Moreover, liraglutide protected against Scn1a KO-induced apoptosis, which was manifested in the phosphorylation of mTOR (KO+NS: 1.99 ± 0.31 vs. KO+Lira: 0.97 ± 0.18, P = 0.0004), as well as the downregulation of cleaved caspase-3 (KO+NS: 0.49 ± 0.04 vs. KO+Lira: 0.30 ± 0.01, P = 0.0003) and restoration of the imbalance between BAX (KO+NS: 0.90 ± 0.02 vs. KO +Lira: 0.75 ± 0.04, P = 0.0005) and BCL-2 (KO+NS: 0.46 ± 0.02 vs. KO+Lira: 0.61 ± 0.02, P = 0.0006). Collectively, these results show that liraglutide reduces seizure susceptibility and cognitive dysfunction in the mouse model of Dravet syndrome, and exerts anti-apoptotic and neuroprotective effects in Scn1a KO mice and cells.

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Purpose: Eosinophils are proven to play a role in the prognosis of some malignant-tumors. The prognostic value of eosinophils in glioma patients is, however, scarcely reported. The authors of this article have designed a novel prognostic indicator based on eosinophils and the neutrophil-to-lymphocyte ratio (NLR), named ENS, to predict the survival of patients with glioma. Methods: A retrospective study was conducted on 217 glioma patients. The cutoff values for eosinophil, NLR, and other clinical variables were determined by the receiver operating characteristic (ROC) curve analysis. Patients with both low eosinophil count (<0.08 ×10 9 /L) and high NLR (≥1.70) were given a score of 2. Those with one or neither got a score of 1 or 0, respectively. The nomogram was based on ENS and several other clinical variables, its performance was determined by the concordance index (c-index). Results: Our results showed that ENS is an independent prognostic indicator for overall survival (OS). The three-year OS rates for low-grade glioma patients (LGGs) were 84.0%, 69.0%, and 46.4% for ENS=0, ENS=1, and ENS=2, respectively (P=0.014). The three-year OS incidence for LGGs stratified into eosinophils count ≥0.08×109/L and<0.08×109/L subgroups were 88.1% and 80.0%, respectively (P=0.043). ENS was positively correlated with glioma grade (r=0.311, P<0.001). The c-index for OS prognosis was 0.80 using this nomogram in LGGs. Conclusion: Preoperative ENS can predict OS to some extent for LGGs and can increase prognostic accuracy for individual OS in LGGs postoperatively when incorporating other clinical variables compose a nomogram.

Exendin-4 (Ex4), a long-lasting glucagon-like peptide-1 analog, was reported to exert favourable actions on inhibiting cocaine-associated rewarding and reinforcing effects of drug in animal models of addiction. However, the therapeutic potential of different dose of GLP-1 receptor agonist Ex4 in different behavioral paradigms and the underlying pharmacological mechanisms of action are incompletely understood. Herein, we firstly investigated the effects of Ex4 on cocaine-induced condition place preference (CPP) as well as extinction and reinstatement in male C57BL/6J mice. Additionally, we sought to elucidate the underlying pharmacological mechanism of these actions of Ex4. The paradigm of cocaine-induced CPP was established using 20 mg/kg cocaine or saline alternately during conditioning, while the reinstatement paradigm was modeled using 10 mg/kg cocaine on the reinstatement day. Different dose of Ex4 was administrated intraperitoneally either during conditioning or during extinction state or only on the test day. To elucidate the molecular mechanism underlying the potential effects of Ex4 on maladaptive behaviors of cocaine, the TLR4-related inflammation within the hippocampus was observed by immunofluorescence staining, and the expression levels of toll-like receptor 4 (TLR4), tumor necrosis factor (TNF)-α, and interleukin (IL)-1β were detected by Western blotting. As a consequence, systemic administration of different dose of Ex4 was sufficient to inhibit the acquisition and expression of cocaine-induced CPP, facilitate the extinction of cocaine-associated reward and attenuate reinstatement of cocaine-induced behavior. Furthermore, Ex4 treatment diminished expression levels of TLR4, TNF-α, and IL-1β, which were up-regulated by cocaine exposure. Altogether, our results indicated that Ex4 effectively ameliorated cocaine-induced behaviors likely through neurobiological mechanisms partly attributable to the inhibition of TLR4, TNF-α and IL-1β in mice. Consequently, our findings improved our understanding of the efficacy of Ex4 for the amelioration of cocaine-induced behavior and suggested that Ex4 may be applied as a drug candidate for cocaine addiction.

BackgroundDravet syndrome (DS) is a severe epileptic encephalopathy mainly caused by haploinsufficiency of the gene SCN1A, which encodes the voltage-gated sodium channel NaV1. 1 in the brain. While SCN1A mutations are known to be the primary cause of DS, other genes that may cause DS are poorly understood. Several genes with pathogenic mutations result in DS or DS-like phenotypes, which may require different drug treatment approaches. Therefore, it is urgent for clinicians, especially epilepsy specialists to fully understand these genes involved in DS in addition to SCN1A. Particularly for healthcare providers, a deep understanding of these pathogenic genes is useful in properly selecting and adjusting drugs in a more effective and timely manner.ObjectiveThe purpose of this study was to identify genes other than SCN1A that may also cause DS or DS-like phenotypes.MethodsA comprehensive search of relevant Dravet syndrome and severe myoclonic epilepsy in infancy was performed in PubMed, until December 1, 2021. Two independent authors performed the screening for potentially eligible studies. Disagreements were decided by a third, more professional researcher or by all three. The results reported by each study were narratively summarized.ResultsA PubMed search yielded 5,064 items, and other sources search 12 records. A total of 29 studies published between 2009 and 2021 met the inclusion criteria. Regarding the included articles, seven studies on PCDH19, three on SCN2A, two on SCN8A, five on SCN1B, two on GABRA1, three on GABRB3, three on GABRG2, and three on STXBP1 were included. Only one study was recorded for CHD2, CPLX1, HCN1 and KCNA2, respectively. It is worth noting that a few articles reported on more than one epilepsy gene.ConclusionDS is not only identified in variants of SCN1A, but other genes such as PCDH19, SCN2A, SCN8A, SCN1B, GABRA1, GABRB3, GABRG2, KCNA2, CHD2, CPLX1, HCN1A, STXBP1 can also be involved in DS or DS-like phenotypes. As genetic testing becomes more widely available, more genes associated with DS and DS-like phenotypes may be identified and gene-based diagnosis of subtypes of phenotypes in this spectrum may improve the management of these diseases in the future.

BACKGROUND Incontinentia pigmenti (IP) is a rare X-linked dominant genetic disorder that can be fatal in male infants. It is a disease that affects many systems of the human body. In addition to characteristic skin changes, patients may also have pathological features of the eyes, teeth, and central nervous system. Therefore, the lesions in these systems may be the first symptoms for which patients seek treatment. To date, no cases of IP complicated by intracranial arachnoid cyst (IAC) have been reported. This paper aims to report a case of IP with IAC in order to share the diagnosis and treatment experience of this rare case with other clinicians. CASE SUMMARY An 11-year-old female patient suffered intermittent limb convulsions for five months and was sent to hospital. In the initial stage, the patient was considered to have primary epilepsy. Further investigation of the patient's medical history, physical examination and imaging examination led to the diagnosis of IP combined with intracranial space-occupying lesions, and secondary epilepsy. The patient was treated with craniotomy, and postoperative pathology revealed an IAC. The patient recovered well after craniotomy and had no obvious surgery-related complications. During the follow-up period, the patient did not have recurrent epilepsy symptoms. CONCLUSION IP is a multi-system disease that presents with typical skin lesions at birth, but the long-term prognosis of this disease depends on the involvement of systems other than the skin, especially nervous system and ocular lesions.

BackgroundDravet syndrome (DS) is a refractory developmental and epileptic encephalopathy (EE) with a variety of comorbidities, including cognitive impairment, autism-like behavior, speech dysfunction, and ataxia, which can seriously affect the quality of life of patients and impose a great burden on society and their families. Currently, the pharmacological therapy is patient dependent and may work or not. Neuromodulation techniques, including vagus nerve stimulation (VNS), deep brain stimulation (DBS), transcranial magnetic stimulation (TMS), responsive neurostimulation (RNS), and chronic subthreshold cortical stimulation (CSCS), have become common adjuvant therapies for neurological diseases, but their efficacy in the treatment of DS is unknown.MethodsWe searched Web of Science, PubMed, and SpringerLink for all published cases related to the neuromodulation techniques of DS until January 15, 2022. The systematic review was supplemented with relevant articles from the references. The results reported by each study were summarized narratively.ResultsThe Web of science, PubMed and SpringerLink search yielded 258 items. A total of 16 studies published between 2016 and 2021 met the final inclusion criteria. Overall, 16 articles (109 cases) were included in this study, among which fifteen (107 patients) were involved VNS, and one (2 patients) was involved DBS. After VNS implantation, seizures were reduced to ≥50% in 60 cases (56%), seizure free were found in 8 cases (7.5%). Only two DS patients received DBS treatment, and the initial outcomes of DBS implantation were unsatisfactory. The seizures significantly improved over time for both DBS patients after the addition of antiepileptic drugs.ConclusionMore than half of the DS patients benefited from VNS, and VNS may be effective in the treatment of DS. However, it is important to note that VNS does not guarantee improvement of seizures, and there is a risk of infection and subsequent device failure. Although DBS is a safe and effective strategy for the treatment of refractory epilepsy, the role of DBS in DS needs further study, as the sample size was small. Thus far, there is no strong evidence for the role of DBS in DS.

Mutations in the GABRG2 gene encoding the γ-aminobutyric acid (GABA) A receptor gamma 2 subunit are associated with genetic epilepsy with febrile seizures plus, febrile seizures plus, febrile seizures, and other symptoms of epilepsy. However, the mechanisms underlying Gabrg2-mediated febrile seizures are poorly understood. Here, we used the Cre/loxP system to generate conditional knockout (CKO) mice with deficient Gabrg2 in the hippocampus and neocortex. Heterozygous CKO mice (Gabrg2fl/wtCre+) exhibited temperature-dependent myoclonic jerks, generalised tonic-clonic seizures, increased anxiety-like symptoms, and a predisposition to induce seizures. Cortical electroencephalography showed the hyperexcitability in response to temperature elevation in Gabrg2fl/wtCre+ mice, but not in wild-type mice. Gabrg2fl/wtCre+ mice exhibited spontaneous seizures and susceptibility to temperature-induced seizures. Loss of neurons were observed in cortical layers V–VI and hippocampus of Gabrg2fl/wtCre+ mice. Furthermore, the latency of temperature- or pentylenetetrazol-induced seizures were significantly decreased in Gabrg2fl/wtCre+ mice compared with wild-type mice. In summary, Gabrg2fl/wtCre+ mice with Gabrg2 deletion in the neocortex and hippocampus reproduce many features of febrile seizures and therefore provide a novel model to further understand this syndrome at the cellular and molecular level.