Nano-Hydrogel for the Treatment of Depression and Epilepsy.

This article first combines nano-carrier technology, the electrophysiological mechanism of seizures, and brain targeting technology to prepare new nano-hydrogels. Secondly, through the discharge information generated during the seizure and the electric field responsiveness of the nano-hydrogel, the free drug concentration in the brain area related to the seizure is increased, thereby, limiting the abnormal discharge of the focus to the local area and suppressing it in time. Finally, this article examines the impact of nano-hydrogel on the epilepsy and depression using relevant studies. The experimental observations revealed that the yield of the nano-hydrogel synthesized after 24 h of sapon-free emulsion polymerization was 50 to 70%, the swelling rate was 400 to 1700%, and the viscosity of the 20 mg/mL nano-hydrogel dispersion was 3.9 to 17.0 mPa· s. Furthermore, because the total efficiency was 0.952, the nano-hydrogels have a reduced recurrence rate and a better effect on the depression improvement.

Advanced age is associated with increased adverse outcomes in patients undergoing middle cerebral artery stenting.

Purpose: This study tried to evaluate whether advanced age has an increased incidence of major complications in patients undergoing MCA stenting. Methods: A total of 348 patients who underwent MCA stenting were reviewed from a prospectively maintained database. Ninety-day ischemic stroke, intracerebral hemorrhage, and death outcomes were compared among the young (≤40 years old), middle (41-60 years old) and old (≥61 years old) groups. Univariate analysis and multivariable logistic regression analysis were used to investigate different variables associated with 90-day major adverse events. Kaplan-Meier analysis was performed to determine long-term outcomes during follow-up. Results: The incidence of 90-day ischemic stroke was 9.26% in the old group, 2.86% in the middle group, and 0% in the young group (P = 0.024). The incidence of all 90-day major adverse events was 3.33% in patients ≤40 years old, 19.90% in patients 41-60 years old, and 24.07% in patients ≥61 years old, with statistical significance (P = 0.04). Advanced age was associated with increased 90-day ischemic stroke (OR = 1.074, 95% CI: 1.019-1.132, P = 0.007; adjusted OR: 1.071, 95% CI: 1.008-1.138, P = 0.026) and 90-day death (OR = 1.072, 95% CI: 1.012-1.135, P = 0.018; adjusted OR: 1.095, 95% CI: 1.015-1.182, P = 0.018). Meanwhile, advanced age was also associated with decreased long-term survival and ischemic stroke-free survival during follow-up. Conclusion: Our data indicated that MCA stenting in elderly patients is associated with a high risk of adverse events and should be cautiously considered.

Association between mossy fiber sprouting and expression of semaphorin-3f protein in dentate gyrus of hippocampus in lithium-pilocarpine-induced status epilepticus mouse model.

OBJECTIVES: Mossy fiber sprouting is involved in the pathogenesis of mesial temporal lobe epilepsy. But the exact mechanism of formation of mossy fiber sprouting is still unclear. Semaphorin-3f protein could inhibit the growth of neuron axons. The aim of this research is to evaluate the association between semaphorin-3f expression and mossy fiber sprouting. METHODS: We established pilocarpine-induced status epilepticus (PISE) models firstly. Then, mossy fiber sprouting in the hippocampus of PISE models was examined by Timm staining. Expression of semaphorin-3f was evaluated by western blot analysis and immunohistochemical examination. Expression of semaphorin-3f protein in different subregions of hippocampus and its relationship with mossy fiber sprouting were studied. RESULTS: We found that in PISE group, mossy fiber sprouting appeared in dentate gyrus (DG) region. It started to develop in the latent phase of PISE group and increased significantly in the chronic phase. Expression of semaphorin-3f protein in DG region started to decrease in the latent phase, and stayed at low level in the chronic phase. No such change was found in the other groups. CONCLUSIONS: These results indicate that the decrease in semaphorin-3f expression in DG region was in parallel to the change of mossy fiber sprouting in PISE models, suggesting that mossy fiber sprouting is closely associated with reduced expression of semaphorin-3f in this model.

STE20/SPS1-related proline/alanine-rich kinase is involved in plasticity of GABA signaling function in a mouse model of acquired epilepsy.

The intracellular concentration of chloride ([Cl(-)]i) determines the strength and polarity of GABA neurotransmission. STE20/SPS1-related proline/alanine-rich kinase (SPAK) is known as an indirect regulator of [Cl(-)]i for its activation of Na-K-2 Cl(-)co-transporters (NKCC) and inhibition of K-Cl(-)co-transporters (KCC) in many organs. NKCC1 or KCC2 expression changes have been demonstrated previously in the hippocampal neurons of mice with pilocarpine-induced status epilepticus (PISE). However, it remains unclear whether SPAK modulates [Cl(-)]i via NKCC1 or KCC2 in the brain. Also, there are no data clearly characterizing SPAK expression in cortical or hippocampal neurons or confirming an association between SPAK and epilepsy. In the present study, we examined SPAK expression and co-expression with NKCC1 and KCC2 in the hippocampal neurons of mice with PISE, and we investigated alterations in SPAK expression in the hippocampus of such mice. Significant increases in SPAK mRNA and protein levels were detected during various stages of PISE in the PISE mice in comparison to levels in age-matched sham (control) and blank treatment (control) mice. SPAK and NKCC1 expression increased in vitro, while KCC2 was down-regulated in hippocampal neurons following hypoxic conditioning. However, SPAK overexpression did not influence the expression levels of NKCC1 or KCC2. Using co-immunoprecipitation, we determined that the intensity of interaction between SPAK and NKCC1 and between SPAK and KCC2 increased markedly after oxygen-deprivation, whereas SPAK overexpression strengthened the relationships. The [Cl(-)]i of hippocampal neurons changed in a corresponding manner under the different conditions. Our data suggests that SPAK is involved in the plasticity of GABA signaling function in acquired epilepsy via adjustment of [Cl(-)]i in hippocampal neurons.

Anomalous expression of chloride transporters in the sclerosed hippocampus of mesial temporal lobe epilepsy patients.

The Na(+)-K(+)-Cl(-) cotransporter 1 and K(+)-Cl(-) cotransporter 2 regulate the levels of intracellular chloride in hippocampal cells. Impaired chloride transport by these proteins is thought to be involved in the pathophysiological mechanisms of mesial temporal lobe epilepsy. Imbalance in the relative expression of these two proteins can lead to a collapse of Cl(-) homeostasis, resulting in a loss of gamma-aminobutyric acid-ergic inhibition and even epileptiform discharges. In this study, we investigated the expression of Na(+)-K(+)-Cl(-) cotransporter 1 and K(+)-Cl(-) cotransporter 2 in the sclerosed hippocampus of patients with mesial temporal lobe epilepsy, using western blot analysis and immunohistochemistry. Compared with the histologically normal hippocampus, the sclerosed hippocampus showed increased Na(+)-K(+)-Cl(-) cotransporter 1 expression and decreased K(+)-Cl(-) cotransporter 2 expression, especially in CA2 and the dentate gyrus. The change was more prominent for the Na(+)-K(+)-Cl(-) cotransporter 1 than for the K(+)-Cl(-) cotransporter 2. These experimental findings indicate that the balance between intracellular and extracellular chloride may be disturbed in hippocampal sclerosis, contributing to the hyperexcitability underlying epileptic seizures. Changes in Na(+)-K(+)-Cl(-) cotransporter 1 expression seems to be the main contributor. Our study may shed new light on possible therapies for patients with mesial temporal lobe epilepsy with hippocampal sclerosis.

[Impacts on repeated common cold for the adults with different constitutions treated by acupoint application in the dog days and the three nine-day periods after the winter solstice].

OBJECTIVE: To observe the impacts on repeated common cold for the adults with different constitutions treated by acupoint application in the dog days (the three periods of the hottest days) and the three nine-day periods after the winter solstice (the three periods of the coldest days). METHODS: One hundred and fifty-two cases of repeated common cold were divided into four zones according to the body constitution. Each zone was sub-divided into a group of the dog days + the three nine-day periods of the coldest days (group A), and a simple group of the dog periods (group B). In both groups, Dazhui (GV 14), Feishu (BL 13), Tiantu (CV 22), Danzhong (CV 17), Zhongfu (LU 1) and Shenshu (BL 23) were selected. In group A, the acupoint application was given on the 1st or 2nd day of the first, second and third periods of the hottest days in 2010, as well as the 1st or 2nd day of the first, second and third periods of the coldest days in 2010 separately. In group B, the acupoint application was only given on the 1st or 2nd day of the first, second and third periods of the hottest days in 2010. The follow-up visit was conducted before the acupoint application in the three periods of the coldest days in 2010 and before the acupoint application in the three periods of the hottest days in 2011. Additionally, the frequency of disease attack and the symptom score in sickness were taken as the observation indices for the efficacy assessment in both groups. RESULTS: (1) In both groups, the attack frequency was reduced obviously in half a year after the three periods of the hottest days for the patients of qi deficiency constitution, yang deficiency constitution and qi stagnation constitution and the clinical symptom score were reduced apparently (all P<0.01), which were superior to those for the patients of phlegm damp constitution (P<0.01, P<0.05). For the patients of phlegm damp constitution, only the clinical symptom score was reduced (P<0.01). (2) In group A, the improvements were received in the attack frequency and the clinical symptom score in half a year after the three periods of the coldest days for the patients of those four constitutions as compared with those before treatment (all P<0.01). In group B, the attack frequency and the clinical symptom score were all back to the level as those before treatment. (3) In group A, in half a year after the three periods of the coldest days, the efficacy for reducing the attack frequency and the improvements in the clinical symptoms were better than those in group B (all P<0.01). CONCLUSION: The acupoint application in the dog days and the three nine-day periods after the winter solstice reduces the attack frequency and relieves the clinical symptoms of common cold for the adults of individual constitutions to different extents. The efficacy can be further improved in the treatment with the acupoint application in the three nine-day periods after the winter solstice half a year after the acupoint application in the dog days.

[Observation of the therapeutic effect on COPD of cold phlegm blocking the lung type at stable stage treated with acupoint sticking therapy in different season].

OBJECTIVE: To systematically observe the clinical effect on chronic obstructive pulmonary disease (COPD) at the stable stage, differentiated as cold phlegm blocking the lung type, treated with acupoint sticking therapy during the dog days and the three nine-day periods after the winter solstice so as to propose the latest clinical idea and theoretic evidence for the treatment of COPD. METHODS: One hundred and fifty cases of COPD at stable stage, which were in accordance with the inclusive standard were randomly divided into three groups, named group A (treatment in dog days and the three nine-day periods after the winter solstice), group B (treatment in dog days) and group C (treatment in the three nine-day periods after the winter solstice), 50 cases in each group. The ingredients (Semen Brassicae, Euphoribia Kansui, Asarum, Rhizome Corydalis, Cinnamon, ginger juice) and doses of herbal medicine plaster were same in each group. The herbal plaster was applied to Feishu (BL 13), Shenshu (BL 23), Dazhui (GV 14), Tiantu (CV 22), Danzhong (CV 17) and Zhongfu (LU 1). In group B, the treatment was given once on the 1st day of each dog-day period, totally 3 treatments were included. In group C, the treatment was given once on the 1st day of each nine-day periods after the winter solstice, totally, 3 treatments were involved. In group A, the treatment was given once on the 1st day of each dog-day period and each nine-day periods after the winter solstice separately, totally 6 treatments were required. The therapeutic effect was evaluated in 4 aspects, named comprehensive clinical efficacy, survival quality (the scores for symptoms, activity limitation and influence on daily life), the attach frequency and pulmonary function. RESULTS: The total effective rate was 88.0% (46/50) in group A, which was superior to 76.0% (38/50) in group B and 70.0% (35/50) in group C separately (P < 0.01, P < 0.001). The results of the attack frequency, clinical symptom score and pulmonary function indices after treatment were all improved apparently as compared with those before treatment in each group (all P < 0.01). All the above indices in group A were improved much apparently as compared with the other two groups (P < 0.01, P < 0.001). Except for the level of forced vital capacity (FVC), the results of clinical symptom score and the other pulmonary function indices in group B were all improved significantly as compared with group C (P < 0.05, P < 0.001). CONCLUSION: Acupoint sticking therapy during different season of the year achieves a superior clinical efficacy for the patients with COPD at stable stage. This therapy can reduce the attack frequency and improve the survival quality and pulmonary function for the patients. It is concluded that the efficacy of the treatment in dog days and the three nine-day periods after the winter solstice is superior to simple dog-day treatment and the treatment in the three nine-day periods after the winter solstice, and the efficacy of dog days treatment is better than that in the three nine-day periods after the winter solstice.

Analyzing clinical and electrophysiological characteristics of Paroxysmal Dyskinesia.

The classification, clinical and electrophysiological characteristics, treatment outcome and pathogenesis of paroxysmal dyskinesia were summarized and analyzed. Paroxysmal dyskinesia was classified into three types. Different types had different incentives in clinical practice. Patients were mostly male adolescents, and the attacks, which were in various forms, manifested as dysmyotonia of choreoathetosis, body torsion and facemaking; no disturbance of consciousness during attacks. Electroencephalogram and other examinations showed no specific abnormalities during both the attacks and interictal period. Paroxysmal dyskinesia was an independent disease and different from epilepsy.

Association between HLA-B*1502 allele and carbamazepine-induced severe cutaneous adverse reactions in Han people of southern China mainland.

Previous studies have found a strong association between HLA-B*1502 and carbamazepine-induced Stevens-Johnson syndrome in Asian areas including Taiwan, Hongkong and Thailand. This study explores the association between HLA-B*1502 allele and carbamazepine-induced cutaneous adverse reactions in Han Chinese of southern China mainland, and find the genetic marker that can predict carbamazepine-induced cutaneous adverse reactions. HLA-B*1502 allele genotyping was performed by a polymerase chain reaction-sequence specific primers (PCR-SSP) method in 48 Han Chinese subjects who had carbamazepine-induced cutaneous adverse reactions, including 9 severe cutaneous adverse reaction patients with Stevens-Johnson syndrome (SJS) or toxic epidermal necrolysis (TEN) and 39 cutaneous adverse reaction patients with maculopapular eruption (MPE). Meanwhile 80 carbamazepine-tolerant controls and 62 healthy individuals were also tested. The frequency of HLA-B*1502 allele among SJS/TEN patients (100%) is significantly higher than carbamazepine-tolerant controls (13.75%, P<0.001) and healthy individuals (17.74%, P<0.001). But the frequency between MPE patients and carbamazepine-tolerant controls (25.64% vs.13.75%, P=0.110) did not have any significant difference. The data showed that HLA-B*1502 allele is strongly associated with carbamazepine-induced SJS/TEN but not MPE in Han Chinese of southern China mainland.

Long-term increasing co-localization of SCN8A and ankyrin-G in rat hippocampal cornu ammonis 1 after pilocarpine induced status epilepticus.

Voltage-gated sodium channels (VGSC) are important determinants of neuronal excitability which are implicated in the pathogenesis of epilepsy. Ankyrin-G contributes to the distribution and regulation of VGSC. Here we investigated the alterations of the two alpha-subunits SCN8A and SCN1A and their adapter ankyrin-G in the hippocampal cornu ammonis 1 (CA1) of rats after pilocarpine induced status epilepticus (PISE), compared to the sham-control group (C1) and blank-control group (C2). Significant increase of SCN8A mRNA (41.08% increase compared to C1, P<0.001; 30.88% increase compared to C2, P=0.011) was detected 60 days after PISE. At D1 SCN8A mRNA reduced but no significant changes were detected when compared to controls (one-way ANOVA, F=1.232, P=0.276). After measuring the optical density of Western blot, we detected significant differences between the levels of SCN8A protein in different groups but no difference between the protein levels of SCN1A at D1 and D60 after pilocarpine treatment compared to the control. At D60 the relative copies of ankyrin-G mRNA on internal control beta-actin in PISE group increased significantly compared to C1 and C2 (one-way ANOVA, F=16.537, P<0.001). Significantly increase of ankyrin-G immunoreactivity in Western blot from the PISE group 1 day and 60 days after PISE was observed, compared to the controls (one-way ANOVA, F=24.255 at D1, P<0.001; F=29.280 at D60, P<0.001). After analyzing the double-stained cells counting, we detected significant differences between the numbers of SCN8A+/ankyrin-G+ immunoreactive cells in different groups in acute and chronic period following PISE (two way-ANOVA, F(group)=37.905, P<0.001; F(day)=45.310, P<0.001). The data revealed that both SCN8A and ankyrin-G increased significantly in the CA1 subfield of the rat hippocampus 60 days following pilocarpine induced status epilepticus and co-localized with each other.