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Objective:To explore any effect of repeated transcranial magnetic stimulation (rTMS) on the recovery of neurological functioning and the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and inflammatory factors after ischemic stroke.Methods:Sixty-four C57BL/6J mice were randomly divided into a normal control group, a model group, a sham stimulation group and an observation group, each of 16. All mice except those of the normal control group received middle cerebral artery occlusion using the suture method to model an ischemic stroke. After the modeling the observation group was given 1Hz rTMS daily for 7 consecutive days, while the sham stimulation group was given sham rTMS. After the intervention, Zea-Longa scores were used for all of the groups, and the size of the cerebral infarct was measured using triphenyltetrazolium chloride staining. The expression of NLRP3 around the cerebral infarction was detected using immunofluorescence, while that in the brain tissue was measured using Western blotting. The expression of interleukin-1β and IL-18 in the brain tissue was detected using enzyme-linked immunosorbent assays.Results:Compared with the normal control group, a significant increase was observed in the other groups′ average neurological function impairment scores. Expression of NLRP3, IL-1β and IL-18 in the model and sham stimulation groups also increased, with large cerebral infarcts in the cortex and hippocampus. Compared with the sham stimulation and model groups, there was a significant decrease in the average neurological dysfunction scores, the area of cerebral infarction in the cortex and hippocampus, as well as the expression of NLRP3, IL-1β and IL-18 in the observation group.Conclusions:Low-frequency rTMS can promote the recovery of damaged nerve function after an ischemic stroke, at least in mice. It can reduce the size of cerebral infarction, and inhibit neuronal pyroptosis, which is closely related to the down-regulation of NLRP3, IL-1β and IL-18 expression.
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Objective To analyze the clinical and electrophysiological features in a family with spinal muscular atrophy (SMA), and assess the probable causative gene mutations for the family. Methods To identify the nosogenesis of the proband with weakness and atrophy in the double lower proximal limbs, clinical data of his 12 family members were collected, and the proband and his mother were selected for clinical examinations, including laboratory tests, electromyogram (EMG), F-wave, H-reflex, X-ray of the spine and double lower limbs, brain and spinal cord magnetic resonance imaging, etc. Moreover, human whole exome sequencing was performed on blood sample from the proband, then its deleterious effects were assessed according to the Standards and guidelines for the interpretation of sequence variants, a joint consensus recommendation of the American College of Medical Genomics (ACMG) and the Association for Molecular Pathology (AMP). Subsequently, the strong pathogenic mutation was validated by Sanger sequencing. Results Familial investigation showed seven of 12 family members presented with weakness in the double lower proximal limbs. Among them, three had the main manifestation of atrophy in the double lower proximal limbs, one had high arched foot as the main presentation, and the others had weakness in the double lower proximal limbs. EMG studies showed the abnormal results in the anterior horn of the spinal cord. The strong pathogenic mutation in DYNC1H1 gene (exon8, c.2327C＞T, p.P776L) was identified from the proband according to ACMG and AMP guidelines. Sanger sequencing revealed six patients had this variant and it was passed mainly from his maternal grandmother. Conclusions A pathogenic mutation of the DYNC1H1 p.P776L in six Chinese pedigrees which cosegregated with SMA was identified. There existed individual differences in clinical presentations. This finding may have important implications for the study of SMA in Chinese patients.
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Objective To evaluate the potential value of next-generation sequencing ( NGS) as a diagnostic method for listeria infection in central nervous system ( CNS ) . Methods To identify the potentially pathogenic microorganisms ( PPMs) of the five patients with CNS infection in the Department of Neurology, People's Hospital of Zhengzhou University from June 2017 to November 2017, blood or cerebrospinal fluid ( CSF ) was detected not only using common laboratory tests , including routine , biochemical, cytologic, culture and Gram-staining methods, etc, but also using the BGISEQ-100 sequencing platform to identify the PPMs of CSF .Concomitantly , we collected concurrent clinical data , then performed a comprehensive analysis of their clinical , laboratory , and auxiliary examination data .Results Of the five cases (male :female: 1:4, age ranges: 26 -61 years), the disease mainly occurred in summer.Three patients received immunosuppressants treatment before infection , and three patients had gastrointestinal syndrome in the prodromal period .Infection of CNS led to fever , headache and meningeal irritation sign in all the patients.The medical imaging examinations showed the invasion of meninges , brainstem, and the periventricular gray matter.The cell count of CSF was more than 500 ×106/L.NGS techniques showed listeria genome sequence ranged from 57 to 2611, and the coverage of listeria varied from 0.23％ to 14.00％, and PCR results supported the existence of listeria .Conclusion NGS is beneficial to make the diagnosis of listeria infection in CNS , and can help guide early treatment .
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Objective To investigate the correlation of plasma interleukin ( IL)-17 level and IL-17 receptor (IL-17R) expression in the thymus of patients with myasthenia gravis (MG).Methods The blood samples of 63 patients (38 with glucocorticoid treatment, 25 with thymus removal) who admitted to Henan Provincial People′s Hospital between 2010 and 2014 were collected at three different stages: pre-treatment, 1 week post-treatment and 1 month post-treatment.The blood samples of 42 healthy controls were also collected.Enzyme linked immunosorbent assay was used to evaluate the levels of IL-17 in plasma.Twenty-five thymus tissues from MG patients and another 12 thymus tissues from patients with congenital heart disease who had surgery therapy were also collected.Reverse transcription polymerase chain reaction was used to evaluate the mRNA levels of IL-17R.The possible correlation between the expression of IL-17 and IL-17R with MG was analyzed.Results Before treatment, the levels of IL-17 in the plasma were much higher in all the MG patients ( both ocular and generalized) when compared to the healthy controls ( controls (3.2 ±0.7) pg/ml, MG patients (8.5 ±1.7) pg/ml, t =2.450, P 0.05, compared to the healthy controls).In the surgery therapy cases, the IL-17 levels were also reduced after the thymus removal ( pre-surgery (8.8 ±1.4) pg/ml, 1 week after surgery (5.3 ±0.7) pg/ml, t=1.950, P<0.05;1 month after surgery (3.0 ±0.4) pg/ml, t=2.683, P<0.01).In the thymus tissues of the MG patients, the mRNA levels of IL-17R were much higher than that of the controls ( relative level 2.31 folds, t =2.682, P <0.01).Meanwhile, a positive correlation was found between the plasma IL-17 levels and the relative IL-17R levels in thymus tissues ( r =0.945 4, P <0.01 ).Furthermore, IL-17 was positively correlated with quantitative myasthenia gravis scores (QMGS) either pre-treatment (r =0.798 1, P <0.01) or post-treatment (r=0.906 5, P<0.01).And IL-17R was positively correlated with QMGS pre-treatment (r=0.775 5, P<0.01).Conclusions IL-17 is increased in the plasma of MG patients (both ocular and generalized) , and is decreased upon the glucocorticoid treatment or surgery therapy, suggesting that it can be used as a parameter to determine the therapeutic effects.IL-17R is increased in the thymus tissues of MG patients, suggesting that it can potentially be used as a pathological diagnosis parameter.
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Objective To observe the relationship between 5-Hydroxytryptamine(5-HT)-like immunoreactive terminals and the vestibulo-parabrachial nucleus projection neurons which may express 5-HT1A receptor in the vestibular nuclear complex(VNC). Methods Retrograded-tract tracing technique combined with double labeling of immunofluorescence histochemical was used,and the stained sections were observed under a confocal laser-scanning microscope. Results Following injection of tetramethylrhodamine(TMR) into the parabrachial nucleus, many retrogradely labeled neurons were observed bilaterally within VNC,but with an ipsilateral predominance.Immunofluorescence histochemical staining showed that many neurons expressed(5-HT1A) receptor-like immunoreactivity and a large number of 5-HT immunostained fibers or terminals were found in the medial,spinal,superior,lateral vestibular nucleus(MVe,SpVe,SuVe,LVe),X nucleus and Y nucleus.Confocal laser-scanning microscopy revealed that some TMR-labeled neurons were 5-HT_1AR immunopositive,and some of the cell bodies or dendrites of TMR/5-HT1AR double-labeled neurons were closely apposed by 5-HT-like immunoreactive terminals.Conclusion The present study suggests that 5-HT may modulate vestibular signals along the VNC-parabrachial nucleus pathway via 5-HT1A receptor.