Neurological Motor Research Articles

Mepivacaine Versus Bupivacaine Spinal Anesthesia for Primary Total Joint Arthroplasty: A Systematic Review and Meta-Analysis

BackgroundMepivacaine is an intermediate acting amide local anesthetic that can be used for neuraxial anesthesia in total joint arthroplasty (TJA) with a shorter duration of action (1.5-2 hours) compared to the more commonly used local anesthetic bupivacaine. The purpose of this study was to perform a systematic review and meta-analysis comparing bupivacaine and mepivacaine spinal anesthesia during elective TJA and the surgical outcomes of the time to full neurologic motor return, pain, mobility, length of stay (LOS), and complications including transient neurologic symptoms and urinary function. MethodsPubMed, Ovid MEDLINE, and Ovid Embase were screened for “arthroplasty, spinal anesthesia, bupivacaine, and mepivacaine,” in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 159 studies were screened and 5 studies were evaluated. Data were compared regarding motor function return, mobility (distance ambulated), pain (visual analog scale [VAS]), LOS, and postoperative complications. ResultsFull-text screening yielded 5 studies (3 randomized controlled trials and 2 retrospective cohort studies), with a total of 1,550 patients. Mepivacaine spinals had an earlier return to motor function (154 minutes vs 170 minutes, 95% CI: [−31.6, −0.9], P = .04), shorter LOS (25.95 hours vs 29.96 hours, 95% CI: [−6.8, −1.2], P = .01), and decreased urinary retention (7.15% vs 10.58%, 95% CI: [−6.3%, −0.6%], P = .02) with no differences in pain (VAS 3.57 vs 3.68, 95% CI: [−2.1, 1.9], P = .90) or distance ambulated (94.2 ft vs 89.1 ft, 95% CI: [−15, 25.2], P = .60) compared to bupivacaine spinal anesthesia. ConclusionsThe method of anesthesia administration has been an increasing area of focus for quicker and safer recovery to allow for early ambulation and facility discharge. The rapid recovery facilitated by mepivacaine may further enable outpatient TJA and enhance patient recovery. Level of EvidenceIII.

A Randomized Controlled Trial of Motor Imagery Combined with Virtual Reality Techniques in Patients with Parkinson's Disease.

Background: Parkinson’s disease is the second most common neurological disease, affecting balance, motor function, and activities of daily living. Virtual reality and motor imagery are two emerging approaches for the rehabilitation of patients with Parkinson’s disease. This study aimed to determine the combined effects of virtual reality and motor imagery techniques with routine physical therapy on the motor function components of individuals with Parkinson’s disease. Methods: The study was a prospective, two-arm, parallel-design randomized controlled trial. Forty-four patients with idiopathic Parkinson’s disease were randomly assigned to one of two groups. Virtual reality and motor imagery were given together with physical therapy in the experimental group (N: 20), while physical therapy treatment alone was given in the control group (N: 21). Both groups received allocated treatment for 12 weeks, 3 days a week, on alternate days. Motor function was assessed at baseline, six weeks, twelve weeks, and sixteen weeks after discontinuing treatment with the Unified Parkinson’s Disease Rating Scale part III. SPSS 24 was used to analyze the data. Results: Study results indicate that the experimental group showed significant improvements in the motor function components: tremor at rest at the 6th week (p = 0.028), 12th week (p = 0.05), and 16th week (p = 0.001), rigidity at the 6th week (p = 0.03), 12th week (p = 0.000), and 16th week (p = 0.001), posture at the 12th week (p = 0.005) and 16th week (p = 0.004), and gait at the 6th week with a p-value of (p = 0.034). Conclusions: This study demonstrated that virtual reality and motor imagery training in combination with routine physical therapy can significantly improve resting tremors, rigidity, posture, gait, and body bradykinesia in individuals with PD in comparison to patients receiving only routine physical therapy.

Haptoglobin Regulates Macrophage/Microglia-Induced Inflammation and Prevents Ischemic Brain Damage Via Binding to HMGB1.

BackgroundHMGB1 (high‐mobility group box 1) is known to worsen the functional prognosis after cerebral ischemia. Hp (haptoglobin) binds and sequesters HMGB1. Furthermore, Hp‐HMGB1 complexes are rapidly cleared by scavenger receptors on macrophages/microglia and modulate polarization of macrophages/microglia toward the M2 phenotype. Therefore, Hp may prevent aggravation by HMGB1 after cerebral ischemia and promote tissue repair by M2 macrophages/microglia. The aim of this study was to investigate the effects of Hp on ischemic brain damage induced by a high systemic HMGB1 level in mice subjected to 4 hours of middle cerebral artery occlusion (MCAO).Methods and ResultsOne day after MCAO, Hp was administered intraperitoneally at a dose of 20 or 200 U/kg once daily for 7 days. Neurological scores, motor coordination, and plasma HMGB1 levels were measured 1, 3, and 7 days after MCAO. Expression of M1 and M2 macrophage/microglia markers, such as CD16/32 and CD206, were evaluated by immunostaining 7 days after MCAO. Treatment with Hp for 7 days improved the neurological score, motor coordination, and survival and prevented brain damage after MCAO. The systemic HMGB1 level increased 1 to 7 days after MCAO and was higher at 7 days than at day 1. Hp significantly decreased the systemic HMGB1 level and increased the M2 phenotype when compared with the M1 phenotype after MCAO.ConclusionsHp improved functional outcomes, including survival, motor function, and brain damage by binding to HMGB1 and modulating the polarization of macrophages/microglia. Hp may be an effective option in the treatment of cerebral ischemia.

Ferroptosis in oligodendrocyte progenitor cells mediates white matter injury after hemorrhagic stroke

Oligodendrocyte progenitor cells (OPCs) differentiate to myelin-producing mature oligodendrocytes and enwrap growing or demyelinated axons during development and post central nervous diseases. Failure of remyelination owing to cell death or undifferentiation of OPCs contributes to severe neurologic deficits and motor dysfunction. However, how to prevent the cell death of OPCs is still poorly understood, especially in hemorrhagic diseases. In the current study, we injected autologous blood into the mouse lateral ventricular to study the hemorrhage-induced OPC cell death in vivo. The integrity of the myelin sheath of the corpus callosum was disrupted post intraventricular hemorrhage (IVH) assessed by using magnetic resonance imaging, immunostaining, and transmission electron microscopy. Consistent with the severe demethylation, we observed massive cell death of oligodendrocyte lineages in the periventricular area. In addition, we found that ferroptosis is the major cell death form in Hemin-induced OPC death by using RNA-seq analysis, and the mechanism was glutathione peroxidase 4 activity reduction-resulted lipid peroxide accumulation. Furthermore, inhibition of ferroptosis rescued OPC cell death in vitro, and in vivo attenuated IVH-induced white matter injury and promoted recovery of neurological function. These data demonstrate that ferroptosis is an essential form of OPC cell death in hemorrhagic stroke, and rescuing ferroptotic OPCs could serve as a therapeutic target for stroke and related diseases.

"Prefrontal Cortex Neuromodulation Improves Motor-Cognitive Components in Latinx Hispanic People Living with HIV"

Background: HIV is an immunodeficiency virus that currently has no cure but is managed with antiretroviral medication (ART). ART has increased the life expectancy of those living with HIV. Evidence shows a correlation between the increase in life expectancy and increases in neurological motor-cognitive impairments, thus leading to a decline in functional mobility and overall quality of life. The current study aimed to address neurological motor cognitive impairments in Latinx HIV+ individuals using transcranial direct current stimulation (tDCS).Methods: Female and male participants, ages 18-65, with an HIV diagnosis by a medical doctor and a CD4 count of >300 were obtained from an HIV clinic in La Perla de Gran Precio in Puerto Rico. Spatiotemporal data were collected; each subject participated in a dual cognitive ambulation task and completed the HIV dementia scale.Results: Dual cognitive tasks were calculated for cadence, gait cycle, gait speed, single limb, double limb, stance, stride, swing, and sway were analyzed. After the application of tDCS, the only statistically significant difference found among the subjects was an improvement in gait speed (p≤.05). In addition, the cognitive component showed an improvement in the HIV dementia scale total (p≤.05), including an increase in motor speed and memory recall (p≤.05).Conclusion: tDCS may be a feasible and effective treatment option for this population to alleviate motor-cognitive alterations in those living with HIV. Future research should consider the benefits of tDCS combined with diverse training, such as gait or balance activities.

Brain network topology early after stroke relates to recovery.

Analyses of alterations of brain networks have gained an increasing interest in stroke rehabilitation research. Compared with functional networks derived from resting-state analyses, there is limited knowledge of how structural network topology might undergo changes after stroke and, more importantly, if structural network information obtained early after stroke could enhance recovery models to infer later outcomes. The present work re-analysed cross-sectional structural imaging data, obtained within the first 2 weeks, of 45 acute stroke patients (22 females, 24 right-sided strokes, age 68 ± 13 years). Whole-brain tractography was performed to reconstruct structural connectomes and graph-theoretical analyses were employed to quantify global network organization with a focus on parameters of network integration and modular processing. Graph measures were compared between stroke patients and 34 healthy controls (15 females, aged 69 ± 10 years) and they were integrated with four clinical scores of the late subacute stage, covering neurological symptom burden (National Institutes of Health Stroke Scale), global disability (modified Rankin Scale), activity-related disability (Barthel Index) and motor functions (Upper-Extremity Score of the Fugl-Meyer Assessment). The analyses were employed across the complete cohort and, based on clustering analysis, separately within subgroups stratified in mild to moderate (n = 21) and severe (n = 24) initial deficits. The main findings were (i) a significant reduction of network’s global efficiency, specifically in patients with severe deficits compared with controls (P = 0.010) and (ii) a significant negative correlation of network efficiency with the extent of persistent functional deficits at follow-up after 3–6 months (P ≤ 0.032). Specifically, regression models revealed that this measure was capable to increase the explained variance in future deficits by 18% for the modified Rankin Scale, up to 24% for National Institutes of Health Stroke Scale, and 16% for Barthel Index when compared with models including the initial deficits and the lesion volume. Patients with mild to moderate deficits did not exhibit a similar impact of network efficiency on outcome inference. Clustering coefficient and modularity, measures of segregation and modular processing, did not exhibit comparable structure–outcome relationships, neither in severely nor in mildly affected patients. This study provides empirical evidence that structural network efficiency as a graph-theoretical marker of large-scale network topology, quantified early after stroke, relates to recovery. Notably, this contribution was only evident in severely but not mildly affected stroke patients. This suggests that the initial clinical deficit might shape the dependency of recovery on global network topology after stroke.

New spinocerebellar ataxia subtype caused by SAMD9L mutation triggering mitochondrial dysregulation (SCA49).

Spinocerebellar ataxias consist of a highly heterogeneous group of inherited movement disorders clinically characterized by progressive cerebellar ataxia variably associated with additional distinctive clinical signs. The genetic heterogeneity is evidenced by the myriad of associated genes and underlying genetic defects identified. In this study, we describe a new spinocerebellar ataxia subtype in nine members of a Spanish five-generation family from Menorca with affected individuals variably presenting with ataxia, nystagmus, dysarthria, polyneuropathy, pyramidal signs, cerebellar atrophy and distinctive cerebral demyelination. Affected individuals presented with horizontal and vertical gaze-evoked nystagmus and hyperreflexia as initial clinical signs, and a variable age of onset ranging from 12 to 60 years. Neurophysiological studies showed moderate axonal sensory polyneuropathy with altered sympathetic skin response predominantly in the lower limbs. We identified the c.1877C > T (p.Ser626Leu) pathogenic variant within the SAMD9L gene as the disease causative genetic defect with a significant log-odds score (Zmax = 3.43; θ = 0.00; P < 3.53 × 10−5). We demonstrate the mitochondrial location of human SAMD9L protein, and its decreased levels in patients’ fibroblasts in addition to mitochondrial perturbations. Furthermore, mutant SAMD9L in zebrafish impaired mobility and vestibular/sensory functions. This study describes a novel spinocerebellar ataxia subtype caused by SAMD9L mutation, SCA49, which triggers mitochondrial alterations pointing to a role of SAMD9L in neurological motor and sensory functions.

Behavioral Testing Design for Evaluation of Cognitive Disabilities.

Intellectual disabilities (ID) constitute a class of human neurodevelopmental diseases and are a major medical and socioeconomic problem owing to their high incidence and enormous burden to the families of those affected. In the past three decades, mutant mouse technologies have provided powerful tools for elucidating the pathophysiological mechanisms underlying behavioral and developmental alterations related to IDs and for addressing new therapeutic strategies, and major progress has been made revealing previously unidentified genes involved in ID. However, the pathological hallmarks of IDs are very heterogeneous in regard to both the functional deficits observed and the severity of the phenotype, even within the same mutation types. For this reason, an appropriate experimental design is required to reduce the risk of false negatives and positives in animal functional genomic studies. This experimental design should address functions important to evaluate, tests, and the appropriate workflow. Here, we propose an extensive behavioral screen with detailed protocols, which was successfully used in a systematic mouse functional genomic approach to gain pathway-based insights into mechanisms leading to cognitive dysfunction in humans. © 2022 Wiley Periodicals LLC. Basic Protocol 1: Assessment of circadian activity and ingestive behavior Basic Protocol 2: Assessment of neurological reflexes and motor abilities using the grip and rotarod tests Basic Protocol 3: Evaluation of anxiety-related behavior using the elevated plus maze Basic Protocol 4: Evaluation of recognition memory using the object recognition task Basic Protocol 5: Evaluation of social behavior using the social recognition test Basic Protocol 6: Evaluation of working memory using the Y-maze spontaneous alternation test Basic Protocol 7: Evaluation of emotional learning and memory using the fear conditioning test.

Abstract 18: Targeting Neutrophil Extracellular Traps Improves Ischemic Stroke Outcomes

Rationale: Ischemic stroke prompts an inflammatory response which is associated with worse outcomes. Classic anti-inflammatory strategies were unsuccessful in clinical trials, implying other mechanisms contribute to injurious inflammation in stroke. In response to stimuli, neutrophils can release DNA web-like structures called neutrophil extracellular traps (NETs). Recently, a role for NETs in cardiovascular disease has emerged. Here, we studied whether NETs contribute to ischemic stroke outcomes. Methods: Markers of NET formation were assessed in brain tissue and plasma from ischemic stroke patients. For murine studies, we used male and female mice that were subjected to transient middle cerebral artery occlusion. Stroke outcomes were assessed 24 hours or 7 days after stroke. Results: NETs were found in brain tissue from deceased ischemic stroke patients. Ischemic stroke patients had significantly increased plasma biomarkers of NET formation including citrullinated histone H3 (p&lt;0.0001) and MPO-DNA complexes (p&lt;0.001) compared to matched controls. NET biomarkers positively correlated with worse stroke outcomes at discharge (p&lt;0.05) while they did not correlate with stroke severity at admission. To target NET formation in ischemic stroke, we investigated the therapeutic potential of a recently discovered neonatal NET inhibitory factor (nNIF). nNIF specifically blocks NET formation in human and murine neutrophils without affecting other critical neutrophil functions. Mice prophylactically treated with nNIF had significantly reduced brain and plasma NETs after stroke while cerebral neutrophil recruitment remained unaffected. The reduction in NET formation was associated with significantly reduced neuronal apoptosis and smaller brain infarcts (p&lt;0.0001). Furthermore, nNIF treated mice had improved neurological behavior and motor function, and enhanced 7-day survival after ischemic stroke (p&lt;0.001). Importantly, these results were confirmed in diabetic mice and &gt;18-month-old mice and nNIF was still effective when administered therapeutically, 1 hour after stroke onset. Conclusions: Our results support a pathological role for NETs in ischemic stroke and warrant further investigation into nNIF to improve stroke outcomes.

Symptom distribution and development in thoracic disc surgery – A retrospective case series of 664 patients

ObjectiveThe incidence of surgically treated thoracic disc herniations in the U.S. is estimated to be 1:116,338 [1]. The disease poses 2 main challenges: 1) Surgical removal and 2) early and correct diagnosis. It is without doubt that herniated thoracic discs can be difficult to remove; Equally difficult is often enough attributing the correct symptoms to the disease that lead to the diagnosis, because there is a great variability and supposedly low specificity of the clinical symptoms, especially concerning pain related symptoms, which are often attributed to muscular or joint related causes.The series published so far are comparatively small (up to a maximum of 200) to give a good and valid overview of the symptoms that the disease can cause.The aim of this study was therefore to verify and falsify the previously published data that were obtained with small series on the basis of a much larger series. MethodsWe used our practice's own database that was designed to included only patients with thoracic disc herniations since the senior author focused on this disease about 25 years ago. The patient's symptoms were initially recorded descriptively on the basis of the medical record. Then the patients were contacted and the development of symptoms after surgery and new symptoms were recorded. Results664 patients were included in the study. Mean follow-up period was 57.89 months. 151 (22.74%) patients reported neurological motor deficits, 313 (47.13%) reported neurological sensory deficits, 542 (81.62%) thoracic back pain, 125 (18.82%) bladder and rectal dysfunction and 46 (6.92%) atypical symptoms. 137 (20%) of the patients were completely symptom-free. The rate of improvement/ symptom stability was about 90% for neurological symptoms, pain-improvement 40%, 65% improvement in bladder and rectal dysfunction, and 80% improvement in atypical symptoms. ConclusionThe results of this largest series to date of patients who were operated on for a thoracic disc herniation show that not only neurological but also algetic symptoms are dominating in patients harboring this disease. The postoperative results primarily help to advise the patient on their prognosis.

Morin Attenuated Cerebral Ischemia/Reperfusion Injury Through Promoting Angiogenesis Mediated by Angiopoietin-1-Tie-2 Axis and Wnt/β-Catenin Pathway.

Cerebral damage following cerebral ischemia/reperfusion injury affects the neurological deficits and motor impairment of stroke patients in the long-term period. Angiogenesis, the essential process for restoration of cerebral blood flow (CBF) in the ischemic brain, promotes the recovery of neurological function following ischemia. The aim of this study was to investigate the long-term effects of morin on angiogenesis and functional outcomes in a middle cerebral artery occlusion (MCAO) and reperfusion model. Male Wistar rats were subjected to MCAO, and they were administered 30mg/kg of morin at reperfusion via i.p. injection daily for 14days. Fourteen days after I/R injury, the rats were evaluated for the brain damage, and angiogenic factors involved in Ang1/Tie-2 and Wnt/β-catenin signaling. In addition, at 1, 7, and 14days after reperfusion, rotarod and pole tests were performed to investigate the functional recovery. We found morin significantly reduced the infarct size, blood-brain barrier (BBB) leakage, and apoptotic cells at 14days after I/R injury. It also promoted angiogenesis via boosting the expression of angiogenic proteins, such as angiopoietin 1 (Ang1), Tie-2, Wnt3α, β-catenin, and cyclin D1. Morin-mediated angiogenesis was confirmed by a significant increase in microvessel's density in the penumbra area and an increase in von Willebrand factor (vWF) protein expression of the morin-treated rats. Moreover, the rotarod and pole tests also demonstrated morin increased functional recovery in the morin-treated rats compared to the vehicle rats. Therefore, our data exposed that morin promotes angiogenesis and improves functional outcomes in MCAO and reperfusion rats.

Management of Two Cases of Spina Bifida and Neonatal Genital Prolapse at the University Hospital of Parakou and Review of the Literature

Spina bifida, or spinal dysraphism, is a malformative pathology related to an anomaly in the development of the nervous system, occurring during embryogenesis. The neural tube does not close properly around the 28th day of life and affects the development of the spinal column and spinal cord. Spina bifida is characterised by damage to the nervous system and will generate handicaps and damage of varying degrees: neurological motor, sensory, cognitive, genito-phincter (bladder and anorectal) deficits with consequences for the quality of life of these people. The literature describes the association between spinal dysraphism and genital prolapse. However, genital prolapse is an exceptional and rare entity in newborns. We report the observations of two newborns: the first case of a newborn born at term, at 7 days of age, who presented a prolapse of the uterine cervix in association with myelomeningocele, without any neuromuscular repercussions, and the second case of a newborn at 10 days of age, presenting with a lumbosacral spina bifida and a uterine prolapse. They benefited from conservative medical treatment characterised by manual reduction of the prolapse in both cases with a favourable evolution. In the case of spina bifida, a cure of myelomeningocele was performed surgically with simple postoperative course.

Association between Skeletal Muscle Mass Index and Convalescent Rehabilitation Ward Achievement Index in Older Patients.

ABSTRACTObjective:The aim of the current study was to investigate the association between the skeletal muscle mass index (SMI) and the convalescent rehabilitation ward achievement index (CRWAI) in older patients with functional impairment.Methods:We conducted a retrospective cohort study at a single rehabilitation center in Japan to include patients admitted to the convalescent rehabilitation ward because of neurological disease, motor disorder, or disuse syndrome. Patients with missing SMI data, those who died or were transferred to other hospitals due to comorbidities, those aged less than 65 years, and those hospitalized for <7 days were excluded from the study. We divided patients into two groups based on their SMI – the high SMI group (SMI ≥7.0 kg/m2 in men and SMI ≥5.7 kg/m2 in women) and the low SMI group (SMI <7.0 kg/m2 in men and SMI <5.7 kg/m2 in women); we then evaluated the association between SMI and the CRWAI score.Results:Of the 319 recruited patients, 84 (26%) were in the high SMI group. The medians and interquartile ranges of the CRWAI scores in the high SMI and low SMI groups were 38.6 (23.1–61) and 31.8 (10.1–57.5), respectively (P=0.029). A high SMI was independently and negatively associated with the CRWAI score (β=− 0.16, P=0.014).Conclusions:Our study showed that a high SMI was an independent factor negatively influencing the CRWAI score in older patients in a convalescent rehabilitation ward.

Chapter 7 - Breathing disturbances in Rett syndrome

Rett Syndrome is an X-linked neurological disorder characterized by behavioral and neurological regression, seizures, motor deficits, and dysautonomia. A particularly prominent presentation includes breathing abnormalities characterized by breathing irregularities, hyperventilation, repetitive breathholding during wakefulness, obstructive and central apneas during sleep, and abnormal responses to hypoxia and hypercapnia. The condition and pathology of the respiratory system is further complicated by dysfunctions of breathing-motor coordination, which is reflected in dysphagia. The discovery of the X-linked mutations in the MECP2 gene has transformed our understanding of the cellular and molecular mechanisms that are at the root of various clinical phenotypes. However, the genotype-phenotype relationship is complicated by various factors which include not only X-inactivation but also consequences of the intermittent hypoxia and oxidative stress associated with the breathing abnormalities.

Berberine Protects against Neurological Impairments and Blood-Brain Barrier Injury in Mouse Model of Intracerebral Hemorrhage

Background: Elevation of AMP-activated protein kinase (AMPK)/peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α) signaling can suppress intracerebral hemorrhage (ICH)-induced neurological impairments. As an isoquinoline alkaloid, Berberine exerts neuroprotective effects in neurological disease models with activated AMPK/PGC1α signaling. Aim: We aim to study the effect of Berberine on ICH-induced brain injury and explore the potential molecular mechanism. Methods: ICH model was established in mice through intracerebral injection of autologous whole blood, followed by treatment with Berberine. Neurological impairments were assessed by the modified neurological severity score and behavioral assays. Brain edema and blood-brain barrier (BBB) integrity were assessed by water content in the brain, amount of extravasated Evans blue, and BBB tight junction components. Neuroinflammatory responses were assessed by inflammatory cytokine levels. AMPK/PGC1α signaling was examined by AMPK mRNA expression and phosphorylated AMPK and PGC1α protein levels. Results: Berberine (200 mg/kg) attenuated ICH-induced neurological deficits, motor and cognitive impairment, and BBB disruption. Berberine also suppressed ICH-induced inflammatory responses indicated by reduced production of inflammatory cytokines. Finally, Berberine drastically elevated AMPK/PGC1α signaling in the hemisphere of ICH mice. Conclusion: Our findings suggest that Berberine plays an important neuroprotective role against ICH-induced neurological impairments and BBB injury, probably by inhibition of inflammation and activation of AMPK/PGC1α signaling.

Clinical Practice Guidelines of Chinese Medicine Rehabilitation for Ischemic Stroke （Cerebral Infarction）

Ischemic stroke (cerebral infarction) is a common clinical disease of ischemic necrosis or softening of localized brain tissue, which belongs to stroke disease in traditional Chinese medicine (TCM). In recent years, its incidence rate has gradually increased, the age of onset tends to be younger, and seriously affects the quality of life of patients with cerebral infarction. TCM rehabilitation is one of the effective methods to improve clinical symptoms and prevent recurrence. The clinical practice guideline of TCM rehabilitation of cerebral infarction based on the concept and method of evidence-based medicine is of great significance, which is helpful to standardize the operation technique of TCM rehabilitation of cerebral infarction and obtain better curative effect. This guideline standardizes the diagnosis and rehabilitation treatment of cerebral infarction in terms of scope, terminology, diagnosis of TCM and western medicine, rehabilitation assessment, TCM rehabilitation treatment and nursing, in order to provide guidance and reference for clinicians or rehabilitation doctors in diagnosis and treatment. ① Diagnosis: it is divided into TCM diagnosis and western medicine diagnosis, TCM diagnosis includes disease differentiation and syndrome differentiation (meridian involved style and viscera involved style), and western medicine diagnosis includes diagnosis basis, clinical stage and quantitative classification of clinical condition. ② Rehabilitation assessment: it mainly includes the assessment of neurological impairment, motor function, balance function, speech function, swallowing function, cognitive function, psychological assessment and quality of life. ③ Rehabilitation treatment of traditional Chinese medicine (TCM): it mainly stipulates the diagnosis and treatment technologies of traditional Chinese medicine treatment, acupuncture therapy, massage therapy, traditional functional methods, rehabilitation treatment and nursing in the ultra early stage, acute stage, recovery stage and sequelae stage of cerebral infarction. The guideline could provide guidance for the rehabilitation treatment of cerebral infarction in different levels and kinds of rehabilitation institutions, traditional Chinese medicine hospitals or general hospitals. It has good clinical applicability and effectiveness.

Inhibition of CDK1 attenuates neuronal apoptosis and autophagy and confers neuroprotection after chronic spinal cord injury in vivo

Chronic spinal cord injury (CSCI) results from progressive compression of the spinal cord over time. A variety of factors cause CSCI, and its exact pathogenesis is unknown. Cyclin-dependent kinase 1 (CDK1) is closely related to the apoptosis pathway, but no CSCI-related studies on CDK1 have been conducted. In this study, the role of CDK1 in CSCI was explored in a rat model. The CSCI model was established by screw compression using the cervical anterior approach for twelve weeks. The neurological function of the rats was evaluated using the neurological severity scores (NSS) and motor evoked potentials (MEPs). Pathological changes in spinal cord tissue were observed by hematoxylin-eosin (HE) staining, and Nissl staining was performed to assess the survival of motor neurons in the anterior horn of the spinal cord. Changes in autophagy and apoptosis in anterior horn of spinal cord tissue were detected using transmission electron microscopy and the terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay, respectively. The expression levels of glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor (IBA) and choline acetyltransferase (CHAT) in the anterior horn were determined using immunohistochemistry assays to investigate astrocytes, microglia and motor neurons, respectively, in the anterior horn. Western blot assays were used to detect the expression levels of CDK1, Bcl-2, Bax, Caspase 3, LC3 and Beclin1. Changes in the expression of CDK1, LC3 and Beclin1 were also observed using immunohistochemistry. The results indicated that CSCI resulted in neuronal injury and a decrease in the NSS. In the CSCI model group, anterior horn astrocytes and microglia were activated, and motor neurons were decreased. Neuronal apoptosis was promoted, and the number of autophagic vacuoles was elevated. Rats treated with the CDK1 shRNA lentivirus exhibited better NSS, more surviving motor neurons, and fewer apoptotic neurons than the model rats. The occurrence of autophagy and the expression of proapoptotic and autophagy-related proteins were lower in the CDK1 shRNA group than the model group. In conclusion, CDK1 downregulation suppressed the activation of anterior horn astrocytes and microglia, promoted motor neuron repair, and inhibited neurons apoptosis and autophagy to promote the recovery of motor function after spinal cord injury.

Neonatal hypoxic-ischaemic encephalopathy: Motor impairment beyond cerebral palsy

Research investigating neuromotor function in the absence of cerebral palsy (CP) for children who had neonatal HIE is limited.To investigate school-age neurological and neuromotor function, and correlations with attention, neonatal Magnetic Resonance Imaging (MRI), and neuromotor assessments at toddler age.Twenty-seven children with neonatal HIE without CP who underwent hypothermia treatment and a comparison group of 20 children were assessed at age 5-7 years for Minor Neurological Dysfunction (MND; simplified Touwen), motor skills (Movement Assessment Battery for Children-2; MABC-2), parental concern over motor function (MABC Checklist), general cognition (Wechsler Preschool and Primary Scale of Intelligence-IV, WPPSI), and attention (DuPaul ADHD Rating Scale). Neurological examination and motor development, using Bayley-3 scales, at age 24-months was extracted from the clinical database. Clinical neonatal MRI was assessed for hypoxic-ischaemic injury.In the HIE group, MND was more prevalent (p = 0.026) and M-ABC performance (total score p = 0.006; balance subtest p = 0.008) was worse; parents were more concerned about children's motor function (p = 0.011). HIE group inattention scores were higher (p = 0.032), which correlated with lower MABC-2 scores (rs = -0.590, p = 0.004). Neurological examination at 24-months correlated with MND (rs = 0.437, p = 0.033); Bayley-3 motor scores did not correlate with M-ABC-2 scores (rs = 368, p = 0.133). Neonatal MRI findings were not associated with school-age MND (rs = 0.140, p = 0.523) or MABC-2 (rs = 0.300, p = 0.165).Children with neonatal HIE, without CP, treated with hypothermia may be more likely to develop MND and motor difficulties than typically developing peers. Inattention may contribute to motor performance. In the absence of CP, neonatal MRI and toddler age assessment of motor development have limited predictive value for school-age outcome. Since this was an exploratory study with a small sample size, findings should be confirmed by a definite larger study.

Long-term hypogonadism diminishes the neuroprotective effects of dietary genistein in young adult ovariectomized rats after transient focal ischemia.

Increasing age disproportionately increases the risk of stroke among women compared to men of similar age, especially after menopause. One of the reasons for this observation is a sharp drop in circulating estrogens. However, the timing of initiation of estrogen replacement after menopause is associated with mixed beneficial and detrimental effects, hence contributing to widespread mistrust of estrogen use. Agents including soy isoflavones are being assessed as viable alternatives to estrogen therapy. In this study, we hypothesized that the neuroprotective effects of genistein, a soy isoflavone are less sensitive to the length of hypogonadism in young adult ovariectomized rats following cerebral ischemia. We expected that long-term hypogonadism will worsen motor and cognitive function, increase post-stroke inflammation with no effect on the neuroprotection of genistein. We compared the effect of treatment with dietary genistein (GEN) on short-term (2weeks) and long-term hypogonadism (12weeks) in young adult ovariectomized Sprague-Dawley rats on sensorimotor function, cognition and inflammation after focal ischemia. Dorsal Silastic implant of 17β-estradiol (E2) was used as a control for hormone therapy. Long-term hypogonadism stroked rats performed worse than the short-term hypogonadism stroked rats on the motor and cognitive function tests. GEN did not improve neurological assessment and motor learning after either short-term or long-term hypogonadism. GEN improved cognitive flexibility after short-term hypogonadism but not after the long-term. Both GEN and E2 reduced tissue loss after short-term hypogonadism and reduced GFAP expression at the contralateral side of ischemia after long-term hypogonadism. The length of hypogonadism may differentially influence the neuroprotective effects of both GEN and E2 on the motor and cognitive functions in young adult rats.

Reduced GFAP Expression in Bergmann Glial Cells in the Cerebellum of Sigma-1 Receptor Knockout Mice Determines the Neurobehavioral Outcomes after Traumatic Brain Injury.

Neuroprotective effects of Sigma-1 receptor (S1R) ligands have been observed in multiple animal models of neurodegenerative diseases. Traumatic brain injury (TBI)-related neurodegeneration can induce long-lasting physical, cognitive, and behavioral disabilities. The aim of our study was to evaluate the role of S1R in the development of neurological deficits after TBI. Adult male wild-type CD-1 (WT) and S1R knockout (S1R-/-) mice were subjected to lateral fluid percussion injury, and behavioral and histological outcomes were assessed for up to 12 months postinjury. Neurological deficits and motor coordination impairment were less pronounced in S1R-/- mice with TBI than in WT mice with TBI 24 h after injury. TBI-induced short-term memory impairments were present in WT but not S1R-/- mice 7 months after injury. Compared to WT animals, S1R-/- mice exhibited better motor coordination and less pronounced despair behavior for up to 12 months postinjury. TBI induced astrocyte activation in the cortex of WT but not S1R-/- mice. S1R-/- mice presented a significantly reduced GFAP expression in Bergmann glial cells in the molecular layer of the cerebellum compared to WT mice. Our findings suggest that S1R deficiency reduces TBI-induced motor coordination impairments by reducing GFAP expression in Bergmann glial cells in the cerebellum.