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Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is an anti-neuronal surface antigen autoimmune encephalitis and is relatively rare. Our study evaluated a patient who developed anti-AMPA2 receptor encephalitis with memory deficits and refractory focal seizures as paroxysmal jerking on right face as well as dystonic seizure on right hand. On this patient, the combination treatment of levetiracetam, carbamazepine, and clonazepam, monthly periodic intravenous immunoglobin and immunosuppressive therapies for 5 months was not effective for the focal seizures, while his memory loss was slightly improved. However, adjunctive perampanel treatment led to a rapid relief of seizures. Perampanel is suggested in seizures associated with anti-AMPA receptor encephalitis by directly attenuating nerve hyperexcitability caused by glutamate and Ca2+-permeable GluA4 subunit of AMPA receptors.

Objectives Generalized epilepsy with febrile seizures plus (GEFS+) is a new epilepsy syndrome named by the International League Against Epilepsy (ILAE) in 2001. The SCN2A gene encoding α2 subunit of the neuronal sodium channel has been reported to be associated with BFNIS, GFES+, Dravet syndrome and some intractable childhood epilepsies. This study aimed to develop an approach based on next-generation sequencing to determine the genetic defects in a monozygotic twin family with GEFS+. Patients and methods We collected a twin family with GEFS+. The DNA of the twin patients was extracted from their peripheral venous whole blood. A total of 308 known genes related to epilepsies were selected for deep exon resequencing. The patients family’s DNA was sequenced through Sanger's sequencing for expanded validation. Through systematic data analysis using established bioinformatics pipeline and segregation analysis techniques, a number of genetic variants were released. Results Through detailed data analysis, we found a new heterozygous mutation c.1399G > A on exon11 of SCN2A (Nav1.2) which has not been reported in the HGMD (Human Gene Mutation Database), in the twin patients. Then we tested and verified the presence of the same mutation site in all individuals of the family. Asymptomatic individuals of this family didn’t show this mutation. Conclusion The methodology provides a reliable strategy for routine gene diagnosis of GEFS+. This observation of a potentially pathogenic mutation of SCN2A (Nav1.2) indicates that this gene should be further evaluated in order to determine possible routes of causation of GEFS+.

Idiopathic hypereosinophilic syndrome is an uncommon leukoproliferative systemic disorder characterized by the sustained eosinophilia and target organ damage. We report the case of a 56-year-old man presenting with multiple cerebral embolism, Löffler endocarditis, and hypereosinophilia. This patient also had pleural, bone marrow, and skin involvement. The unique feature was multifocal embolisms in the brain.

Temporal lobe epilepsy is characterized by spontaneous recurrent seizures (SRS) and associated with behavioral problems. However, the molecular mechanisms underlying these problems are not yet clear. In this study, kainic acid (KA) was systemically administered to immature male Wistar rats to induce SRS. The behavior of the immature rats was evaluated with a water maze, elevated-plus mazes, and open field tests. The expression patterns of synaptophysin, SNAP-25, and synaptotagmin 1 (Syt 1) were examined by reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blot analysis. KA-treated rats with SRS demonstrated learning and memory deficits, reduced anxiety, and increased locomotor activity, compared with placebo-treated rats and KA-treated rats without SRS. No neuronal cell loss was observed in the hippocampus 6 weeks after exposure to KA. However, RT-PCR and Western blot analyses revealed decreased synaptophysin, SNAP-25, and Syt 1 expression in KA-treated rats with SRS. Synaptophysin, SNAP-25, and Syt1 expression levels were found to be positively correlated with learning and memory but negatively correlated with anxiety and locomotor activity. These data suggested that SRS may induce changes in synaptophysin, SNAP-25, and Syt1 expression and may be functionally related to SRS-induced behavioral deficits.

Oxidative stress is a mechanism of cell death induced by seizures. Antioxidant compounds have neuroprotective effects due to their ability to inhibit free radical production. Autophagy is a process in which cytoplasmic components such as organelles and proteins are delivered to the lysosomal compartment for degradation, and plays an essential role in the maintenance of cellular homeostasis. The activity of autophagy is enhanced during oxidative stress. The objectives of this work were first to study the inhibitory action of antioxidant ascorbic acid on behavioral changes and brain damage induced by high doses of pilocarpine, then to study the effect of ascorbic acid on oxidative stress (MDA and SOD were used to estimate oxidative stress) and activated autophagy (beclin 1 was used to estimate autophagy) induced by seizures, aiming to further clarify the mechanism of action of this antioxidant compound. In order to determinate neuroprotective effects, we studied the effects of ascorbic acid (500 mg/kg, i.p.) on the behavior and brain lesions observed after seizures induced by pilocarpine (340 mg/kg, i.p., P340 model) in rats. Ascorbic acid injections prior to pilocarpine suppressed behavioral seizure episodes by increasing the latency to the first myoclonic, clonic and tonic seizure and decreasing the percentage of incidence of clonic and tonic seizures as well as the mortality rate. These findings suggested that oxidative stress can be produced and autophagy is increased during brain damage induced by seizures. In the P340 model, ascorbic acid significantly decreased cerebral damage, reduced oxidative stress and inhibited autophagy by reducing de novo synthesis of beclin 1. Antioxidant compound can exert neuroprotective effects associated with inhibition of free radical production and autophagy. These results highlighted the promising therapeutic potential of ascorbic acid in treatment for seizures.

BACKGROUND Benign rolandic epilepsy (BRE) is one of the most common focal epilepsies in childhood, but less typical clinical presentations may lead to misdiagnosis and incorrect treatment. The focus of this study was therefore to retrospectively investigate the less typical features of BRE in Chinese children. METHODS Data on 316 Chinese children with BRE were collected and analyzed. RESULTS A total of 7.3% of children complained of tension, fear and terror at the onset of a seizure, and 5.4% had been misdiagnosed with mesial temporal lobe epilepsy. Approximately 12.3% had post-ictal Todd's paresis, with 6.6% having been misdiagnosed and given incorrect treatment. Nineteen children (6%) had neuroradiologic abnormalities, which could lead to a diagnosis of symptomatic epilepsy. Twenty-five patients (8.0%) had cognitive deficits. CONCLUSIONS Greater recognition of, and further investigation into, the spectrum of BRE are needed.

Objective: Alternating hemiplegia of childhood (AHC) is a rare and intractable disorder. The etiology and standard therapy of AHC remain unknown. The long-term effects of flunarizine or topiramate on patients with AHC are still not clear. Methods: Fifteen patients were investigated in this study. Their neurological disturbance and mental retardation after drug therapy were evaluated. Results: Nine patients treated with flunarizine therapy and three children with topimarate treatment presented with shorter duration or less frequency of the hemiplegic attacks. These drug responsive patients also showed improvements on neurological disturbance including eye movement disorder, choreoathetotic movements, dystonia, and ataxia. However, seizure episodes and cognitive impairments were not alleviated in AHC with long-term drug therapy. Conclusions: The findings from the present study support flunarizine or topitamate as the rational treatment for AHC.

Mitochondrial dysfunction has been suggested to be a contributing factor of epilepsy, but the underlying mechanisms are not completely explored. Mitochondrial biogenesis is involved in regulation of mitochondrial content, morphology, and function. In the current study, we show mitochondrial biogenesis severely impaired in hippocampi of rats with chronic seizures induced by pilocarpine, as evidenced by decreased mitochondrial DNA (mtDNA) content and decreased mtDNA-encoded protein level. Furthermore, we show mtDNA transcription and replication reduced in rats with chronic seizures. These defects were independent of downregulation of mitochondrial biogenesis-related factors, such as peroxisome proliferator-activated receptor gamma coactivator-1α, nuclear respiratory factor-1, and mitochondrial transcription factor A (Tfam), but depended on reduced Tfam–DNA binding activity. The present study suggests novel mechanisms for mitochondrial dysfunction during chronic seizures.

Status epilepticus (SE) can cause severe neuronal loss and oxidative damage. Peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) can be neuroprotective by inducing the antioxidant system, so we evaluated the role of PGC-1α in SE. The expression of PGC-1α and one of its target genes, uncoupling protein 2 (UCP2), was upregulated after SE, which may represent an endogenous neuroprotective mechanism. Furthermore, pretreatment with an adenosine monophosphate-activated protein kinase (AMPK) inhibitor significantly attenuated both AMPK and PGC-1α activation, followed by downregulation of UCP2 and enhanced oxidative stress and hippocampal neuronal damage. AMPK/PGC-1α may be neuroprotective in SE-induced brain damage, at least in part via UCP2.

Peroxisome proliferator-activated receptor (PPAR) γ coactivator 1-α (PGC-1α) is a transcriptional coactivator identified as an upstream regulator of lipid catabolism, mitochondrial number and function. PGC-1α protects neurons against oxidative damage by inducing several members of the mitochondrial antioxidant system such as superoxide dismutase 2 (SOD2) and uncoupling protein 2 (UCP2). Its role in seizure-induced oxidative stress has not been studied. Here we showed that pilocarpine-induced status epilepticus (SE) stimulates the PGC-1α/mitochondrial antioxidant system signaling pathway in the rat hippocampus. Because nitric oxide (NO) is the key factor of mitochondrial biogenesis through the transcriptional induction of PGC-1α, we investigated whether NO is involved in activation of the PGC-1α/mitochondrial antioxidant system after SE. Treatment with the NO synthase (NOS) inhibitor N(G)-nitro-l-argininemethyl ester (l-NAME) attenuated the increased expression of the PGC-1α/mitochondrial antioxidant system after SE and enhanced oxidative stress. These results suggest that SE can induce the PGC-1α/mitochondrial antioxidant system signaling pathway, which may represent a protective mechanism against SE-induced oxidative stress. Furthermore, NO may positively regulate the mitochondrial antioxidant system by inducing PGC-1α in pilocarpine-induced SE.

Apoptosis and autophagy are common physiological and pathological processes in the human body. Death-associated kinase protein 1 (DAPK1), which participates in the process of cell death, has attracted people's attention for its potential risk with late-onset Alzheimer's disease (LOAD). A recent study identified two single nucleotide polymorphisms (SNPs) in DAPK1 that show significant association with LOAD in Caucasians. In order to clarify the role of these genetic variations in Chinese population, we examined the genetic variations of DAPK1/rs4877365 and DAPK1/rs4878104 in a group of 400 LOAD patients and 400 healthy controls. All samples were recruited from Northern Han Chinese population. Data collected from this study showed that there were significant differences in genotype (P = 0.02) and allele (P = 0.007) frequencies of DAPK1/rs4878104 but not in DAPK1/rs4877365 between LOAD patients and controls. The “C” allele of rs4878104 worked as a protective factor of LOAD (P = 0.0026, odds ratio/OR = 0.75) in Han Chinese. Logistic regression analysis revealed that homozygosity was strongly associated with LOAD under a recessive model (P = 0.003, OR = 0.23). No significant association was observed between rs4877365 and LOAD. Haplotype analysis identified the G/T haplotype as a risk factor for LOAD (P = 0.007, OR = 1.33, 95% CI = 1.08–1.64). This study provides the evidence that variation in DAPK1 gene influences susceptibility to LOAD in the Northern Han Chinese population.

Valproic acid (VPA), a widely prescribed drug for seizures and bipolar disorder, induces apoptosis in microglia, but the underlying mechanism by which microglia apoptosis in response to VPA is not yet known. In this study, we found that the mitochondrial pathway played an important role in VPA-induced apoptosis in both BV-2 microglia and mouse primary microglial cells. In addition, VPA increased the level of phospho-p38 mitogen-activated protein kinase (MAPK), but had no effects on phospho-ERK and phospho-JNK MAPKs. Moreover, p38 inhibitor SB203580 strongly inhibited VPA-induced apoptosis and caspase-3 activation. Taken together, our results clearly demonstrated that VPA could induce apoptosis of microglia via p38 MAPK and mitochondrial apoptosis pathway.

Oxidative damage to mitochondrial DNA (mtDNA) has been implicated as an important mechanism underlying mitochondrial deficiency in epileptic seizures. In focusing on the role of the DNA repair pathway, we determined the response of the mitochondrial base excision repair (mtBER) pathway in pilocarpine-induced status epilepticus (SE) in hippocampi of male Wistar rats. The expression of 8-oxoguanine DNA glycosylase (OGG1) and polymerase gamma (polgamma) was decreased at both the cellular mRNA and mitochondrial protein levels at 3, 9 and 25h after the onset of SE. The mRNA and protein levels of APE1 were maintained, but the mitochondrial protein level decreased at 3 and 9h and recovered at 25h. Therefore, the mtBER pathway failed to respond to SE induced by pilocarpine. The failure of mitochondrial import might be an important factor responsible for the lowered mtBER enzymes in mitochondria. We hypothesize that the down-regulation of mtBER enzymes may aggravate mtDNA damage and mitochondrial deficiency after the onset of SE.

Calcineurin (CaN) is a neuronally enriched, calcium-dependent phosphatase, which plays an important role in a number of neuronal processes including development of learning and memory, and modulation of receptor's function and neuronal excitability as well as induction of apoptosis. It has been established in kindling model that the status epilepticus (SE)-induced increase in CaN activity is involved in the development of seizures through down-regulation of gamma-aminobutyric acid A receptor (GABA(A)R) activation. However, the mechanism by which CaN mediates GABA(A) receptor dephosphorylation in SE is not fully understood. Here, using a model of kainic acid (KA)-induced SE and CaN inhibitor FK506, we observed the behaviors induced by KA and levels of CaN activity and CaN expression in hippocampus by immunobloting. The results showed that the SE-induced CaN activity was time-dependent, with a peak at 2h and a return to basal level at 24h, whereas a significant increase in CaN expression was seen at 24h after SE. It is proposed that the rapid elevation in CaN activity after KA-induced SE is not likely due to an increase in CaN expression but rather an increase in CaN activation state or kinetics. In addition, we also demonstrated that pre-treatment with FK506 remarkably suppressed the SE-induced CaN activity and its expression, and reversed the SE-induced dephosphorylation of GABA(A)R 2/3 subunits. Taken together, our data suggest that down-regulation in inhibition of GABA(A)R 2/3 by CaN activity contributes to an elevation in neuronal excitability of hippocampus, which may be involved in development of chronic processes of seizures.

Seizures and status epilepticus induce an excessive production of reactive oxygen species leading to oxidative stress. Vitamin E, a classic antioxidant, has a neuroprotective effect on rats with seizures by regulating reactive oxygen species production. The activity of chaperone-mediated autophagy, a selective pathway for the degradation of cytosolic proteins in lysosomes, is enhanced during oxidative stress. Whether chaperone-mediated autophagy is induced during status epilepticus is not established. To address this problem, we used pilocarpine to elicit status epilepticus in rats. Lysosome-associated membrane protein 2a was used to estimate chaperone-mediated autophagy. We showed that compared to control animals, lysosome-associated membrane protein 2a at lysosomal membranes increased significantly in rats at 8 h, 16 h, and 24 h after induction of status epilepticus, which directly correlated with chaperone-mediated autophagy activity. Since reactive oxygen species are believed to be important in the pathogenesis of status epilepticus and are essential for the process of chaperone-mediated autophagy, we also sought to determine if pretreatment with vitamin E reduced chaperone-mediated autophagy. Pretreatment with vitamin E reduced oxidative stress and partially inhibited chaperone-mediated autophagy in brain at 24 h after status epilepticus versus vehicle. Taken together, these data show that chaperone-mediated autophagy is increased in rats with pilocarpine-induced status epilepticus through upregulation of de novo synthesis of lysosome-associated membrane protein 2a. Antioxidants such as vitamin E may partially inhibit activated chaperone-mediated autophagy.

Autophagy, a process of bulk degradation of cellular constituents through autophagosome-lysosomal pathway, is enhanced during oxidative stress. Whether autophagy is induced during status epilepticus (SE), which induces an excess production of reactive oxygen species (ROS) and leads to oxidative stress, is not established. We also sought to determine if pretreatment with Vitamin E reduced autophagy. We used pilocarpine to elicit SE in rats. The ratio of LC3 II to LC3 I and beclin 1 were used to estimate autophagy. We found that ratio of LC3 II to LC3 I and beclin 1 increased significantly at 2, 8, 16, 24 and 72 h, peaking at 24 h after SE onset. Pretreatment with Vitamin E partially inhibited autophagy by reducing LC3 II formation and de novo synthesis of beclin 1 at 24 h after seizures. These data show that autophagy is increased in rats with pilocarpine-induced SE, and Vitamin E have a partial inhibition on autophagy.

Status epilepticus (SE) is a severe clinical manifestation of epilepsy which causes brain damage. The pathological process and underlying mechanisms involved in the programmed cell death (PCD) are still not fully clear. In the current study, rats were induced SE by lithium-pilocarpine administration. Our data showed hippocampal neurons death appeared at 6h after SE and sustained for 7 days. By blotting the activation of mu-calpain and its specific cleavage of nonerythroid alpha-spectrin (alphaSpII) (145 kDa) was evident at 1 and 3 days after SE, which coincided with Bid activation, apoptosis inducing factor (AIF) translocation and cytochrome c release from mitochondria, whereas, activated caspase-3 and caspase-3-specific fragments of alphaSpII (120 kDa) predominantly appeared at 5 and 7 days after SE. Moreover, MDL-28170, a calpain inhibitor, partially rescued the neuron death and attenuated the expression of activated mu-calpain, cleavage of Bid (15 kDa), AIF translocation and cytochrome c release. Taken together, our study indicated that mu-calpain mediated hippocampal neuron PCD is prior to caspase-3 activation. It functioned via translocation of Bid, AIF and cytochrome c release.

This study reports a Chinese family that has suffered from occipital encephalocele over five generations with a pattern of autosomal dominant inheritance. There were 113 family members in this family, and 21 of them had an occipital subscalp encephalocele. The patients with the disease showed normal or nearly normal neurological function.

Mitochondrial dysfunction has been implicated as a contributing factor in epileptic seizures. Present studies were carried out to decipher seizure-dependent changes in mitochondrial function and ultrastructure in the chronic condition of temporal lobe epilepsy (TLE) induced by pilocarpine in rat hippocampus. Enzyme assay revealed significant depression of the activity of mitochondrial- and nuclear-encoded cytochrome oxidase (COX). Conversely, the activity of nuclear-encoded succinate dehydrogenase (SDH) remained unchanged. Discernible mitochondrial ultrastructural damage, varying from swelling to disruption of membrane, was observed in the hippocampus. Quantitative real-time PCR and Western blotting showed the expression of mitochondrial-encoded COX subunit III (COXIII) dropped significantly during the chronic seizure activity; the corresponding expression of COX subunit IV (COXIV) displayed no significant change. Most likely, our results suggest that dysfunction of mitochondrial COX respiratory enzyme and mitochondrial ultrastructural damage in the hippocampus are associated with prolonged seizure during experimental TLE and mitochondria are more vulnerable to epilepsy.

Sjogren’s syndrome is primarily a chronic systemic autoimmune disease that involves many systems. However, Sjogren’s syndrome involving the central nervous system lesions, particularly in the central nervous system symptoms as the first performers is uncommon. In this report, we present a 33-year-old woman having PSs with CNS involvement, whose first symptoms presented progressive weakness on the left leg, 2 years later the left upper limb appeared the same symptoms, being diagnosed with Sjogren’s syndrome. To give methylprednisolone pulse therapy, combined with cyclophosphamide and anetholtrithione treatment, her condition improved. After six months’ following-up, no recurrence.

Sirtuin 1 (SIRT1) regulates numerous neuronal processes, including metabolism, antioxidation and aging, through activation of peroxisome proliferator-activated receptor coactivator 1-α (PGC-1α), an upstream regulator of mitochondrial biogenesis and function. However, the role of SIRT1 in the oxidative stress induced by seizures has yet to be elucidated. The present study aimed to investigate whether SIRT1 was involved in the activation of the PGC-1α/mitochondrial antioxidant system following status epilepticus (SE) in rats. The data demonstrated that SIRT1 expression and activity were enhanced in the rat hippocampus following SE. SIRT1 inhibition effectively blocked the SE-associated increase in PGC-1α and mitochondrial antioxidant enzymes, including superoxide dismutase 2 (SOD2) and uncoupling protein 2 (UCP2). Additionally, it was also demonstrated that the activation of SIRT1 enhanced mitochondrial electron transport chain complex I activity and increased ATP content. In conclusion, the present results suggest that SIRT1 activation may alleviate mitochondrial oxidative stress induced by seizures partially via PGC-1α signaling.

Mitochondrial fission has been reported to be involved in oxidative stress, apoptosis and many neurological diseases. However, the role of mitochondrial fission in seizures, which could induce oxidative stress and neuronal loss, remains unknown. In this study, we used pilocarpine to elicit seizures in rats. Meanwhile, we used mitochondrial division inhibitor 1 (mdivi-1), a selective inhibitor of mitochondrial fission protein dynamin-related protein1 (Drp1), to suppress mitochondrial fission in epileptic model of rats in vivo. We found that mitochondrial fission was increased after seizures and the inhibition of mitochondrial fission by mdivi-1 significantly attenuated oxidative stress and reduced neuronal loss after seizures, shown by the decreased 8-hydroxy deoxyguanosine (8-oHdG) content, the increased superoxide dismutase (SOD) activity, the reduced expression of cytochrome c and caspase3 and the increased surviving neurons in the hippocampus. These results indicated that mitochondrial fission is up-regulated after seizures and the inhibition of mitochondrial fission is protective against neuronal injury in seizures, the underlying mechanism may be through the mitochondria/reactive oxygen species (ROS)/cytochrome c pathway.

The aim of this study was to investigate the value of T(2) (*)-weighted gradient echo imaging (GRE T(2) (*)-WI) for the detection of familial cerebral cavernous malformation (FCCM). Twenty-six members of 2 families with FCCM were examined using computed tomography (CT), conventional magnetic resonance imaging (MRI) and GRE T(2) (*)-WI sequences. We identified 12 cases of FCCM using GRE T(2) (*)-WI sequences. These 12 patients had multiple lesions (mean 23). The lesions were most commonly located in the ganglia. Other areas included the cortex-subcortex, thalamus, cerebellum and brainstem. These lesions appeared as a reticulated core of mixed signal intensity with a surrounding rim of decreased signal intensity representing hemosiderin from previous hemorrhages. The mean numbers of lesions and cases of FCCM identified by various conventional MRI sequences were 5-17 and 3-9, respectively. Conventional MRI examination involved T(1)-weighted imaging (T(1)WI), T(2)-weighted imaging (T(2)WI), T(2)-fluid-attenuated inversion recovery (T(2)Flair), diffusion-weighted imaging (DWI) and spin-echo imaging (SE) sequences, in that order. The numbers of lesions identified by MRI were fewer than those identified by GRE T(2) (*)-WI. CT only identified 3 cases with large lesions combined with hemorrhage and calcification. These findings suggest that GRE T(2) (*)-WI is the first choice when diagnosing FCCM compared with CT and conventional MRI.

Resveratrol is indicated to be involved in neuroprotection and anti-inflammation in epileptic rats. The molecular mechanism is still not fully understood. In this study, we investigated the role of resveratrol in nuclear factor-kappa B associated inflammatory responses induced by status epilepticus. Our data showed that seizures activated mammalian target of rapamycin (mTOR), increased the activity of nuclear factor-kappa B and promoted the expressions of inflammatory molecules including inducible nitric oxide synthase, cyclooxygenase-2 and interleukin-1β. Futhermore, resveratrol significantly inhibited the activation of nuclear factor-kappa B and the production of proinflammatory molecules via mTOR pathway. Additionally, we also proved that the inhibition of mTOR signal by resveratrol was mostly attributed to AMP-activated kinase (AMPK) activation. Altogether, our results suggest that resveratrol suppresses inflammatory responses induced by seizures partially via AMPK/mTOR pathway.

Toll-like receptors 2 (TLR2) and TLR4 are involved in the microglia-mediated inflammatory response, Aβ plaque formation and Aβ clearance in Alzheimer's disease (AD). Our previous studies have shown that variants in the TLR2 and TLR4 genes are associated with the risk of AD. Therefore, we hypothesize that there may be significant changes in TLR2 and TLR4 expressions on peripheral blood mononuclear cells (PBMCs) from patients with AD when compared to healthy control subjects.Sixty patients with late-onset AD (LOAD) and 60 healthy controls matched for sex and age were recruited. Flow cytometry (FCM) was used to detect expressions of TLR2 and TLR4 proteins and real-time quantitative RT-PCR was performed to determine TLR2 and TLR4 mRNAs.Compared with controls, expressions of TLR2 and TLR4 mRNAs were up-regulated in LOAD patients (TLR2/beta-actin mRNA: 0.390±0.204 versus 0.281±0.167, P0.01; TLR4/beta-actin mRNA: 0.503±0.195 versus 0.322±0.183, P0.01). The proteins levels were higher in LOAD patients than in controls (TLR2: 97.12±1.67% versus 41.07±18.44%, P0.01, TLR4: 66.56±23.74% versus 14.83±4.31, P0.01). In both cases, either AD or control group, TLR2 and TLR4 mRNAs expressions were positively correlated with the levels of proteins (TLR2: r=0.980 and 0.976,P0.01; TLR4: r=0.938 and 0.970, P0.01), respectively. There were significant negative correlations between TLR levels and MMSE score (TLR2: r=-0.32; P=0.01; TLR4: r=-0.29; P=0.02). In addition, CC genotype can increase the expression of TLR4 in AD patients.This study gives the first evidence that expressions of TLR2 and TLR4 in PBMCs were markedly elevated in LOAD patients.

Diazoxide (DZ), a highly selective opener of the mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel, has neuroprotective effects. However, the mechanism of DZ protecting hippocampal neurons against cell death in pilocarpine-induced seizures is unknown. In this study, we investigated DZ attenuating neuronal loss caused by pilocarpine-induced seizures in rat hippocampus. DZ inhibited seizure-induced change in phospho-Akt expression, translocation of apoptosis-inducing factor (AIF), release of cytochrome c (CytC) and caspase-3 activation, which could be abolished by preincubation with 5-hydroxydecanoic acid, an inhibitor of mitoK(ATP). In addition, wortmannin, an inhibitor of phosphatidylinositol-3-kinase (PI3K), attenuated the translocation of AIF, CytC release and caspase-3 activation after seizures. DZ could reduce neuronal death induced by seizures in hippocampus by suppressing the translocation of AIF, CytC release and the activation of caspase-3 via the PI3K/Akt pathway.

In this study, we demonstrated a decreased level of mitochondrial DNA (mtDNA) with a large number of oxidized bases in hippocampi of rats with epilepsy induced by pilocarpine. In order to verify the underlying mechanism of mtDNA impairment, we detected the response of antioxidant defense system and mitochondrial base excision repair (mtBER) pathway. Superoxide dismutase2 (SOD-2) and glutathione (GSH) were significantly decreased in the experimental group, manifesting a decreased capacity of scavenging free radicals. Mitochondrial base excision repair (mtBER) pathway, which is the main repair pathway for the removal of oxidative base modifications, displayed unbalanced expression in epileptic group. DNA polymerasegamma (polgamma) increased, while apurinic/apyrimidinic endonuclease (APE1), one of mtBER initiators, decreased in mitochondria in the chronic phase of epileptogenesis. In conclusion, mtDNA was impaired during chronic recurrent seizures, whereas the endogenous antioxidants and the mtBER pathway failed to respond to the elevated mtDNA damage.

Opioids have been widely applied in clinics as one of the most potent pain relievers for centuries, but their abuse has deleterious physiological effects beyond addiction. We previously reported that opioids inhibit cell growth and trigger apoptosis in lymphocytes. However, the underlying mechanism by which microglia apoptosis in response to opioids is not yet known. In this study, we show that morphine induces microglia apoptosis and caspase-3 activation in an opioid-receptor dependent manner. Morphine decreased the levels of microglia phosphorylated Akt (p-Akt) and p-GSK-3β (glycogen synthase kinase-3 beta) in an opioid-receptor dependent manner. More interestingly, GSK-3β inhibitor SB216763 significantly increases morphine-induced apoptosis in both BV-2 microglia and mouse primary microglial cells. Moreover, co-treatment of microglia with SB216763 and morphine led to a significant synergistic effect on the level of phospho-p38 mitogen-activated protein kinase (MAPK). In addition, inhibition of p38 MAPK by its specific inhibitor SB203580 significantly inhibited morphine-induced apoptosis and caspase-3 activation. Taken together, our data clearly demonstrates that morphine-induced apoptosis in microglial cells, which is mediated via GSK-3β and p38 MAPK pathways.

Ghrelin, a 28-amino-acid peptide, is mainly secreted by the stomach. Evidence has shown ghrelin to have neuroprotective effects. However, whether ghrelin protects hippocampal neurons against cell death in pilocarpine-induced seizures is unknown. We used Nissl staining to show that ghrelin attenuated the neuronal loss caused by pilocarpine-induced seizures in the hippocampus. Ghrelin exerted the protective action through regulating the phosphatidylinositol-3-kinase and Akt pathway. Moreover, ghrelin treatment reversed the decreased ratio of Bcl-2 to Bax induced by seizures while inhibiting the activated caspase-3. Ghrelin can inhibit hippocampal neuronal damage caused by pilocarpine-induced seizures, which might have therapeutic value in seizures.

We retrospectively evaluated the clinical and electroencephalogram (EEG) characteristics of benign rolandic epilepsy (BRE) in Chinese children. Two hundred and seventy-six patients with BRE were enrolled in this study. All patients had their first seizure between the ages of 3 and 12 years. 39.5% (109 cases) of patients ceased to have further BRE seizures by the age of 6 years, 93.1% (257 cases) recovered by the age of 12 years and 96.7% (267 cases) recovered by the age of 18 years. Two hundred and twenty-seven patients suffered only simple partial seizures, whereas 49 patients suffered generalized seizures from onset of BRE. The EEG scans of 239 patients showed repetitive diphasic spikes or sharp waves with high amplitude, which were most dominant in the central or centrotemporal areas. The spikes were confined to one hemisphere in 180 patients and occurred bilaterally in 59 patients. Ninety-eight patients were treated with antiepileptic drugs (AEDs): carbamazepine (CBZ) or valproate (VPA). The study showed that, in Chinese children, BRE is remarkably characteristic in its clinical and EEG presentation. Although BRE is usually benign in terms of ease of control with AEDs and spontaneous seizure remission, for those patients with a high frequency of seizures, AEDs should be prescribed positively.