Loss Of Neurological Function Research Articles

Artificial Intelligence in The Management of Neurodegenerative Disorders.

Neurodegenerative disorders are characterized by a gradual but irreversible loss of neurological function. The ability to detect and treat these conditions successfully is crucial for ensuring the best possible quality of life for people who suffer from them. The development of effective new methods for managing and treating neurodegenerative illnesses has been made possible by recent developments in computer technology. In this overview, we take a look at the prospects for applying computational approaches, such as drug design, AI, ML, and DL, to the treatment of neurodegenerative diseases. To review the current state of the field, this article discusses the potential of computational methods for early disease detection, quantifying disease progression, and understanding the underlying biological mechanisms of neurodegenerative diseases, as well as the challenges associated with these approaches and potential future directions. Moreover, it delves into the creation of computational models for the individualization of care for neurodegenerative diseases. The article concludes with suggestions for future studies and clinical applications, highlighting the advantages and disadvantages of using computational techniques in the treatment of neurodegenerative diseases.

Impact of Stroke on the Quality of Life of its Survivors

Introduction: Ischemic Stroke is due to sudden loss of blood circulation to an area of the brain, resulting in loss of neurologic function. The incidence in India ranges between 105-152/100,000 people/year. Despite all the advancements in care, stroke continues to be the 2nd leading cause of mortality and the 1st cause of long-term disability. The activities of daily living of patients with chronic stroke affect their Quality of Life (QoL). The majority of stroke survivors continue to live with disabilities, and this can have a profound impact on their QoL. Aims & Objectives: To assess the impact of stroke on the various domains of the quality of life of its survivors, who are treated by the Department of Neurological Sciences, Christian Medical College, Vellore. Methods: A descriptive study design employing a non-probability purposive sampling technique was used to recruit 90 stroke survivors. Written consent was obtained, demographic and clinical variables were collected using interviews, and the impact of stroke on its survivors was assessed using the Stroke Specific Quality of Life (SS-QoL) scale. Results: The participant's mean age group was 48.92±12.97 ranging between 26 -78 years respectively; 67.8% were males, 34.4% of them were unskilled workers, 66.7% had a thrombotic type of ischemic stroke, 56.7% had a moderate National Institutes of Health Stroke Scale grade at admission, 26.7% and 25.6% had a modified Rankin Score of 2 and 1, respectively. Among the participants, 47.8% of them had a stroke at the ages of 31-50 years, and the majority (91.1%) of them had comorbidities. The majority (44.77%) of them had a moderate QoL. Among the SS-QoL domains, the mean scores were the highest in the vision domain (4±1.26) and the lowest in the energy domain (2.47±1.25). There was a significant association between the QoL of stroke survivors and their socioeconomic status (p=0.033), type of ischemic stroke (p=0.047), and limb involvement (p=0.034). A positive correlation (p=0.00) was observed among various QoL domains. Conclusion: These findings provided not just insight into the impact of stroke on the QoL of its survivors but also emphasized the need to sensitize the healthcare care professionals to provide care during both the acute period and also continue to ensure all the domains of a good QoL is addressed during the follow-up and rehabilitation. Keywords: Ischemic Stroke, Quality of Life, Stroke Survivor

ROS-responsive nanoparticle delivery of ferroptosis inhibitor prodrug to facilitate mesenchymal stem cell-mediated spinal cord injury repair

Spinal cord injury (SCI) is a traumatic condition that results in impaired motor and sensory function. Ferroptosis is one of the main causes of neural cell death and loss of neurological function in the spinal cord, and ferroptosis inhibitors are effective in reducing inflammation and repairing SCI. Although human umbilical cord mesenchymal stem cells (Huc-MSCs) can ameliorate inflammatory microenvironments and promote neural regeneration in SCI, their efficacy is greatly limited by the local microenvironment after SCI. Therefore, in this study, we constructed a drug-release nanoparticle system with synergistic Huc-MSCs and ferroptosis inhibitor, in which we anchored Huc-MSCs by a Tz-A6 peptide based on the CD44-targeting sequence, and combined with the reactive oxygen species (ROS)-responsive drug nanocarrier mPEG-b-Lys-BECI-TCO at the other end for SCI repair. Meanwhile, we also modified the classic ferroptosis inhibitor Ferrostatin-1 (Fer-1) and synthesized a new prodrug Feborastatin-1 (Feb-1). The results showed that this treatment regimen significantly inhibited the ferroptosis and inflammatory response after SCI, and promoted the recovery of neurological function in rats with SCI. This study developed a combination therapy for the treatment of SCI and also provides a new strategy for the construction of a drug-coordinated cell therapy system.

Comparison Between Mirror Therapy and Mental Imagery in Improving Ankle Motor Recovery in Acute Stroke Patients: Experimental Study

Introduction: Stroke is the sudden loss of neurological function caused by an interruption of the blood flow to the brain. Initially, some 80% of all patients with stroke experience motor impairments of the contralateral limb, i.e hemiparesis. Mirror therapy is relatively new therapeutic intervention that focuses on moving the unimpaired limb. Likewise, another technique called Mental imagery is the cognitive rehearsal of a task in the absence of movement. Aim and Objectives: To compare mirror therapy and mental imagery in improving ankle motor recovery in acute stroke patients. Methodology: 30 stroke patients were selected in the study, and were randomly assigned into two groups. Group A i.e. Mirror Therapy group (n=15) or the Group B i.e. Mental Imagery group (n=15). Both the groups received 30 minutes of their respective therapy that is mirror therapy and mental imagery and in addition to 30 minutes of conventional therapy which included neuro developmental facilitation technique, stretching, gait training that is a total of 1 hour per day for 5 days a week for 4 weeks. Modified Ashworth Scale, 10 Meter Walk test (10MWT), Fugl-Meyer assessment Lower extremity (FMA-LE) scale were administered pre and post intervention to assess the ankle motor function. Results: Only Fugl Meyer Assessment scores on comparison between Group A (Mirror Therapy) and Group B (Mental Imagery) revealed that statistically significant improvement was found in Group B (Mental Imagery) (t-value: 2.140; p-value: .041*). Conclusion: The present study concluded that Mental Imagery proved to be more effective than Mirror Therapy in improving ankle motor recovery in acute stroke patients.

A genetic algorithm based federated learning model for stroke risk prediction

A Stroke is a sudden loss of blood circulation in certain parts of the brain that results in a loss of neurological function. To save a patient from stroke, an immediate diagnosis and treatment plan must be implemented. Artificial intelligence-based machine learning algorithms play a major role in the prediction. To predict a person likely to have a stroke, stroke healthcare data records must be accessed, which is very sensitive. Data shared for machine learning training pose security risks and have concerns about privacy. To overcome this issue, Genetic Algorithm and Federated Learning (GA-FL) –based hybridization approach is proposed to predict the risk of stroke in a person. Federated Learning was developed by Google, which can provide security to the data during the training process because every client participating in this training process needs to exchange only the training parameters without sharing the data. In addition to the security features, a genetic algorithm was used to optimize the parameters required to train a model using the perceptron neural network model. The experimental results show that our proposed research model (GA-FL) provides security and predicts the risk of stroke more accurately than any other existing algorithm.

Constructing Nerve Guidance Conduit using dECM‐Doped Conductive Hydrogel to Promote Peripheral Nerve Regeneration

AbstractPeripheral nerve injury often leads to the loss of neurological functions due to the slow regeneration rate and inefficient functional reconstruction. Current clinical treatments using nerve guidance conduits (NGCs) still face challenges in providing a biomimetic microenvironment to promote nerve repair. Herein, decellularized extracellular matrix (dECM) is obtained from porcine Achilles tendon and crosslinked with 3‐amino‐4‐methoxybenzoic acid grafted gelatin (PAMB‐G) to obtain conductive hydrogels. Then, a novel nerve guidance conduit is developed by assembling poly(vinyl alcohol) (PVA) conduit and conductive ECM@PAMB‐G hydrogel. This bioengineered ECM@PAMB‐G/PVA conduit demonstrated excellent cytocompatibility, electrical conductivity, mechanical properties, and biodegradability. In vitro experiments confirmed that the ECM@PAMB‐G hydrogel significantly promotes the proliferation and migration of PC12 cells and primary Schwann cells, as well as the growth of dorsal root ganglion (DRG) axons. Furthermore, in vivo studies in a rat sciatic nerve model exhibited improvements in axonal regeneration, Schwann cell migration, myelin sheath formation, and functional recovery mediated by the ECM@PAMB‐G/PVA conduit. This work demonstrates the synergistic effects of extracellular matrix and electrical cues in enhancing peripheral nerve regeneration. The ECM@PAMB‐G/PVA nerve guidance conduit shows potential as an alternative to autografts for supporting peripheral nerve reconstruction.

Effects of Cognitive Sensory Motor Training Versus Repetitive Facilitation Exercises of Upper Limb in Hemiparetic Patients

Stroke [CVA] is the sudden loss of neurological function caused by an interruption of blood flow to the brain. Large numbers of people who survive a stroke are left with permanent impairment of arm and hand function, even after completion of conventional rehabilitation programs. The standard neuro physiological facilitation technique use for hemiplegic upper limb have not been confirmed to promote functional recovery of hemiplegic limb. This promote that more research needs to be conducted for same. Cognitive Sensory Motor Training Therapy & The repetitive facilitation exercises (RFEs) Both techniques will promote functional recovery of hemiparetic upper limb and hand by improving joint perception and realization of movement. Hence, this study aims to compare the effectiveness of cognitive sensory motor training versus repetitive facilitation exercises on quality of movement of upper limb, functional activity and Range of motion of upper limb in hemiparetic patients. A blinded randomized clinical trial was conducted 30 patients were divided into 2 groups (GROUP A and GROUP B)- those who performed cognitive Sensory Motor exercises(GROUP A- experimental group) and those who performed repetitive facilitation exercises (GROUP B-control group) Data for measures quality of movement performance of the hemiparetic arm and hand on MESUPES scale, Barthel Index (BI) measures the extent to which somebody can function independently and has mobility in their &, goniometer measuring the joint ranges in each plane of the joint was collected on day 1 (pretreatment session), and on 190 day after the experiment. This study produced a stastically significant increase in overall on quality of movement, functional activity and range of motion in both the group of upper limb in hemiplegic patients. This research also provides evidence that training exercise may be a valuable and important tool in clinical practice and is consistent with the current use by clinical physiotherapist in the treatment of upper limb in hemiplegic patients.

Single-Cell Multiome Analysis Reveals Neuroprotection by Elovanoids in Experimental Ischemic Stroke

Ischemic stroke results in severe loss of neurological functions, and a large proportion of survivors display the onset of cognitive impairments. Administration of a novel class of very long-chain polyunsaturated fatty acids (VLC-PUFAs) termed elovanoids (ELV-N34) or its VLC-PUFA precursor (C34:6) are protective against both in vitro and in vivo models of uncompensated oxidative stress and ischemic stress. We found that ELV-N34 or C34:6 delivery attenuates sensorimotor deficits after ischemic stroke. Furthermore, we uncovered that ELV and its precursors protect against ischemic damage by modulating inflammatory signaling and increasing the expression of neuroprotective genes. We used 10X Single Cell Multiome (ATAC + Gene Expression) to compare genomic and epigenomic responses in naïve rats and after experimental ischemic treatment. Adult Sprague-Dawley rats underwent 2 hours of middle cerebral artery occlusion (MCAo) via intraluminal suture. Rats received vehicle, ELV-N34, or C34:6 delivered intranasally 1 hour, 1 day, and 2 days after 2 hours of MCAo. Brains were harvested on day 3 from the ipsilesional cortex (penumbra region) and subcortex. Nuclei were isolated and processed according to 10X Genomics Single Cell Multiome protocol. ELV-N34 or C34:6 treatment reduced neurological deficits after MCAo. Joint single-cell analysis revealed increases in microglia and leukocyte abundance as well as a loss of neuronal populations after MCAo. Differential gene expression revealed that ELV or its precursors protected against MCAo through complex mechanisms involving anti- inflammatory signaling and promoted neuroregeneration in microglia, astrocytes, neurons, and other neural cells. ELV/precursors exert their bioactivity by modulating conversion to neuroprotective cell phenotypes in neurodegenerative diseases such as stroke or Alzheimer's disease.

Oral tributyrin supplementation attenuates Alzheimer’s disease‐associated neuropathology and prevents cognitive and behavioral deficits in the 3xTg‐AD mouse model

AbstractBackgroundDysbiosis of the gut microbiome is associated with various diseases, including Alzheimer’s Disease (AD). A decrease in intestinal butyrate‐producing bacteria has been indicated by pre‐clinical and clinical studies in AD; therefore, we assessed the effects of long‐term oral administration of tributyrin (TB: a butyrate pro‐drug) on the development of memory and neuromuscular deficits, and CNS pathology in 3xTg‐AD (3xTg) mice.MethodOral gavage with tributyrin (2 mg/kg) was given twice weekly to female 3xTg mice between 6‐ and 17‐months of age. Treatment was stopped and mice were tested for spatial memory (Y‐maze and novel object recognition test‐NORT) and neuromuscular function (RotaRod and grip tests). Brains from untreated (2‐, 12‐, or 18‐month‐old untreated or TB treated 18‐month‐old mice were formalin‐fixed, paraffin‐embedded for microscopic analysis of AD‐associated pathology, neuroinflammation, and oxidative stress markers.ResultShort‐term, episodic memory and spatial memory along with balance and coordination and grip strength were all significantly decreased in untreated 3xTg mice at 17‐months of age compared to 2‐ or 10‐month‐old mice. TB treatment, however, attenuated these effects in 17‐month mice. TB treatment did not affect the accumulation of either Aβ or Tau in the subiculum at 18‐months. However, pTau hyperphosphorylation—as indicated by co‐staining with both pTau(Ser404) and AT‐8 pTau (Ser202/Thr205) mAb—was effectively prevented with TB treatment. Similarly, significant age‐dependent neuroinflammation indicated by IBA1 (microglia) and GFAP (astrocytes) staining was increased in the hippocampus of 18‐month 3xTg mice and was effectively prevented by TB treatment. Additionally, markers of oxidative stress, 4‐HNE and acrolein adducts, were also increased in the molecular layer of the hippocampus and attenuated in TB treated mice.ConclusionThese studies demonstrate that TB treatment after initiation of Aβ deposition in the subiculum dramatically abrogates the loss of neurologic function in 3xTg mice as demonstrated by increased memory, cognition, and neuromuscular function. Moreover, these increases coincide with attenuated AD‐associated pathology in the hippocampus of TB‐treated 3xTg mice. Importantly, these data indicate that treatment with a butyrate pro‐drug can be integrated into treatment strategies to preserve cognitive and neuromuscular functions in patients in the prodromal phase of AD.

Aerobic physical exercise versus dual-task cognitive walking in cognitive rehabilitation of people with stroke: a randomized clinical trial.

Stroke is a neurological deficit caused by an acute focal injury to the central nervous system due to vascular injury that can result in loss of neurological function, lasting brain damage, long-term disability and, in some cases, death. The literature reports that aerobic physical exercise, as well as dual-task cognitive walking, are used for the cognitive recovery of people with stroke. We aimed to assess whether aerobic physical exercise influences post-stroke cognitive recovery, namely performance on selective and sustained attention. We tested the hypothesis that post-stroke aerobic physical exercise leads to more significant gains than post-stroke dual-task cognitive walking. We used a Randomized Clinical Trial, single-blind, parallel group, to verify the existence of differences between two groups. A total of 34 patients with subacute to chronic stroke were divided into two groups to train three times a week for 12 weeks: the aerobic physical exercise (PE) group engaged in 20 min on a treadmill, 20 min on a stationary bicycle and 5 min on a desk bike pedal exerciser per session; the dual-task (DT) gait exercise group walked for 45 min while simultaneously performing cognitive tasks per session. All participants were assessed on cognitive functioning with the Mini-Mental State Examination (MMSE) and d2 Test of Attention before acute interventions and post interventions. We have also applied a Visual Analog Scale to monitor the participants' perceived difficulty, pre-, post-acute, and post-chronic interventions. Participants also responded to a Borg Scale of perceived exertion following the acute and the final session of chronic training. A mixed model ANOVA revealed a significant interaction effect with a large effect size for most of the cognitive variables under study. The variables associated with the d2 Test of Attention showed significant differences between the groups, mainly from T0 to T2. Also for MMSE, an ANOVA revealed a significant interaction effect with significant improvements from T0 to T2. Our results strongly suggest that aerobic physical exercise is more beneficial than dual-task cognitive-gait exercise since in the PE group, cognitive attention scores increase, and cognitive impairment and perception of exertion decrease, compared to the DT group. These findings support that PE provides more significant benefits for patients post-stroke when compared to DT.

How Can Radiomics Help the Clinical Management of Patients with Acute Ischemic Stroke?

Acute ischemic stroke (AIS) is the loss of neurological function due to a sudden reduction in cerebral blood flow and is a leading cause of disability and death worldwide. The field of radiological imaging has experienced growth in recent years, which could be boosted by the advent of artificial intelligence. One of the latest innovations in artificial intelligence is radiomics, which is based on the fact that a large amount of quantitative data can be extracted from radiological images, from which patterns can be identified and associated with specific pathologies. Since its inception, radiomics has been particularly associated with the field of oncology and has shown promising results in a wide range of clinical situations. The performance of radiomics in non-tumour pathologies has been increasingly explored in recent years, and the results continue to be promising. The aim of this review is to explore the potential applications of radiomics in AIS patients and to theorize how radiomics may change the paradigm for these patients in the coming years.

Difference in management of patients with prostate cancer and spinal cord compression in teaching vs non-teaching hospitals in the United States.

e17116 Background: Spinal Cord Compression (SCC) secondary to metastatic prostate cancer is a complication that can lead to irreversible loss of neurologic function. Many factors including age, comorbidities, severity of the compression, and neurological deficit can affect the treatment from conservative management to radiation and surgery. We aimed to study the difference in practice patterns and their outcomes in teaching hospitals (TH) vs non-teaching hospitals (NTH) in the United States. Methods: Utilizing the National Inpatient Sample Database (NIS), we conducted a retrospective cohort study on hospitalizations with prostate cancer and SCC between 2016 and 2020 across the US. Patients were divided into two groups of TH and NTH. Demographics, comorbidities, treatment modality, length of hospitalization, costs, and mortality were compared between the two groups. We also studied patients’ characteristics and outcomes in TH and NTH according to their treatment strategy. Results: We identified 11,380 metastatic prostate cancer patients with SCC admitted to the hospitals with a 7-day median length of stay. While 27.4% underwent surgical procedure and 11.5% received inpatient radiation, 61.2% were treated conservatively. The median cost of hospitalization was $21,922 in TH and $15,141 in NTH ( P< 0.001). Although the median age and Charlson Comorbidity Index did not differ between two groups ( P =0.12 & 0.66 respectively), patients in TH were more likely to receive intervention (either radiation or surgery) compared to NTH (Surgery: 28.2% in TH vs 23.0% in NTH; P <0.01 & Radiation: 12.1% in TH vs 8.2% in NTH; P <0.01). Mortality rate was lower in TH than NTH (4.5% vs 7.9%; P < 0.01). In both TH and NTH, patients with private insurance were more likely to undergo surgery (TH: Surgery 25.1% vs Radiation 18.8%; P< 0.05 & NTH: Surgery 27.0% vs 6.9% P< 0.05). Among different races, black patients were more likely to receive radiation than surgery in TH (34.2% vs 26.8%; P <0.05). With no difference in comorbidities between surgery and radiation group in TH ( P =0.16), all-cause mortality was higher for those who received radiation than for surgery (4.4% vs 1.9%; P <0.05) . Conclusions: This study indicated that practice pattern for the management of SCC in prostate cancer is different in teaching and non-teaching hospitals. In addition to more surgery being performed in teaching hospitals, the mortality rate was also lower. There was an association between race and insurance type with different treatment modalities. We also revealed that all-cause mortality was higher with radiation therapy compared to surgery in teaching hospitals.

Artificial Intelligence and Machine Learning in the Diagnosis and Management of Stroke: A Narrative Review of United States Food and Drug Administration-Approved Technologies.

Stroke is an emergency in which delays in treatment can lead to significant loss of neurological function and be fatal. Technologies that increase the speed and accuracy of stroke diagnosis or assist in post-stroke rehabilitation can improve patient outcomes. No resource exists that comprehensively assesses artificial intelligence/machine learning (AI/ML)-enabled technologies indicated for the management of ischemic and hemorrhagic stroke. We queried a United States Food and Drug Administration (FDA) database, along with PubMed and private company websites, to identify the recent literature assessing the clinical performance of FDA-approved AI/ML-enabled technologies. The FDA has approved 22 AI/ML-enabled technologies that triage brain imaging for more immediate diagnosis or promote post-stroke neurological/functional recovery. Technologies that assist with diagnosis predominantly use convolutional neural networks to identify abnormal brain images (e.g., CT perfusion). These technologies perform comparably to neuroradiologists, improve clinical workflows (e.g., time from scan acquisition to reading), and improve patient outcomes (e.g., days spent in the neurological ICU). Two devices are indicated for post-stroke rehabilitation by leveraging neuromodulation techniques. Multiple FDA-approved technologies exist that can help clinicians better diagnose and manage stroke. This review summarizes the most up-to-date literature regarding the functionality, performance, and utility of these technologies so clinicians can make informed decisions when using them in practice.

Oxygen-Glucose Deprivation in Organotypic Hippocampal Cultures Leads to Cytoskeleton Rearrangement and Immune Activation: Link to the Potential Pathomechanism of Ischaemic Stroke.

Ischaemic stroke is characterized by a sudden loss of blood circulation to an area of the brain, resulting in a corresponding loss of neurologic function. As a result of this process, neurons in the ischaemic core are deprived of oxygen and trophic substances and are consequently destroyed. Tissue damage in brain ischaemia results from a complex pathophysiological cascade comprising various distinct pathological events. Ischaemia leads to brain damage by stimulating many processes, such as excitotoxicity, oxidative stress, inflammation, acidotoxicity, and apoptosis. Nevertheless, less attention has been given to biophysical factors, including the organization of the cytoskeleton and the mechanical properties of cells. Therefore, in the present study, we sought to evaluate whether the oxygen-glucose deprivation (OGD) procedure, which is a commonly accepted experimental model of ischaemia, could affect cytoskeleton organization and the paracrine immune response. The abovementioned aspects were examined ex vivo in organotypic hippocampal cultures (OHCs) subjected to the OGD procedure. We measured cell death/viability, nitric oxide (NO) release, and hypoxia-inducible factor 1α (HIF-1α) levels. Next, the impact of the OGD procedure on cytoskeletal organization was evaluated using combined confocal fluorescence microscopy (CFM) and atomic force microscopy (AFM). Concurrently, to find whether there is a correlation between biophysical properties and the immune response, we examined the impact of OGD on the levels of crucial ischaemia cytokines (IL-1β, IL-6, IL-18, TNF-α, IL-10, IL-4) and chemokines (CCL3, CCL5, CXCL10) in OHCs and calculated Pearsons' and Spearman's rank correlation coefficients. The results of the current study demonstrated that the OGD procedure intensified cell death and nitric oxide release and led to the potentiation of HIF-1α release in OHCs. Moreover, we presented significant disturbances in the organization of the cytoskeleton (actin fibers, microtubular network) and cytoskeleton-associated protein 2 (MAP-2), which is a neuronal marker. Simultaneously, our study provided new evidence that the OGD procedure leads to the stiffening of OHCs and a malfunction in immune homeostasis. A negative linear correlation between tissue stiffness and branched IBA1 positive cells after the OGD procedure suggests the pro-inflammatory polarization of microglia. Moreover, the negative correlation of pro- and positive anti-inflammatory factors with actin fibers density indicates an opposing effect of the immune mediators on the rearrangement of cytoskeleton induced by OGD procedure in OHCs. Our study constitutes a basis for further research and provides a rationale for integrating biomechanical and biochemical methods in studying the pathomechanism of stroke-related brain damage. Furthermore, presented data pointed out the interesting direction of proof-of-concept studies, in which follow-up may establish new targets for brain ischemia therapy.

Insights into Advanced Neurological Dysfunction Mechanisms Following DBS Surgery in Parkinson's Patients: Neuroinflammation and Pyroptosis.

Parkinson's disease is a severe neurodegenerative disorder. Currently, deep brain electrical stimulation (DBS) is the first line of surgical treatment. However, serious neurological impairments such as speech disorders, disturbances of consciousness, and depression after surgery limit the efficacy of treatment. In this review, we summarize the recent experimental and clinical studies that have explored the possible causes of neurological deficits after DBS. Furthermore, we tried to identify clues from oxidative stress and pathological changes in patients that could lead to the activation of microglia and astrocytes in DBS surgical injury. Notably, reliable evidence supports the idea that neuroinflammation is caused by microglia and astrocytes, which may contribute to caspase-1 pathway-mediated neuronal pyroptosis. Finally, existing drugs and treatments may partially ameliorate the loss of neurological function in patients following DBS surgery by exerting neuroprotective effects.

Analysis of the efficacy of microdissection of paravebous sinus meningiomas invading large venous sinuses

ObjectiveThe management of paravebous sinus meningiomas that invade major venous sinuses is a subject of debate, particularly concerning the necessity of complete resection of the tumor and reconstruction of the venous sinus. This article aims to demonstrate the outcomes of total removal of the lesion (including the invading venous sinus portion) and the effects of restoring or not restoring venous circulation in terms of recurrence of the tumor, mortality, and post-operative complications.MethodsThe authors conducted a study involving 68 patients with paravebous sinus meningiomas. Of the 60 parasagittal meningiomas, 23 were located in the anterior third, 30 in the middle third, and 7 in the posterior third. Additionally, 3 lesions were located in the sinus confluence area, and 5 in the transverse sinus. All patients underwent surgery, and the degree of venous sinus involvement was classified into six types. For type I meningiomas, the outer layer of the sinus wall was stripped off. For types II to VI, two strategies were employed: non-constitutional, wherein the tumor and affected venous sinuses were removed without repair, and reconstructive, wherein the tumor was completely removed and the venous sinuses were sutured or repaired. Karnofsky Performance Status (KPS) scale and Magnetic Resonance Venography (MRV) were utilized to assess the outcomes of the surgical procedures.ResultsThe study group of 68 patients underwent complete tumor resection in 97.1%, with sinus reconstruction attempted in 84.4% of cases with sinus wall and sinus cavity invasion. The recurrence rate of this group was 5.9%, with follow-up ranging from 33 to 57 months. It was found that the recurrence rate was significantly higher in cases with incomplete resection than in those with complete resection. The overall mortality rate was 4.4%, with all cases resulting from malignant brain swelling due to the failure to perform venous reconstruction after resectioning of the meningioma type VI. Furthermore, 10.3% of patients experienced worsening symptoms of neurological deficits or complete loss of neurological function, with a significantly higher incidence in those without venous reconstruction than in the venous reconstruction group (P < 0.0001, Fisher test). No statistically significant pre-operative and post-operative KPS differences were observed in patients with type I to V. However, in patients with type VI (who did not receive venous reconstruction), the post-operative KPS score was significantly worse.ConclusionThe results of this study suggest the necessity of a complete resection of the tumor, including the invasive venous sinus component, as the recurrence rate was found to be relatively low at 5.9%. Moreover, patients who did not undergo venous reconstruction showed significant deterioration in their clinical condition compared to other subgroups, thus highlighting the importance of venous sinus reconstruction.

Brain region dependent molecular signatures and myelin repair following chronic demyelination.

Multiple sclerosis (MS) is the most prevalent demyelinating disease of the central nervous system, characterized by myelin destruction, axonal degeneration, and progressive loss of neurological functions. Remyelination is considered an axonal protection strategy and may enable functional recovery, but the mechanisms of myelin repair, especially after chronic demyelination, remain poorly understood. Here, we used the cuprizone demyelination mouse model to investigate spatiotemporal characteristics of acute and chronic de- and remyelination and motor functional recovery following chronic demyelination. Extensive remyelination occurred after both the acute and chronic insults, but with less robust glial responses and slower myelin recovery in the chronic phase. Axonal damage was found at the ultrastructural level in the chronically demyelinated corpus callosum and in remyelinated axons in the somatosensory cortex. Unexpectedly, we observed the development of functional motor deficits after chronic remyelination. RNA sequencing of isolated brain regions revealed significantly altered transcripts across the corpus callosum, cortex and hippocampus. Pathway analysis identified selective upregulation of extracellular matrix/collagen pathways and synaptic signaling in the chronically de/remyelinating white matter. Our study demonstrates regional differences of intrinsic reparative mechanisms after a chronic demyelinating insult and suggests a potential link between long-term motor function alterations and continued axonal damage during chronic remyelination. Moreover, the transcriptome dataset of three brain regions and over an extended de/remyelination period provides a valuable platform for a better understanding of the mechanisms of myelin repair as well as the identification of potential targets for effective remyelination and neuroprotection for progressive MS.

Administration of prosaposin-derived neurotrophic factor to neural tube defects facilitates regeneration and restores neurological functions.

Neural tube defects (NTDs) cause fetal and pediatric deaths or lifelong neurological disabilities. No effective treatment is currently available for NTDs. We attempted to elucidate the pathogenesis of NTDs and propose a therapeutic strategy. Intra-amniotic treatment with prosaposin-derived 18-mer peptide (PS18) protected the spinal cord from secondary damage and rescued neurological function in an established chicken model of spina bifida aperta (SBA), the severe type of NTDs. PS18 promoted the formation of a neuroectodermal covering over the defective neural tube within 24-h after treatment, enhanced the regeneration/restoration process, and decreased apoptotic activity in the developing spinal cord. PS18 reduced the SBA wound and almost completely formed the spinal cord. SBA chicks that received PS18 exhibited relatively normal walking and sensorimotor responses, and reduced pain-associated behavior in postnatal life. In conclusion, PS18 is a promising therapeutic agent for NTDs and may be useful for treating other types of spinal cord injuries.

Experimental Treatments for Spinal Cord Injury: A Systematic Review and Meta-Analysis.

Spinal cord injury (SCI) is characterized by a complex and prolonged injury process that exacerbates the damage induced by the primary injury and inhibits the potential for regeneration. SCI frequently results in the devastating loss of neurological functions and thus has serious consequences on patient quality of life. Current treatments are limited and focus on early interventions for the acute management of complications. Therefore, the development of novel treatments targeting ongoing injury processes is required to improve SCI outcomes. We aimed to systematically review studies published in the last 10 years that examined experimental treatments with neuroregenerative and neuroprotective capabilities for the improvement of SCI. We analyzed treatments from 44 studies that were identified through a systematic literature search using three databases: PubMed, Web of Science and EMBASE (searched through Ovid). We performed a meta-analysis for Basso-Beattie-Bresnahan (BBB) locomotion test data and collected immunohistochemistry results to demonstrate neuroregenerative and neuroprotective properties of the treatments, respectively. The two treatments that illustrated the most significant improvements in functional recovery using the BBB test were the combined use of tetrahedral framework nucleic acid (tFNA) with neural stem cells (NSCs) and Fortasyn® Connect (FC) supplementation. Both treatments also attenuated secondary injury processes as demonstrated through immunohistochemistry. Combined tFNA with NSCs and FC supplementation are promising treatments for the improvement of SCI as they both demonstrate neuroregenerative and neuroprotective properties. Further pre-clinical testing is required to validate and determine the long-term efficacies of these treatments for the improvement of SCI.

Comprehensive analysis of m6A methylation modification in chronic spinal cord injury in mice.

Chronic spinal cord injury (CSCI) is a catastrophic disease of the central nervous system (CNS), resulting in partial or complete loss of neurological function. N6-methyladenosine (m6A) is the most common form of reversible posttranslational modification at the RNA level. However, the role of m6A modification in CSCI remains unknown. In this study, we established a CSCI model using a water-absorbable polyurethane polymer, with behavioral assessment, electrophysiological analysis, and histochemical staining for validation. Methylated RNA immunoprecipitation sequencing (meRIP-seq) and messenger RNA sequencing (mRNA-seq) were jointly explored to compare the differences between CSCI spinal tissue and normal spinal tissue. Furthermore, real-time quantitative reverse transcription pcr (qRT-PCR), western blot analysis, and immunofluorescence staining were used to analyze m6A modification-related proteins. We found that water-absorbable polyurethane polymer simulated well chronic spinal cord compression. Basso mouse scale scores and electrophysiological analysis showed continuous neurological function decline after chronic compression of the spinal cord. meRIP-seq identified 642 differentially modified m6A genes, among which 263 genes were downregulated and 379 genes were upregulated. mRNA-seq showed that 1544 genes were upregulated and 290 genes were downregulated after CSCI. Gene Ontologyterms and enriched Kyoto Encyclopedia of Genes and Genomespathways were also identified. qRT-PCR, western blotting, and immunofluorescence staining showed that Mettl14, Ythdf1, and Ythdf3 were significantly upregulated after CSCI. Our study revealed a comprehensive profile of m6A modifications in CSCI which may act as a valuable key for future research on CSCI.