ABI, caregivers, healthcare professionals, and policy makers during a one-day event in British Columbia, Canada. Manifest content analysis was used with a constructivist perspective to analyze data. RESULTS: 90 participants (including 34 people with ABI) provided insights during 15 simultaneous focus groups. Three categories were identified: (1) complexity of ABI, (2) supports, (3) structure of care. Complexity of ABI outlined the ongoing basic needs after ABI and highlighted the need for public awareness of ABI. Supports outlined healthcare professional and community-based supports. Structure of care described people with ABI needing to meet criteria for support, experiences of navigating through the system and necessity of integrated services. CONCLUSIONS: These findings highlight the facilitators and barriers of healthcare services for ABI and concurrent conditions and provide insights into the changes that may be needed. Doing so can improve the accessibility and quality of ABI healthcare services.

Cognitive Motor Dissociation in Disorders of Consciousness.

BACKGROUND: Patients with brain injury who are unresponsive to commands may perform cognitive tasks that are detected on functional magnetic resonance imaging (fMRI) and electroencephalography (EEG). This phenomenon, known as cognitive motor dissociation, has not been systematically studied in a large cohort of persons with disorders of consciousness. METHODS: In this prospective cohort study conducted at six international centers, we collected clinical, behavioral, and task-based fMRI and EEG data from a convenience sample of 353 adults with disorders of consciousness. We assessed the response to commands on task-based fMRI or EEG in participants without an observable response to verbal commands (i.e., those with a behavioral diagnosis of coma, vegetative state, or minimally conscious state-minus) and in participants with an observable response to verbal commands. The presence or absence of an observable response to commands was assessed with the use of the Coma Recovery Scale-Revised (CRS-R). RESULTS: Data from fMRI only or EEG only were available for 65% of the participants, and data from both fMRI and EEG were available for 35%. The median age of the participants was 37.9 years, the median time between brain injury and assessment with the CRS-R was 7.9 months (25% of the participants were assessed with the CRS-R within 28 days after injury), and brain trauma was an etiologic factor in 50%. We detected cognitive motor dissociation in 60 of the 241 participants (25%) without an observable response to commands, of whom 11 had been assessed with the use of fMRI only, 13 with the use of EEG only, and 36 with the use of both techniques. Cognitive motor dissociation was associated with younger age, longer time since injury, and brain trauma as an etiologic factor. In contrast, responses on task-based fMRI or EEG occurred in 43 of 112 participants (38%) with an observable response to verbal commands. CONCLUSIONS: Approximately one in four participants without an observable response to commands performed a cognitive task on fMRI or EEG as compared with one in three participants with an observable response to commands. (Funded by the James S. McDonnell Foundation and others.).

CO-OP Approach With Children and Youth With Executive Function Deficits After Acquired Brain Injury: A Qualitative Study of Care Partners' Involvement.

IMPORTANCE: Care partners' involvement is a key feature of the Cognitive Orientation to daily Occupational Performance (CO-OP) approach that can enhance rehabilitation outcomes and promote the generalization and transfer of strategies and skills to everyday life. Gaining insight into care partners' experience with their child's CO-OP intervention is critical to understanding how to enhance care partners' involvement. OBJECTIVE: To gain insight into the experience of care partners whose child with acquired brain injury (ABI) participated in CO-OP intervention. METHOD: A qualitative descriptive research design was used. Semistructured interviews were conducted at three time points (immediate postintervention and at 2 and 6 mo postintervention). SETTING: Two rehabilitation centers. PARTICIPANTS: Thirteen care partners of 12 children or youth with severe ABI. RESULTS: Three themes emerged from the analysis of 33 interviews: (1) The child is an active agent in their therapy, (2) the care partner is the keystone who helps solidify the elements of CO-OP, and (3) CO-OP mastery requires time and practice, and its use evolves over time. CONCLUSIONS AND RELEVANCE: These themes highlight the progressive nature of proficiency in CO-OP for both care partners and children. This was evident not only in the children's improvement in task performance, but also in their ability to problem solve. Care partners' role in supporting the CO-OP approach also unfolds over time as their confidence in their child's problem-solving abilities, and in their own ability to adequately provide guidance, increases. Engagement seems to be central in facilitating this progression for both children and their care partners. Plain-Language Summary: This is the first study to provide insights into the involvement of care partners in the Cognitive Orientation to daily Occupational Performance (CO-OP) approach for children and youth with executive function deficits after acquired brain injury. This is also the first study to explore the evolution of care partners' experiences over time. Involving care partners is a key feature of the CO-OP. Understanding care partners' experiences with their child's CO-OP intervention can improve a child's rehabilitation outcomes. The study found that care partners' role in supporting their child's CO-OP approach improved over time as their confidence in their child's problem-solving abilities increased. The care partners' own ability to adequately provide guidance to their child also increased over time. Engagement seems to be central in facilitating this progression for both children and their care partners. It is hoped that occupational therapists will consider the findings of this study to better support care partners in implementing the CO-OP approach with their child in their real-life context.

Astrocyte-derived lactate aggravates brain injury of ischemic stroke in mice by promoting the formation of protein lactylation.

Aim: Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether the role of accumulated lactate at the ischemia phase is neuroprotection or not remains largely unknown. Thus, in this study, we aimed to investigate the roles and mechanisms of accumulated brain lactate at the ischemia stage in regulating brain injury of ischemic stroke. Methods and Results: Pharmacological inhibition of lactate production by either inhibiting LDHA or glycolysis markedly attenuated the mouse brain injury of ischemic stroke. In contrast, additional lactate supplement further aggravates brain injury, which may be closely related to the induction of neuronal death and A1 astrocytes. The contributing roles of increased lactate at the ischemic stage may be related to the promotive formation of protein lysine lactylation (Kla), while the post-treatment of lactate at the reperfusion stage did not influence the brain protein Kla levels with neuroprotection. Increased protein Kla levels were found mainly in neurons by the HPLC-MS/MS analysis and immunofluorescent staining. Then, pharmacological inhibition of lactate production or blocking the lactate shuttle to neurons showed markedly decreased protein Kla levels in the ischemic brains. Additionally, Ldha specific knockout in astrocytes (Aldh1l1 CreERT2; Ldha fl/fl mice, cKO) mice with MCAO were constructed and the results showed that the protein Kla level was decreased accompanied by a decrease in the volume of cerebral infarction in cKO mice compared to the control groups. Furthermore, blocking the protein Kla formation by inhibiting the writer p300 with its antagonist A-485 significantly alleviates neuronal death and glial activation of cerebral ischemia with a reduction in the protein Kla level, resulting in extending reperfusion window and improving functional recovery for ischemic stroke. Conclusion: Collectively, increased brain lactate derived from astrocytes aggravates ischemic brain injury by promoting the protein Kla formation, suggesting that inhibiting lactate production or the formation of protein Kla at the ischemia stage presents new therapeutic targets for the treatment of ischemic stroke.

Prognosis of patients with prolonged disorders of consciousness after brain injury: a longitudinal cohort study.

Background: The findings regarding the prognosis of prolonged disorders of consciousness (PDOC) vary widely among different studies. This study aims to investigate the mortality, consciousness recovery and disabilities of patients with PDOC after brain injury. Methods: A total of 204 patients with PDOC were included in a longitudinal cohort study, including 129 males and 75 females. There were 112 cases of traumatic brain injury (TBI), 62 cases of cerebral hemorrhage (CH), 13 cases of cerebral infarction (CI) and 17 cases of ischemic hypoxic encephalopathy (IHE). The status of consciousness at 1, 2, 3, 6, 12, 18, 24, 36, 48 months of the disease course was assessed or followed up using the Revised Coma Recovery Scale (CRS-R). If the patients were conscious, the disability Rating Scale (DRS) was also performed. The prognosis of different PDOC including coma, vegetative state (VS) and minimal conscious state (MCS) was analyzed. The survival patients were screened for variables and included in multivariate binary Logistic regression to screen the factors affecting the recovery of consciousness. Results: The mortality rates at 12, 24, 36, and 48 months were 10.7, 23.4, 38.9, and 68.4%, respectively. The median time of death was 18 months (8.75, 29). The probability of MCS regaining consciousness was higher than VS (p < 0.05), with the degree of disability left lower than VS (p < 0.05). There was no significant difference between MCS- and MCS+ groups in terms of the probability of regaining consciousness, the extent of residual disability, and mortality rates (p > 0.05). The mortality rate of coma was higher than that of other PDOC (p < 0.05). The mortality rate of MCS was lower than that of VS, but the difference was not statistically significant (p > 0.05). The probability of consciousness recovery after TBI was the highest and the mortality rate was the lowest. The possibility of consciousness recovery in IHE was the least, and the mortality rate of CI was the highest. The cause of brain injury and initial CRS-R score were the factors affecting the consciousness recovery of patients (p < 0.05). Conclusion: The prognosis of MCS is more favorable than VS, with comparable outcomes between MCS- and MCS+, while comatose patients was the poorest. TBI has the best prognosis and IHE has the worst prognosis.

Estimating highest capacity propulsion performance using backward-directed force during walking evaluation for individuals with acquired brain injury.

There are over 5.3 million Americans who face acquired brain injury (ABI)-related disability as well as almost 800,000 who suffer from stroke each year. To improve mobility and quality of life, rehabilitation professionals often focus on walking recovery soon after hospital discharge for ABI. Reduced propulsion capacity (force output of the lower limbs to counteract ground reaction forces) negatively impacts walking ability and complicates recovery during rehabilitation for brain injured people. We describe a method, using backward-directed resistance (BDR) in a robotic-based treadmill device, to allow measurement of maximum walking propulsion force (MWPF) that is not otherwise possible during overground walking assessment. Our objective was to test the construct validity of a maximum walking propulsion force (MWPF) measure that reflects a person's propulsive strength against applied BDR, while walking on a robotic treadmill-based device for participants with acquired brain injury (ABI). Our study enrolled 14 participants with ABI at an in inpatient rehabilitation in Galveston, TX from 8/1/21 - 4/31/22. The range of weight-adjusted MWPF was 2.6-27.1% body weight (%BW), mean 16.5 ± 8.4%BW, reflecting a wide range of propulsive force capability. The strongest correlation with overground tests was between the 6-minute walk test (6-MWT) distance and the MWPF values (r = 0.83, p < 0.001) with moderate correlations between the 10-meter walk tests at comfortable (CWS) and fast speeds (FWS). The Five Times Sit-to-Stand (used as a standard clinical measure of functional lower extremity strength) and MWPF tests were poorly correlated (r = 0.26, p = 0.4). Forward model selection included 6-MWT distance, age, and overground CWS as significant partial predictors of MWPF. We conclude that this novel MWPF measure is a valid representation of maximum propulsive force effort during walking for people post-ABI. Additional research could help determine the impact of interventions designed to increase propulsive force generation during rehabilitation training to improve overground walking performance.

Covert Consciousness in the ICU.

OBJECTIVES: For critically ill patients with acute severe brain injuries, consciousness may reemerge before behavioral responsiveness. The phenomenon of covert consciousness (i.e., cognitive motor dissociation) may be detected by advanced neurotechnologies such as task-based functional MRI (fMRI) and electroencephalography (EEG) in patients who appear unresponsive on the bedside behavioral examination. In this narrative review, we summarize the state-of-the-science in ICU detection of covert consciousness. Further, we consider the prognostic and therapeutic implications of diagnosing covert consciousness in the ICU, as well as its potential to inform discussions about continuation of life-sustaining therapy for patients with severe brain injuries. DATA SOURCES: We reviewed salient medical literature regarding covert consciousness. STUDY SELECTION: We included clinical studies investigating the diagnostic performance characteristics and prognostic utility of advanced neurotechnologies such as task-based fMRI and EEG. We focus on clinical guidelines, professional society scientific statements, and neuroethical analyses pertaining to the implementation of advanced neurotechnologies in the ICU to detect covert consciousness. DATA EXTRACTION AND DATA SYNTHESIS: We extracted study results, guideline recommendations, and society scientific statement recommendations regarding the diagnostic, prognostic, and therapeutic relevance of covert consciousness to the clinical care of ICU patients with severe brain injuries. CONCLUSIONS: Emerging evidence indicates that covert consciousness is present in approximately 15-20% of ICU patients who appear unresponsive on behavioral examination. Covert consciousness may be detected in patients with traumatic and nontraumatic brain injuries, including patients whose behavioral examination suggests a comatose state. The presence of covert consciousness in the ICU may predict the pace and extent of long-term functional recovery. Professional society guidelines now recommend assessment of covert consciousness using task-based fMRI and EEG. However, the clinical criteria for patient selection for such investigations are uncertain and global access to advanced neurotechnologies is limited.

Sleep-like cortical dynamics during wakefulness and their network effects following brain injury.

By connecting old and recent notions, different spatial scales, and research domains, we introduce a novel framework on the consequences of brain injury focusing on a key role of slow waves. We argue that the long-standing finding of EEG slow waves after brain injury reflects the intrusion of sleep-like cortical dynamics during wakefulness; we illustrate how these dynamics are generated and how they can lead to functional network disruption and behavioral impairment. Finally, we outline a scenario whereby post-injury slow waves can be modulated to reawaken parts of the brain that have fallen asleep to optimize rehabilitation strategies and promote recovery.

Childhood Health and Educational outcomes afteR perinatal Brain injury (CHERuB): protocol for a population-matched cohort study.

INTRODUCTION: Over 3000 infants suffer a brain injury around the time of birth every year in England. Although these injuries can have important implications for children and their families, our understanding of how these injuries affect children's lives is limited. METHODS AND ANALYSIS: The aim of the CHERuB study (Childhood Health and Educational outcomes afteR perinatal Brain injury) is to investigate longitudinal childhood health and educational outcomes after perinatal brain injury through the creation of a population-matched cohort study. This study will use the Department of Health and Social Care definition of perinatal brain injury which includes infants with intracranial haemorrhage, preterm white matter injury, hypoxic ischaemic encephalopathy, perinatal stroke, central nervous system infections, seizures and kernicterus. All children born with a perinatal brain injury in England between 2008 and 2019 will be included (n=54 176) and two matched comparator groups of infants without brain injury will be created: a preterm control group identified from the National Neonatal Research Data Set and a term/late preterm control group identified using birth records. The national health, education and social care records of these infants will be linked to ascertain their longitudinal childhood outcomes between 2008 and 2023. This cohort will include approximately 170 000 children. The associations between perinatal brain injuries and survival without neurosensory impairment, neurodevelopmental impairments, chronic health conditions and mental health conditions throughout childhood will be examined using regression methods and time-to-event analyses. ETHICS AND DISSEMINATION: This study has West London Research Ethics Committee and Confidential Advisory Group approval (20/LO/1023 and 22/CAG/0068 issued 20/10/2022). Findings will be published in open-access journals and publicised via the CHERuB study website, social media accounts and our charity partners.

Transition from rehabilitation hospital to the National Disability Insurance Scheme (NDIS) for people with brain injury and spinal cord injury: a data linkage protocol.

INTRODUCTION: Traumatic brain injury (TBI) and spinal cord injury (SCI) are both major contributors to permanent disability globally, with an estimated 27 million new cases of TBI and 0.93 million new cases of SCI globally in 2016. In Australia, the National Disability Insurance Scheme (NDIS) provides support to people with disability. Reports from the NDIS suggest that the cost of support for people with TBI and SCI has been increasing dramatically, and there is a lack of independent analysis of the drivers of these increases. This data linkage seeks to better understand the participant transition between rehabilitation hospitals and the NDIS and the correlation between functional independence in rehabilitation and resource allocation in the NDIS. METHODS AND ANALYSIS: This is a retrospective, population-based cohort study using Australia-wide NDIS participant data and rehabilitation hospital episode data. The linked dataset provides a comparison of functional independence against which to compare the NDIS resource allocation to people with TBI and SCI. This protocol outlines the secure and separated data linkage approach employed in linking partially identified episode data from the Australasian Rehabilitation Outcomes Centre (AROC) with identified participant data from the NDIS. The linkage employs a stepwise deterministic linkage approach. Statistical analysis of the linked dataset will consider the relationship between the functional independence measure score from the rehabilitation hospital and the committed funding supports in the NDIS plan. This protocol sets the foundation for an ongoing data linkage between rehabilitation hospitals and the NDIS to assist transition to the NDIS. ETHICS AND DISSEMINATION: Ethics approval is from the Macquarie University Human Research Ethics Committee. AROC Data Governance Committee and NDIS Data Management Committee have approved this project. Research findings will be disseminated to key stakeholders through peer-reviewed publications in scientific journals and presentations to clinical and policy audiences via AROC and NDIS.

Process evaluation of a randomised controlled trial intervention designed to improve rehabilitation services for Aboriginal Australians after brain injury: the Healing Right Way Trial.

BACKGROUND: Healing Right Way (HRW) aimed to improve health outcomes for Aboriginal Australians with stroke or traumatic brain injury by facilitating system-level access to culturally secure rehabilitation services. Using a stepped-wedge randomised controlled trial (RCT) design (ACTRN12618000139279, 30/01/2018), a two-pronged intervention was introduced in four rural and four urban hospitals, comprising 1.Cultural security training (CST) for staff and 2.Training/employment of Aboriginal Brain Injury Coordinators (ABIC) to support Aboriginal patients for 6-months post-injury. Three-quarters of recruited patients lived rurally. The main outcome measure was quality-of-life, with secondary outcomes including functional measures, minimum processes of care (MPC); number rehabilitation occasions of service received, and improved hospital experience. Assessments were undertaken at baseline, 12- and 26-weeks post-injury. Only MPCs and hospital experience were found to improve among intervention patients. We report on the process evaluation aiming to support interpretation and translation of results. METHODS: Using mixed methods, the evaluation design was informed by the Consolidated Framework for Implementation Research. Data sources included minutes, project logs, surveys, semi-structured interviews, and observations. Four evaluation questions provided a basis for systematic determination of the quality of the trial. Findings from separate sources were combined to synthesise the emerging themes that addressed the evaluation questions. Three components were considered separately: the trial process, CST and ABIC. RESULTS: The complex HRW trial was implemented to a satisfactory level despite challenging setting factors, particularly rural-urban system dynamics. Patient recruitment constraints could not be overcome. The vulnerability of stepped-wedge designs to time effects influenced recruitment and trial results, due to COVID. Despite relatively high follow-up, including to rural/remote areas, data points were reduced. The lack of culturally appropriate assessment tools influenced the quality/completeness of assessment data. The ABIC role was deemed feasible and well-received. The CST involved complex logistics, but rated highly although online components were often incomplete. Project management was responsive to staff, patients and setting factors. CONCLUSIONS: Despite mostly equivocal results, the ABIC role was feasible within mainstream hospitals and the CST was highly valued. Learnings will help build robust state-wide models of culturally secure rehabilitation for Aboriginal people after brain injury, including MPC, workforce, training and follow-up.

Daily life without cranial bone protection while awaiting cranioplasty: a qualitative study.

PURPOSE: Decompressive craniectomy is occasionally performed as a life-saving neurosurgical intervention in patients with acute severe brain injury to reduce refractory intracranial hypertension. Subsequently, cranioplasty (CP) is performed to repair the skull defect. In the meantime, patients are living without cranial bone protection, and little is known about their daily life. This study accordingly explored daily life among patients living without cranial bone protection after decompressive craniectomy while awaiting CP. METHODS: A multiple-case study examined six purposively sampled patients, patients' family members, and healthcare staff. The participants were interviewed and the data were analyzed using qualitative content analysis. RESULTS: The cross-case analysis identified five categories: "Adapting to new ways of living," "Constant awareness of the absence of cranial bone protection," "Managing daily life requires available staff with adequate qualifications," "Impact of daily life depends on the degree of recovery," and "Daily life stuck in limbo while awaiting cranioplasty." The patients living without cranial bone protection coped with daily life by developing new habits and routines, but the absence of cranial bone protection also entailed inconveniences and limitations, particularly among the patients with greater independence in their everyday living. Time spent awaiting CP was experienced as being in limbo, and uncertainty regarding planning was perceived as frustrating. CONCLUSION: The results indicate a vulnerable group of patients with brain damage and communication impairments struggling to find new routines during a waiting period experienced as being in limbo. Making this period safe and reducing some problems in daily life for those living without cranial bone protection calls for a person-centered approach to care involving providing contact information for the correct healthcare institution and individually planned scheduling for CP.

Cognitive communication disorders after brain injury: A systematic COSMIN review of measurement instruments.

BACKGROUND: There is a lack of consensus on standardized measurement instruments (MIs) for the assessment of cognitive communication disorders in individuals with acquired brain injury (ABI). OBJECTIVES: To identify and describe the currently available MIs for the assessment of cognitive communication disorders in individuals with ABI and to evaluate the psychometric properties of MIs. METHODS: A search was conducted in 6 databases on March 12, 2024 using a validated methodological search filter. We included studies that evaluated psychometric properties of MIs used to assess cognitive communication disorders in individuals with ABI. We applied the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) to evaluate the psychometric properties of the MIs. RESULTS: We included 48 records reporting on 44 MIs. Of all MIs, the La Trobe Communication Questionnaire (LCQ) and the St Andrew's-Swansea Neurobehavioural Outcome Scale (SASNOS) were studied most extensively. No MIs had undergone exhaustive methodological evaluation. CONCLUSIONS: Based on the COSMIN, only 1 of 44 MIs can be recommended as its results can be trusted. Most MIs have the potential to be recommended but require further research to assess their psychometric quality. The development of new tools is not necessary but further methodological studies should be conducted on promising tools. This review may help clinicians and researchers to select an MI for the assessment of cognitive communication disorders and may facilitate diagnosis and research. TRIAL REGISTRATION: PROSPERO database (registration number: CRD42020196861). No funding.

Levosimendan Ameliorates Hypoxia-Induced Brain Injury in Rats by Modulating PTEN/Akt Signaling Pathway-Mediated Ferroptosis.

BACKGROUND: Levosimendan (Levo) is a drug commonly used to treat heart failure. Recent studies have suggested that Levo may have neuroprotective effects, but it is still unknown how exactly it contributes to hypoxia-induced brain damage. Thus, the aim of this study was to investigate how Levo affects hypoxia-induced brain damage and to clarify any possible underlying mechanisms. METHODS: One group of rats (Levo group) was pretreated with Levo via oral force-feeding for four weeks. Another group (Ferrostatin-1 (Fer-1) group) was pretreated with intraperitoneal injections of Fer-1 for four weeks. A rat model of chronic hypoxia was created by treating rats with 13% O2 for 14 days in a closed hypoxia chamber. For each group (Control, Model, Levo, Fer-1), we evaluated learning and memory capacity and the morphology and structure of neurons in the rats' brain tissue. Other measurements included tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1ß), and interleukin-6 (IL-6); malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px); Fe2+; apoptosis; cleaved caspase-3, caspase-3; phosphatase and tensin homolog (PTEN), protein kinase B (Akt), phosphorylated Akt (p-Akt); and ferroptosis-related proteins Nuclear factor erythroid 2-related factor 2 (Nrf2), glutathione peroxidase 4 (GPX4), and solute carrier family 7 member 11 (SLC7A11). RESULTS: The Model group rats had considerably fewer neurons than the Control group, with loosely arranged cells, and markedly impaired learning and memory abilities (p < 0.05). Oxidative damage and inflammation in brain tissues of the Model group were significantly intensified, accompanied by a substantial increase in neuronal apoptosis (p < 0.05). PTEN protein, Fe2+ concentration, and cleaved caspase-3 expression were all significantly upregulated, whereas p-Akt, Nrf2, GPX4, and SLC7A11 proteins were dramatically downregulated (p < 0.05). Both the Levo and Fer-1 groups demonstrated significantly more neurons and closely arranged cells than the Model group, along with a notable improvement in learning and memory abilities (p < 0.05). Oxidative damage and inflammation in brain tissues of the Levo and Fer-1 groups were markedly alleviated, and neuronal apoptosis was suppressed (p < 0.05). p-Akt, Nrf2, GPX4, and SLC7A11 proteins were dramatically upregulated, whereas the expression of cleaved caspase-3, PTEN protein, and Fe2+ content was considerably downregulated (p < 0.05). CONCLUSIONS: Levo effectively mitigates brain injury in rats with chronic hypoxia, likely by regulating ferroptosis via the PTEN/Akt signaling pathway.

MiR-23b-3p Improves Brain Damage after Status Epilepticus by Reducing the Formation of Pathological High-Frequency Oscillations via Inhibition of cx43 in Rat Hippocampus.

In order to investigate the effectiveness and safety of miR-23b-3p in anti-seizure activity and to elucidate the regulatory relationship between miR-23b-3p and Cx43 in the nervous system, we have established a lithium chloride-pilocarpine (PILO) status epilepticus (SE) model. Rats were randomly divided into the following groups: seizure control (PILO), valproate sodium (VPA+PILO), recombinant miR-23b-3p overexpression (miR+PILO), miR-23b-3p sponges (Sponges+PILO), and scramble sequence negative control (Scramble+PILO) (n = 6/group). After experiments, we got the following results. In the acute phase, the time required for rats to reach stage IV after PILO injection was significantly longer in VPA+PILO and miR+PILO. In the chronic phase after SE, the frequency of spontaneous recurrent seizures (SRSs) in VPA+PILO and miR+PILO was significantly reduced. At 10 min before seizure cessation, the average energy expression of fast ripples (FRs) in VPA+PILO and miR+PILO was significantly lower than in PILO. After 28 days of seizure, Cx43 expression in PILO was significantly increased, and Beclin1expression in all groups was significantly increased. After 28 days of SE,the number of synapses in the CA1 region of the hippocampus was significantly higher in the VPA+PILO and miR+PILO groups compared to that in the PILO group. After 28 days of SE ,hippocampal necrotic cells in the CA3 region were significantly lower in the VPA+PILO and miR+PILO groups compared to those in the PILO group. There were no significant differences in biochemical indicators among the experimental group rats 28 days after SE compared to the seizure control group. Based on the previous facts, we can reach the conclusion that MiR-23b-3p targets and blocks the expression of hippocampal Cx43 which can reduce the formation of pathological FRs, thereby alleviating the severity of seizures, improving seizure-induced brain damage.

Machine learning for automating subjective clinical assessment of gait impairment in people with acquired brain injury - a comparison of an image extraction and classification system to expert scoring.

BACKGROUND: Walking impairment is a common disability post acquired brain injury (ABI), with visually evident arm movement abnormality identified as negatively impacting a multitude of psychological factors. The International Classification of Functioning, Disability and Health (ICF) qualifiers scale has been used to subjectively assess arm movement abnormality, showing strong intra-rater and test-retest reliability, however, only moderate inter-rater reliability. This impacts clinical utility, limiting its use as a measurement tool. To both automate the analysis and overcome these errors, the primary aim of this study was to evaluate the ability of a novel two-level machine learning model to assess arm movement abnormality during walking in people with ABI. METHODS: Frontal plane gait videos were used to train four networks with 50%, 75%, 90%, and 100% of participants (ABI: n = 42, healthy controls: n = 34) to automatically identify anatomical landmarks using DeepLabCut™ and calculate two-dimensional kinematic joint angles. Assessment scores from three experienced neurorehabilitation clinicians were used with these joint angles to train random forest networks with nested cross-validation to predict assessor scores for all videos. Agreement between unseen participant (i.e. test group participants that were not used to train the model) predictions and each individual assessor's scores were compared using quadratic weighted kappa. One sample t-tests (to determine over/underprediction against clinician ratings) and one-way ANOVA (to determine differences between networks) were applied to the four networks. RESULTS: The machine learning predictions have similar agreement to experienced human assessors, with no statistically significant (p < 0.05) difference for any match contingency. There was no statistically significant difference between the predictions from the four networks (F = 0.119; p = 0.949). The four networks did however under-predict scores with small effect sizes (p range = 0.007 to 0.040; Cohen's d range = 0.156 to 0.217). CONCLUSIONS: This study demonstrated that machine learning can perform similarly to experienced clinicians when subjectively assessing arm movement abnormality in people with ABI. The relatively small sample size may have resulted in under-prediction of some scores, albeit with small effect sizes. Studies with larger sample sizes that objectively and automatically assess dynamic movement in both local and telerehabilitation assessments, for example using smartphones and edge-based machine learning, to reduce measurement error and healthcare access inequality are needed.