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1.
BMC Neurol ; 24(1): 148, 2024 May 02.
Article in English | MEDLINE | ID: mdl-38698310

ABSTRACT

BACKGROUND: During episodes of benign paroxysmal positional vertigo (BPPV), individuals with migraine, compared with individuals without migraine, may experience more severe vestibular symptoms because of their hyperexcitable brain structures, more adverse effects on quality of life, and worse recovery processes from BPPV. METHODS: All patients with BPPV were assigned to the migraine group (MG, n = 64) and without migraine group (BPPV w/o MG, n = 64) and completed the Vertigo Symptom Scale (VSS), Vertigo Dizziness Imbalance Symptom Scale (VDI-SS), VDI Health-Related Quality of Life Scale (VDI-HRQoLS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI) at the time of BPPV diagnosis (baseline) and on the one-month follow-up. Headache Impact Test-6 and Migraine Disability Assessment Scale were used for an assessment of headache. Motion sickness was evaluated based on the statement of each patient as present or absent. RESULTS: Compared with the BPPV w/o MG, the MG had higher VSS scores at baseline [19.5 (10.7) vs. 11.3 (8.5); p < 0.001] and on one-month follow-up [10.9 (9.3) vs. 2.2 (2.7), p < 0.001]; experienced more severe dizziness and imbalance symptoms based on the VDI-SS at baseline (61.9% vs. 77.3%; p < 0.001) and after one month (78.9% vs. 93.7%, p < 0.001); and more significantly impaired quality of life according to the VDI-HRQoLS at baseline (77.4% vs. 91.8%, p < 0.001) and after one month (86.3% vs. 97.6%, p < 0.001). On the one-month follow-up, the subgroups of patients with moderate and severe scores of the BAI were higher in the MG (39.2%, n = 24) than in the BPPV w/o MG (21.8%, n = 14) and the number of patients who had normal scores of the BDI was lower in the MG than in the BPPV w/o MG (67.1% vs. 87.5%, p = 0.038). CONCLUSION: Clinicians are advised to inquire about migraine when evaluating patients with BPPV because it may lead to more intricate and severe clinical presentation. Further studies will be elaborated the genuine nature of the causal relationship between migraine and BPPV.


Subject(s)
Benign Paroxysmal Positional Vertigo , Migraine Disorders , Quality of Life , Humans , Male , Benign Paroxysmal Positional Vertigo/diagnosis , Benign Paroxysmal Positional Vertigo/epidemiology , Benign Paroxysmal Positional Vertigo/complications , Female , Migraine Disorders/diagnosis , Migraine Disorders/epidemiology , Middle Aged , Adult , Quality of Life/psychology , Recovery of Function/physiology , Follow-Up Studies , Dizziness/diagnosis , Dizziness/epidemiology , Aged
2.
Neuroreport ; 35(9): 549-557, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38739900

ABSTRACT

Neuroinflammation after traumatic brain injury (TBI) exhibits a strong correlation with neurological impairment, which is a crucial target for improving the prognosis of TBI patients. The involvement of CXCL5/CXCR2 signaling in the regulation of neuroinflammation in brain injury models has been documented. Therefore, the effects of CXCL5 on post-TBI neuroinflammation and its potential mechanisms need to be explored. Following TBI, C57BL/6 mice were administered intraperitoneal injections of a CXCL5 neutralizing antibody (Nab-CXCL5) (5 mg/kg, 2 times/day). Subsequently, the effects on neuroinflammation, nerve injury, and neurological function were assessed. Nab-CXCL5 significantly reduced the release of inflammatory factors, inhibited the formation of inflammatory microglia and astrocytes, and reduced the infiltration of peripheral immune cells in TBI mice. Additionally, this intervention led to a reduction in neuronal impairment and facilitated the restoration of sensorimotor abilities, as well as improvements in learning and memory functions. Peripheral administration of the Nab-CXCL5 to TBI mice could suppress neuroinflammation, reduce neurological damage, and improve neurological function. Our data suggest that neutralizing antibodies against CXCL5 (Nab-CXCL5) may be a promising agent for treating TBI.


Subject(s)
Brain Injuries, Traumatic , Chemokine CXCL5 , Mice, Inbred C57BL , Neuroinflammatory Diseases , Recovery of Function , Animals , Brain Injuries, Traumatic/immunology , Brain Injuries, Traumatic/drug therapy , Chemokine CXCL5/metabolism , Neuroinflammatory Diseases/drug therapy , Mice , Male , Recovery of Function/drug effects , Recovery of Function/physiology , Antibodies, Neutralizing/pharmacology , Microglia/drug effects , Microglia/metabolism
3.
Neuron ; 112(10): 1595-1610, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38754372

ABSTRACT

Recovery of consciousness after coma remains one of the most challenging areas for accurate diagnosis and effective therapeutic engagement in the clinical neurosciences. Recovery depends on preservation of neuronal integrity and evolving changes in network function that re-establish environmental responsiveness. It typically occurs in defined steps: it begins with eye opening and unresponsiveness in a vegetative state, then limited recovery of responsiveness characterizes the minimally conscious state, and this is followed by recovery of reliable communication. This review considers several points for novel interventions, for example, in persons with cognitive motor dissociation in whom a hidden cognitive reserve is revealed. Circuit mechanisms underlying restoration of behavioral responsiveness and communication are discussed. An emerging theme is the possibility to rescue latent capacities in partially damaged human networks across time. These opportunities should be exploited for therapeutic engagement to achieve individualized solutions for restoration of communication and environmental interaction across varying levels of recovery.


Subject(s)
Coma , Recovery of Function , Humans , Coma/physiopathology , Coma/therapy , Recovery of Function/physiology , Consciousness/physiology , Persistent Vegetative State/physiopathology , Persistent Vegetative State/rehabilitation
4.
Acta Neurochir (Wien) ; 166(1): 228, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780808

ABSTRACT

PURPOSE: Regarding surgical indications for carpal tunnel syndrome (CTS), the hypothesis that the recovery processes of subjective symptoms differ among pain, sensory, and motor symptoms and correlate with recovery in objective nerve conduction studies was examined in the present study. METHODS: The global symptom score (GSS) is a method used to assess clinical outcomes and covers subjective symptoms, including pain (pain and nocturnal awakening), sensory (numbness and paresthesia), and motor (weakness/clumsiness) symptoms. The relationships between long-term changes in GSS and recovery in nerve conduction studies were investigated. RESULTS: Forty patients (40 hands) were included (mean age 65 years; 80% female; 68% with moderate CTS: sensory nerve conduction velocity < 45 m/s and motor nerve distal latency > 4.5 ms). Pain and nocturnal awakening rapidly subsided within 1 month after surgery and did not recur in the long term (median 5.6 years). Paresthesia significantly decreased 3 months after surgery and in the long term thereafter. Weakness/clumsiness significantly decreased at 1 year. Sensory nerve distal latency, conduction velocity, and amplitude significantly improved 3 months and 1 year after surgery, and correlated with nocturnal awakening in the short term (3 months) in moderate CTS cases. The patient satisfaction rate was 91%. CONCLUSION: Rapid recovery was observed in pain and nocturnal awakening, of which nocturnal awakening correlated with the recovery of sensory nerve conduction velocity. Patients with pain symptoms due to moderate CTS may benefit from surgical release.


Subject(s)
Carpal Tunnel Syndrome , Neural Conduction , Humans , Carpal Tunnel Syndrome/surgery , Carpal Tunnel Syndrome/physiopathology , Carpal Tunnel Syndrome/diagnosis , Female , Male , Aged , Middle Aged , Neural Conduction/physiology , Treatment Outcome , Adult , Aged, 80 and over , Median Nerve/surgery , Median Nerve/physiopathology , Paresthesia/etiology , Paresthesia/physiopathology , Paresthesia/surgery , Recovery of Function/physiology
5.
Aging Clin Exp Res ; 36(1): 118, 2024 May 23.
Article in English | MEDLINE | ID: mdl-38780814

ABSTRACT

OBJECTIVE: Foot massage is known to be effective on the emotional state (anxiety, depression, etc.) in the postoperative period. However, studies on its effect on functional level are insufficient. AIM: The study aimed to investigate the impact of foot plantar massage on functional recovery in older adults undergoing general surgery, employing a randomized clinical trial design. METHODS: A total of 70 older adults aged 65 years and above who underwent abdominal surgery were included. Various assessments were conducted, including pain levels (Visual Analogue Scale), fear of mobility (Tampa Scale for Kinesiophobia), functional independence (Functional Independence Measure), balance (Berg Balance Scale), basic mobility (Rivermead Mobility Index), mental function status (Standardized Mini-Mental State Examination), and delirium (Nu-DESC). RESULTS: Statistically significant differences were observed in some assessment parameters within the groups during the 2nd and 3rd measurement times, with the intervention group demonstrating significant mean differences. DISCUSSIONS: The literature underscores the increase in kinesiophobia scores post-general/abdominal surgery in older adults, emphasizing the importance of evaluating functional level and kinesiophobia to expedite discharge processes and potentially plan early post-discharge rehabilitation to mitigate readmissions for functional reasons. CONCLUSIONS: Ultimately, foot massage was found to be effective in reducing kinesiophobia, improving balance, mobility, daily living skills, and mental status in older adults post-abdominal surgery, thereby advocating for the facilitation of post-discharge rehabilitation programs or the reduction of readmission rates. THE CLINICAL TRIALS NUMBER: NCT05534490.


Subject(s)
Foot , Massage , Humans , Aged , Massage/methods , Female , Male , Foot/surgery , Recovery of Function/physiology , Aged, 80 and over , Postural Balance/physiology
6.
Neurology ; 102(10): e209387, 2024 May 28.
Article in English | MEDLINE | ID: mdl-38701386

ABSTRACT

BACKGROUND AND OBJECTIVES: Motor outcomes after stroke relate to corticospinal tract (CST) damage. The brain leverages surviving neural pathways to compensate for CST damage and mediate motor recovery. Thus, concurrent age-related damage from white matter hyperintensities (WMHs) might affect neurologic capacity for recovery after CST injury. The role of WMHs in post-stroke motor outcomes is unclear. In this study, we evaluated whether WMHs modulate the relationship between CST damage and post-stroke motor outcomes. METHODS: We used data from the multisite ENIGMA Stroke Recovery Working Group with T1 and T2/fluid-attenuated inversion recovery imaging. CST damage was indexed with weighted CST lesion load (CST-LL). WMH volumes were extracted with Freesurfer's SAMSEG. Mixed-effects beta-regression models were fit to test the impact of CST-LL, WMH volume, and their interaction on motor impairment, controlling for age, days after stroke, and stroke volume. RESULTS: A total of 223 individuals were included. WMH volume related to motor impairment above and beyond CST-LL (ß = 0.178, 95% CI 0.025-0.331, p = 0.022). Relationships varied by WMH severity (mild vs moderate-severe). In individuals with mild WMHs, motor impairment related to CST-LL (ß = 0.888, 95% CI 0.604-1.172, p < 0.001) with a CST-LL × WMH interaction (ß = -0.211, 95% CI -0.340 to -0.026, p = 0.026). In individuals with moderate-severe WMHs, motor impairment related to WMH volume (ß = 0.299, 95% CI 0.008-0.590, p = 0.044), but did not significantly relate to CST-LL or a CST-LL × WMH interaction. DISCUSSION: WMHs relate to motor outcomes after stroke and modify relationships between motor impairment and CST damage. WMH-related damage may be under-recognized in stroke research as a factor contributing to variability in motor outcomes. Our findings emphasize the importance of brain structural reserve in motor outcomes after brain injury.


Subject(s)
Pyramidal Tracts , Stroke , White Matter , Humans , Pyramidal Tracts/diagnostic imaging , Pyramidal Tracts/pathology , Male , Female , Aged , White Matter/diagnostic imaging , White Matter/pathology , Stroke/diagnostic imaging , Stroke/pathology , Stroke/complications , Stroke/physiopathology , Middle Aged , Magnetic Resonance Imaging , Recovery of Function/physiology , Aged, 80 and over
7.
J Rehabil Med ; 56: jrm35095, 2024 May 07.
Article in English | MEDLINE | ID: mdl-38712968

ABSTRACT

OBJECTIVE: This study aimed to investigate the predictive functional factors influencing the acquisition of basic activities of daily living performance abilities during the early stages of stroke rehabilitation using classification and regression analysis trees. METHODS: The clinical data of 289 stroke patients who underwent rehabilitation during hospitalization (164 males; mean age: 62.2 ± 13.9 years) were retrospectively collected and analysed. The follow-up period between admission and discharge was approximately 6 weeks. Medical records, including demographic characteristics and various functional assessments with item scores, were extracted. The modified Barthel Index on discharge served as the target outcome for analysis. A "good outcome" was defined as a modified Barthel Index score ≥ 75 on discharge, while a modified Barthel Index score < 75 was classified as a "poor outcome." RESULTS: Two classification and regression analysis tree models were developed. The first model, predicting activities of daily living outcomes based on early motor functions, achieved an accuracy of 92.4%. Among patients with a "good outcome", 70.9% exhibited (i) ≥ 4 points in the "sitting-to-standing" category in the motor assessment scale and (ii) 32 points on the Berg Balance Scale score. The second model, predicting activities of daily living outcome based on early cognitive functions, achieved an accuracy of 82.7%. Within the "poor outcome" group, 52.2% had (i) ≤ 21 points in the "visuomotor organization" category of Lowenstein Occupational Therapy Cognitive Assessment, (ii) ≤ 1 point in the "time orientation" category of the Mini Mental State Examination. CONCLUSION: The ability to perform "sitting-to-standing" and visuomotor organization functions at the beginning of rehabilitation emerged as the most significant predictors for achieving successful basic activities of daily living on discharge after stroke.


Subject(s)
Activities of Daily Living , Decision Trees , Stroke Rehabilitation , Humans , Stroke Rehabilitation/methods , Male , Female , Middle Aged , Aged , Retrospective Studies , Stroke/physiopathology , Recovery of Function/physiology , Disability Evaluation , Treatment Outcome , Independent Living
8.
J Neuroeng Rehabil ; 21(1): 90, 2024 May 29.
Article in English | MEDLINE | ID: mdl-38812037

ABSTRACT

BACKGROUND: Movement smoothness is a potential kinematic biomarker of upper extremity (UE) movement quality and recovery after stroke; however, the measurement properties of available smoothness metrics have been poorly assessed in this group. We aimed to measure the reliability, responsiveness and construct validity of several smoothness metrics. METHODS: This ancillary study of the REM-AVC trial included 31 participants with hemiparesis in the subacute phase of stroke (median time since stroke: 38 days). Assessments performed at inclusion (Day 0, D0) and at the end of a rehabilitation program (Day 30, D30) included the UE Fugl Meyer Assessment (UE-FMA), the Action Research Arm Test (ARAT), and 3D motion analysis of the UE during three reach-to-point movements at a self-selected speed to a target located in front at shoulder height and at 90% of arm length. Four smoothness metrics were computed: a frequency domain smoothness metric, spectral arc length metric (SPARC); and three temporal domain smoothness metrics (TDSM): log dimensionless jerk (LDLJ); number of submovements (nSUB); and normalized average rectified jerk (NARJ). RESULTS: At D30, large clinical and kinematic improvements were observed. Only SPARC and LDLJ had an excellent reliability (intra-class correlation > 0.9) and a low measurement error (coefficient of variation < 10%). SPARC was responsive to changes in movement straightness (rSpearman=0.64) and to a lesser extent to changes in movement duration (rSpearman=0.51) while TDSM were very responsive to changes in movement duration (rSpearman>0.8) and not to changes in movement straightness (non-significant correlations). Most construct validity hypotheses tested were verified except for TDSM with low correlations with clinical metrics at D0 (rSpearman<0.5), ensuing low predictive validity with clinical metrics at D30 (non-significant correlations). CONCLUSIONS: Responsiveness and construct validity of TDSM were hindered by movement duration and/or noise-sensitivity. Based on the present results and concordant literature, we recommend using SPARC rather than TDSM in reaching movements of uncontrolled duration in individuals with spastic paresis after stroke. TRIAL REGISTRATION: NCT01383512, https://clinicaltrials.gov/ , June 27, 2011.


Subject(s)
Movement , Stroke Rehabilitation , Stroke , Upper Extremity , Humans , Male , Female , Upper Extremity/physiopathology , Middle Aged , Movement/physiology , Aged , Biomechanical Phenomena , Stroke/physiopathology , Stroke/complications , Stroke Rehabilitation/methods , Reproducibility of Results , Paresis/etiology , Paresis/rehabilitation , Paresis/physiopathology , Adult , Recovery of Function/physiology
10.
Jt Dis Relat Surg ; 35(2): 448-454, 2024 Feb 13.
Article in English | MEDLINE | ID: mdl-38727128

ABSTRACT

Several surgical procedures are used to treat dynamic pronation position of the forearm and flexion deformity of the wrist in cerebral palsy. Postoperative results of pronator teres rerouting were explored, while specially designed postoperative physiotherapy and its outcomes were limited. Herein, we present a case in whom the outcomes of electromyographic biofeedback (EMG-BF) training were assessed after pronator teres rerouting and brachioradialis tendon to extensor carpi radialis brevis tendon transfer combined with derotation osteotomy. The peak value increased, while the resting value decreased for the muscles after the intervention. Range of motion, hand function, manual ability, functional independence, and quality of life levels were improved. In conclusion, EMG biofeedback training may have a positive effect on neuromuscular control of pronator teres and brachioradialis. Free use of the upper extremity and improved manual ability positively affect the activity and quality of life of the patients.


Subject(s)
Cerebral Palsy , Muscle, Skeletal , Range of Motion, Articular , Tendon Transfer , Humans , Tendon Transfer/methods , Cerebral Palsy/surgery , Cerebral Palsy/rehabilitation , Cerebral Palsy/physiopathology , Muscle, Skeletal/surgery , Muscle, Skeletal/physiopathology , Male , Forearm/surgery , Electromyography , Quality of Life , Treatment Outcome , Biofeedback, Psychology/methods , Osteotomy/methods , Pronation/physiology , Recovery of Function/physiology
11.
Trials ; 25(1): 254, 2024 Apr 11.
Article in English | MEDLINE | ID: mdl-38605413

ABSTRACT

BACKGROUND AND PURPOSE: Research to date has lacked definitive evidence to determine whether mirror therapy promotes the recovery of upper extremity function after stroke. Considering that previous studies did not stratify patients based on structural retention, this may be one of the reasons for the negative results obtained in many trials. The goal evaluates the efficacy of TBMT (utilizing an innovatively designed mirror) versus standard occupational therapy for stroke patient's upper limb functionality. METHODS AND ANALYSIS: This single-center randomized controlled trial will involve 50 patients with stroke. All patients will be randomly assigned to either the task-based mirror therapy or the control group. The interventions will be performed 5 days per week for 4 weeks. The primary outcomes will be the mean change in scores on both the FMA-UE and modified Barthel Index (MBI) from baseline to 4 weeks intervention and at 12 weeks follow-up between the two groups and within groups. The other outcomes will include the Action Research Arm Test (ARAT), the Nine Hole Peg Test (9HPT), the Functional Independence Measure, and MRI. DISCUSSION: This trial will not only to establish that task-based mirror therapy (TBMT) could improve the recovery of hand function after stroke but also to explore the underlying mechanisms. We expect that this finding will clarify the brain activation and brain network mechanisms underlying the improvement of hand function with task-oriented mirror therapy and lead to new ideas for stroke hand function rehabilitation. TRIAL REGISTRATION: URL: https://www.chictr.org.cn ; Unique identifier: ChiCTR2300068855. Registered on March 1, 2023.


Subject(s)
Stroke Rehabilitation , Stroke , Humans , Mirror Movement Therapy , Hemiplegia/diagnosis , Hemiplegia/etiology , Recovery of Function/physiology , Stroke/diagnosis , Stroke/therapy , Upper Extremity , Stroke Rehabilitation/methods , Treatment Outcome , Randomized Controlled Trials as Topic
12.
J Clin Neurosci ; 123: 130-136, 2024 May.
Article in English | MEDLINE | ID: mdl-38574684

ABSTRACT

BACKGROUND: Aphasia is a language disorder acquired secondary to brain damage. This study aims to evaluate clinical and radiological profile of patients with post stroke aphasia and factors affecting its recovery. METHODS: We conducted a prospective study of patients with first left Middle or Anterior Cerebral Artery infarct or Intracerebral Hemorrhage (ICH) with aphasia admitted within 14 days of stroke onset. Aphasia Quotient (AQ) was assessed at 2 weeks (AQ1) and 3 months (AQ2) using Western Aphasia Battery-Hindi version. Magnetic Resonance Imaging of brain with Diffusion Tensor Imaging (DTI) of bilateral Arcuate Fasciculus (AF) and Corticospinal Tract was done at admission, and stroke volume, Laterality Indices of Fractional Anisotropy (LI-FA), Mean Diffusivity (LI-MD), Radial Diffusivity (LI-RD), Axial Diffusivity (LI-AD) and Apparent Diffusion Coefficient (LI-ADC) were obtained. RESULTS: 36 patients [8 ICH and 28 Acute Ischemic Stroke (AIS)] were included. AQ1 and AQ2 were significantly higher in subcortical stroke than cortical. AQ2 and increase in AQ scores (including its subscores) were significantly higher in ICH than AIS. National Institutes of Health Stroke Scale score at admission and volume of stroke had significant negative correlation with AQ1 and AQ2. Laterality Index of Fractional Anisotropy of Arcuate Fasciculus [LI-FA (AF)] had significant positive correlation with AQ2 and naming score at 3 months. Laterality Index of Mean Diffusivity of Arcuate Fasciculus [LI-MD (AF)] had significant negative correlation with AQ1, AQ2 and all subcomponents of AQ2. Significant positive correlation was seen between improvements in Modified Rankin Scale score and AQ. CONCLUSION: The study shows that DTI can be used to predict severity of aphasia at follow up and recovery in language and motor functions occur in parallel.


Subject(s)
Aphasia , Diffusion Tensor Imaging , Stroke , Humans , Male , Female , Middle Aged , Aphasia/etiology , Aphasia/diagnostic imaging , Prospective Studies , India , Stroke/complications , Stroke/diagnostic imaging , Aged , Follow-Up Studies , Adult , Brain/diagnostic imaging , Brain/pathology , Recovery of Function/physiology
13.
J Vestib Res ; 34(2-3): 145-157, 2024.
Article in English | MEDLINE | ID: mdl-38669501

ABSTRACT

BACKGROUND: Individuals after a vestibular schwannoma resection (VSR) experience significant vestibular symptoms that can be provoked with turning. Vestibular rehabilitation assists in recovery of function and symptom relief, however turning response is unknown. OBJECTIVE: Examine peak turning speed response to surgery and rehabilitation. METHODS: Eight participants with a vestibular schwannoma (PwVS) and five healthy controls (HC) participated in this study. Peak turning speed (PTS) was captured with inertial measurement units (IMU) at the head and/or trunk during turning tasks at a pre-operative, post-operative and post-treatment assessment. Vestibular rehabilitation was provided twice weekly for six weeks. Linear mixed models were used to assess change in PTS across time points. RESULTS: PwVS performed slower PTS than HC prior to surgery. PTS was significantly slower post-operatively compared to pre-operative during walking with head turns (B = -61.03, p = 0.004), two-minute walk test (B = -37.33, p = 0.015), 360° turn (B range from 50.05 to -57.4, p < 0.05) and complex turning course (CTC) at the trunk (B = -18.63, p = 0.009). Post-treatment PTS was significantly faster than pre-operative during CTC at the head (B = 18.46, p = 0.014) and trunk (B = 15.99, p = 0.023). CONCLUSION: PwVS may have turning deficits prior to surgical resection. PTS was significantly affected post-operatively, however improved with rehabilitation.


Subject(s)
Neuroma, Acoustic , Recovery of Function , Humans , Neuroma, Acoustic/surgery , Neuroma, Acoustic/rehabilitation , Female , Male , Middle Aged , Adult , Recovery of Function/physiology , Walking/physiology , Aged , Postural Balance/physiology
14.
Cell Mol Neurobiol ; 44(1): 39, 2024 Apr 22.
Article in English | MEDLINE | ID: mdl-38649645

ABSTRACT

Spinal-cord injury (SCI) is a severe condition that can lead to limb paralysis and motor dysfunction, and its pathogenesis is not fully understood. The objective of this study was to characterize the differential gene expression and molecular mechanisms in the spinal cord of mice three days after spinal cord injury. By analyzing RNA sequencing data, we identified differentially expressed genes and discovered that the immune system and various metabolic processes play crucial roles in SCI. Additionally, we identified UHRF1 as a key gene that plays a significant role in SCI and found that SCI can be improved by suppressing UHRF1. These findings provide important insights into the molecular mechanisms of SCI and identify potential therapeutic targets that could greatly contribute to the development of new treatment strategies for SCI.


Subject(s)
CCAAT-Enhancer-Binding Proteins , Spinal Cord Injuries , Ubiquitin-Protein Ligases , Animals , Spinal Cord Injuries/physiopathology , Ubiquitin-Protein Ligases/metabolism , Ubiquitin-Protein Ligases/genetics , Mice , CCAAT-Enhancer-Binding Proteins/metabolism , CCAAT-Enhancer-Binding Proteins/genetics , Motor Activity/physiology , Mice, Inbred C57BL , Recovery of Function/physiology , Female , Spinal Cord/metabolism , Spinal Cord/pathology , Gene Expression Regulation
15.
J Neuroinflammation ; 21(1): 106, 2024 Apr 24.
Article in English | MEDLINE | ID: mdl-38658922

ABSTRACT

BACKGROUND: Intracerebral hemorrhage (ICH) is a devastating neurological disease causing severe sensorimotor dysfunction and cognitive decline, yet there is no effective treatment strategy to alleviate outcomes of these patients. The Mas axis-mediated neuroprotection is involved in the pathology of various neurological diseases, however, the role of the Mas receptor in the setting of ICH remains to be elucidated. METHODS: C57BL/6 mice were used to establish the ICH model by injection of collagenase into mice striatum. The Mas receptor agonist AVE0991 was administered intranasally (0.9 mg/kg) after ICH. Using a combination of behavioral tests, Western blots, immunofluorescence staining, hematoma volume, brain edema, quantitative-PCR, TUNEL staining, Fluoro-Jade C staining, Nissl staining, and pharmacological methods, we examined the impact of intranasal application of AVE0991 on hematoma absorption and neurological outcomes following ICH and investigated the underlying mechanism. RESULTS: Mas receptor was found to be significantly expressed in activated microglia/macrophages, and the peak expression of Mas receptor in microglia/macrophages was observed at approximately 3-5 days, followed by a subsequent decline. Activation of Mas by AVE0991 post-treatment promoted hematoma absorption, reduced brain edema, and improved both short- and long-term neurological functions in ICH mice. Moreover, AVE0991 treatment effectively attenuated neuronal apoptosis, inhibited neutrophil infiltration, and reduced the release of inflammatory cytokines in perihematomal areas after ICH. Mechanistically, AVE0991 post-treatment significantly promoted the transformation of microglia/macrophages towards an anti-inflammatory, phagocytic, and reparative phenotype, and this functional phenotypic transition of microglia/macrophages by Mas activation was abolished by both Mas inhibitor A779 and Nrf2 inhibitor ML385. Furthermore, hematoma clearance and neuroprotective effects of AVE0991 treatment were reversed after microglia depletion in ICH. CONCLUSIONS: Mas activation can promote hematoma absorption, ameliorate neurological deficits, alleviate neuron apoptosis, reduced neuroinflammation, and regulate the function and phenotype of microglia/macrophages via Akt/Nrf2 signaling pathway after ICH. Thus, intranasal application of Mas agonist ACE0991 may provide promising strategy for clinical treatment of ICH patients.


Subject(s)
Hematoma , Hemorrhagic Stroke , Mice, Inbred C57BL , Receptors, G-Protein-Coupled , Recovery of Function , Animals , Mice , Hematoma/drug therapy , Hematoma/pathology , Hematoma/metabolism , Male , Hemorrhagic Stroke/pathology , Hemorrhagic Stroke/drug therapy , Receptors, G-Protein-Coupled/agonists , Receptors, G-Protein-Coupled/metabolism , Recovery of Function/drug effects , Recovery of Function/physiology , Proto-Oncogene Proteins/metabolism , Brain Edema/etiology , Brain Edema/metabolism , Brain Edema/drug therapy , Microglia/drug effects , Microglia/metabolism
16.
J Neurophysiol ; 131(5): 865-871, 2024 May 01.
Article in English | MEDLINE | ID: mdl-38568478

ABSTRACT

Motor disturbances predominantly characterize hypoxic-ischemic encephalopathy (HIE). Among its intervention methods, environmental enrichment (EE) is strictly considered a form of sensory intervention. However, limited research uses EE as a single sensory input intervention to validate outcomes postintervention. A Sprague-Dawley rat model subjected to left common carotid artery ligation and exposure to oxygen-hypoxic conditions is used in this study. EE was achieved by enhancing the recreational and stress-relief items within the cage, increasing the duration of sunlight, colorful items exposure, and introducing background music. JZL184 (JZL) was administered as neuroprotective drugs. EE was performed 21 days postoperatively and the rats were randomly assigned to the standard environment and EE groups, the two groups were redivided into control, JZL, and vehicle injection subgroups. The Western blotting and behavior test indicated that EE and JZL injections were efficacious in promoting cognitive function in rats following HIE. In addition, the motor function performance in the EE-alone intervention group and the JZL-alone group after HIE was significantly improved compared with the control group. The combined EE and JZL intervention group exhibited even more pronounced improvements in these performances. EE may enhance motor function through sensory input different from the direct neuroprotective effect of pharmacological treatment.NEW & NOTEWORTHY Rarely does literature assess motor function, even though it is common after hypoxia ischemic encephalopathy (HIE). Previously used environmental enrichment (EE) components have not been solely used as sensory inputs. Physical factors were minimized in our study to observe the effects of purely sensory inputs.


Subject(s)
Hypoxia-Ischemia, Brain , Rats, Sprague-Dawley , Animals , Hypoxia-Ischemia, Brain/therapy , Hypoxia-Ischemia, Brain/physiopathology , Rats , Disease Models, Animal , Neuroprotective Agents/pharmacology , Male , Environment , Recovery of Function/physiology , Motor Activity/physiology
17.
J Neurosci ; 44(21)2024 May 22.
Article in English | MEDLINE | ID: mdl-38565290

ABSTRACT

Left-sided spatial neglect is a very common and challenging issue after right-hemispheric stroke, which strongly and negatively affects daily living behavior and recovery of stroke survivors. The mechanisms underlying recovery of spatial neglect remain controversial, particularly regarding the involvement of the intact, contralesional hemisphere, with potential contributions ranging from maladaptive to compensatory. In the present prospective, observational study, we assessed neglect severity in 54 right-hemispheric stroke patients (32 male; 22 female) at admission to and discharge from inpatient neurorehabilitation. We demonstrate that the interaction of initial neglect severity and spared white matter (dis)connectivity resulting from individual lesions (as assessed by diffusion tensor imaging, DTI) explains a significant portion of the variability of poststroke neglect recovery. In mildly impaired patients, spared structural connectivity within the lesioned hemisphere is sufficient to attain good recovery. Conversely, in patients with severe impairment, successful recovery critically depends on structural connectivity within the intact hemisphere and between hemispheres. These distinct patterns, mediated by their respective white matter connections, may help to reconcile the dichotomous perspectives regarding the role of the contralesional hemisphere as exclusively compensatory or not. Instead, they suggest a unified viewpoint wherein the contralesional hemisphere can - but must not necessarily - assume a compensatory role. This would depend on initial impairment severity and on the available, spared structural connectivity. In the future, our findings could serve as a prognostic biomarker for neglect recovery and guide patient-tailored therapeutic approaches.


Subject(s)
Diffusion Tensor Imaging , Perceptual Disorders , Recovery of Function , Stroke , White Matter , Humans , Male , Female , Perceptual Disorders/etiology , Perceptual Disorders/physiopathology , Perceptual Disorders/rehabilitation , Stroke/complications , Stroke/diagnostic imaging , Stroke/physiopathology , Aged , White Matter/diagnostic imaging , White Matter/pathology , Middle Aged , Recovery of Function/physiology , Functional Laterality/physiology , Prospective Studies , Severity of Illness Index , Neural Pathways/physiopathology , Neural Pathways/diagnostic imaging , Neural Pathways/pathology , Aged, 80 and over
18.
Exp Neurol ; 377: 114803, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38679281

ABSTRACT

Disruption of corticospinal tracts (CST) is a leading factor for motor impairments following intracerebral hemorrhage (ICH) in the striatum. Previous studies have shown that therapeutic hypothermia (HT) improves outcomes of ICH patients. However, whether HT has a direct protection effect on the CST integrity and the underlying mechanisms remain largely unknown. In this study, we employed a chemogenetics approach to selectively activate bilateral warm-sensitive neurons in the preoptic areas to induce a hypothermia-like state. We then assessed effects of HT treatment on the integrity of CST and motor functional recovery after ICH. Our results showed that HT treatment significantly alleviated axonal degeneration around the hematoma and the CST axons at remote midbrain region, ultimately promoted skilled motor function recovery. Anterograde and retrograde tracing revealed that HT treatment protected the integrity of the CST over an extended period. Mechanistically, HT treatment prevented mitochondrial swelling in degenerated axons around the hematoma, alleviated mitochondrial impairment by reducing mitochondrial ROS accumulation and improving mitochondrial membrane potential in primarily cultured cortical neurons with oxyhemoglobin treatment. Serving as a proof of principle, our study provided novel insights into the application of HT to improve functional recovery after ICH.


Subject(s)
Cerebral Hemorrhage , Hypothermia, Induced , Mitochondria , Pyramidal Tracts , Animals , Pyramidal Tracts/pathology , Cerebral Hemorrhage/pathology , Cerebral Hemorrhage/complications , Cerebral Hemorrhage/metabolism , Mice , Mitochondria/metabolism , Mitochondria/pathology , Male , Hypothermia, Induced/methods , Mice, Inbred C57BL , Recovery of Function/physiology , Cells, Cultured
19.
Stroke ; 55(6): 1629-1640, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38639087

ABSTRACT

BACKGROUND: Cortical excitation/inhibition dynamics have been suggested as a key mechanism occurring after stroke. Their supportive or maladaptive role in the course of recovery is still not completely understood. Here, we used transcranial magnetic stimulation (TMS)-electroencephalography coupling to study cortical reactivity and intracortical GABAergic inhibition, as well as their relationship to residual motor function and recovery longitudinally in patients with stroke. METHODS: Electroencephalography responses evoked by TMS applied to the ipsilesional motor cortex were acquired in patients with stroke with upper limb motor deficit in the acute (1 week), early (3 weeks), and late subacute (3 months) stages. Readouts of cortical reactivity, intracortical inhibition, and complexity of the evoked dynamics were drawn from TMS-evoked potentials induced by single-pulse and paired-pulse TMS (short-interval intracortical inhibition). Residual motor function was quantified through a detailed motor evaluation. RESULTS: From 76 patients enrolled, 66 were included (68.2±13.2 years old, 18 females), with a Fugl-Meyer score of the upper extremity of 46.8±19. The comparison with TMS-evoked potentials of healthy older revealed that most affected patients exhibited larger and simpler brain reactivity patterns (Pcluster<0.05). Bayesian ANCOVA statistical evidence for a link between abnormally high motor cortical excitability and impairment level. A decrease in excitability in the following months was significantly correlated with better motor recovery in the whole cohort and the subgroup of recovering patients. Investigation of the intracortical GABAergic inhibitory system revealed the presence of beneficial disinhibition in the acute stage, followed by a normalization of inhibitory activity. This was supported by significant correlations between motor scores and the contrast of local mean field power and readouts of signal dynamics. CONCLUSIONS: The present results revealed an abnormal motor cortical reactivity in patients with stroke, which was driven by perturbations and longitudinal changes within the intracortical inhibition system. They support the view that disinhibition in the ipsilesional motor cortex during the first-week poststroke is beneficial and promotes neuronal plasticity and recovery.


Subject(s)
Electroencephalography , Evoked Potentials, Motor , Motor Cortex , Neural Inhibition , Recovery of Function , Stroke , Transcranial Magnetic Stimulation , Humans , Female , Male , Transcranial Magnetic Stimulation/methods , Aged , Middle Aged , Stroke/physiopathology , Motor Cortex/physiopathology , Recovery of Function/physiology , Evoked Potentials, Motor/physiology , Neural Inhibition/physiology , Aged, 80 and over
20.
J Orthop Surg Res ; 19(1): 270, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38689328

ABSTRACT

BACKGROUND: Rotator cuff tears (RCTs) are a common musculoskeletal disorder, and arthroscopic rotator cuff repair (ARCR) is widely performed for tendon repair. Handgrip strength correlates with rotator cuff function; however, whether preoperative grip strength can predict functional outcomes in patients undergoing ARCR remains unknown. This study aimed to investigate the correlation between preoperative grip strength and postoperative shoulder function following ARCR. METHODS: A total of 52 patients with full-thickness repairable RCTs were prospectively enrolled. Baseline parameters, namely patient characteristics and intraoperative findings, were included for analysis. Postoperative shoulder functional outcomes were assessed using the Quick Disabilities of the Arm, Shoulder, and Hand (QDASH) questionnaire and Constant-Murley scores (CMSs). Patients were followed up and evaluated at three and six months after ARCR. The effects of baseline parameters on postoperative outcomes were measured using generalized estimating equations. RESULTS: At three and six months postoperatively, all clinical outcomes evaluated exhibited significant improvement from baseline following ARCR. Within 6 months postoperatively, higher preoperative grip strength was significantly correlated with higher CMSs (ß = 0.470, p = 0.022), whereas increased numbers of total suture anchors were significantly correlated with decreased CMSs (ß = - 4.361, p = 0.03). Higher body mass index was significantly correlated with higher postoperative QDASH scores (ß = 1.561, p = 0.03) during follow-up. CONCLUSIONS: Higher baseline grip strength predicts more favorable postoperative shoulder function following ARCR. A preoperative grip strength test in orthopedic clinics may serve as a predictor for postoperative shoulder functional recovery in patients undergoing ARCR.


Subject(s)
Arthroscopy , Hand Strength , Rotator Cuff Injuries , Humans , Male , Female , Middle Aged , Arthroscopy/methods , Hand Strength/physiology , Rotator Cuff Injuries/surgery , Rotator Cuff Injuries/physiopathology , Aged , Prospective Studies , Preoperative Period , Postoperative Period , Treatment Outcome , Predictive Value of Tests , Recovery of Function/physiology , Rotator Cuff/surgery , Rotator Cuff/physiopathology , Follow-Up Studies , Adult , Shoulder/surgery , Shoulder/physiopathology
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