Modulation of the LIMK Pathway by Myricetin: A Protective Strategy Against Neurological Impairments in Spinal Cord Injury.

OBJECTIVE: Spinal cord injury (SCI), one of the major disabilities concerning central nervous system injury, results in permanent tissue loss and neurological impairment. The existing therapeutic options for SCI are limited and predominantly consist of chemical compounds. In this study, we delved into the neuroprotective effects of myricetin, a natural flavonoid compound, and the underlying mechanisms, specifically in the context of SCI, utilizing an in vivo model. Previously, our investigations revealed an elevation in the phosphorylated form of Lin-11, Isl-1, and Mec-3 kinase1 (LIMK1) at chronic time points postinjury, coinciding with neuronal loss and scar formation. Our primary objective here was to assess the potential neuroprotective properties of myricetin in SCI and to ascertain if these effects were linked to LIMK inhibition, a hitherto unexamined pathway to date. METHODS: Computational docking and molecular dynamics simulation studies were performed to assess myricetin's potential to bind with LIMK. Then, using a rat contusion model, SCI was induced and different molecular techniques (Western blot, Evans Blue assay, quantitative reverse transcription polymerase chain reaction and immunohistochemistry) were performed to determine the effects of myricetin. RESULTS: Remarkably, computational docking models identified myricetin as having a better interaction profile with LIMK than standard. Subsequent to myricetin treatment, a significant downregulation in phosphorylated LIMK expression was observed at chronic time points. This reduction correlated with a notable decrease in glial and fibrotic scar formation, and enhanced neuroprotection indicating a positive outcome in vivo. CONCLUSION: In summary, our findings underscore myricetin's potential as a bioactive compound capable of attenuating SCI-induced injury cascades by targeting the LIMK pathway.

Natural Phycocyanin/Paclitaxel Micelle Delivery of Therapeutic P53 to Activate Apoptosis for HER2 or ER Positive Breast Cancer Therapy.

The P53 gene is commonly mutated in breast cancer, protein based the gene as anticancer drugs could provide efficient and stable advantages by restoring the function of the wild-type P53 protein. In this study, we describe the creation and utilization of a micelle composed by natural phycocyanin and paclitaxel and grafting anti-HER2 (PPH), which effectively packages and transports recombinant P53 protein with anti-ER (PE), resulting in a new entity designated as PE@PPH, to address localization obstacles and modify cellular tropism to the cell membrane or nucleus. The results indicate that PE@PPH has strong antitumor properties, even at low doses of PTX both in vitro and in vivo. These findings suggest that PE@PPH could be an enhancing micelle for delivering therapeutic proteins and promoting protein functional recovery, particularly in addressing the challenges posed by tumor heterogeneity in breast cancer.

Nose-to-brain delivery of stem cells in stroke: the role of extracellular vesicles.

Stem cell transplantation offers a promising therapy that can be administered days, weeks, or months after a stroke. We recognize 2 major mitigating factors that remain unresolved in cell therapy for stroke, notably: (1) well-defined donor stem cells and (2) mechanism of action. To this end, we advance the use of ProtheraCytes, a population of non-adherent CD34+ cells derived from human peripheral blood and umbilical cord blood, which have been processed under good manufacturing practice, with testing completed in a phase 2 clinical trial in post-acute myocardial infarction (NCT02669810). We also reveal a novel mechanism whereby ProtheraCytes secrete growth factors and extracellular vesicles (EVs) that are associated with angiogenesis and vasculogenesis. Our recent data revealed that intranasal transplantation of ProtheraCytes at 3 days after experimentally induced stroke in adult rats reduced stroke-induced behavioral deficits and histological damage up to 28 days post-stroke. Moreover, we detected upregulation of human CD63+ EVs in the ischemic brains of stroke animals that were transplanted with ProtheraCytes, which correlated with increased levels of DCX-labeled neurogenesis and VEGFR1-associated angiogenesis and vasculogenesis, as well as reduced Iba1-marked inflammation. Altogether, these findings overcome key laboratory-to-clinic translational hurdles, namely the identification of well-characterized, clinical grade ProtheraCytes and the elucidation of a potential CD63+ EV-mediated regenerative mechanism of action. We envision that additional translational studies will guide the development of clinical trials for intranasal ProtheraCytes allografts in stroke patients, with CD63 serving as a critical biomarker.

Improving patient outcomes in acute and subacute stroke using a wearable device-assisted rehabilitation system: a randomized controlled trial.

OBJECTIVE: Multidisciplinary rehabilitation facilitates post-stroke functional recovery, but is associated with resource and accessibility barriers. This study evaluated the combination of a wearable device-assisted system (WEAR) and conventional therapy for post-stroke rehabilitation. METHODS: This randomized, controlled, parallel group, clinical trial was conducted at two rehabilitation centers. A WEAR system was developed featuring sensors and application program-embedded smartphones. Stroke patients within 12 weeks of onset and modified Rankin Scale (mRS) scores of 2 to 4 were randomized into a wearable group (WG, WEAR + conventional rehabilitation) or control group (CG, conventional rehabilitation) for 90 days. The primary outcome was mRS score changes within 90 days. RESULTS: Among 127 stroke patients enrolled (76 men [59.8%]; mean age: 57.5 years), 63 and 64 patients were randomized to WG and CG, respectively. Both groups showed significant improvements in mRS scores. Between-group repeated measures analysis adjusted for sex, age and number of rehabilitation sessions showed greater improvement in mRS scores within 90 days in the WG than in the CG (estimate: 0.73). CONCLUSIONS: This combined WEAR and conventional rehabilitation approach may improve post-stroke functional recovery compared with conventional rehabilitation alone. The WEAR system permits remote monitoring and recording of rehabilitation in various settings.This clinical trial was retrospectively registered at www.clinicaltrials.gov with the Unique Identifier NCT04997408.

A Comprehensive Review of Graft Choices and Surgical Techniques in Primary Anterior Cruciate Ligament Reconstruction: An Outcome Analysis.

Anterior cruciate ligament (ACL) injuries are among the most prevalent knee injuries, particularly in athletes engaged in high-impact sports. ACL reconstruction is a widely performed surgical procedure to restore knee stability, prevent further knee damage, and enable patients to return to their previous physical activity levels. However, the success of ACL reconstruction is influenced by various factors, including the choice of graft and the surgical technique employed. This comprehensive review explores the outcomes of different graft options - autografts, allografts, and synthetic grafts - and various surgical techniques such as single-bundle versus double-bundle reconstruction and anatomic versus non-anatomic tunnel placement. The review analyzes the short- and long-term outcomes, including functional recovery, return to sports, complication rates, and the impact of patient-specific factors such as age, activity level, and comorbidities. Additionally, the review discusses the role of rehabilitation protocols in optimizing surgical outcomes. By synthesizing current evidence, this review aims to provide clinicians with insights into the most effective graft choices and surgical techniques for primary ACL reconstruction, ultimately guiding the optimization of patient outcomes and highlighting areas for future research.

A dietary intervention with conjugated linoleic acid enhances microstructural white matter reorganization in experimental stroke.

Background: A dietary supplementation with conjugated linoleic acid (CLA) was shown to attenuate inflammation and increase the proportions of circulating regulatory T cells (Tregs) and M2-type macrophages in disease models such as autoimmune encephalitis and arteriosclerosis. Since Tregs and anti-inflammatory (M2-type) macrophages were found to enhance stroke recovery, we hypothesized that CLA-supplementation might improve stroke recovery via immune modulatory effects. Methods: Functional assessment was performed over 90 days after induction of experimental photothrombotic stroke in wild type mice (n = 37, sham n = 10). Subsequently, immunological characterization of different immunological compartments (n = 16), ex vivo magnetic resonance (MR, n = 12) imaging and immunohistochemical staining (n = 8) was performed. Additionally, we tested the effect of CLA in vitro on peripheral blood mononuclear cells from human stroke patients and healthy controls (n = 12). Results: MR diffusion tensor imaging (DTI) demonstrated enhanced microstructural reorganization of interhemispheric white matter tracts, dependent on lesion size. Functional recovery over 90 days remained unaffected. Detailed immunological analyses across various compartments revealed no significant long-term immunological alterations due to CLA. However, analyses of human blood samples post-stroke showed reduced levels of pro-inflammatory interferon-γ (IFN-γ) and tumor necrosis factor alpha (TNF-α) release by T-lymphocytes following in vitro treatment with CLA. Conclusion: We aimed to explore the efficacy of a dietary intervention with minimal known side effects that could be accessible to human stroke patients, regardless of the degree of disability, and without the risks associated with aggressive immunomodulatory therapies. Our main findings include improved microstructural reorganization in small infarcts and a reduced inflammatory response of human T cells in vitro.

Recovery of Muscular Strength Following Total Hip Replacement: A Narrative Review.

This narrative review analyzes muscle strength recovery following total hip replacement (THR) and looks at various factors affecting postoperative muscle function restoration. The review synthesizes evidence from various studies regarding the timing and degree of muscular strength recovery, different rehabilitation protocols, and patient-specific variables such as age, preoperative physical condition, and comorbidities, among others. Overall, it appears that THR is associated with improved hip function and quality of life, but this usually takes a long time due to individualized physical therapy interventions. In addition, postoperative rehabilitation has been found not to exist without any personal factors involved such as age or gender whereby for instance senior citizens have no alternative but to go for THR surgery, making their lower limbs weaker than those who are younger. Based on the findings in this review on muscle recovery after THR surgeries, one may conclude that this endeavor should begin as early as possible and include regular resistance training programs with performance-focused functional training after surgery. In addition, more longitudinal studies should be conducted regarding post-surgical outcomes comparing other traditional medical practices.

Comparison of Neural Recovery Effects of Botulinum Toxin Based on Administration Timing in Sciatic Nerve-Injured Rats.

This study aimed to assess the effects of the timing of administering botulinum neurotoxin A (BoNT/A) on nerve regeneration in rats. Sixty 6-week-old rats with a sciatic nerve injury were randomly divided into four groups: the immediately treated (IT) group (BoNT/A injection administered immediately post-injury), the delay-treated (DT) group (BoNT/A injection administered one week post-injury), the control group (saline administered one week post-injury), and the sham group (only skin and muscle incisions made). Nerve regeneration was assessed 3, 6, and 9 weeks post-injury using various techniques. The levels of glial fibrillary acid protein (GFAP), astroglial calcium-binding protein S100ß (S100ß), growth-associated protein 43 (GAP43), neurofilament 200 (NF200), and brain-derived neurotrophic factor (BDNF) in the IT and DT groups were higher. ELISA revealed the highest levels of these proteins in the IT group, followed by the DT and control groups. Toluidine blue staining revealed that the average area and myelin thickness were higher in the IT group. Electrophysiological studies revealed that the CMAP in the IT group was significantly higher than that in the control group, with the DT group exhibiting significant differences starting from week 8. The findings of the sciatic functional index analysis mirrored these results. Thus, administering BoNT/A injections immediately after a nerve injury is most effective for neural recovery. However, injections administered one week post-injury also significantly enhanced recovery. BoNT/A should be administered promptly after nerve damage; however, its administration during the non-acute phase is also beneficial.

Cost-effectiveness of MLC601 in post-stroke functional recovery compared with placebo - the CHIMES & CHIMES-E studies.

BACKGROUND: Despite progress in stroke therapy (e.g., revascularisation interventions by thrombolysis and/or thrombectomy, organised stroke care), many stroke survivors will have impairment of neurological function. We aimed to compare the cost-effectiveness of an oral natural formulation, MLC601, versus placebo in functional recovery among subjects receiving standard of care after an ischemic stroke of intermediate severity assessed with NIH Stroke Scale at baseline (b-NIHSS 8-14). METHODS: A Markov cohort model with a 2-year time horizon was developed to simulate patients from a published randomised placebo-controlled clinical trial of MLC601 in their post-stroke functional recovery assessed by modified Rankin Score (mRS), from a health system perspective. Transition probabilities were derived from a multi-centre clinical trial in South East Asia. As cost and utility data were not collected in the trial, therefore we extracted them from the published literature. The main outcomes were incremental cost, incremental quality-adjusted life-year (QALY) gained, and incremental cost-effectiveness ratio (ICER). Besides base-case and sensitivity analyses, we performed subgroup analyses to explore the heterogeneity of patients with poor-prognosis factors (b-NIHSS 10-14, stroke onset to treatment time > 48 h, rehabilitation during first 3 month). All costs are expressed in 2022 Euro and USD, with an annual discount rate of 3% applied to costs and QALYs. RESULTS: Base-case analysis showed that MLC601 was cost-effective compared with placebo, with €5,080 saved and 0.45 QALY gained, resulting in an ICER of -€11,352.50 per QALY gained. Similarly, results from subgroup analyses indicated that the use of MLC601 was a dominant strategy in all subgroups with poor-prognosis factors. Sensitivity analyses revealed the results were robust. CONCLUSION: Compared with placebo on top of standard stroke care, MLC601 was cost-effective in post-stroke functional recovery over two years. Due to the lack of cost and utility data from the study population, the results might not be generalizable to other settings. Further studies with country-specific data are needed to confirm the results of this study. TRIAL REGISTRATION: URL http://www. CLINICALTRIALS: gov . Unique identifier NCT00554723 November 7, 2007.

Role of NADPH Oxidases in Stroke Recovery.

Stroke is one of the most significant causes of death and long-term disability globally. Overproduction of reactive oxygen species by NADPH oxidase (NOX) plays an important role in exacerbating oxidative stress and causing neuronal damage after a stroke. There is growing evidence that NOX inhibition prevents ischemic injury and that the role of NOX in brain damage or recovery depends on specific post-stroke phases. In addition to studies on post-stroke neuroprotection by NOX inhibition, recent reports have also demonstrated the role of NOX in stroke recovery, a critical process for brain adaptation and functional reorganization after a stroke. Therefore, in this review, we investigated the role of NOX in stroke recovery with the aim of integrating preclinical findings into potential therapeutic strategies to improve stroke recovery.

The impact of changes in physical activity on functional recovery for older inpatients in post-acute rehabilitation units.

PURPOSE: The effect of increased physical activity duration on functional recovery in older inpatients in subacute settings is not well established. This study aimed to investigate the relationship between physical activity and functional recovery in older patients receiving post-acute and subacute care. METHODS: We analyzed cohort data of hospitalized older patients (age ≥ 65 years) in the post-acute rehabilitation units. The main outcome was functional independence measure (FIM) gain. Physical activity was measured using a triaxial accelerometer. Changes in sedentary behavior and total physical activity time from admission to discharge were measured as changes in each physical activity time. Logistic regression analysis was performed to examine the relationship between changes in physical activity and FIM gain. RESULTS: A total of 210 patients were eligible for analysis. The mean age of the study patients was 83.6 ± 7.2 years, and 63.8% (n = 134) were female. According to the multivariate regression analysis, changes in sedentary behavior time were significantly associated with high recovery of FIM gain (odds ratio [OR] 0.996, 95% confidence interval [CI]: 0.993-1.000; p = 0.026), and changes in total physical activity time also showed a similar association (OR 1.006, 95% CI 1.000-1.011; p = 0.041). CONCLUSION: Decreased sedentary behavior time and increased total physical activity time were significantly associated with high functional recovery in post-acute rehabilitation units. These results suggest that interventions for physical activity duration may be effective in improving activities of daily living in older post-acute and subacute patients.

Return-to-Work After Attempted Digit Replantation: A Systematic Review of 31 Studies.

BACKGROUND: Traumatic digit amputation is a common injury with life-altering consequences for thousands of patients each year. In this study, we aim to update and expand the reported outcomes of return-to-work (RTW) and functional recovery in patients treated with digit replant after traumatic amputation. METHODS: A PRISMA-guided systematic review was performed to identify all published articles related to digit replantation following amputation. We queried the following 4 databases: Scopus, Embase, Web of Science, and PubMed-MEDLINE. A total of 31 studies were included in the analysis of return-to-work data. RESULTS: Of the 31 included studies, 26 studies reported that 1976 digits were successfully replanted, while 27 studies reported that 300 replants failed (86.8% success rate). Among 1087 patients in these studies, 82.9% who underwent replantation returned to work. The mean RTW time in 16 studies was 4.7 months (weighted average). Return-to-work time ranged from 0 to 26 months in 12 studies. Of 352 patients who returned to work in 17 studies, 90.9% resumed their previous occupation, while 29 (8.2%) changed occupations. The RTW for finger-only replantations was significantly lower compared to thumb-only, distal digit-only, and any digit replantations (66.0% vs 82.8%; 66.0% vs 87.6%; 66.0% vs 82.9%). CONCLUSION: Despite a declining prevalence of digit replantation surgery in recent years, this study illustrates that replantation provides beneficial outcomes for patients with a high return-to-work rate.

Orosomucoid 2 is an endogenous regulator of neuronal mitochondrial biogenesis and promotes functional recovery post-stroke.

Development of functional recovery therapies is critical to reduce the global impact of stroke as the leading cause of long-term disability. Our previous studies found that acute-phase protein orosomucoid (ORM) could provide an up to 6h therapeutic time window to reduce infarct volume in acute ischemic stroke by improving endothelial function. However, its role in neurons and functional recovery post-stroke remains largely unknown. Here, we showed that exogenous ORM administration with initial injection at 0.5h (early) or 12h (delayed) post-MCAO daily for consecutive 7 days significantly decreased infarct area, improved motor and cognitive functional recovery, and promoted mitochondrial biogenesis after MCAO. While neuron-specific knockout of ORM2, a dominant subtype of ORM in the brain, produced opposite effects which could be rescued by exogenous ORM. In vitro, exogenous ORM protected SH-SY5Y cells from OGD-induced damage and promoted mitochondrial biogenesis, while endogenous ORM2 deficiency worsened these processes. Mechanistically, inactivation of CCR5 or AMPK eliminated the protective effects of ORM on neuronal damage and mitochondrial biogenesis. Taken together, our findings demonstrate that ORM, mainly ORM2, is an endogenous regulator of neuronal mitochondrial biogenesis by activating CCR5/AMPK signaling pathway, and might act as a potential therapeutic target for the functional recovery post-stroke.

Development and Testing of the Spinal Cord Injury Bladder and Bowel Control Questionnaire (SCI-BBC-Q).

INTRODUCTION: Recovery of lower urinary tract (LUT) and lower gastrointestinal tract (LGIT) is a high priority for people with lived experience following spinal cord injury (SCI). A universally accepted validated patient-reported outcome (PRO) measure of the individual sensory and motor components of LGIT and LUT function, which allows tracking of recovery is lacking. To address this literature gap, the SCI Bladder and Bowel Control Questionnaire (SCI-BBC-Q) was developed. METHODS: The SCI-BBC-Q was developed as a direct assessment of the micturition and defecation experiences of an individual with SCI with possible neurogenic LUT and LGIT dysfunction. The SCI-BBC-Q development process consisted of two phases, measure development and evaluation. Measure development was guided by a conceptual framework, review of existing instruments and literature, and an iterative process of item incorporation, review, feedback, and consensus revision. Evaluation included cognitive interviewing, and assessments of feasibility, reliability, and content validity. RESULTS: The final 6-item SCI-BBC-Q is a PRO, which assesses motor and sensory function related to micturition and defecation, requiring ~5 min to complete. Assessments of clarity of the instrument components with regard to understanding of what is being asked in the questionnaire, feasibility of administration, reliability, internal consistency, and agreement with proxy measures have demonstrated that the SCI-BBC-Q provides consistent, stable, and reproducible data. Significant correlations were found between SCI-BBC-Q scores and the anorectal motor and sensory components of the International Standards for the Neurological Classification of SCI. CONCLUSION: The SCI-BBC-Q is a practical and reliable method for baseline and ongoing evaluation of patients with neurogenic LUT and LGIT dysfunction, especially in the acute and subacute period when function is changing due to neurological plasticity. It is also appropriate for use in monitoring response to treatments related to neurological recovery.

Repeated intrathecal injections of peripheral nerve-derived stem cell spheroids improve outcomes in a rat model of traumatic brain injury.

BACKGROUND: Traumatic brain injury (TBI) is a major cause of disability and mortality worldwide. However, existing treatments still face numerous clinical challenges. Building on our prior research showing peripheral nerve-derived stem cell (PNSC) spheroids with Schwann cell-like phenotypes can secrete neurotrophic factors to aid in neural tissue regeneration, we hypothesized that repeated intrathecal injections of PNSC spheroids would improve the delivery of neurotrophic factors, thereby facilitating the restoration of neurological function and brain tissue repair post-TBI. METHODS: We generated PNSC spheroids from human peripheral nerve tissue using suspension culture techniques. These spheroids were characterized using flow cytometry, immunofluorescence, and reverse-transcription polymerase chain reaction. The conditioned media were evaluated in SH-SY5Y and RAW264.7 cell lines to assess their effects on neurogenesis and inflammation. To simulate TBI, we established a controlled cortical impact (CCI) model in rats. The animals were administered intrathecal injections of PNSC spheroids on three occasions, with each injection spaced at a 3-day interval. Recovery of sensory and motor function was assessed using the modified neurological severity score (mNSS) and rotarod tests, while histological (hematoxylin and eosin, Luxol fast blue staining) and T2-weighted magnetic resonance imaging analyses, alongside immunofluorescence, were conducted to evaluate the recovery of neural structures and pathophysiology. RESULTS: PNSC spheroids expressed high levels of Schwann cell markers and neurotrophic factors, such as neurotrophin-3 and Ephrin B3. Their conditioned medium was found to promote neurite outgrowth, reduce reactive oxygen species-mediated cell death and inflammation, and influence M1-M2 macrophage polarization. In the CCI rat model, rats receiving repeated triple intrathecal injections of PNSC spheroids showed significant improvements in sensory and motor function, with considerable neural tissue recovery in damaged areas. Notably, this treatment promoted nerve regeneration, axon regrowth, and remyelination. It also reduced glial scar formation and inflammation, while encouraging angiogenesis. CONCLUSION: Our findings suggest that repeated intrathecal injections of PNSC spheroids can significantly enhance neural recovery after TBI. This effect is mediated by the diverse neurotrophic factors secreted by PNSC spheroids. Thus, the strategy of combining therapeutic cell delivery with multiple intrathecal injections holds promise as a novel clinical treatment for TBI recovery.

Effect of whole-body cryotherapy on recovery after high-intensity training in elite rowers.

The purpose of this study was to investigate the effect of whole-body cryotherapy (WBC) on acute recovery after a single high-intensity training day. Twelve elite professional male rowers from the national aquatic training base. They were randomly divided into a WBC group (n = 6) and a control group (CON group, n = 6). They performed a high-intensity training program, with a single session immediately followed by WBC (-110°C, 3 min) or recovered naturally for 3 min (CON group). Rowing performance, skin temperature, heart rate, blood pressure, and blood lactate concentrations were recorded before training, immediately, 5 min, and 15 min after the intervention. Blood samples were collected early in the morning of the day of intervention and that of the following day. The results indicated that 1) the blood lactate concentrations after WBC were significantly lower than pre-training (p < 0.05); 2) the maximum power significantly decreased immediately after WBC compared to pre-training (p < 0.05); 3) a significant main effect of time was observed for average speed, which significantly decreased after WBC (p < 0.05); 4) a significant main effect of time for blood parameters was observed. Specifically, hematocrit, cortisol, and hemoglobin were significantly lower after WBC than pre-intervention, whereas testosterone/cortisol was significantly higher than pre-intervention (p < 0.05). The results of this study showed that a single session of WBC had a positive effect on accelerating the elimination of blood lactate after HIT, but did not significantly change rowing performance and physiological parameters. A single session of WBC was not an effective strategy for elite rowers for acute recovery after HIT.

Compensatory changes after spinal cord injury in a remyelination deficient mouse model.

The development of therapeutic strategies to reduce impairments following spinal cord injury (SCI) motivates an active area of research, because there are no effective therapies. One strategy is to address injury-induced demyelination of spared axons by promoting endogenous or exogenous remyelination. However, previously, we showed that new myelin was not necessary to regain hindlimb stepping following moderate thoracic spinal cord contusion in 3-month-old mice. The present analysis investigated two potential mechanisms by which animals can re-establish locomotion in the absence of remyelination: compensation through intact white matter and conduction through spared axons. We induced a severe contusion injury to reduce the spared white matter rim in the remyelination deficient model, with no differences in recovery between remyelination deficient animals and injured littermate controls. We investigated the nodal properties of the axons at the lesion and found that in the remyelination deficient model, axons express the Nav1.2 voltage-gated sodium channel, a sub-type not typically expressed at mature nodes of Ranvier. In a moderate contusion injury, conduction velocities through the lesions of remyelination deficient animals were similar to those in animals with the capacity to remyelinate after injury. Detailed gait analysis and kinematics reveal subtle differences between remyelination deficient animals and remyelination competent controls, but no worse deficits. It is possible that upregulation of Nav1.2 channels may contribute to establishing conduction through the lesion. This conduction could contribute to compensation and regained motor function in mouse models of SCI. Such compensatory mechanism may have implications for interpreting efficacy results for remyelinating interventions in mice and the development of therapies for improving recovery following SCI.

Changes in Noradrenergic Synthesis and Dopamine Beta-Hydroxylase Activity in Response to Oxidative Stress after Iron-induced Brain Injury.

Noradrenaline (NA) levels are altered during the first hours and several days after cortical injury. NA modulates motor functional recovery. The present study investigated whether iron-induced cortical injury modulated noradrenergic synthesis and dopamine beta-hydroxylase (DBH) activity in response to oxidative stress in the brain cortex, pons and cerebellum of the rat. Seventy-eight rats were divided into two groups: (a) the sham group, which received an intracortical injection of a vehicle solution; and (b) the injured group, which received an intracortical injection of ferrous chloride. Motor deficits were evaluated for 20 days post-injury. On the 3rd and 20th days, the rats were euthanized to measure oxidative stress indicators (reactive oxygen species (ROS), reduced glutathione (GSH) and oxidized glutathione (GSSG)) and catecholamines (NA, dopamine (DA)), plus DBH mRNA and protein levels. Our results showed that iron-induced brain cortex injury increased noradrenergic synthesis and DBH activity in the brain cortex, pons and cerebellum at 3 days post-injury, predominantly on the ipsilateral side to the injury, in response to oxidative stress. A compensatory increase in contralateral noradrenergic activity was observed, but without changes in the DBH mRNA and protein levels in the cerebellum and pons. In conclusion, iron-induced cortical injury increased the noradrenergic response in the brain cortex, pons and cerebellum, particularly on the ipsilateral side, accompanied by a compensatory response on the contralateral side. The oxidative stress was countered by antioxidant activity, which favored functional recovery following motor deficits.

The association between social networks and functional recovery after stroke.

BACKGROUND AND PURPOSE: Social determinants of health (SDOH), including social networks, impact disability and quality of life post-stroke, yet the direct influence of SDOH on functional change remains undetermined. We aimed to identify which SDOH predict change on the modified Rankin Scale (mRS) within 90 days after stroke hospitalization. METHODS: Stroke patients from the Transitions of Care Stroke Disparities Study (TCSDS) were enrolled from 12 hospitals in the Florida Stroke Registry. TCSDS aims to identify disparities in hospital-to-home transitions after stroke. SDOH were collected by trained interviewers at hospital discharge. The mRS was assessed at discharge, 30- and 90-day post-stroke. Multinomial logistic regression models examined contributions of each SDOH to mRS improvement or worsening (compared to no change) from discharge to 30- and 90-day, respectively. RESULTS: Of 1190 participants, median age was 64 years, 42% were women, 52% were non-Hispanic White, and 91% had an ischemic stroke. Those with a limited social support network had greater odds of functional decline at 30 days (aOR = 1.39, 1.17-1.66), adjusting for age and onset to arrival time and at 90 days (aOR = 1.50, 1.10-2.05) after adjusting for age. Results were consistent after further adjustment for additional SDOH and participant characteristics. Individuals living with a spouse/partner had reduced odds of functional decline at 90 days (aOR = 0.74, 0.57-0.98); however, results were inconsistent with more conservative modeling approaches. CONCLUSION: The findings highlight the importance of SDOH, specifically having a greater number of individuals in your social network in functional recovery after stroke.

Prospective study on the effects of mechanical bowel preparation under the enhanced recovery after surgery concept on electrolyte disturbances and functional recovery after robotic surgery for urologic tumors in older adults.

BACKGROUND: Mechanical bowel preparation (MBP) involves the cleansing of bowel excreta and secretions using methods such as preoperative oral laxatives, retrograde enemas, and dietary adjustments. When combined with oral antibiotics, preoperative MBP can effectively lower the risk of anastomotic leakage, minimize the occurrence of postoperative infections, and reduce the likelihood of other complications. To study the effects of MBP under the Enhanced Recovery After Surgery (ERAS) concept on postoperative electrolyte disorders and functional recovery in older people with urological tumors undergoing robot-assisted surgery. METHODS: Older people with urological tumors undergoing robot-assisted surgery were randomly divided into two groups. The experimental group (n = 76) underwent preoperative MBP, while the control group (n = 72) did not. The differences in electrolyte levels and functional recovery between the two groups after radical surgery for urological tumors were observed. RESULTS: The incidence of postoperative electrolyte disorders was significantly higher in the experimental group compared to the control group, with incidence rates of 42.1% and 19.4%, respectively (P < 0.05). Subgroup analysis showed that the electrolyte disorder was age-related (P < 0.05). There were no significant differences between the two groups in terms of postoperative complications, gastrointestinal function recovery, laboratory indicators of infection, body temperature, and length of hospital stay (P > 0.05). CONCLUSION: Under the accelerated recovery background, preoperative MBP increases the risk of postoperative electrolyte disorders in older people with urological tumors and does not reduce the incidence of postoperative complications or promote postoperative functional recovery.