Butylphthalide Inhibits TLR4/NF-κB Pathway by Upregulation of miR-21 to Have the Neuroprotective Effect

Stroke is a disease with the highest incidence rate and the highest mortality rate in the world. The study aims to verify the neuroprotective effect of Butylphthalide. The mice were divided into sham group, MCAO group, and MCAO + Butylphthalide-treated group. The mice in MCAO + Butylphthalide-treated group were administered with 70 mg/kg Butylphthalide injection intraperitoneally after cerebral ischemia-reperfusion. The normal saline with the same volume was administered intraperitoneally for the mice in the MCAO group and sham group. The levels of miR-21 in brain tissue and cells were detected by qPCR. The OGD/R injury model of Neuro2A cells was used to simulate the hypoxic-ischemic environment of neurons in vitro. The proliferation rate of Neuro2A cells was detected with CCK-8. The production of ROS was detected with DCFH-DA. Compared with the mice in MCAO group, a decrease ( P < 0.01 ) was observed in the functional neurologic impairment scoring, cerebral infarction volume, and brain loss volume in the mice treated with MCAO + Butylphthalide, but an increase ( P < 0.01 ) was observed in the level of miR-21, which was positively correlated with functional neurologic impairment scoring (r = −0.8933, P < 0.001 ). MTT assay showed that the cell viability of OGD/R + Butylphthalide group was significantly higher than that of other groups ( P < 0.001 ), and the activity of ROS was significantly decreased ( P < 0.001 ). The WB results showed that, compared with OGD/R + miR-NC and control groups, the ratio of Bcl-2/Bax in OGD/R + Butylphthalide group and OGD/R + miR-21 mimics group was significantly higher ( P < 0.05 ), while the ratio of caspase-3/GAPDH was significantly lower ( P < 0.05 ). In conclusion, Butylphthalide has neuroprotective effect on the mouse model of MCAO. It may upregulate the level of miR-21 to inhibit neuronal apoptosis and ROS production and improve the proliferation activity. The specific mechanism may lie in inhibiting TLR4/NF-κB pathway.

A Pragmatic Approach to Assessment of Chronic and Recurrent Pain in Children with Severe Neurologic Impairment

The term “severe neurologic impairment” (SNI) is used to describe a group of disorders of the central nervous system which arise in childhood, resulting in motor impairment, cognitive impairment and medical complexity. As a result, much assistance is required with activities of daily living. Since these patients are often unable to self-report pain, or they may exhibit uncommon behaviors when suffering, pain manifestations may go unrecognized. In this article, the basic principles of how to approach pain in children with SNI are discussed.

Hyperacute Gullain Barre Syndrome (GBS); The Catastrophic Variant- A Rare Case Report

Guillain-Barré syndrome (GBS) also known as acute demyelinating polyradiculoneuropathy (AIDP) is an immunologically mediated rare neurological disorder. The basic pathogenic mechanism is regulated by molecular mimicry. Usually there is a history of preceding infection which occurs some weeks before the attack. The infections are gastroenteritis or upper respiratory. The clinical spectrum of ranges from mild weakness to devastating paralysis including respiratory failure. Majority of the cases recover but a few continue to have residual neurodeficit. The usual clinical course of GBS from the starting of weakness to development of maximum neurologic progression usually progresses over 4 weeks. Hyperacute GBS is a term used when the progression of weakness occurs within hours to days to maximum neurologic impairment. In this case report we present a 28 year old female who developed rapidly progressive, areflexic quadriparesis with respiratory muscle involvement requiring mechanical ventilatory support within nine hours. Clinical , laboratory and nerve conduction studies suggested a diagnosis of GBS.

Trends in Health Care Use and Spending for Young Children With Neurologic Impairment

BACKGROUND AND OBJECTIVES: Children with neurologic impairment (NI) are a growing subset of children who frequently use health care. We examined health care use and spending trends across services for children with NI during their first 5 years of life. METHODS: This was a retrospective study of 13 947 children with NI in the multistate IBM Medicaid MarketScan Database (2009–2017). We established birth cohorts of children with NI and analyzed claims from birth to 5 years. NI, identified by using International Classification of Diseases, 9th Revision, diagnosis codes, was defined as ≥1 neurologic diagnosis that was associated with functional and/or intellectual impairment. We measured annual health care use and per-member-per-year spending by inpatient, emergency department (ED), and outpatient services. Population trends in use and spending were assessed with logistic and linear regression, respectively. RESULTS: During their first versus fifth year, 66.8% vs 5.8% of children with NI used inpatient services, and 67.8% vs 44.4% used ED services. Annual use in both categories decreased over 0–5 years (inpatient odds ratio: 0.35, 95% confidence interval: 0.34 to 0.36; ED odds ratio: 0.78, 95% confidence interval: 0.77 to 0.79). The use of outpatient services (primary care, specialty care, home health) decreased gradually. Per-member-per-year spending on inpatient services remained the largest spending category: $83 352 (90.2% of annual spending) in the first year and $1944 (25.5%) in the fifth year. CONCLUSIONS: For children with early-onset NI from 0–5 years, use and spending on inpatient services decreased dramatically; ED and outpatient service use decreased more gradually. These findings may help systems, clinicians, and families optimize care by anticipating and adjusting for shifting use of health care services.

Evaluation of Pain in Adults With Childhood-Onset Disabilities and Communication Difficulties

Adults with childhood-onset disabilities, particularly those with central nervous system impairment, commonly experience pain. Because many such individuals have difficulties in communication, caregivers and medical professionals must identify and interpret non-verbal behaviors as indicators of pain. This process is challenging and can lead to poor outcomes through delayed or incorrect diagnosis and treatment. Most research in the evaluation of pain in individuals with neurologic impairment has focused on the pediatric population, and evidence-based guidelines do not exist for adults. The purpose of this paper is to review current recommendations for pain assessment in adults with communication impairment. This approach includes guidance for history-taking, pharmacologic review, physical examination, and the judicious use of laboratory and imaging tests. Finally, we discuss adult-specific diagnoses to consider when evaluating pain in adults with childhood-onset disabilities and communication difficulties.

Weaker Connectivity of the Cortical Networks Is Linked with the Uncharacteristic Gait in Youth with Cerebral Palsy

Cerebral palsy (CP) is the most prevalent pediatric neurologic impairment and is associated with major mobility deficiencies. This has led to extensive investigations of the sensorimotor network, with far less research focusing on other major networks. The aim of this study was to investigate the functional connectivity (FC) of the main sensory networks (i.e., visual and auditory) and the sensorimotor network, and to link FC to the gait biomechanics of youth with CP. Using resting-state functional magnetic resonance imaging, we first identified the sensorimotor, visual and auditory networks in youth with CP and neurotypical controls. Our analysis revealed reduced FC among the networks in the youth with CP relative to the controls. Notably, the visual network showed lower FC with both the sensorimotor and auditory networks. Furthermore, higher FC between the visual and sensorimotor cortices was associated with larger step length (r = 0.74, pFDR = 0.04) in youth with CP. These results confirm that CP is associated with functional brain abnormalities beyond the sensorimotor network, suggesting abnormal functional integration of the brain’s motor and primary sensory systems. The significant association between abnormal visuo-motor FC and gait could indicate a link with visuomotor disorders in this patient population.

Nanoliposomes Reduce Stroke Injury Following Middle Cerebral Artery Occlusion in Mice

Neuroprotective strategies for stroke remain inadequate. Nanoliposomes comprised of phos-phatidylcholine, cholesterol and monosialogangliosides (NL) induced an antioxidant protective response in endothelial cells exposed to amyloid insults. We tested the hypotheses that NL will preserve SH-SY5Y neuroblastoma cell viability following hypoxic injury and will reduce injury in mice following middle cerebral artery occlusion (MCAO). Neuroblastoma were exposed to 20-hour physoxic (5% oxygen) or hypoxic (1% oxygen) condition without or with NL (100 or 300 µg/mL). Viability was measured using calcein-AM fluorescence and SH-SY5Y gene expression of antioxidant proteins heme oxygenase-1 (HO-1), NAD(P)H quinone dehydrogenase 1 (NQO1) and superoxide dismutase 1 (SOD1) were measured by quantitative polymerase chain reaction. C57BL/6J mice were treated with saline (N=8) or NL (10000 ug/mL, N=7) while undergoing 60-minute MCAO followed by reperfusion. Day 2 post-injury neurologic impairment score and infarction size were compared. Neuroblastoma showed reduced viability following hypoxia that was reversed by NL. NL increased gene expression of HO-1, NQO1 and SOD1 versus controls. NL-treated mice showed reduced neurologic impairment and brain infarct size (18.8±2% versus 27.3±2.3%, p=0.017) versus controls. NL reduced stroke injury in mice subjected to MCAO likely through induction of an antioxidant stress response. NL is a candidate novel agent for stroke.