Severe Motor Dysfunction Research Articles

Characterizing eye-gaze positions of people with severe motor dysfunction: Novel scoring metrics using eye-tracking and video analysis.

Nonverbal communication with people who have physical disabilities is difficult. Eye-tracking technologies have recently been developed and applied to help people with physical disabilities in their communication. However, the eye-gaze patterns of people with severe motor dysfunction (SMD) have not been analyzed in detail. To clarify characterization of people with SMD, we aimed to develop gaze position-based evaluation metrics and analyze detailed eye-gaze patterns of people with SMD. We developed two new scoring metrics: (1) saliency score based on three saliency maps-spectral residual (SR), fine grained (FG), and motion (Mo); and (2) the distance score, which represents to what extent people can chase an object in a video. The evaluation was performed on 102 participants, consisting of 35 subjects with profound intellectual and multiple disabilities (PIMD; SMD with IQ < 20), 19 with severe physical disabilities (SPD; SMD with IQ ≥ 20), and 48 healthy individuals. We observed that two saliency scores (SR and FG) and the distance score showed significant differences between the PIMD/SPD and healthy groups for the entire video, whereas Mo scores did not. Moreover, the distance score was analyzed separately for each scene, where scenes were categorized into three patterns-running, explanation, and hiding-according to the behavior of the moving objects. In the SPD and healthy groups, the explanation scenes accounted for the highest percentage of all scenes with the best distance score (63.6% and 61.9%, respectively), whereas in the PIMD group, the running scenes accounted for the highest percentage (54.5%). In conclusion, the new metrics were successful in quantitatively assessing the gaze responsiveness of people with SMD, which could not be assessed using a conventional metric, gaze-acquisition time. This study is expected to expand the possibilities of nonverbal communication using eye-tracking devices for people with SMD.

Motor organization of unilateral polymicrogyria associated with ipsilateral brainstem atrophy – a case report

BackgroundPolymicrogyria refers to the disruption of normal cerebral cortical development late in neuronal migration or in early cortical organization. Although patients with polymicrogyria feature relatively favorable motor outcomes, polymicrogyric lesions accompanied by extensive unilateral hemispheric atrophy and ipsilateral brainstem atrophy may induce poorer motor outcomes. This study is the first to employ transcranial magnetic stimulation (TMS) and diffusion tensor imaging (DTI) to characterize changes to motor organization and white matter tracts induced by polymicrogyria.Case presentationWe document a case of a 16-year-old female with left hemiplegic unilateral polymicrogyria associated with ipsilateral brainstem atrophy. Magnetic resonance imaging (MRI) of the brain revealed unilateral polymicrogyria to have affected anterior cortical areas, including the perisylvian region on the right side. The right halves of the brain and brainstem were significantly smaller than the left halves. Although our patient was found to exhibit cortical dysplasia of the right frontoparietal and sylvian fissure areas and a decreased number of fibers in the corticospinal tract (CST) of the affected side on DTI, the connectivity of the CST was preserved up to the motor cortex. We also measured the cross-sectional area of the CST at the level of the pons. In TMS, contralateral motor evoked potentials (MEPs) were evoked from both hands, but the ipsilateral MEPs were evoked only from the left hand. The left hand featured a long duration, polyphasic pattern of contralateral MEPs.Discussion and conclusionTMS revealed that the concurrent bilateral projections to the paretic hand from the affected and unaffected hemispheres and contralateral MEPs in the paretic hand were polyphasic, indicating delayed electrophysiological maturation or a pathologic condition of the corticospinal motor pathways. In DTI, the cross-sectional area of the CST at the level of the pons on the affected side was smaller than that on the unaffected side. These DTI findings reveal an inadequate CST volume. Despite extensive brain malformation and ipsilateral brainstem atrophy, our patient had less severe motor dysfunction and presented with involuntary mirror movements. Mirror movements in the paretic hand are considered to indicate ipsilateral corticospinal projections from the unaffected hemisphere and may suggest favorable motor outcomes in early brain injury.

Gene Editing and Rett Syndrome: Does It Make the Cut?

Rett syndrome (RTT) is a rare neurogenetic disorder caused by pathogenic variants of the Methyl CpG binding protein 2 (MECP2) gene. The RTT is characterized by apparent normal early development followed by regression of communicative and fine motor skills. Comorbidities include epilepsy, severe cognitive impairment, and autonomic and motor dysfunction. Despite almost 60 clinical trials and the promise of a gene therapy, no cure has yet emerged with treatment remaining symptomatic. Advances in understanding RTT has provided insight into the complexity and exquisite control of MECP2 expression, where loss of expression leads to RTT and overexpression leads to MECP2 duplication syndrome. Therapy development requires regulated expression that matches the spatiotemporal endogenous expression of MECP2 in the brain. Gene editing has revolutionized gene therapy and promises an exciting strategy for many incurable monogenic disorders, including RTT, by editing the native locus and retaining endogenous gene expression. Here, we review the literature on the currently available editing technologies and discuss their limitations and applicability to the treatment of RTT.

Mesenchymal Stromal Cell Therapy in Spinal Cord Injury: Mechanisms and Prospects.

Spinal cord injury (SCI) often leads to severe motor, sensory, and autonomic dysfunction in patients and imposes a huge economic cost to individuals and society. Due to its complicated pathophysiological mechanism, there is not yet an optimal treatment available for SCI. Mesenchymal stromal cells (MSCs) are promising candidate transplant cells for use in SCI treatment. The multipotency of MSCs, as well as their rich trophic and immunomodulatory abilities through paracrine signaling, are expected to play an important role in neural repair. At the same time, the simplicity of MSCs isolation and culture and the bypassing of ethical barriers to stem cell transplantation make them more attractive. However, the MSCs concept has evolved in a specific research context to encompass different populations of cells with a variety of biological characteristics, and failure to understand this can undermine the quality of research in the field. Here, we review the development of the concept of MSCs in order to clarify misconceptions and discuss the controversy in MSCs neural differentiation. We also summarize a potential role of MSCs in SCI treatment, including their migration and trophic and immunomodulatory effects, and their ability to relieve neuropathic pain, and we also highlight directions for future research.

Exosomes Secreted from circZFHX3-modified Mesenchymal Stem Cells Repaired Spinal Cord Injury Through mir-16-5p/IGF-1 in Mice.

Spinal cord injury (SCI) is a devastating neurological event that leads to severe motor and sensory dysfunction. Exosome-mediated transfer of circular RNAs (circRNAs) was associated with SCI, and exosomes have been reported to be produced by mesenchymal stem cells (MSCs). This study is designed to explore the mechanism of exosomal circZFHX3 on LPS-induced MSCs injury in SCI. Exosomes were detected by transmission electron microscope and nanoparticle tracking analysis. CD9, CD63, CD81, and TSC101, B-cell lymphoma-2 (Bcl-2), Bcl-2 related X protein (Bax), Cleaved caspase 3, and Insulin-like growth factor 1 (IGF-1) protein levels were measured by western blot assay. CircZFHX3, microRNA-16-5p (miR-16-5p), and IGF-1 level were detected by real-time quantitative polymerase chain reaction (RT-qPCR). Cell viability and apoptosis were detected by Cell Counting Kit-8 (CCK-8) and flow cytometry assay. Levels of IL-1β, IL-6, and TNF-α were assessed using Enzyme-linked immunosorbent assays (ELISA). ROS, LDH, and SOD levels were measured by the special kits. The binding between miR-16-5p and circZFHX3 or IGF-1 was predicted by Starbase and DianaTools and then verified by a dual-luciferase reporter and RNA Immunoprecipitation (RIP) assays. The biological role of exosomal circZFHX3 on SCI mice was examined in vivo. CircZFHX3 and IGF-1 were decreased, and miR-16-5p was increased in SCI mice. Also, exosomal circZFHX3 boosted cell viability and repress apoptosis, inflammation, and oxidative stress in LPS-treated BV-2 cells in vitro. Mechanically, circZFHX3 acted as a sponge of miR-16-5p to regulate IGF-1 expression. Exosomal circZFHX3 reduced cell injury of SCI in vivo. Exosomal circZFHX3 inhibited LPS-induced BV-2 cell injury partly by regulating the miR-16-5p/ IGF-1 axis, hinting at a promising therapeutic strategy for the SCI treatment.

Tau accelerates α-synuclein aggregation and spreading in Parkinson’s disease

The aggregation and prion-like propagation of α-synuclein are involved in the pathogenesis of Parkinson's disease. However, the underlying mechanisms regulating the assembly and spreading of α-synuclein fibrils remain poorly understood. Tau co-deposits with α-synuclein in the brains of Parkinson's disease patients, suggesting a pathological interplay between them. Here we show that tau interacts with α-synuclein and accelerates its aggregation. Compared with pure α-synuclein fibrils, the tau-modified α-synuclein fibrils show enhanced seeding activity, inducing mitochondrial dysfunction, synaptic impairment and neurotoxicity in vitro. Injection of the tau-modified α-synuclein fibrils into the striatum of mice induces more severe α-synuclein pathology, motor dysfunction and cognitive impairment when compared with the mice injected with pure α-synuclein fibrils. Knockout of tau attenuates the propagation of α-synuclein pathology and Parkinson's disease-like symptoms both in mice injected with α-syn fibrils and α-syn A53T transgenic mice. In conclusion, tau facilitates α-synuclein aggregation and propagation in Parkinson's disease.

Mechanism of stress-induced attacks in an episodic neurologic disorder.

Stress is the most common trigger among episodic neurologic disorders. In episodic ataxia type 2 (EA2), physical or emotional stress causes episodes of severe motor dysfunction that manifest as ataxia and dystonia. We used the tottering (tg/tg) mouse, a faithful animal model of EA2, to dissect the mechanisms underlying stress-induced motor attacks. We find that in response to acute stress, activation of α1-adrenergic receptors (α1-Rs) on Purkinje cells by norepinephrine leads to their erratic firing and consequently motor attacks. We show that norepinephrine induces erratic firing of Purkinje cells by disrupting their spontaneous intrinsic pacemaking via a casein kinase 2 (CK2)–dependent signaling pathway, which likely reduces the activity of calcium-dependent potassium channels. Moreover, we report that disruption of this signaling cascade at a number of nodes prevents stress-induced attacks in the tottering mouse. Together, our results suggest that norepinephrine and CK2 are required for the initiation of stress-induced attacks in EA2 and provide previously unidentified targets for therapeutic intervention.

Neuropathological changes in advanced Parkinson’s disease

AbstractPatients with advanced Parkinson’s disease (PD) show severe motor dysfunction, wearing‐off, dyskinesia, dementia, and autonomic failure. These symptoms correlate with the development of neuropathological findings such as severe nigrostriatal and non‐dopaminergic neuron loss and gliosis, and phosphorylated alpha‐synuclein (pSyn) accumulation in the central and peripheral nervous systems. In addition, there are often co‐pathological changes, including Alzheimer‐related tau and amyloid accumulations. According to Braak’s PD progression hypothesis, at the time of clinical diagnosis of PD, accumulation of pSyn‐positive structures is already widespread in the brainstem and peripheral nervous system, and in advanced PD, these pSyn‐positive structures have spread to the limbic system and neocortex. In this review, we describe the basic neuropathology of PD, with particular attention given to the Braak hypothesis and the distribution of pSyn‐positive structures in advanced PD.

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

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

A novel variant in UBE3A in a family with multigenerational intellectual disability and developmental delay.

BackgroundAngelman syndrome (AS) is a rare neurodevelopmental disorder and is characterized by severe cognitive disability, motor dysfunction, speech impairment, hyperactivity, and frequent seizures. Although the maternal chromosomal region 15q11.2‐q13 deletion is the most common mechanism of AS, ~10% of individuals with AS are caused by the intragenic variants in the maternally inherited UBE3A, which encodes an E3 ubiquitin ligase.MethodsClinical diagnoses were based on detailed clinical findings. Trio‐based exome sequencing was performed on the proband and her parents to identify the underlying genetic variants. The candidate variants were confirmed by Sanger sequencing following PCR amplification. In silico analyses were conducted to predict the effect of the identified variant on the function of UBE3A protein.ResultsWe identified a novel variant c.2029G>C (p. Gly677Arg) in UBE3A as the most promising candidate. In silico analyses showed that p.Gly677Arg in the UBE3A affects a highly conserved residue. Her mother had the variant at this locus. Sanger sequencing results showed that II‐2, II‐5, II‐7, IV‐1, III‐5, III‐7, III‐8, and III‐9 have the variant c.2029G>C, and all patients inherited maternally variant in UBE3A, while the offsprings of the male carrier were unaffected.ConclusionsWe identified a novel variant (c.2029G>C) in the UBE3A in a Chinese family with multigenerational intellectual disability and developmental delay. Our findings expanded the genotypic spectrum of AS and provided important information for genetic counseling.

Human umbilical cord mesenchymal stem cells contribute to the reconstruction of bladder function after acute spinal cord injury via p38 mitogen-activated protein kinase/nuclear factor-kappa B pathway

ABSTRACT The association between spinal cord injury (SCI) and bladder symptoms has been intensively described. Human umbilical cord mesenchymal stem cell (hUC-MSC) treatment is beneficial to the recovery of bladder function after SCI, but its mechanism is unclear. We established an SCI model, and prepared hUC-MSCs in advance, followed by verification using flow cytometry. The Basso, Beattie and Bresnahan (BBB) score and urodynamic index were employed to evaluate motor function and bladder functions, respectively. Hematoxylin–eosin staining, luxol fast blue staining, and Masson’s trichrome staining were utilized to assess pathological changes. Real-time quantitative PCR and Western blot were used to determine the mRNA and protein expressions in bladder tissues. The immunophenotypes of the HUC-MSCs were CD90+ and CD105+, but CD34−, CD45− and HLA-DR−. Rats appeared severe motor dysfunction after SCI, but the BBB score was increased in hUC-MSCs after the second week. Pathologically, the improvement of the lesion area on the dorsal spinal cord, augmented anterior gray horn neuron cells of the spinal cord and lessened bladder tissue remodeling (fibrosis, collagen deposition) as well as modulated inflammation could be observed. Besides, SCI increased bladder weight, bladder capacity, urine volume and residual urine volume, and decreased urination efficiency. HUC-MSCs ameliorated SCI-induced pathological changes and bladder functions, the expressions of Collagen I, Collagen III, fibroblast growth factor 2 (FGF2), phospho-p38, transient receptor potential vanilloid 1, Toll-like receptor 4 and phospho-nuclear factor-kappa B (p-NF-κB). To sum up, HUC-MSCs contribute to the reconstruction of bladder function after SCI by repressing p38 MAPK/NF-κB pathway.

Late onset neuromyelitis optica spectrum disorder with anti-aquaporin 4 and anti-myelin oligodendrocyte glycoprotein antibodies.

This study aimed to evaluate the clinical characteristics and prognosis of late onset (≥50years) neuromyelitis optica spectrum disorder (LO-NMOSD), and compare them with those of early onset (<50years) NMOSD (EO-NMOSD) and NMOSD with various antibody serostatuses. From January 2015 to December 2020, 360 anti-aquaporin 4 antibody (AQP4-ab)-positive and 130 anti-myelin oligodendrocyte glycoprotein antibody (MOG-ab)-positive patients presented to the Huashan Hospital, China. We retrospectively reviewed their medical records, including the Expanded Disability Status Scale (EDSS) score at each visit and the annualized relapse rate (ARR). Prognostic outcomes included the time to first relapse, blindness, motor dysfunction, severe motor dysfunction, and death. Correlations between the age at onset, lesion location, and clinical parameters were analyzed. This study included 122 (24.9%) patients with LO-NMOSD, 101 with AQP4-ab and 21 with MOG-ab. Compared with EO-NMOSD patients, those with LO-NMOSD had higher EDSS scores and more frequent disease onset with transverse myelitis, blindness, motor dysfunction, and severe motor dysfunction. Compared with LO-NMOSD patients with MOG-ab, those with AQP4-ab had a worse prognosis. Age at disease onset had a significantly positive correlation with EDSS score at the last follow-up of all NMOSD patients, but a negative correlation with ARR-1 (ARR excluding the first attack, calculated from disease onset to final follow-up) in NMOSD patients with AQP4-ab. Patients with LO-NMOSD, especially those with AQP4-ab, had a worse prognosis compared with patients with EO-NMOSD. Age at disease onset and antibody serostatus predicted blindness and motor dysfunction.

Involvement of healthcare professionals for children with severe motor dysfunction and their mothers in postural care by using Early Activity System at home

Involvement of healthcare professionals for children with severe motor dysfunction and their mothers in postural care by using Early Activity System at home

Creatine transporter-deficient rat model shows motor dysfunction, cerebellar alterations, and muscle creatine deficiency without muscle atrophy.

Creatine (Cr) is a nitrogenous organic acid and plays roles such as fast phosphate energy buffer to replenish ATP, osmolyte, antioxidant, neuromodulator, and as a compound with anabolic and ergogenic properties in muscle. Cr is taken from the diet or endogenously synthetized by the enzymes arginine:glycine amidinotransferase and guanidinoacetate methyltransferase, and specifically taken up by the transporter SLC6A8. Loss‐of‐function mutations in the genes encoding for the enzymes or the transporter cause creatine deficiency syndromes (CDS). CDS are characterized by brain Cr deficiency, intellectual disability with severe speech delay, behavioral troubles, epilepsy, and motor dysfunction. Among CDS, the X‐linked Cr transporter deficiency (CTD) is the most prevalent with no efficient treatment so far. Different animal models of CTD show reduced brain Cr levels, cognitive deficiencies, and together they cover other traits similar to those of patients. However, motor function was poorly explored in CTD models, and some controversies in the phenotype exist in comparison with CTD patients. Our recently described Slc6a8 Y389C knock‐in rat model of CTD showed mild impaired motor function, morphological alterations in cerebellum, reduced muscular mass, Cr deficiency, and increased guanidinoacetate content in muscle, although no consistent signs of muscle atrophy. Our results indicate that such motor dysfunction co‐occurred with both nervous and muscle dysfunctions, suggesting that muscle strength and performance as well as neuronal connectivity might be affected by this Cr deficiency in muscle and brain.

Neural Stem Cells Overexpressing Nerve Growth Factor Improve Functional Recovery in Rats Following Spinal Cord Injury via Modulating Microenvironment and Enhancing Endogenous Neurogenesis.

Spinal cord injury (SCI) is a devastating event characterized by severe motor, sensory, and autonomic dysfunction. Currently, there is no effective treatment. Previous studies showed neural growth factor (NGF) administration was a potential treatment for SCI. However, its targeted delivery is still challenging. In this study, neural stem cells (NSCs) were genetically modified to overexpress NGF, and we evaluated its therapeutic value following SCI. Four weeks after transplantation, we observed that NGF-NSCs significantly enhanced the motor function of hindlimbs after SCI and alleviated histopathological damage at the lesion epicenter. Notably, the survival NGF-NSCs at lesion core maintained high levels of NGF. Further immunochemical assays demonstrated the graft of NGF-NSCs modulated the microenvironment around lesion core via reduction of oligodendrocyte loss, attenuation of astrocytosis and demyelination, preservation of neurons, and increasing expression of multiple growth factors. More importantly, NGF-NSCs seemed to crosstalk with and activate resident NSCs, and high levels of NGF activated TrkA, upregulated cAMP-response element binding protein (CREB) and microRNA-132 around the lesion center. Taken together, the transplantation of NGF-NSCs in the subacute stage of traumatic SCI can facilitate functional recovery by modulating the microenvironment and enhancing endogenous neurogenesis in rats. And its neuroprotective effect may be mediated by activating TrkA, up-regulation of CREB, and microRNA-132.

Long-term efficacy and safety of eladocagene exuparvovec in patients with AADC deficiency

Aromatic L-amino acid decarboxylase deficiency results in decreased neurotransmitter levels and severe motor dysfunction. Twenty-six patients without head control received bilateral intraputaminal infusions of a recombinant adeno-associated virus type 2 vector containing the human aromatic L-amino acid decarboxylase gene (eladocagene exuparvovec) and have completed 1-year evaluations. Rapid improvements in motor and cognitive function occurred within 12months after gene therapy and were sustained during follow-up for>5 years. An increase in dopamine production was demonstrated by positron emission tomography and neurotransmitter analysis. Patient symptoms (mood, sweating, temperature, and oculogyric crises), patient growth, and patient caretaker quality of life improved. Although improvements were observed in all treated participants, younger age was associated with greater improvement. There were no treatment-associated brain injuries, and most adverse events were related to underlying disease. Post-surgery complications such as cerebrospinal fluid leakage were managed with standard of care. Most patients experienced mild to moderate dyskinesia that resolved in a few months. These observations suggest that eladocagene exuparvovec treatment for aromatic L-amino acid decarboxylase deficiency provides durable and meaningful benefits with a favorable safety profile.

Nimodipine Promotes Functional Recovery After Spinal Cord Injury in Rats.

Spinal cord injury (SCI) is a devastating condition that results in severe motor, sensory, and autonomic dysfunction. The L-/T-type calcium channel blocker nimodipine (NMD) exerts a protective effect on neuronal injury; however, the protective effects of long-term administration of NMD in subjects with SCI remain unknown. Thus, the aim of this study was to evaluate the role of long-term treatment with NMD on a clinically relevant SCI model. Female rats with SCI induced by 25 mm contusion were subcutaneously injected with vehicle or 10 mg/kg NMD daily for six consecutive weeks. We monitored the motor score, hind limb grip strength, pain-related behaviors, and bladder function in this study to assess the efficacy of NMD in rats with SCI. Rats treated with NMD showed improvements in locomotion, pain-related behaviors, and spasticity-like symptoms, but not in open-field spontaneous activity, hind limb grip strength or bladder function. SCI lesion areas and perilesional neuronal numbers, gliosis and calcitonin gene-related peptide (CGRP+) fiber sprouting in the lumbar spinal cord and the expression of K+–Cl− cotransporter 2 (KCC2) on lumbar motor neurons were also observed to further explore the possible protective mechanisms of NMD. NMD-treated rats showed greater tissue preservation with reduced lesion areas and increased perilesional neuronal sparing. NMD-treated rats also showed improvements in gliosis, CGRP+ fiber sprouting in the lumbar spinal cord, and KCC2 expression in lumbar motor neurons. Together, these results indicate that long-term treatment with NMD improves functional recovery after SCI, which may provide a potential therapeutic strategy for the treatment of SCI.

Perillaldehyde Alleviates Spinal Cord Ischemia-Reperfusion Injury Via Activating the Nrf2 Pathway

Spinal Cord ischemia-reperfusion injury (SCII) is one of the most destructive complications in thoracic-abdominal aortic surgery, which can cause physical abnormalities, paralysis and even brain death. Evidence has shown that perillaldehyde (PAH) can ameliorate rat's cerebra ischemia-reperfusion injury. However, the effect of PAH on SCII remains unknown. The current study established SCII rat models and oxygen and glucose deprivation/reoxygenation-induced BV2 microglia models to explore whether PAH could alleviate SCII symptoms and to investigate underlying mechanism. SCII rats underwent severe neurologic motor dysfunction and histopathologic injury compared with the normal rats, which are exhibited by loss of motor neurons and decrease of nissl bodies. Treatment with PAH significantly ameliorated motor dysfunction and neuron damage. PAH downregulated the expression of NLR family pyrin domain containing 3, cleaved/pro caspase-1, interleukin-1β and interleukin-18 in spinal cord tissues of SCII rats. Besides, the contents of oxidative stress-related factors superoxide dismutase, manganese-dependent superoxide dismutase, catalase and glutathione peroxidase were significantly increased and malondialdehyde content was decreased after PAH treatment. PAH treatment upregulated the expression of nuclear factor-E2-related factor 2 and heme oxygenase-1 in spinal cord tissues of SCII rats. Our in vitro study confirmed that PAH inhibited microglial activation by activating the nuclear factor-E2-related factor 2/heme oxygenase-1 pathway, exhibited by alleviated inflammation and oxidative stress. This study elucidates that PAH has the potential value for treating SCII, which provides an experimental basis for clinical trials in the future.

Neuropeptide S Receptor as an Innovative Therapeutic Target for Parkinson Disease

Parkinson disease (PD) is a neurodegenerative disease mainly characterized by the loss of nigral dopaminergic neurons in the substantia nigra pars compacta. Patients suffering from PD develop severe motor dysfunctions and a myriad of non-motor symptoms. The treatment mainly consists of increasing central dopaminergic neurotransmission and alleviating motor symptoms, thus promoting severe side effects without modifying the disease’s progress. A growing body of evidence suggests a close relationship between neuropeptide S (NPS) and its receptor (NPSR) system in PD: (i) double immunofluorescence labeling studies showed that NPSR is expressed in the nigral tyrosine hydroxylase (TH)-positive neurons; (ii) central administration of NPS increases spontaneous locomotion in naïve rodents; (iii) central administration of NPS ameliorates motor and nonmotor dysfunctions in animal models of PD; (iv) microdialysis studies showed that NPS stimulates dopamine release in naïve and parkinsonian rodents; (v) central injection of NPS decreases oxidative damage to proteins and lipids in the rodent brain; and, (vi) 7 days of central administration of NPS protects from the progressive loss of nigral TH-positive cells in parkinsonian rats. Taken together, the NPS/NPSR system seems to be an emerging therapeutic strategy for alleviating motor and non-motor dysfunctions of PD and, possibly, for slowing disease progress.

Evaluation of immunization status in patients with cerebral palsy: a multicenter CP-VACC study.

Children with chronic neurological diseases, including cerebral palsy (CP), are especially susceptible to vaccine-preventable infections and face an increased risk of severe respiratory infections and decompensation of their disease. This study aims to examine age-appropriate immunization status and related factors in the CP population of our country. This cross-sectional prospective multicentered survey study included 18 pediatric neurology clinics around Turkey, wherein outpatient children with CP were included in the study. Data on patient and CP characteristics, concomitant disorders, vaccination status included in the National Immunization Program (NIP), administration, and influenza vaccine recommendation were collected at a single visit. A total of 1194 patients were enrolled. Regarding immunization records, the most frequently administrated and schedule completed vaccines were BCG (90.8%), hepatitis B (88.9%), and oral poliovirus vaccine (88.5%). MMR was administered to 77.3%, and DTaP-IPV-HiB was administered to 60.5% of patients. For the pneumococcal vaccines, 54.1% of children received PCV in the scope of the NIP, and 15.2% of children were not fully vaccinated for their age. The influenza vaccine was administered only to 3.4% of the patients at any time and was never recommended to 1122 parents (93.9%). In the patients with severe (grades 4 and 5) motor dysfunction, the frequency of incomplete/none vaccination of hepatitis B, BCG, DTaP-IPV-HiB, OPV, and MMR was statistically more common than mild to moderate (grades 1-3) motor dysfunction (p = 0.003, p < 0.001, p < 0.001, p < 0.00, and p < 0.001, respectively). Physicians' influenza vaccine recommendation was higher in the severe motor dysfunction group, and the difference was statistically significant (p = 0.029).Conclusion: Children with CP had lower immunization rates and incomplete immunization programs. Clinicians must ensure children with CP receive the same preventative health measures as healthy children, including vaccines. What is Known: • Health authorities have defined chronic neurological diseases as high-risk conditions for influenza and pneumococcal infections, and they recommend vaccines against these infections. • Children with CP have a high risk of incomplete and delayed immunization, a significant concern given to their increased healthcare needs and vulnerability to infectious diseases. What is New: • Influenza vaccination was recommended for patients hospitalized due to pneumonia at a higher rate, and patients were administered influenza vaccine more commonly. • Children with CP who had higher levels of motor dysfunction (levels 4 and 5) were more likely to be overdue immunizations.