Neurological Deficiency Research Articles

Different Ways to Die: Cell Death Pathways and Their Association With Spinal Cord Injury.

Cell death is a systematic/nonsystematic process of cessation of normal morphology and functional properties of the cell to replace and recycle old cells with new also promoting inflammation in some cases. It is a complicated process comprising multiple pathways. Some are well-explored, and others have just begun to be. The research on appropriate control of cell death pathways after acute and chronic damage of neuronal cells is being widely researched today due to the lack of regeneration and recovering potential of a neuronal cell after sustaining damage and the inability to control the direction of neuronal growth. In the progression and onset of various neurological diseases, impairments in programmed cell death signaling processes, like necroptosis, apoptosis, ferroptosis, pyroptosis, and pathways directly or indirectly linked, like autophagy as in nonprogrammed necrosis, are observed. Spinal cord injury (SCI) involves the temporary or permanent disruption of motor activities due to the death of a neuronal and glial cell in the spinal cord accompanied by axonal degeneration. Recent years have seen a significant increase in research on the intricate biochemical interactions that occur after a SCI. Different cell death pathways may significantly impact the subsequent damage processes that lead to the eventual neurological deficiency after an injury to the spinal cord. A better knowledge of the molecular basis of the involved cell death pathways might help enhance neuronal and glial survival and neurological deficits, promoting a curative path for SCI.

Synergic neurotoxic and paraneoplastic neurological syndrome during cysplatin chemotherapy in case of transplanted experimental rat lymphoma

The aim of the study is assessment of combined effect of homotransplanted rat lymphoma (Pliss Lymphosrcoma) growth and antitumor therapy (cysplatin) upon the functioning of the nervous system was accomplished in 160 male Wistar rats, divided into four groups: intact animals, rats treated with cysplatin, rats with transplanted lymphoma, and rats with transplanted lymphoma that received cysplatin treatment. The neurologic deficiency degree as well as basic myelin protein peripheral blood level (nervous system impairment hematological marker) were comparatively assessed. Tumor development was accompanied with emergence and subsequent growth of neurologic deficit in locomotory, sensory and coordinative spheres as well as pronounced growth of basic myeline protein plasma level thus making this model a valid test-system for studying paraneoplastic neurologic syndrome. Cysplatin has produced a non-selective toxic effect upon the nervous system of the experimental animals within its therapeutic window range documented by neurotoxic syndrome. Subsequently along with elimination of cysplatin and its derivates from the organism, systemic neurotoxic effect intensity decreased and the nervous system functional state parameters returned to control values. Using cysplatin for the treatment of homotransplanted experimental rat lymphoma results in synergic neurotoxic and paraneoplastic neurological syndrome through combined injury of the nervous system.

Safety, Feasibility and Efficacy of Lokomat® and Armeo®Spring Training in Deconditioned Paediatric, Adolescent and Young Adult Cancer Patients

Rehabilitation robotics is a field of study which aims to understand and augment rehabilitation through the use of robotics devices. This proof of concept study aimed to test the safety (no. adverse events, incidence of infection), feasibility (program demand, adherence, participant satisfaction) and efficacy (Peak Oxygen uptake (VO2peak), 6-min walk test, gait speeds, Canadian Occupational Performance Measure, quality of life) of Lokomat® and Armeo®Spring training in children and adolescents and young adults (AYAs) during or soon after cancer treatment. This was a 6-week single arm pre-post study. Cancer patients with significant musculoskeletal, neurological, gait and/or upper limb deficiency aged 5 to 25 years were recruited. The rehabilitation program included access to two robotic orthoses: the Lokomat® and/or Armeo®Spring. Robotic devices utilised real-time biofeedback and computer games to engage and guide participants through a repetitive functional range of movement aimed at improving functional deficiencies. Progressive increases in exercise intensity and duration were encouraged. Twentey-eight participants were approached for study; twenty-one consented. Seventy-six percent completed the six-week intervention with an overall adherence of 83%. The mean participant satisfaction score was 8.8/10. Forty-nine adverse events were recorded throughout the course of the study, forty-five grade 1, three grade 2 and one grade 3. No adverse events led to withdrawal from the study. Preliminary efficacy results indicate large beneficial effects on VO2peak (r = 0.63), 10 m comfortable pace walk (r = 0.51) and maximal pace walk (r = 0.60), 6-min walk test (r = 0.60), maximal back and leg strength (r = 0.71), trunk flexibility (r = 0.60), The European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ C30) (r = 0.61), Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT F) r = 0.53 and the Canadian Occupational Performance Measure, satisfaction (r = 0.88) and performance scores (r = 0.83), and moderate beneficial effects on Leisure Score Index (LSI) (r = 0.30). Our results suggest that Lokomat® and Armeo®Spring training is safe and feasible for use in children and AYAs who are currently undergoing or have recently completed cancer therapy. A larger controlled trial investigating the efficacy of robotics rehabilitation in this cohort is warranted.

Recurrence rate of intervertebral disc disease in surgically treated French Bulldogs: a retrospective study (2009–2019)

BackgroundIntervertebral disc disease (IVDD) is a common diagnosis and well-investigated pathological condition in French Bulldogs with neurological deficiencies. However there is currently only one recently published retrospective descriptive study looking for recurrence rates of IVDD in French Bulldogs. Medical reports of French Bulldogs with a first episode of IVDD and surgical treatment were evaluated and reviewed for clinical signs of recurrence. Risk factors for Total-Recurrence, Cervical- and Thoracolumbar-Recurrence were evaluated by means of logistic regression models. The aim of this study was to assess frequency and risk factors associated with the recurrence of IVDD in French Bulldogs.ResultsOne hundred twenty-seven French Bulldogs with a first episode of IVDD and surgical treatment were evaluated. 52.7% (67/127) of these patients showed signs of recurrence. The recurrence rate in the cervical spine was slightly lower (47%) compared to the thoracolumbar spine (56.6%). A significant association with recurrence could be found for the factor age: French Bulldogs with a first episode of IVDD ≤ 3 years seem to be prone for Total-Recurrence (P = 0.002) and Cervical-Recurrence (with ORs ranging from 0.02 to 0.03 for patients older than 3 years). 50% of the recurrences (median) occurred within the first 12 month after the first episode of IVDD.ConclusionsRecurrence of IVDD can be expected in more than half of French Bulldogs affected by IVDD. Especially young French Bulldogs are prone for recurrence in cervical spine. Almost every fourth patient with IVDD suffers from a recurrence within 12 months. Future dog owners should be informed about the risk of IVDD and the early onset of recurrences in French Bulldogs.

Comparison of Outcome in Unilateral and Bilateral Sphinctorotomy in Patients of Haemorrhoidectomy

The anal canal is the site of the dilated veins known as haemorrhoids. They're essential for achieving and maintaining complete continence. In the anal canal, they can be either internal or external. Haemorrhoids can cause pain, pruritis, mucous discharge, mucosal prolapse, bleeding (which is often painless), and brilliant red haemorrhage. 2 There are four different types of haemorrhoids, ranging from first degree (just bleeding) to fourth degree (prolapse and stay reduced on reduction) (permanently prolapsed).3 Even though every case of haemorrhoids bleeds, there are different categories based on how far the haemorrhoids have prolapsed. Only when things get complicated do you see any signs. 4 Objective and Methodology: This research aims to compare the rates of pain experienced by patients after undergoing haemorrhoidectomy, lateral internal sphincterotomy, and bilateral internal sphincterotomy. A Randomized Controlled Trial (RCT) study design was used for this investigation. The investigation took place at the Surgery Department of Allied Hospital in Faisalabad (March to September 2021). In all, 140 patients aged 25-65 with severe haemorrhoids (grades III and IV) were chosen. Any neurological deficiency or chronic pain syndrome, renal disease, or bleeding disorders, as well as patients with recurring haemorrhoids or other anorectal pathology (fistula in ano, anal fissures, etc.), were not included in the study. Hemorrhoidectomy with bilateral internal sphincterotomy (Group BL) and hemorrhoidectomy with lateral internal sphincterotomy (Group UL) were performed on patients. After 24 postoperative hours, all patients were evaluated for postoperative pain. Results: Patients in Group BL had a mean age of 45.36 10.33 years, whereas those in Group UL had a mean age of 43.94 10.22 years. A whopping 76 (54.29%) of the patients fell within the 25-45-year-old age range. The ratio of male to female patients was 2.1:1, with 95 males (67.86%) and 45 females (32.14%) in a total of 140 patients. Pain was experienced by 4 (5.71%) of my patients following haemorrhoidectomy with bilateral internal sphincterotomy and by 25 (35.71%) of my patients following haemorrhoidectomy with lateral internal sphincterotomy (p 0.0001). Conclusion: Patients undergoing hemorrhoidectomy were less likely to experience postoperative pain if bilateral internal sphincterotomy was performed. Keywords: Haemorrhoids, internal sphincterotomy, post-operative pain.

Статистика патологий, приводящих к развитию сирингомиелии

Syringomyelia is a neurological disease caused by the presence of a fluid-filled cavity in the parenchyma of the spinal cord or the central canal. This pathology is widespread among dogs of small breeds. This pathology is widespread among dogs of small breeds. This is usually observed in combination with a malformation – Chiari malformation. The article deals with pathologies leading to the development of syringomyelia as a result of other deformities of the spinal column. The only and sufficiently effective method of investigation for diagnosis is magnetic resonance imaging. This article is based on a study of 100 dogs with neurological deficiency, body weight from 2 to 15 kg, where syringomyelia was the main and secondary pathology. The studied animals are representatives of different breeds.

Диагностика и лечение сирингомиелии у собак

This work is devoted to the methods of diagnosis and treatment of syringomyelia in different breeds of dogs. Magnetic resonance imaging is the only and sufficiently effective diagnostic method for making a diagnosis. A small and asymptomatic sirin often does not require treatment, surgical intervention is indicated when analgesics do not eliminate discomfort or in the presence of a neurological deficiency. Medication may be chosen for patients with minor pain. This article was a study of 240 dogs, weighing from 2 to 25 kg, with neurological deficiency, where syringomyelia was the main and secondary pathology, the studied animals were representatives of different dog breeds.

Serum brain damage biomarkers as a diagnostic and prognostic tool in ischemic stroke

To study serum quantities of neuron specific enolase (NSE), glial fibrillary acidic protein (GFAP) and NR2-antibodies (NR2-ab) in various cerebrovascular pathology and assess their value as a panel used as a diagnostic and predictive tool for stroke. NSE, GFAP and NR2-ab serum levels were measured twice for 84 patients with ischemic stroke (IS) and 8 patients with hemorrhagic stroke (HI), once for 8 patients with transient ischemic attack (TIA), 26 patients with chronic brain ischemia (CBI), 27 healthy volunteers (HV). NSE and GFAP levels were significantly higher in IS than in CBI and HV patients, and NR2-ab levels in IS were higher than in TIA and lower than in HV. In patients with more pronounced neurological deficiency and less favorable functional outcome by day 10-14 of IS, the levels of NSE, GFAP and NR2-ab were higher. Sensitivity and specificity of biomarker panel was higher than with their separate application. The NSE, GFAP and NR2-ab biomarkers have a diagnostic and predictive value for IS.

Диагностические критерии формирования морфологических изменений головного мозга у детей с перинатальным гипоксическим поражением нервной системы

Objective. To determine the diagnostic criteria of morphological changes in children with perinatal hypoxic brain injury. Patients and Methods. The study included 58 full-term newborns with severe hypoxic brain damages who, according to MRI of brain performed on 2–10 days of life, had low rates of diffusion processes of the white matter of the cerebral hemispheres – diffusion coefficient (Ds) of less than 1.35 × 10–3 mm2/s. Children received treatment in the intensive care unit of the regional perinatal center of Krasnodar Children's Clinical Hospital. Follow-up MRI was performed at the 4th week of life. Observation of children was carried out up to 2 years of age. Results. Denominated destructive changes in the nervous tissue with multicystic encephalomalacia were identified in 23 (40%) newborns (group 1). The range of values of Ds of the white matter of cerebral hemispheres in children of the 1st group was 0.60–1.11 × 10–3 m2/s. In the remaining 35 (60%) children (group 2), hypoxic brain damage was manifested by the expansion of the subarachnoid space, the interhemispheric fissure, and the lateral ventricles. These changes were reflected in a decrease in the volume of brain parenchyma with the persistent neurological deficiency in the future (disorders of psycho-speech development, cerebral palsy, structural epilepsy). The range of values of the Ds of the white matter of the cerebral hemispheres in children of the second group was 1.14–1.35 × 10–3 mm2/s. Conclusions. Using the modern high-tech methods of neuroimaging makes it possible to determine the diagnostic criteria for damaging effects of hypoxia in children with perinatal brain injury and in early stage to identify morphological changes in brain tissue. Key words: hypoxia, brain, children, magnetic resonance imaging, neurological outcome

Методы оценки деформации грудного отдела позвоночного столба при кифозе у собак

Kyphotic deformity of the vertebral column is determined by a significant decrease in the ability to support the pelvic limbs, the presence of pain syndrome, and in severe cases, pelvic limb plegia in dogs. The diagnostic component of this disease and the prognosis of surgical intervention, as well as the postoperative course, require the search for an algorithm for controlling the development of the pathological process and performing operations. The study was conducted in order to present a comparative characteristic of methods for measuring kyphotic deformity in the sagittal plane and is based on the observation and surgical treatment of 11 dogs of chondrodystrophic breeds for the period from 2017 to 2020 with a diagnosis of kyphosis of the thoracic spine. The following breeds were under observation: 4 pugs, 5 French bulldogs, 2 Boston terriers. All animals at the time of observation were aged from 9 months to 1,5 years. A comparative evaluation of the Cobb–Lipmann and Ferguson methods for dogs was performed. The analysis was carried out on the basis of the following data: breed, gender, age, body weight, duration of clinical signs until the moment of treatment at the clinic, the results of neurological examination at the initial consultation, the results of magnetic resonance imaging (MRI), computed tomography (CT) and radiography of the thoracic spine. As a result of the study, it was found that the average angles of kyphosis in animals with physiological kyphosis and the absence of neurological deficiency vary from 20 ° to 28 °. In the presence of pronounced deformity and manifestation of neurological deficit of varying degrees, the angle will be from 36 ° to 49 °.

Relationship to Bariatric Surgery and their Gastrointestinal Hormones: how we Weight Loss?

Obesity is a disease related to severe metabolic comorbidities due to the high accumulation of body fat. In the context of this pandemic, bariatric surgery is the most effective treatment for the long-term resolution of the disease, having both structural and anatomic and hormonal effects on the gastrointestinal tract. The hormones analyzed in this review are cholecystokinin, secrete, gastrin, glucagon-like peptide 1 (GLP-1), peptide YY, pancreatic polypeptide, leptin, adiponectin, ghrelin, glucose, cholesterol, gastric inhibitory peptide, insulin, and glucagon. After bariatric procedures, changes in vitamins and micronutrients are also observed, which can lead to anemia, changes in coagulation, bone metabolism, neurological, and immunological deficiencies.

Up-regulation of lncRNA NEAT1 in cerebral ischemic stroke promotes activation of astrocytes by modulation of miR-488-3p/RAC1

We aim to research the molecular mechanism of lncRNA NEAT1 in the activation of astrocytes in a cerebral ischemia-reperfusion injury model. Mouse model of cerebral ischemia-reperfusion injury was constructed, and shNEAT1 was transfected. The infarct area, brain water content, and neurological deficiency were detected. Immunofluorescence detection and fluorescence in situ hybridization (FISH) assay were processed to detect glial fibrillary acidic protein (GFAP) expression. Astrocyte cells were cultured for oxygen-glucose deprivation/re-oxygenation (OGD)/re-oxygenation model construction. After treatment by shNEAT1, miR-488-3p mimic, miR-488-3p inhibitor, Q-PCR assay, western blot and ELISA were undertaken to detect the expressions of NEAT1, miR-488-3p, RAC1, inflammatory cytokines, RAC1 and GFAP. Dual luciferase reporter assay and RNA-binding protein immunoprecipitation (RIP) assay were used to verify the binding of NEAT1, miR-488-3p and RAC1. The expression of NEAT1 in brain tissue was significantly higher than that in Sham operation group. Knockdown of NEAT1 inhibited the brain damage caused by middle cerebral artery occlusion (MCAO) treatment, reduced the inflammatory response, and suppressed the activation of astrocytes. By constructing an in vitro OGD/R cell model, it was found that NEAT1 knockdown also inhibited the activation of astrocytes caused by OGD/R. Knockdown of NEAT1 caused the up-regulation of miR-488-3p and the down-regulation of RAC1. Knockdown of miR-488-3p or over-expression of RAC1 reversed the inhibitory effect of shNEAT1 on OGD/R-induced astrocyte activation. Over-expression of NEAT1 in cerebral ischemic stroke promotes activation of astrocytes by modulation miR-488-3p/RAC1, which is proved in vitro. Our study may provide a new idea for the diagnosis and treatment of MCAO.

Novel localization of folate transport systems in the murine central nervous system

BackgroundFolates are a family of B9 vitamins that serve as one-carbon donors critical to biosynthetic processes required for the development and function of the central nervous system (CNS) in mammals. Folate transport is mediated by three highly specific systems: (1) folate receptor alpha (FRα; FOLR1/Folr1), (2) the reduced folate-carrier (RFC; SLC19A1/Slc19a1) and (3) the proton-coupled folate transporter (PCFT; SLC46A1/Slc46a1). Folate transport into and out of the CNS occurs at the blood–cerebrospinal fluid barrier (BCSFB), mediated by FRα and PCFT. Impairment of folate transport at the BCSFB results in cerebral folate deficiency in infants characterized by severe neurological deficiencies and seizures. In contrast to the BCSFB, CNS folate transport at other brain barriers and brain parenchymal cells has not been extensively investigated. The aim of this study is to characterize folate transport systems in the murine CNS at several known barriers encompassing the BCSFB, arachnoid barrier (AB), blood–brain barrier (BBB) and parenchymal cells (astrocytes, microglia, neurons).MethodsApplying immunohistochemistry, localization of folate transport systems (RFC, PCFT, FRα) was examined at CNS barriers and parenchymal sites in wildtype (C57BL6/N) mice. Subcellular localization of the folate transport systems was further assessed in an in vitro model of the mouse AB. Gene and protein expression was analyzed in several in vitro models of brain barriers and parenchyma by qPCR and western blot analysis.ResultsRFC, PCFT, and FRα expression was localized within the BCSFB and BBB consistent with previous reports. Only RFC and PCFT expression was detected at the AB. Varied levels of RFC and PCFT expression were detected in neuronal and glial cells.ConclusionsLocalization of RFC and PCFT within the AB, described here for the first time, suggest that AB may contribute to folate transport between the peripheral circulation and the CSF. RFC and PCFT expression observed in astrocytes and microglia is consistent with the role that one or both of these transporters may play in delivering folates into cells within brain parenchyma. These studies provide insights into mechanisms of folate transport in the CNS and may enhance our understanding of the critical role folates play in neurodevelopment and in the development of novel treatment strategies for disorders of brain folate deficiency due to impaired transporter function.

Effects of cranioplasty in cerebral blood perfusion using quantification with 99m-Tc HMPAO SPECT-CT.

Syndrome of the trephined or sinking skin flap syndrome is an underdiagnosed condition of craniectomized patients that usually improves after cranioplasty. Among the pathophysiological theories proposed, the changes of cerebral blood perfusion (CBP) caused by cranial defects might have a role in the neurological deficiencies observed. We aim to assess the regional cortex changes in CBP after cranioplasty with Technetium 99m hexamethylpropylene-amine oxime (99mTc-HMPAO) SPECT-CT. Twenty-eight craniectomized patients subject to cranioplasty were studied with 99mTc-HMPAO SPECT-CT in three different times, before cranioplasty, a week, and 3months after. The images were processed with quantification software comparing CBP of 24 cortical areas with a reference area, and with a database of controls. A mixed effects model and T-Student were used. CBP increased significantly in both hemispheres after cranioplasty, either using ratio (β=.019, p-value=.030 first postsurgical SPECT-CT and β=.021, p-value=.015 in the second study, vs. presurgical) or Z-score (β=.220, p-value=.026 and β=.279, p-value=.005, respectively). Nine areas of the damaged side had a significant lower CBP ratio and Z-score than the undamaged. Posterior cingulate showed an increased CBP ratio (p-value=.034) and Z-score (p-value=.028) in the first postsurgical SPECT-CT. These posterior cingulate changes represent a 4.83% increase in ratio and 91.04% in Z-Score (p-value=.035 and .040, respectively). CBP changes significantly in specific cortical areas after cranioplasty. Posterior cingulate changes might explain some improvements in attention impairments. SPECT-CT could be a useful tool to assess CBP changes in these patients and might be helpful in their clinical management.

SAP Principle Guided Free Hand Technique: A Secret for T1 to S1 Pedicle Screw Placement

Existing freehand techniques of screw placement mainly emphasized on various entry points and complex trajectory reference. The aim of this study is to illustrate a standardized and reliable freehand technique of pedicle screw insertion for open pedicle screw fixation with a universal entry point and a stereoscopic trajectory reference system and report the results from a single surgeon's clinical experience with the technique. In this study, the author respectively reviewed a total of 200 consecutive patients who had undergone open freehand pedicle screw fixation with Superior Articular Process (SAP) technique from January 2019 to May 2020. For accuracy and safety, all 200 cases had undergone postoperative X-ray while 33 cases including spinal deformity, infection, and tumor had received additional CT-scan. Screw accuracy was analyzed via a CT-based classification system with Student's t test. A total of 1126 screws had been placed from T1-S1 with SAP-guided freehand technique and the majority had been confirmed safe in X-ray without the need of CT scan. A total of 316 screws in deformity or infectious or tumor cases had undergone additional CT scan with 95.5% (189 of 198 screws) accuracy in thoracic group and 94.9% (112 of 118 screws) in lumbar group. The accuracy had been 90.5% (114 of 126 screws) in deformity group and 95.8% (182 of 190 screws) in non-deformity group. All perforation cases had been rated Grade B (<2 mm) without significant difference between the medial and the lateral (p < 0.05). No cases had been detected with significant neurological deficiencies. The mean intraoperative X-ray shots were 0.73 per screw. SAP-guidance is a reliable freehand technique for thoracic and lumbar pedicle screw instrument. It allows accurate and safe screw insertion in both non-deformity and deformity cases with less radiation exposure.

Cervical immobilization in trauma patients: soft collars better than rigid collars? A systematic review and meta-analysis.

Rigid cervical spine following trauma immobilization is recommended to reduce neurological disability and provide spinal stability. Soft collars have been proposed as a good alternative because of the complications related to rigid collars. The purpose of this study was to perform a systematic review on soft and rigid collars in the prehospital management of cervical trauma. A systematic review was performed following the PRISMA guidelines. Search terms were (immobilization) AND (collar) AND ((neck) OR (cervical)) to evaluate the range of motion (ROM) and evidence of clinical outcome for soft and rigid collars. A total of 18 studies met eligibility criteria including 2 clinical studies and 16 articles investigating the range of motion (ROM). Four hundred and ninety-six patients at a mean age of 32.5years (SD 16.8) were included. Measurements were performed in a seated position in twelve studies. Eight articles reported the ROM without a collar, 7 with a soft collar, and 15 with a rigid collar. There was no significant difference in flexion/extension, bending and rotation following immobilization with soft collars compared to no collar. Rigid collars provided significantly higher stability compared to no collar (p < 0.005) and to soft collars in flexion/extension and rotation movements (p < 0.05). The retrospective clinical studies showed no significant differences in secondary spinal cord injuries for soft collar (0.5%) and for rigid collar (1.1%). One study, comparing immobilization without a collar compared to that with a rigid collar, found a significant difference in neurologic deficiency and supraclavicular nerve lesion. Although rigid collars provide significant higher stability to no collar and to soft collars in flexion/ extension and rotation movements, clinical studies could not confirm a difference in neurological outcome. II, Systematic Review.

Analysis of Perioperative Nursing Intervention Effect of Cerebrovascular Intervention Patients Based on Intelligent Internet of Things.

The postoperative results of cerebrovascular surgery patients have been successfully used in medical practice using the Internet. The results obtained through data analysis were used in the study. So far, 120 patients who underwent cerebrovascular surgery from February 2018 to December 2018 have been enrolled. The selected class was divided into two groups: 60 psychiatric patients, a control group and an observation group. The former is medical treatment and the latter is postoperative treatment. Results: The results showed that the blood pressure of control group was lower than that of control group, and the incidence of adverse events was lower than that of control group (P < 0.05). Meanwhile, the average hospitalization rate of cerebrovascular disease patients in control group was lower than that in control group (P < 0.05). Conclusion: For patients with cerebrovascular disease, postoperative nursing can reduce the incidence of postoperative complications, reduce the risk of surgery, and improve the effect of surgery. Acute ischemic stroke refers to a kind of clinical syndrome caused by abnormal blood supply in the brain, resulting in ischemia, hypoxic brain tissue necrosis, and focal or comprehensive neurological deficiency. Among them, progressive cerebral infarction accounted for about 20~35%, and most occurred in the early stage of the disease (48~72)h.

Edaravone Dexborneol Alleviates Cerebral Ischemic Injury via MKP-1-Mediated Inhibition of MAPKs and Activation of Nrf2.

The edaravone and dexborneol concentrated solution for injection (edaravone-dexborneol) is a medication used clinically to treat neurological impairment induced by ischemic stroke. This study was aimed at investigating the preventive effects and the underlying mechanisms of edaravone-dexborneol on cerebral ischemic injury. A rat four-vessel occlusion (4-VO) model was established, and the neuronal injury and consequent neurological impairment of rats was investigated. Brain tissue malondialdehyde (MDA), myeloperoxidase (MPO), and nitric oxide (NO) levels were determined. The levels of proteins in mitogen-activated protein kinases (MAPKs), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor-κB (NF-κB) signaling pathways were determined by western immunoblotting. The function of mitogen-activated protein kinase phosphatase 1 (MKP-1) was investigated using both western blot and immunofluorescence methods, and the effect of the MKP-1 inhibitor, (2E)-2-benzylidene-3-(cyclohexylamino)-3H-inden-1-one (BCI), was investigated. The results indicated that edaravone-dexborneol alleviated neurological deficiency symptoms and decreased apoptosis and neuron damage in the hippocampal CA1 area of the ischemic rats. Edaravone-dexborneol increased the MKP-1 level; decreased the phosphorylation of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (p38 MAPK); inhibited NF-κB p65 activation; and boosted Nrf2 activation, all of which were partially reversed by the MKP-1 inhibitor, BCI. The above results indicated that the upregulation of MKP-1 contributed to the protective effects of edaravone-dexborneol against ischemic brain injury. Our findings support the hypothesis that edaravone-dexborneol can alleviate cerebral ischemic injury via the upregulation of MKP-1, which inhibits MAPKs and activates Nrf2.

Flufenamic acid improves survival and neurologic outcome after successful cardiopulmonary resuscitation in mice

BackgroundBrain injury is the main cause of high mortality and disability after successful cardiopulmonary resuscitation (CPR) from sudden cardiac arrest (CA). The transient receptor potential M4 (TRPM4) channel is a novel target for ameliorating blood–brain barrier (BBB) disruption and neuroinflammation. Herein, we tested whether flufenamic acid (FFA), which is reported to block TRPM4 with high potency, could confer neuroprotection against brain injury secondary to CA/CPR and whether its action was exerted by blocking the TRPM4 channel.MethodsWild-type (WT) and Trpm4 knockout (Trpm4−/−) mice subjected to 10-min CA/CPR were randomized to receive FFA or vehicle once daily. Post-CA/CPR brain injuries including neurologic deficits, survival rate, histological damage, edema formation, BBB destabilization and neuroinflammation were assessed.ResultsIn WT mice subjected to CA/CPR, FFA was effective in improving survival and neurologic outcome, reducing neuropathological injuries, attenuating brain edema, lessening the leakage of IgG and Evans blue dye, restoring tight junction protein expression and promoting microglia/macrophages from the pro-inflammatory subtype toward the anti-inflammatory subtype. In comparison to WT mice, Trpm4−/− mice exhibited less neurologic deficiency, milder histological impairment, more BBB integrity and more anti-inflammatory microglia/macrophage polarization. As expected, FFA did not provide a benefit of superposition compared with vehicle in the Trpm4−/− mice after CA/CPR.ConclusionsFFA mitigates BBB breach and modifies the functional status of microglia/macrophages, thereby improving survival and neurologic deficits following CA/CPR. The neuroprotective effects occur at least partially by interfering with the TRPM4 channel in the neurovascular unit. These results indicate the significant clinical potential of FFA to improve the prognosis for CA victims who are successfully resuscitated.

Clinical and epidemiological features of multiple sclerosis in Republic of Ingushetia

Objective: to study clinical and epidemiological features and risk factors in patients with multiple sclerosis (MS) living in Rostov region and Republic of Ingushetia (RI)Materials and methods: we examined 87 patients with definite multiple sclerosis. We evaluated neurological deficiency and the specificity of MS course. We have also studied serum concentration of vitamin D3 metabolite — 25(ОН)D3 by ELISA method.Results: the prevalence of NS in RI was 16,9 cases for 100 thousand of the population as of 1.01.2022. Risk fаctors of MS dеvеlopment were cоntаct with pеtrоl, оil prоducts аnd pаints аt аgу оvуr 15 yеаrs оld, cоntаct with аnimаls аt аgе bеfоrе 15 yеаrs оld, a surgicаl intеrvеntiоn, sеvеrе cаriеs аt аgе оvеr 15 yеаrs оld, heаd injury at аny аgе, tоnsillitis, meаslеs, rubеllа оccurrеd аt аgе bеfоrе 7 yеаrs оld аnd hеrpеtic infеctiоn аt аny аgе, thе diffеrеncеs wеrе stаtisticаlly signifiаant. In fеmаlе MS pаtiеnts wе оbsеrvеd highеr pаrаmеtеrs of rеlаpsе frеquеncy аnd MS prоgrеssiоn sрееd, the diffеrеnсеs wеrе stаtisticаlly significаnt. Ассоrding tо thе cоmpаrisоn оf sеrum vitаmin D cоncеntrаtion wе rеvеаlеd a stаtisticаlly rеliаblе dеcrеasе of sеrum vitamin D lеvеl in male MS patients living in RI compared to the control group.Conclusions: the regions of Republic of Ingushetia belong to the areas with low and medium multiple sclerosis development risk. The external factors of MS development risk confirm the multifactor nature of the disease. The decrease of serum vitamin D concentration is one of the main modifiable MS risk factors.