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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.

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.

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.

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.

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.