Impaired Neurological Function Research Articles

NHE1 Protein in Repetitive Mild TBI-Mediated Neuroinflammation and Neurological Function Impairment.

Mild traumatic brain injuries (mTBIs) are highly prevalent and can lead to chronic behavioral and cognitive deficits often associated with the development of neurodegenerative diseases. Oxidative stress and formation of reactive oxygen species (ROS) have been implicated in mTBI-mediated axonal injury and pathogenesis. However, the underlying mechanisms and contributing factors are not completely understood. In this study, we explore these pathogenic mechanisms utilizing a murine model of repetitive mTBI (r-mTBI) involving five closed-skull concussions in young adult C57BL/6J mice. We observed a significant elevation of Na+/H+ exchanger protein (NHE1) expression in GFAP+ reactive astrocytes, IBA1+ microglia, and OLIG2+ oligodendrocytes across various brain regions (including the cerebral cortex, corpus callosum, and hippocampus) after r-mTBI. This elevation was accompanied by astrogliosis, microgliosis, and the accumulation of amyloid precursor protein (APP). Mice subjected to r-mTBI displayed impaired motor learning and spatial memory. However, post-r-mTBI administration of a potent NHE1 inhibitor, HOE642, attenuated locomotor and cognitive functional deficits as well as pathological signatures of gliosis, oxidative stress, axonal damage, and white matter damage. These findings indicate NHE1 upregulation plays a role in r-mTBI-induced oxidative stress, axonal damage, and gliosis, suggesting NHE1 may be a promising therapeutic target to alleviate mTBI-induced injuries and restore neurological function.

A Long-Term Outcome of Symptomatic Middle Cerebral Artery Undergoing Intracranial Angioplasty or Stenting

PurposeFor symptomatic stenosis in the middle cerebral artery (MCA), intracranial angioplasty and stenting are frequently employed. However, limited data exist regarding their long-term impact. Our study demonstrates the long-term advantages in preventing ischemic events through a 5-year follow-up period. MethodsA set of 41 individuals with symptomatic stenosis in the central cerebral artery (MCA) who underwent angioplasty or stenting procedures between October 2004 and April 2018 at various hospitals in Southwest China were prospectively enrolled in the study. The rates of successful revascularization, complications, imaging observations, and clinical outcomes were systematically assessed. ResultsA total of 41 individuals successfully underwent stenting , respectively. After stenting, the extent of stenosis was decreased from 71.8 percent (56 -87.8%) to 24.9 percent (0-45 percent). The mean of follow period is 36.9 ± 13.68 months (range , 11-67 months). There was no deterioration of neurological function or a new ischemic event. A DSA or CTA was conducted after the procedure and demonstrated no in-stent restenosis. No patient experienced restenosis below 50% during the mean follow-up period. The morbidity and mortality rates of the case series were 7.3% and 2.4%, respectively. ConclusionIn the treatment of symptomatic MCA atherosclerotic stenoses, intracranial angioplasty & stenting are demonstrated to be technically feasible and safe. Its early & long-term efficacy on ischemic event prevention is acceptable, with a reduced level of restenosis, although the representative sample is tiny.

Patient with discogenic radiculopathy: diagnostic and treatment algorithms

Low back pain is one of the most common causes of seeking medical care, loss of ability to work, and is a heavy socio-economic burden for the country. In the vast majority of cases, the pain syndrome is musculoskeletal, associated with pathology of joints, muscles and ligaments and is benign in nature. Discogenic compression-ischemic radiculopathy is less common, but this pathology is associated with a wide range of issues in differential diagnosis and correct treatment tactics for patients. This article provides an overview of modern clinical guidelines for the diagnosis and treatment of discogenic radiculopathies. The diagnosis of discogenic radiculopathy is clinical. MRI of the spine is performed to exclude secondary causes of nerve root compression if treatment is ineffective. An important direction in the treatment of radiculopathy is non-drug treatment, which includes informing the patient about the benign nature of the disease, the possibility of spontaneous regression of a disc herniation, therapeutic exercises, maintaining the maximum tolerated amount of physical activity, social and professional activity Treatment of back pain is associated with an increased risk of side effects of non-steroidal anti-inflammatory drugs, which patients often use uncontrollably. The issue of safe relief of pain syndromes remains relevant. This can be achieved using a combination of non-steroidal anti-inflammatory drugs and high-dose B vitamins. B vitamins also have a neurotrophic effect, which allows the restoration of impaired neurological functions.

CD4+ T Cells from Women with Preeclampsia During Pregnancy Contribute to Hypertension, AT1-AA, and Neurovascular Dysfunction in a Pregnant Rat Model of PE

Objective: Preeclampsia (PE) is characterized by new onset hypertension (HTN) during pregnancy and is associated with activated CD4+ T cells and agonistic antibodies against the angiotensin II type 1 receptor (AT1-AA). Interestingly, having had COVID-19 during pregnancy is associated with increased incidence of a PE-like phenotype. Both PE and CV have long lasting neurological implications. We sought examine a role for CD4+ T cells from PE with or without a CV Hx to contribute to a PE phenotype and neurovascular dysfunction postpartum (PP). Methods: We utilized adoptive transfer of one million placental CD4+ T cells from PE and normotensive (NT) patients with or without a CV (Hx) during pregnancy injected i.p. into gestational day (GD) 12 nude athymic rats athymic and determined neurological consequences at 12 weeks PP. At GD19, blood pressure (MAP) and AT1-AA were measured. At 3 months PP, memory and error in navigation were assessed by Barnes maze consecutively for 5 days. CBF was measured by laser Doppler flowmetry. A two-way ANOVA was used for statistical analysis. Results: In pregnant recipient rats, MAP increased in CV Hx PE (113±2, n=8) and PE (115±2 mmHg, n=10) compared to CV Hx NT (104±4, n=7) and NT (98±2 mmHg, n=7 p<0.05). AT1-AA increased in PE (8±2 ΔBPM, n=4) and CV Hx PE (4±2 ΔBPM, n=4) compared to NT (-3±2 ΔBPM, n=4, p<0.05) and CV Hx NT (2±2 ΔBPM, n=2) respectively. At 3 months PP, PE and CV Hx PE had impaired CBF autoregulation compared to CV Hx NT and NT rats, and both PE groups exhibited greater mistakes and latency in maze navigation, however, the scores were worse in those receiving T cells from PE patients without a Hx of CV compared to all other groups. Conclusion: Our findings indicate that pregnant recipients of CD4+ T cells from PE with or without a CV Hx during pregnancy cause HTN and increased AT1-AA compared to recipients of NT or NT Hx CV-19 CD4 + T cells. Interestingly, recipients of T cells from PE patients without a Hx of CV had worse CBF and cognitive function at 3 months PP, demonstrating the importance of CD4+ T cells in HTN and impaired neurological function during pregnancy PP in patients with previous PE. This study was supported by NIH grants RO1HD067541 (BL), F31HD110230 (NC), P20GM121334 (BL, LMA), and American heart association (AHA) early career award 19CDA34670055 (LMA). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

A novel p55PIK signaling peptide inhibitor alleviates neuroinflammation via the STAT3/NF-kB signaling pathway in experimental stroke

BackgroundIschemic stroke remains the predominant contributor to mortality and disability globally. Microglia undergo rapid activation and initiate inflammatory cascade reactions by phenotypic polarization, participating in the regulation of inflammatory injury and tissue repair post-ischemic stroke. Regulating microglia-mediated neuroinflammation is a promising therapeutic strategy for ischemic stroke. Previously, we designed and synthesized a novel p55PIK inhibitor, TAT-N15 polypeptide, which presents inhibitive activity on NF-κB signaling-mediated inflammation in acute conjunctivitis and allergic rhinitis. The present study aimed to explore the therapeutic effect and mechanism of TAT-N15 on ischemia stroke. MethodsThe mouse model of transient cerebral ischemia was made using the intraluminal filament method. After being treated with daily intraperitoneal injections of TAT-N15 (10 mg/kg) for 7 d, the neurological outcomes and the cerebral infarction volume were evaluated. Histopathology of the ischemia cerebral hemisphere was observed by H&E and Nissl staining. Neuronal survival, astrogliosis, and co-labeling of CD86/Iba1 and CD206/Iba1 were detected by immunofluorescence. The cell apoptosis was estimated by TUNEL staining. The expression levels of apoptosis-associated proteins, proinflammatory cytokines, protein markers of M1 and M2 microglia, and the phosphorylation of NF-κB and STAT3 proteins in the ischemic penumbra were detected by Western blot. ResultsTAT-N15 treatment significantly decreased the infarct volume and alleviated neurological functional impairment, neuronal injury, and neuron apoptosis. Meanwhile, TAT-N15 treatment restrained the activation of microglia and astrocytes as well as the protein expression of proinflammatory cytokine in ischemic penumbra. Additionally, the administration of TAT-N15 treatment resulted in a significant reduction in the density of M1 phenotype microglia while concurrently increasing the density of M2 phenotype microglia within the ischemic penumbra. Finally, mechanical analysis unveiled that TAT-N15 exerted a substantial inhibitory effect on the protein expression of phosphorylated STAT3 and NF-κB. ConclusionTAT-N15 may inhibit neuroinflammation via regulating microglia activation and polarization through the STAT3/NF-κB pathway, which exhibits the neuroprotection effect in ischemic stroke.

Neuro-regression Assessment- A Case Report

Introduction: Neuro-regression can occur for various reasons, including neurodegenerative diseases such as Alzheimer's disease, certain genetic disorders, brain injuries, infections, toxic exposures, or metabolic disorders. It is often characterized by a progressive deterioration of neurological function over time. Neuro-regression can be caused by a variety of factors, including, Neurodegenerative diseases, Genetic disorders, Brain injuries, Infections, Toxic exposures, and Metabolic disorders. Objective: The goal of this case report is to highlight the difference between developmental delay and developmental regression also known as Neuro-Regression in terms of differential diagnosis. Case Report: A 2.2-year-old male child, with a background of developmental delay and epilepsy was admitted with multiple episodes of breakthrough seizures. Developmental milestones were age-appropriate till 11 months of age (before the seizure). After the seizure, the child’s motor development regressed and the child was not able to sit, or stand. The speech and language milestones were appropriate to the age before the seizure and regressed after the seizure. Conclusion: In our study, it's very clear that the child experiencing neuro-regression which is evident based on the parents’ report, previous and present clinical assessments as well and clinical observation. Regression is an indication that more investigation is necessary and team members like a Developmental Paediatrician, Neurologist, and Clinical Psychologist should be involved.

Effects of epimedium total flavone capsules on post-stroke cognitive impairment in rats

To investigate the effect of epimedium total flavone capsules on post-stroke cognitive impairment(PSCI) in rats. The transient middle cerebral artery occlusion(tMCAO) model was constructed on selected rats, and rats with impaired neurological function were randomly divided into the model group, low, middle, and high dose groups of epimedium total flavone capsules, and nimodipine tablet group. The cognitive function of rats was measured after administration. Pathological changes in brain tissue were observed after hematoxylin-eosin staining(HE). Neuronal nuclei(NeuN) and glial fibrillary acidic protein(GFAP) distribution in brain tissue were tested by immunofluorescent staining. The level of amyloid beta 1-42(Aβ_(1-42)), neuron specific enolase(NSE), acetylcholine(ACH), dopamine(DA), 5-hydroxytryptamine(5-HT), norepinephrine(NE), interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and hypersensitive C-reactive protein(hs-CRP) in rat serum was tested. Moreover, Western blot was utilized to test the expression of nuclear factor-kappaB(NF-κB), p-NF-κB, alpha inhibitor of NF-κB(IκBα) protein, and p-IκBα protein in the hippocampus. The experimental results showed that epimedium total flavone capsules can improve the cognitive function of model rats, and the mechanism may be related to the regulation of the expression of p-IκBα and p-NF-κB proteins, so as to inhibit inflammatory response induced by ischemia-reperfusion.

RBM3 Ameliorates Acute Brain Injury-induced Inflammation and Oxidative Stress by Stabilizing GAS6 mRNA Through Nrf2 Signaling Pathway

RNA-binding motif protein 3 (RBM3), as a cold-inducible protein, exhibits neuroprotective function in brain disorders. This study was conducted to investigate the effects of RBM3 on acute brain injury (ABI) and its underlying mechanism. The cerebral injury (CI) rat model and oxygen-glucose deprivation (OGD) cell model were established. The neurological severity score, wire-grip score, morris water maze test, and Y-maze test were used to detect the neurological damage, vestibular motor, learning, and memory functions. Cerebral injury, apoptosis, oxidative stress, and inflammatory level were evaluated by hematoxylin-eosin and TUNEL staining and specific kits. Flow cytometry was used to analyze the apoptosis rate. The relationship between RBM3 and growth arrest specific (GAS) 6 was analyzed by RNA immunoprecipitation assay. The results indicated that RBM3 recovered of neurological function and behaviour impairment of CI rats. Additionally, RBM3 reversed the increased oxidative stress, inflammatory level, and apoptosis induced by CI and OGD. RBM3 interacted with GAS6 to activate the Nrf2 signaling pathway, thus playing neuroprotection on ABI. Besides, the results of RBM3 treatment were similar to those of mild hypothermia treatment. In summary, RBM3 exerted neuroprotection and ameliorated inflammatory levels and oxidative stress by stabilizing GAS6 mRNA through the Nrf2 signaling pathway, suggesting that RBM3 might be a potential therapeutic candidate for treating ABI.

BONE MARROW MESENCHYMAL STROMAL CELL-DERIVED EXOSOMAL NRF2 AMELIORATES CEREBRAL ISCHEMIA-REPERFUSION INJURY BY TRANSCRIPTIONALLY ACTIVATING LIN28A.

Background: Cerebral ischemia-reperfusion (I/R) injury (CIRI) have severe consequences on brain function, and the exciting evidence has revealed protective role of acyl-CoA synthetase long chain family member 4 (Lin28a) against cerebral ischemia-reperfusion injury. The present work aims to reveal its molecular mechanism in regulating CIRI, with the hope of providing a therapeutic method for cerebral I/R injury. We hypothesized that the exosomal nuclear factor erythroid 2-related factor 2 (NRF2) derived from bone marrow mesenchymal stromal cells could transcriptionally activate Lin28a and thereby alleviate cerebral ischemia-reperfusion injury. This hypothesis was validated in the present work. Methods: Middle cerebral artery occlusion (MCAO) model was established using C57BL/6J mice, and the neurological deficit, infarct volume, and brain water content were assessed to evaluate neuron injury. Human glioblastoma cells (A172) were subjected to oxygen-glucose deprivation and reoxygenation (OGD/R) treatment to mimic a cerebral I/R injury cell model. Exosome isolation reagent was used to isolate exosomes from cell supernatant of bone marrow mesenchymal stromal cells through sequential centrifugation and filtration steps. mRNA expression level of Lin28a was detected by quantitative real-time polymerase chain reaction. Protein expression was analyzed by western blotting assay. TUNEL cell apoptosis detection kit was used to analyze cell apoptosis in brain tissues. Enzyme-linked immunosorbent assays and commercial kits were used to detect levels of inflammatory markers and oxidative stress markers. Ferrous Iron Colorimetric Assay Kit and Fe 2+ colorimetric assay kit were used to analyze Fe 2+ level. The association of Lin28a and NRF2 was identified by chromatin immunoprecipitation assay and dual-luciferase reporter assay. Results: The treatment of MCAO substantially augmented infarct volume in mice, impaired neurological function, and elevated brain water content. Lin28a was lowly expressed in brain tissues of mice with CIRI, and its overexpression protected against cerebral I/R injury of MCAO mice. Moreover, Lin28a overexpression protected A172 cells against OGD/R treatment-induced injury. Additionally, NRF2 transcriptionally activated Lin28a in A172 cells. Bone marrow mesenchymal stromal cell-derived exosomes increased Lin28a expression in a NRF2-dependent manner. Bone marrow mesenchymal stromal cell-derived exosomal NRF2 improved OGD/R-induced A172 cell injury by inducing Lin28a production. Conclusion: Bone marrow mesenchymal stromal cell-derived exosomal NRF2 improved CIRI by transcriptionally activating Lin28a.

Healthcare utilization and costs associated with autologous haematopoietic stem cell transplantation in Norwegian patients with relapsing remitting multiple sclerosis

Multiple sclerosis (MS) patients experience long-term deterioration of neurological function, reduced quality of life, long-lasting treatment cycles, and an increased risk of early workability loss imposing an economic burden to society. Autologous haematopoietic stem cell transplantation (AHSCT) has shown promising treatment effects for relapsing remitting MS (RRMS). This study employs a micro-costing approach to estimate healthcare utilization and costs associated with AHSCT in Norwegian RRMS patients. Patient-level data were extracted from medical journals of 30 RRMS patients receiving AHSCT treatment at Haukeland University Hospital in the period from January 2015 to January 2018. The time horizon for the analysis was from the pretransplant screening until one year after AHSCT. A correlation was found between patient body weight and total healthcare cost. The average total healthcare cost of AHSCT for RRMS patients was estimated to EUR 66 304 (95% CI: EUR 63 598 – EUR 69 010) including costs associated with the pre-AHSCT period, AHSCT treatment phases and one-year follow-up. The majority of the costs, EUR 64 329, occurred during the treatment phase and within the first 100 days after AHSCT. The results indicate that long-term healthcare cost savings may be achieved using AHSCT in selected patients with aggressive RRMS. This is due to the high costs of most used disease modifying treatments. Further research including long-term clinical data is needed to determine the cost-effectiveness of this treatment.

Correlation analysis between smoke exposure and serum neurofilament light chain in adults: a cross-sectional study

BackgroundSmoke exposure is a prevalent and well-documented risk factor for various diseases across different organ systems. Serum neurofilament light chain (sNfL) has emerged as a promising biomarker for a multitude of nervous system disorders. However, there is a notable paucity of research exploring the associations between smoke exposure and sNfL levels.MethodsWe conducted a comprehensive analysis of the National Health and Nutrition Examination Survey (NHANES) cross-sectional data spanning the years 2013 to 2014. Serum cotinine levels were classified into the following three groups: < 0.05, 0.05–2.99, and ≥ 3 ng/ml. Multiple linear regression models were employed to assess the relationships between serum cotinine levels and sNfL levels. Additionally, we utilized restricted cubic spline analyses to elucidate the potential nonlinear relationship between serum cotinine and sNfL levels.ResultsA total of 2053 participants were included in our present research. Among these individuals, the mean age was 47.04 ± 15.32 years, and males accounted for 48.2% of the total study population. After adjusting the full model, serum cotinine was positively correlated with sNfl in the second group (β = 0.08, 95%CI 0.01–0.15) and in the highest concentration of serum cotinine (β = 0.10, 95%CI 0.01–0.19) compared to the group with the lowest serum cotinine concentrations. Current smokers, in comparison to non-smokers, exhibited a trend toward elevated sNfL levels (β = 0.07, 95%CI 0.01–0.13). Furthermore, subgroup analyses revealed interactions between serum cotinine levels and different age groups (P for interaction = 0.001) and gender stratification (P for interaction = 0.015) on sNfL levels.ConclusionThe study suggested that serum cotinine was significantly and positively associated with sNfl levels in adult participants. Furthermore, current smokers tend to exhibit elevated sNfL levels. This research sheds light on the potential implications of smoke exposure on neurological function impairment and underscores the importance of further exploration in this area.

Abstract WP189: TIGER Study: Effectiveness and Safety of Tigertriever Are Maintained When Treating Large Clot Size

Introduction: Larger volume thrombi are associated with a lower probability of functional independence defined as a modified Rankin Score (mRS) ≤2 and a higher number of retrieval attempts. A subanalysis of the TIGER study data was performed in order to assess the effectiveness and safety of Tigertriever in small and large clot sizes. Methods: The TIGER study was a single arm, prospective, multi-center trial assessing the efficacy and safety of the Tigertriever, a radially-adjustable stent retriever, for LVO-related stroke. The trial enrolled 160 subjects, of which 150 had successful mTICI 2b-3 revascularization (94%) at end of all procedures. The interventionalists evaluated the clot length angiographically prior to the treatment, and analysis was performed to compare the Tigertriever performance in short clots with long clots. Results: Data is available from 135 (78 males) out of the 160 subjects enrolled in the study.The median clot length was 9mm with a range of 1-50mm. Subjects were divided into two subgroups: Group A; subjects with small clot length, ≤9mm (n=69) and group B, subjects with large clot length, &gt;9mm (n=66). Baseline NIHSS was significantly smaller in group A compared to group B (16.9 vs.19, respectively, P=0.02). Median clot size in group A was 6.1mm and 16.5mm in group B. The mean number of passes with Tigertriever to achieve successful revascularization (mTICI 2b-3) was slightly higher in group B, but not statistically different (1.7 in group A vs. 2 in group B, P=0.07). First pass effect (63% vs. 50% NS), good clinical outcome (62% vs. 53% NS), sICH (1.4% vs. 3% NS) and ENT (Embolization to new territory 2.9% vs. 1.5% NS) were comparable in group A and group B, respectively. Conclusions: Despite the impaired neurological functioning as indicated by significantly higher baseline NIHSS in subjects admitted with larger clot length, Tigertriever efficacy and safety were maintained when treating these large clots compared to small clots.

Mitophagy curtails cytosolic mtDNA-dependent activation of cGAS/STING inflammation during aging

Macroautophagy decreases with age, and this change is considered a hallmark of the aging process. It remains unknown whether mitophagy, the essential selective autophagic degradation of mitochondria, also decreases with age. In our analysis of mitophagy in multiple organs in the mito-QC reporter mouse, mitophagy is either increased or unchanged in old versus young mice. Transcriptomic analysis shows marked upregulation of the type I interferon response in the retina of old mice, which correlates with increased levels of cytosolic mtDNA and activation of the cGAS/STING pathway. Crucially, these same alterations are replicated in primary human fibroblasts from elderly donors. In old mice, pharmacological induction of mitophagy with urolithin A attenuates cGAS/STING activation and ameliorates deterioration of neurological function. These findings point to mitophagy induction as a strategy to decrease age-associated inflammation and increase healthspan.

Impact of metastatic epidural spinal cord compression (MESCC) and pathological vertebral compression fracture (pVCF) in neurological and survival prognosis

BackgroundMetastatic epidural spinal cord compression (MESCC) and pathological vertebral compression fractures (pVCF) are the most serious debilitating morbidities of spine metastases (SpMs) causing devastating neurological damages. The respective impact of these two metastasis-spreading entities on survival and on neurological damage is debated. MethodsA French prospective cohort study collected 279 consecutive patients presenting with SpMs between January 2017 and 2021. We compared 174 patients with MESCC and 105 patients with pVCF. ResultsThe median Overall Survival (OS) for the MESCC group was 13.4 months (SD 1.5) vs 19.2 months (SD 2.3) for pVCF patients (p = 0.085). Sixty-five patients (23.3 %) were operated on: 49/65 (75.4 %) in the MESCC group and 16/65 (15.2 %) in the pVCF group, p < 0.0001. At 6 months FU, in the MESCC group, 21/44 (45.4 %) of non-ambulatory patients at onset improved to ambulatory status (Frankel D-E) vs 10/13 (76.9 %) in the pVCF group (p = 0.007). In multivariable analysis with the Cox proportional hazard model, good ECOG-PS and SINS Score 7–12 [HR: 6.755, 95 % CI 2.40–19.00; p = 0.001] were good prognostic factors for preserved ambulatory neurological status. However, SpMs diagnosed synchronously with the primary tumor [HR: 0.397, 95 % CI 0.185–0.853; p = 0.018] and MESCC [HR: 0.058, 95 % CI 0.107–0.456; p = 0.007] were independent risk factors for impaired neurological function. ConclusionContrary to pVCF, MESCC causes neurological damage. Nevertheless, neurological recovery remains possible. MESCC and pVCF have no impact on survival. The management of MESCC remains to be clarified and optimized to reduce neurological damage.

Urolithin B Attenuates Cerebral Ischemia–reperfusion Injury by Modulating Nrf2-regulated Anti-oxidation in Rats

Ischemia-reperfusion (IR) induces a wide range of irreversible injuries. Cerebral IR injury (IRI) refers to additional brain tissue damage that occurs after blood flow is restored following cerebral ischemia. Currently, no established methods exist for treating IRI. Oxidative stress is recognized as a primary mechanism initiating IRI and a crucial focal target for its treatment. Urolithin B, a metabolite derived from ellagitannins, antioxidant polyphenols, has demonstrated protective effects against oxidative stress in various disease conditions. However, the precise mechanism underlying UB’s effect on IRI remains unclear. In our current investigation, we assessed UB's ability to mitigate neurological functional impairment induced by IR using a neurological deficit score. Additionally, we examined cerebral infarction following UB administration through TTC staining and neuron Nissl staining. UB's inhibition of neuronal apoptosis was demonstrated through the TUNEL assay and Caspase-3 measurement. Additionally, we examined UB's effect on oxidative stress levels by analyzing malondialdehyde (MDA) concentration, superoxide dismutase (SOD) activity, and immunohistochemistry analysis of inducible nitric oxide synthase (iNOS) and 8-hydroxyl-2′-deoxyguanosine (8-OHdG). Notably, UB demonstrated a reduction in oxidative stress levels. Mechanistically, UB was found to stimulate the Nrf2/HO-1 signaling pathway, as evidenced by the significant reduction in UB's neuroprotective effects upon administration of ATRA, an Nrf2 inhibitor. In summary, UB effectively inhibits oxidative stress induced by IR through the activation of the Nrf2/HO-1 signaling pathway. These findings suggest that UB holds promise as a therapeutic agent for the treatment of IRI.

Hexahydrocurcumin Attenuates Neuronal Injury and Modulates Synaptic Plasticity in Chronic Cerebral Hypoperfusion in Rats.

Dementia is the most common age-related problem due predominantly to Alzheimer's disease (AD) and vascular dementia (VaD). It has been shown that these contributors are associated with a high amount of oxidative stress that leads to changes in neurological function and cognitive impairment. The aim of study was to explore the mechanism by which hexahydrocurcumin (HHC) attenuates oxidative stress, amyloidogenesis, phosphorylated Tau (pTau) expression, neuron synaptic function, and cognitive impairment and also the potential mechanisms involved in induced permanent occlusion of bilateral common carotid arteries occlusion (BCCAO) or 2-vessel occlusion (2VO) in rats. After surgery, rats were treated with HHC (40mg/kg) or piracetam (600mg/kg) by oral gavage daily for 4weeks. The results showed that HHC or piracetam attenuated oxidative stress by promoting nuclear factor erythroid 2-related factor 2 (Nrf2) activity, and alleviated expression of synaptic proteins (pre- and post-synaptic proteins) mediated by the Wingless/Integrated (Wnt)/β-catenin signaling pathway. Moreover, HHC or piracetam also improved synaptic plasticity via the brain-derived neurotrophic factor (BDNF)/Tyrosine receptor kinase B (TrkB)/cAMP responsive element binding protein (CREB) signaling pathway. In addition, HHC reduced amyloid beta (Aβ) production and pTau expression and improved memory impairment as evidenced by the Morris water maze. In conclusion, HHC exerted remarkable improvement in cognitive function in the 2VO rats possibly via the attenuation of oxidative stress, improvement in synaptic function, attenuation of amyloidogenesis, pTau, and neuronal injury, thereby improving cognitive performance.

The association between multiple sclerosis and migraine: A meta-analysis.

Multiple sclerosis (MS) is a chronic progressive condition marked by the deterioration of myelin and impairment of neurological function. The global prevalence of MS is approximately 2.2 million. Migraines are common in MS patients, with inconclusive data on their relationship. Our systematic review aimed to assess the prevalence and odds of migraine in pwMS and investigate the potential factors that may influence these associations. Through an extensive search and meticulous study selection, we identified pertinent literature investigating the occurrence and odds of migraines among pwMS. Additionally, we explored the comparative risk of migraines in MS patients compared to healthy controls. Data were extracted, including publication details, diagnostic criteria, and migraine prevalence in MS patients. A total of 35 studies were included, involving 279,620 pwMS and 279,603 healthy controls. The overall prevalence of migraine in pwMS was 0.24 (95% CI: 0.21-0.28). Subgroup analyses and meta-regression were conducted to investigate the potential impact of various factors on the relationship between migraine and MS. These factors included age, duration of MS, study design, and the Expanded Disability Status Scale (EDSS), migraine diagnosis method, study design, publication year of the study, country and continent of the study population. The results of these analyses revealed no significant influence of these factors on the relationship between migraine and MS. The meta-analysis indicated that pwMS had significantly increased odds of having migraine compared to healthy controls (OR=1.96, 95% CI: 1.20-3.20). Sensitivity analyses supported the robustness of the findings. Our study highlights that approximately 24% of pwMS experience migraine. The method of diagnosis significantly affects the reported prevalence, with questionnaires yielding higher rates. Furthermore, pwMS have a 1.96-fold increased odds of having migraine compared to healthy individuals. These findings emphasize the importance of further research and interventions to address the significant burden of migraine in the MS population.

Emergent radiotherapy for spinal cord compression/impingement—a narrative review.

Malignant epidural spinal cord compression (MESCC), often presenting with back pain and motor/sensory deficits, is associated with poor survival, particularly when there is loss of ambulation. The purpose of this review is to evaluate the literature and discuss appropriate workup and management of MESCC, specifically in the emergent setting. A PubMed search was conducted on "spinal cord compression" and "radiation therapy." Articles were analyzed for the purpose of this narrative review. If MESCC is suspected, neurologic examination and complete spine imaging are recommended. Emergent treatment is indicated if there is radiographic evidence of highgrade compression and/or clinically significant motor deficits. Treatment involves a combination of medical management, surgical decompression, radiation therapy (RT), and rehabilitation. For motor deficits, emergent initiation of high dose steroids is recommended. Circumferential surgical decompression ± stabilization followed by RT provides superior clinical outcomes than RT alone. For patients whom surgery is not reasonable, RT alone may provide significant treatment response which depends on radioresponsiveness of the pathology. Systemic therapy, if indicated, is typically reserved till after primary treatment of MESCC, but patients with chemoresponsive tumors may receive primary chemotherapy. The selected RT schedule should be personalized to each patient and commonly is 30 Gy in 10 fractions (fx), 20 Gy in 5 fx, or 8 Gy in 1 fx. MESCC recurrence may be treated with additional RT, if within the spinal cord tolerance, or surgery. Stereotactic body radiation therapy (SBRT) has been used for high grade MESCC in patients with relatively intact neurologic function at a few centers with a very robust infrastructure to support rapid initiation of treatment within a short period of time, but is generally not feasible for most clinical practices. SBRT may be advantageous for low grade MESCC, recurrence, or in the post-operative setting. Detection of MESCC prior to development of high-grade compression or deterioration of neurologic function may allow patients to benefit more from advanced therapies and improve prognosis. MESCC is a devastating condition; optimal treatment should be personalized to each patient and approached collaboratively by a multidisciplinary team.

Protective effect of Liujing Toutong Tablets on rats with permanent cerebral ischemia via NF-κB signaling pathway

This study investigated the neuroprotective effects and underlying mechanism of Liujing Toutong Tablets(LJTT) on a rat model of permanent middle cerebral artery occlusion(pMCAO). The pMCAO model was established using the suture method. Eighty-four male SPF-grade SD rats were randomly divided into a sham operation group, a model group, a nimodipine group(0.020 g·kg~(-1)), and high-, medium-, and low-dose LJTT groups(2.8, 1.4, and 0.7 g·kg~(-1)). The Longa score, adhesive removal test and laser speckle contrast imaging technique were used to evaluate the degree of neurological functional impairment and changes in local cerebral blood flow. The survival and mortality of rats in each group were recorded daily. After seven days of continuous administration following the model induction, the rats in each group were euthanized, and brain tissue and blood samples were collected for corresponding parameter measurements. Nissl staining was used to examine pathological changes in brain tissue neurons. The levels of tumor necrosis factor-alpha(TNF-α), interleukin-6(IL-6), IL-1β, vascular endothelial growth factor(VEGF), calcitonin gene-related peptide(CGRP), beta-endorphin(β-EP), and endogenous nitric oxide(NO) in rat serum were measured using specific assay kits. The entropy weight method was used to analyze the weights of various indicators. The protein expression levels of nuclear factor kappa-B(NF-κB), inhibitor kappaB alpha(IκBα), phosphorylated IκBα(p-IκBα), and phosphorylated inhibitor of NF-κB kinase alpha(p-IKKα) in brain tissue were determined using Western blot. Immunohistochemistry was used to detect the protein expression of chemokine-like factor 1(CKLF1) and C-C chemokine receptor 5(CCR5) in rat brain tissue. Compared with the sham operation group, the model group showed significantly higher neurological functional impairment scores, prolonged adhesive removal time, decreased cerebral blood flow, increased neuronal damage, reduced survival rate, significantly increased levels of TNF-α, IL-1β, IL-6, CGRP, and NO in serum, significantly decreased levels of VEGF and β-EP, significantly increased expression levels of NF-κB p65, p-IκBα/IκBα, and p-IKKα in rat brain tissue, and significantly upregulated protein expression of CKLF1 and CCR5. Compared with the model group, the high-dose LJTT group significantly improved the neurological functional score of pMCAO rats after oral administration for 7 days. LJTT at all doses significantly reduced adhesive removal time and restored cerebral blood flow. The high-and medium-dose LJTT groups significantly improved neuronal damage. The LJTT groups at all doses showed reduced levels of TNF-α, IL-1β, IL-6, CGRP, and NO in rat serum, increased VEGF and β-EP levels, and significantly decreased expression levels of NF-κB p65, p-IκBα/IκBα, p-IKKα, and CCR5 protein in rat brain tissue. The entropy weight analysis revealed that CGRP and β-EP were significantly affected during the model induction, and LJTT exhibited a strong effect in reducing the release of inflammatory factors such as TNF-α and IL-1β. LJTT may exert a neuroprotective effect on rats with permanent cerebral ischemia by reducing neuroinflammatory damage, and its mechanism may be related to the inhibition of the NF-κB signaling pathway and the regulation of the CKLF1/CCR5 axis. Additionally, LJTT may exert certain analgesic effects by reducing CGRP and NO levels and increasing β-EP levels.

Non‐osseous intradural tuberculoma of the thoracic spine with compressive myelopathy

Key Clinical MessageAn uncommon form of CNS tuberculosis called non‐osseous IDEM tuberculoma frequently results from paradoxical drug interactions. It should be considered one of the differentials when patients receiving ATT experience acute neurological impairment.AbstractTuberculoma affecting the spinal cord is a rare condition in modern times. The occurrence of non‐osseous intradural tuberculosis, specifically in the spine, is even more exceptional. In fact, it is uncommon to encounter an intradural extramedullary tuberculous granuloma that lacks radiological indications of vertebral involvement, especially within the thoracic region. We present a case of a patient with a neurological deficit caused by a non‐osseous intradural tuberculoma in the thoracic region, without any associated bone involvement. The patient experienced a gradual deterioration of neurological function. An MRI of the thoracic spine revealed the presence of a tuberculoma located intradurally, extramedullary, and juxtamedullary of the T5 vertebra. The compression of the spinal cord resulted in paraparesis which was worsening to paraplegia. A D4–D6 laminectomy and microsurgical excision were performed under intraoperative neurophysiological monitoring (IONM), and the patient showed clinical recovery. Excellent clinical outcomes were achieved. However, it is crucial to consider the possibility of a non‐osseous intradural tuberculoma as a rare condition when encountering a SOL, particularly in patients with a history of tuberculosis and spinal cord compression. In cases where a progressing neurological deficit is present, a combination of surgical intervention and anti‐tuberculous treatment should be considered as the optimal approach.