Subacute Phase Research Articles

Xuefu Zhuyu decoction promotes synaptic plasticity by targeting miR-191a-5p/BDNF-TrkB axis in severe traumatic brain injury

BackgroundXuefu Zhuyu decoction (XFZYD) is a traditional Chinese herbal formula known for its ability to eliminate blood stasis and improve blood circulation, providing neuroprotection against severe traumatic brain injury (sTBI). However, the underlying mechanism is still unclear. PurposeWe aim to investigate the neuroprotective effects of XFZYD in sTBI from a novel mechanistic perspective of miRNA-mRNA. Additionally, we sought to elucidate a potential specific mechanism by integrating transcriptomics, bioinformatics, and conducting both in vitro and in vivo experiments. MethodsThe sTBI rat model was established, and the rats were treated with XFZYD for 14 days. The neuroprotective effects of XFZYD were evaluated using a modified neurological severity score, hematoxylin and eosin staining, as well as Nissl staining. The anti-inflammatory effects of XFZYD were explored using quantitative real-time PCR (qRT-PCR), Western blot analysis, and immunofluorescence. Next, miRNA sequencing of the hippocampus was performed to determine which miRNAs were differentially expressed. Subsequently, qRT-PCR was used to validate the differentially expressed miRNAs. Target core mRNAs were determined using various methods, including miRNA prediction targets, mRNA sequencing, miRNA-mRNA network, and protein-protein interaction (PPI) analysis. The miRNA/mRNA regulatory axis were verified through qRT-PCR or Western blot analysis. Finally, morphological changes in the neural synapses were observed using transmission electron microscopy and immunofluorescence. ResultsXFZYD exhibited significant neuroprotective and anti-inflammatory effects on subacute sTBI rats' hippocampus. The analyses of miRNA/mRNA sequences combined with the PPI network revealed that the therapeutic effects of XFZYD on sTBI were associated with the regulation of the rno-miR-191a-5p/BDNF axis. Subsequently, qRT-PCR and Western blot analysis confirmed XFZYD reversed the decrease of BDNF and TrkB in the hippocampus caused by sTBI. Additionally, XFZYD treatment potentially increased the number of synaptic connections, and the expression of the synapse-related protein PSD95, axon-related protein GAP43 and neuron-specific protein TUBB3. ConclusionsXFZYD exerts neuroprotective effects by promoting hippocampal synaptic remodeling and improving cognition during the subacute phase of sTBI through downregulating of rno-miR-191a-5p/BDNF axis, further activating BDNF-TrkB signaling.

The diagnostic role of resting myocardial blood flow in STEMI patients after revascularization.

The value of semiquantitative resting myocardial perfusion imaging (MPI) in coronary artery disease (CAD) is limited. At present, quantitative MPI can be performed by a new cadmium zinc tellurium single-photon emission computed tomography (CZT-SPECT) scan. The quantitative index of resting myocardial blood flow (MBF) has received little attention, and its manifestations and clinical value in the presence of unstable coronary blood flow have not been clarified. In patients with ST-segment elevation myocardial infarction (STEMI), whether resting MBF can provide additional value of blood flow than semi-quantitative resting MPI is not sure. We also explored the influencing factors of resting MBF. This was a retrospective clinical study. We included 75 patients with STEMI in the subacute phase who underwent resting MPI and dynamic scans after reperfusion therapy. General patient information, STEMI-related data, MPI, gated MPI (G-MPI), and resting MBF data were collected and recorded. According to the clinically provided culprit vessels, the resting MBF was divided into ischemic MBF and non-ischemic MBF. The paired Wilcoxon signed-rank test was used for resting MBF. The receiver operating characteristic (ROC) curves were used to determine the optimal threshold for ischemia, and multiple linear regression analysis was used to analyze the influencing factors of resting MBF. There was a statistically significant difference between the ischemic MBF and non-ischemic MBF [0.59 (0.47-0.72) vs. 0.76 (0.64-0.93), p < 0.0001]. The ROC curve analysis revealed that resting MBF could identify ischemia to a certain extent, with a cutoff value of 0.5975, area under the curve (AUC) = 0.666, sensitivity = 55.8%, and specificity = 68.7%. Male sex and summed rest score (SRS) were influencing factors for resting MBF. To a certain extent, resting MBF can suggest residual ischemia after reperfusion therapy in patients with STEMI. There was a negative correlation between male sex, SRS, and ischemic MBF. A lower resting MBF may be associated with more severe myocardial ischemia.

Diet-induced ketosis in adult patients with subacute acquired brain injury: a feasibility study.

Research in animal models on cerebral metabolism after brain injury highlights the potential benefits of ketosis in reducing secondary brain injury, but studies in humans are lacking. This study aimed to examine if a 6-week ketogenic diet intervention with added medium-chain triglycerides (MCT) was feasible in adult patients with acquired brain injury in the subacute phase, whether ketosis could be achieved and maintained, and to what extent serious adverse reactions, adverse reactions, serious adverse events, and adverse events occured. Patients ≥18 years of age diagnosed with subacute acquired brain injury and an expectation of hospitalisation ≥6 weeks were included in the intervention group. Patients not included in the intervention group were included in a standard care reference group. The intervention consisted of a ketogenic diet supplemented with MCT to obtain a plasma concentration of β-hydroxybutyrate (BHB) ≥0.5 mmol/L. Patients who were enterally fed were given KetoCal® 2.5:1 LQ MCT Multi Fiber (Nutricia A/S, Allerød, Denmark), supplemented with Liquigen® (Nutricia A/S, Allerød, Denmark). Patients consuming oral nutrition were given KetoCal® 2.5:1 LQ MCT Multi Fiber supplemented with Liquigen®, in addition to ketogenic meals. During a 13-week inclusion period, 12 of 13 eligible patients (92% [95% CI: 67% to 99%]) were included in the intervention group, and 17 of 18 excluded patients (94% [95% CI: 74% to 99%]) were included in the reference group. Eight patients (67%) completed the 6-week intervention. It took a median of 1 day to achieve ketosis from starting a 100% MCT ketogenic diet, and it was maintained for 97% of the intervention period after ketosis was obtained. There were no serious adverse reactions to the MCT ketogenic diet, and patients experienced adverse reactions not considered serious in 9.5% of days with the intervention. The MCT ketogenic diet was accepted by patients on all intervention days, and in the two patients transitioning from enteral feeding to oral intake, there were no complications related to transitioning. Intervention with MCT ketogenic diet is feasible and tolerated for 6 weeks in hospitalised adult patients with subacute acquired brain injury. Randomised controlled trials are needed to assess the benefits and harms of the MCT ketogenic diet and the effect on patients' recovery.Clinical trial registration: ClinicalTrials.gov, identifier [NCT04308577].

Fractal analysis of left ventricular trabeculae in post-STEMI: from acute to chronic phase.

The temporal evolution of ventricular trabecular complexity and its correlation with major adverse cardiovascular events (MACE) remain indeterminate in patients presenting with acute ST elevation myocardial infarction (STEMI). This retrospective analysis enrolled patients undergoing primary percutaneous coronary intervention (pPCI) for acute STEMI, possessing cardiac magnetic resonance (CMR) data in the acute (within 7days), subacute (1month after pPCI), and chronic phases (6months after pPCI) from January 2015 to January 2020 at the three participating sites. Fractal dimensions (FD) were measured for the global, infarct, and remote regions of left ventricular trabeculae during each phase. The potential association of FD with MACE was analyzed using multivariate Cox regression. Among the 200 analyzed patients (182 men; median age, 61years; age range, 50-66years), 37 (18.5%) encountered MACE during a median follow-up of 31.2months. FD exhibited a gradual decrement (global FD at acute, subacute, and chronic phases: 1.253 ± 0.049, 1.239 ± 0.046, 1.230 ± 0.045, p < 0.0001), with a more pronounced decrease observed in patients subsequently experiencing MACE (p < 0.001). The global FD at the subacute phase correlated with MACE (hazard ratio 0.89 (0.82, 0.97), p = 0.01), and a global FD value below 1.26 was associated with a heightened risk. In patients post-STEMI, the global FD, serving as an indicator of left ventricular trabeculae complexity, independently demonstrated an association with subsequent major adverse cardiovascular events, beyond factors encompassing left ventricular ejection fraction, indexed left ventricular end-diastolic volume, infarct size, heart rate, NYHA class, and post-pPCI TIMI flow. In patients who have had an ST-segment elevation myocardial infarction, global fractal dimension, as a measure of left ventricular trabeculae complexity, provided independent association with subsequent major adverse cardiovascular event. • Global and regional FD decreased after STEMI, and more so in patients with subsequent MACE. • Lower global FD at the subacute phase and Δglobal FD from acute to subacute phase were associated with subsequent MACE besides clinical and CMR factors. • Global FD at the subacute phase independently correlated with MACE and global FD value below 1.26 was associated with higher risk.

Point of View on Outcome Prediction Models in Post-Stroke Motor Recovery

Stroke is a leading cause of disability worldwide which can cause significant and persistent upper limb (UL) impairment. It is difficult to predict UL motor recovery after stroke and to forecast the expected outcomes of rehabilitation interventions during the acute and subacute phases when using clinical data alone. Accurate prediction of response to treatment could allow for more timely and targeted interventions, thereby improving recovery, resource allocation, and reducing the economic impact of post-stroke disability. Initial motor impairment is currently the strongest predictor of post-stroke motor recovery. Despite significant progress, current prediction models could be refined with additional predictors, and an emphasis on the time dependency of patient-specific predictions of UL recovery profiles. In the current paper a panel of experts provide their opinion on additional predictors and aspects of the literature that can help advance stroke outcome prediction models. Potential strategies include close attention to post-stroke data collection timeframes and adoption of individual-computerized modeling methods connected to a patient’s health record. These models should account for the non-linear and the variable recovery pattern of spontaneous neurological recovery. Additionally, input data should be extended to include cognitive, genomic, sensory, neural injury, and function measures as additional predictors of recovery. The accuracy of prediction models may be further improved by including standardized measures of outcome. Finally, we consider the potential impact of refined prediction models on healthcare costs.

Moving From CT to MRI Paradigm in Acute Ischemic Stroke: Feasibility, Effects on Stroke Diagnosis and Long-Term Outcomes.

The relative value of computed tomography (CT) and magnetic resonance imaging (MRI) in acute ischemic stroke (AIS) is debated. In May 2018, our center transitioned from using CT to MRI as first-line imaging for AIS. This retrospective study aims to assess the effects of this paradigm change on diagnosis and disability outcomes. We compared all consecutive patients with confirmed diagnosis of AIS admitted to our center during the MRI-period (May 2018-August 2022) and an identical number of patients from the preceding CT-period (December 2012-April 2018). Univariable and multivariable analyses were performed to evaluate outcomes, including the number and delay of imaging exams, the rate of missed strokes, stroke mimics treated with thrombolysis, undetermined stroke mechanisms, length of hospitalization, and 3-month disability. The median age of the 2972 included patients was 76 years (interquartile range, 65-84), and 46% were female. In the MRI-period, 80% underwent MRI as first acute imaging. The proportion of patients requiring a second acute imaging modality for diagnostic ± revascularization reasons increased from 2.1% to 5% (Punadj <0.05), but it decreased in the subacute phase from 79.0% to 60.1% (Padj <0.05). In thrombolysis candidates, there was a 2-minute increase in door-to-imaging delay (Padj <0.05). The rates of initially missed AIS diagnosis was similar (3.8% versus 4.4%, Padj=0.32) and thrombolysis in stroke mimics decreased by half (8.6% versus 4.3%; Padj <0.05). Rates of unidentified stroke mechanism at hospital discharge were similar (22.8% versus 28.1%; Padj=0.99). The length of hospitalization decreased from 9 (interquartile range, 6-14) to 7 (interquartile range, 4-12) days (Padj=0.62). Disability at 3 months was similar (common adjusted odds ratio for favorable Rankin shift, 0.98 [95% CI, 0.71-1.36]; Padj=0.91), as well as mortality and symptomatic intracranial hemorrhage. A paradigm shift from CT to MRI as first-line imaging for AIS seems feasible in a comprehensive stroke center, with a minimally increased delay to imaging in thrombolysis candidates. MRI was associated with reduced thrombolysis rates of stroke mimics and subacute neuroimaging needs.

Lower cognitive reserve is related to worse working memory performance in older adults after mTBI. An ERP study

ABSTRACT Objective Older adults (OA) after mild traumatic brain injury (mTBI) have a high risk of developing persistent post-injury cognitive impairments. Lower pre-morbid cognitive reserve (CR) is increasingly investigated as a risk factor for cognitive dysfunction in OA. However, how CR protects against effects of mTBI at the brain level remains largely understudied. Methods We examined 22 OA who sustained mTBI (mean 67.69 years, SD 5.11) in the sub-acute phase and 15 age- and CR-matched healthy OA (mean 68 years, SD 5.55) performing a three-level visual N-back task using electroencephalography. We calculated inverse efficiency scores of performance from accuracy and reaction times. Event-related potentials served as neurocognitive correlates of attentional (P2) and working memory (P3) processing. Results Overall, mTBI OA performed worse than healthy OA (p = 0.031). Lower CR generally decreased performance (p < 0.001). Furthermore, with increasing task difficulty, task performance was more affected by CR (p = 0.004). At the brain level, P2 amplitude was lower in mTBI OA than in healthy OA (p = 0.05). There was no clear effect of CR on P2 or P3 measures. Conclusion As mTBI OA with lower CR performed worse on a working-memory task, lower CR may be a risk factor for worse recovery after mTBI in this group.

Ectopic Expression of Neurod1 Is Sufficient for Functional Recovery following a Sensory-Motor Cortical Stroke.

Stroke is the leading cause of adult disability worldwide. The majority of stroke survivors are left with devastating functional impairments for which few treatment options exist. Recently, a number of studies have used ectopic expression of transcription factors that direct neuronal cell fate with the intention of converting astrocytes to neurons in various models of brain injury and disease. While there have been reports that question whether astrocyte-to-neuron conversion occurs in vivo, here, we have asked if ectopic expression of the transcription factor Neurod1 is sufficient to promote improved functional outcomes when delivered in the subacute phase following endothelin-1-induced sensory-motor cortex stroke. We used an adeno-associated virus to deliver Neurod1 from the short GFAP promoter and demonstrated improved functional outcomes as early as 28 days post-stroke and persisting to at least 63 days post-stroke. Using Cre-based cell fate tracking, we showed that functional recovery correlated with the expression of neuronal markers in transduced cells by 28 days post-stroke. By 63 days post-stroke, the reporter-expressing cells comprised ~20% of all the neurons in the perilesional cortex and expressed markers of cortical neuron subtypes. Overall, our findings indicate that ectopic expression of Neurod1 in the stroke-injured brain is sufficient to enhance neural repair.

Systemic Oxidative Stress in Subacute Stroke Patients Undergoing Rehabilitation Treatment.

The imbalance in oxidative stress in acute stroke has been extensively studied; on the contrary, its investigation in the subacute phase is limited. The aim of this study was to analyse the variation in the systemic oxidative status in subacute post-stroke patients before (T0) and after a six-week rehabilitation treatment (T1) and to investigate the relationship between systemic oxidative status and rehabilitation outcomes. We enrolled 109 subjects in two different centres, and we analysed their serum hydroperoxide levels (d-ROMs), biological antioxidant power (BAP), thiol antioxidant components (-SHp), and relative antioxidant capacity (OSI and SH-OSI indices). Activity of Daily Living (ADL), hand grip strength, and walking endurance were evaluated using the modified Barthel Index, the Hand Grip test, and the 6-min walk test, respectively. At T0, most of the patients showed very high levels of d-ROMs and suboptimal levels of the BAP, OSI, and SH-OSI indices. Comparing the T1 and T0 data, we observed an improvement in the rehabilitation outcomes and a significant decrease in d-ROMs (549 ± 126 vs. 523 ± 148, p = 0.023), as well as an improvement in the OSI and SH-OSI indices (4.3 ± 1.3 vs. 4.7 ± 1.5, p = 0.001; 11.0 ± 0.4 vs. 1.2 ± 0.4, p < 0.001). In addition, significant correlations were seen between the oxidative stress parameters and the rehabilitation outcomes. These results suggest monitoring the systemic oxidative stress status in post-stroke patients in order to plan a tailored intervention, considering its relationship with functional recovery.

Evidence of brain metabolism redistribution from neocortex to primitive brain structures in early acute COVID-19 respiratory syndrome

BackgroundNeuropsychiatric sequelae of COVID-19 have been widely documented in patients with severe neurological symptoms during the chronic or subacute phase of the disease. However, it remains unclear whether subclinical changes in brain metabolism can occur early in the acute phase of the disease. The aim of this study was to identify and quantify changes in brain metabolism in patients hospitalized for acute respiratory syndrome due to COVID-19 with no or mild neurological symptoms.ResultsTwenty-three non-intubated patients (13 women; mean age 55.5 ± 12.1 years) hospitalized with positive nasopharyngeal swab test (RT-PCR) for COVID-19, requiring supplemental oxygen and no or mild neurological symptoms were studied. Serum C-reactive protein measured at admission ranged from 6.43 to 189.0 mg/L (mean: 96.9 ± 54.2 mg/L). The mean supplemental oxygen demand was 2.9 ± 1.4 L/min. [18F]FDG PET/CT images were acquired with a median of 12 (4–20) days of symptoms. After visual interpretation of the images, semiquantitative analysis of [18F]FDG uptake in multiple brain regions was evaluated using dedicated software and the standard deviation (SD) of brain uptake in each region was automatically calculated in comparison with reference values of a normal database. Evolutionarily ancient structures showed positive SD mean values of [18F]FDG uptake. Lenticular nuclei were bilaterally hypermetabolic (> 2 SD) in 21/23 (91.3%) patients, and thalamus in 16/23 (69.6%), bilaterally in 11/23 (47.8%). About half of patients showed hypermetabolism in brainstems, 40% in hippocampi, and 30% in cerebellums. In contrast, neocortical regions (frontal, parietal, temporal and occipital lobes) presented negative SD mean values of [18F]FDG uptake and hypometabolism (< 2 SD) was observed in up to a third of patients. Associations were found between hypoxia, inflammation, coagulation markers, and [18F]FDG uptake in various brain structures.ConclusionsBrain metabolism is clearly affected during the acute phase of COVID-19 respiratory syndrome in neurologically asymptomatic or oligosymptomatic patients. The most frequent finding is marked hypermetabolism in evolutionary ancient structures such as lenticular nucleus and thalami. Neocortical metabolism was reduced in up to one third of patients, suggesting a redistribution of brain metabolism from the neocortex to evolutionary ancient brain structures in these patients.

Chemogenetic activation of astrocytic Gi signaling promotes spinogenesis and motor functional recovery after stroke.

Ischemic stroke is the leading cause of adult disability. The rewiring of surviving neurons is the fundamental process for functional recovery. Accumulating evidence implicates astrocytes in synapses and neural circuits formation, but few studies have further studied how to enhance the effects of astrocytes on synapse and circuits after stroke and its impacts on post-stroke functional recovery. In this study, we made use of chemogenetics to specifically activate astrocytic Gi signaling in the peri-infarcted sensorimotor cortex at different time epochs in a mouse model of photothrombotic stroke. We found that early activation of astrocytic hM4Di after stroke by CNO modulates astrocyte activity and upregulates synaptogenic molecules including thrombospondin-1 (TSP1) as revealed by bulk RNA-sequencing, but no significant improvement was observed in dendritic spine density and behavioral performance in grid walking test. Interestingly, when the manipulation was initiated at the subacute phase of stroke, the recovery of spine density and motor function could be effectively promoted, accompanied by increased TSP1 expression. Our data highlight the important role of astrocytes in synapse remodeling during the repair phase of stroke and suggest astrocytic Gi signaling activation as a potential strategy for synapse regeneration, circuit rewiring, and functional recovery.

Interaction between central nervous system and immune system after ischemic stroke and its therapeutic significance of traditional Chinese medicine

Ischemic stroke is divided into acute phase, subacute phase, and recovery phase, with different pathological and physiological characteristics manifested at each stage. Among them, immune and inflammatory reactions persist for several days and weeks after ischemia. Ischemic stroke not only triggers local inflammation in damaged brain regions but also induces a disorder in the immune system, thereby promoting neuroinflammation and exacerbating brain damage. Therefore, conducting an in-depth analysis of the interaction between the central nervous system and the immune system after ischemic stroke, intervening in the main factors of the interaction between them, blocking pathological cascades, and thereby reducing brain inflammation have become the treatment strategies for ischemic stroke. This study summarizes and sorts out the interaction pathways between the central nervous system and the immune system. The impact of the central nervous system on the immune system can be analyzed from the perspective of the autonomic nervous system, the hypothalamic-pituitary-adrenal axis(HPA), and local inflammatory stimulation. The impact of the immune system on the central nervous system can be analyzed from the dynamic changes of immune cells. At the same time, the relevant progress in the prevention and treatment of traditional Chinese medicine(TCM) is summarized, so as to provide new insights for the analysis of complex mechanisms of TCM in preventing and treating ischemic stroke.

Interleukin-2/anti-interleukin-2 immune complex attenuates cold ischemia-reperfusion injury after kidney transplantation by increasing renal regulatory T cells.

Cold ischemia-reperfusion injury (IRI) is an unavoidable complication of kidney transplantation. We investigated the role of regulatory T cells (Treg) in cold IRI and whether the interleukin (IL)-2/anti-IL-2 antibody complex (IL-2C) can ameliorate cold IRI. We developed a cold IRI mouse model using kidney transplantation and analyzed the IL-2C impact on cold IRI in acute, subacute and chronic phases. Treg transfer attenuated cold IRI, while Treg depletion aggravated cold IRI. Next, IL-2C administration prior to IRI mitigated acute renal function decline, renal tissue damage and apoptosis and inhibited infiltration of effector cells into kidneys and pro-inflammatory cytokine expression on day 1 after IRI. On day 7 after IRI, IL-2C promoted renal regeneration and reduced subacute renal damage. Furthermore, on day 28 following IRI, IL-2C inhibited chronic fibrosis. IL-2C decreased reactive oxygen species-mediated injury and improved antioxidant function. When IL-2C was administered following IRI, it also increased renal regeneration with Treg infiltration and suppressed renal fibrosis. In contrast, Treg depletion in the presence of IL-2C eliminated the positive effects of IL-2C on IRI. Tregs protect kidneys from cold IRI and IL-2C inhibited cold IRI by increasing the renal Tregs, suggesting a potential of IL-2C in treating cold IRI. Interleukin (IL)-2/anti-IL-2 antibody complex attenuated acute renal injury, facilitated subacute renal regeneration and suppressed chronic renal fibrosis after cold ischemia-reperfusion injury (IRI) by increasing the renal Tregs. IL-2/anti-IL-2 antibody complex decreased reactive oxygen species-mediated injury and improved antioxidant function. This study suggests the therapeutic potential of the IL-2/anti-IL-2 antibody complex in kidney transplantation-associated cold IR.

IMPROVE study protocol, investigating post-stroke local muscle vibrations to promote cerebral plasticity and functional recovery: a single-blind randomised controlled trial

IntroductionSpasticity is a frequent disabling consequence following a stroke. Local muscle vibrations (LMVs) have been proposed as a treatment to address this problem. However, little is known about their clinical...

Takotsubo syndrome: left atrial and ventricular myocardial strain impairment in the subacute and convalescent phases assessed by CMR.

We investigated the differences in impairment of left ventricle (LV) and left atrium (LA) contractile dysfunction between subacute and convalescent takotsubo syndrome (TTS), using myocardial strain analysis by cardiac magnetic resonance (CMR) feature-tracking technique. We retrospectively selected 50 patients with TTS clinical-radiological diagnosis who underwent CMR within 30days since symptoms onset: 19 studied during the early subacute phase (sTTS, ≤ 7days) and 31 during the convalescence (cTTS, 8-30days). We measured the following: LV global longitudinal, circumferential, and radial strain (lvGLS, lvGCS, lvGRS) and strain rate (SR) and LA reservoir (laS_r), conduit (laS_cd), and booster pump strain (laS_bp) and strain rate (laSR_r, laSR_cd, laSR_bp). Patients were compared with 30 age- and sex-matched controls. All patients were women (mean age 63years). TTS patients showed altered LV- and LA-strain features, compared to controls. sTTS was associated with increased laS_bp (12.7% versus 9.8%) and reduced lvEF (47.4% versus 54.8%), lvGLS (-12.2% versus 14.6%), and laS_cd (7.0% versus 9.5%) compared to cTTS (p ≤ 0.029). The interval between symptoms onset and CMR was correlated with laS_bp (r = -0.49) and lvGLS (r = 0.47) (p = 0.001 for both). At receiver operating characteristics analysis, laS_bp was the best discriminator between sTTS and cTTS (area under the curve [AUC] 0.815), followed by lvGLS (AUC 0.670). LA dysfunction persists during the subacute and convalescence of TTS. laS_bp increases in subacute phase with progressive decrease during convalescence, representing a compensatory mechanism of LV dysfunction and thus a useful index of functional recovery. Atrial strain has the potential to enhance the delineation of cardiac injury and functional impairment in TTS patients, assisting in the identification of individuals at higher risk and facilitating the implementation of more targeted and personalized medical therapies. • In TTS, after ventricular recovery, atrial dysfunction persists assessable with CMR feature tracking. • Quantitative assessment of atrial strain discriminates atrial functions: reservoir, conduit, and booster pump. • Atrial booster pump changes after acute TTS, regardless of ventricular function. • Atrial strain may serve as a temporal marker in TTS.

The Effects of Combined Virtual Reality Exercises and Robot Assisted Gait Training on Cognitive Functions, Daily Living Activities, and Quality of Life in High Functioning Individuals With Subacute Stroke.

Stroke is a global health concern causing significant mortality. Survivors face physical, cognitive, and emotional challenges, affecting their life satisfaction and social participation. Robot-assisted gait training with virtual reality, like Lokomat, is a promising rehabilitation tool. We investigated its impact on cognitive status, activities of daily living, and quality of life in individuals with stroke. Between September 2022 and August 2023, we exposed 34 first stroke patients (8 women, 26 men; M age = 59.15, SD = 11.09; M height = 170.47, SD = 8.13cm; M weight = 75.97; SD = 10.87kg; M days since stroke = 70.44, SD = 33.65) in the subacute stage (3-6 months post-stroke) to Lokomat exercise. Participant exclusion criteria were Lokamat exercise inability, disabilities incompatible with intended measurements, and any cognitive limitations. The Control Group (CG) received conventional physiotherapy, while the Lokomat Group (LG) received both conventional physiotherapy and robot-assisted gait training with virtual reality, administered by an occupational therapist. Evaluations were conducted by a physiotherapist who was unaware of the participants' group assignments and included assessments with the Montreal Cognitive Assessment, Lawton Brody Instrumental Activities of Daily Living Scale, and Stroke Specific Quality of Life Scale (SS-QoL). Both groups demonstrated an improved quality of life, but the LG outperformed the CG with regard to SS-QoL (p = .01) on measures of Energy (p = .002) and Mobility (p = .005). Both groups showed improvements in cognitive functioning (p < .001) with no between-group difference, and in activities of daily living (p < .05) for which the LG was superior to the CG (p = .023). Thus, adding robot-assisted gait training with Lokomat and virtual reality improved self-reported quality of life and daily activities at levels beyond conventional physiotherapy for patients in the subacute stroke phase. An incremental impact on cognitive functions was not evident, possibly due to rapid cognitive recovery or this was undetected by limited cognitive testing.

Longitudinal observations of the effects of ischemic stroke on binaural perception.

Acute ischemic stroke, characterized by a localized reduction in blood flow to specific areas of the brain, has been shown to affect binaural auditory perception. In a previous study conducted during the acute phase of ischemic stroke, two tasks of binaural hearing were performed: binaural tone-in-noise detection, and lateralization of stimuli with interaural time- or level differences. Various lesion-specific, as well as individual, differences in binaural performance between patients in the acute phase of stroke and a control group were demonstrated. For the current study, we re-invited the same group of patients, whereupon a subgroup repeated the experiments during the subacute and chronic phases of stroke. Similar to the initial study, this subgroup consisted of patients with lesions in different locations, including cortical and subcortical areas. At the group level, the results from the tone-in-noise detection experiment remained consistent across the three measurement phases, as did the number of deviations from normal performance in the lateralization task. However, the performance in the lateralization task exhibited variations over time among individual patients. Some patients demonstrated improvements in their lateralization abilities, indicating recovery, whereas others' lateralization performance deteriorated during the later stages of stroke. Notably, our analyses did not reveal consistent patterns for patients with similar lesion locations. These findings suggest that recovery processes are more individual than the acute effects of stroke on binaural perception. Individual impairments in binaural hearing abilities after the acute phase of ischemic stroke have been demonstrated and should therefore also be targeted in rehabilitation programs.

Exploring Methodological Issues in Mental Practice for Upper-Extremity Function Following Stroke-Related Paralysis: A Scoping Review.

In this scoping review, we aimed to comprehensively clarify the methodology of Mental practice (MP) by systematically mapping studies documenting the application of MP to post-stroke paralytic upper-extremity function. Specifically, when is an MP intervention most commonly applied after stroke onset? What is the corresponding MP load (intervention time, number of intervention days, and intervention period)? What are the most common methods of Motor Imagery (MI) recall and MI tasks used during the application of MP? Is MP often used in conjunction with individual rehabilitation? What are the paralyzed side's upper-limb and cognitive function levels at the start of an MP intervention? The research questions were identified according to PRISMA-ScR. The PubMed, Scopus, Medline, and Cochrane Library databases were used to screen articles published until 19 July 2022. In total, 694 English-language articles were identified, of which 61 were finally included. Most of the studies were conducted in the chronic phase after stroke onset, with limited interventions in the acute or subacute phase. The most common intervention time was ≤30 min and intervention frequency was 5 times/week in MP. An audio guide was most commonly used to recall MI during MP, and 50 studies examined the effects of MP in combination with individual rehabilitation. The Fugl-Meyer Assessment mean for the 38 studies, determined using the Fugl-Meyer Assessment, was 30.3 ± 11.5. Additional research with the aim of unifying the widely varying MP methodologies identified herein is warranted.

Efficacy of Intervention of Participation and Executive Functions (I-PEX) for Adults Following Traumatic Brain Injury: A Preliminary Pilot Randomized Controlled Trial

Background Participation restrictions following traumatic brain injury are associated with executive function (EF) deficits (EFDs). The subacute recovery phase’s specific characteristics (enhanced brain plasticity and impaired self-awareness) and contextual factors (inpatient setting) warrant adjusting cognitive rehabilitation protocols. The Intervention of Participation and Executive Functions (I-PEX) was designed to improve EFDs during subacute inpatient rehabilitation. Objective To investigate the I-PEX’s preliminary efficacy to improve EFDs during the performance of complex daily activities and enhance self-awareness, cognitive self-efficacy, participation, and quality of life postdischarge. Methods A pilot pre-, post-, and follow-up double-blind randomized controlled trial with 25 participants randomly allocated to the I-PEX (n = 13) or treatment-as-usual (n = 12) group. Cognitive assessments were administered pre- and postintervention, and quality of life and participation questionnaires 1-month postdischarge. Data analysis included repeated measures analysis of variance mixed design and independent t-tests, extracting effect sizes. Results Significant group-by-time interaction effect with a medium effect size was found for the primary outcome measure; EFs manifested in complex daily activities, indicating a larger improvement for the experimental group. The group effect was not significant. The experimental group’s mean delta score (pre–post improvement) was significantly higher (1.75 ± 2.89; t(23) = 2.52, P = .019), with a large effect size (d = 1.012, 95% confidence interval [0.166-1.840]). We found no significant group and interaction effects for EFs, self-awareness, and cognitive self-efficacy or no significant differences in participation or quality of life postdischarge. Conclusions Results provide initial evidence for the I-PEX efficacy in treating EFDs in the subacute phase and could help determine effect size for future studies. Clinical Trial Registry Number: ClinicalTrial.gov NCT04292925.

Efficacy of growth factor gene-modified stem cells for motor function after spinal cord injury in rodents: a systematic review and meta‑analysis.

The efficacy of growth factor gene-modified stem cells in treating spinal cord injury (SCI) remains unclear. This study aims to evaluate the effectiveness of growth factor gene-modified stem cells in restoring motor function after SCI. Two reviewers searched four databases, including PubMed, Embase, Web of Science, and Scopus, to identify relevant records. Studies on rodents assessing the efficacy of transplanting growth factor gene-modified stem cells in restoring motor function after SCI were included. The results were reported using the standardized mean difference (SMD) with a 95% confidence interval (95% CI). Analyses showed that growth factor gene-modified stem cell transplantation improved motor function recovery in rodents with SCI compared to the untreated (SMD = 3.98, 95% CI 3.26-4.70, I2 = 86.8%, P < 0.0001) and stem cell (SMD = 2.53, 95% CI 1.93-3.13, I2 = 86.9%, P < 0.0001) groups. Using growth factor gene-modified neural stem/histone cells enhanced treatment efficacy. In addition, the effectiveness increased when viral vectors were employed for gene modification and high transplantation doses were administered during the subacute phase. Stem cells derived from the human umbilical cord exhibited an advantage in motor function recovery. However, the transplantation of growth factor gene-modified stem cells did not significantly improve motor function in male rodents (P = 0.136). Transplantation of growth factor gene-modified stem cells improved motor function in rodents after SCI, but claims of enhanced efficacy should be approached with caution. The safety of gene modification remains a significant concern, requiring additional efforts to enhance its clinical translatability.