An Assessment of the Pathological Classification and Postoperative Outcome of Focal Cortical Dysplasia by Simultaneous Hybrid PET/MRI.

OBJECTIVES: The purpose of this research was to investigate whether MRI and Simultaneous Hybrid PET/MRI images were consistent in the histological classification of patients with focal cortical dysplasia. Additionally, this research aimed to evaluate the postoperative outcomes with the MRI and Simultaneous Hybrid PET/MRI images of focal cortical dysplasia. METHODS: A total of 69 cases in this research were evaluated preoperatively for drug-resistant seizures, and then surgical resection procedures of the epileptogenic foci were performed. The postoperative result was histopathologically confirmed as focal cortical dysplasia, and patients then underwent PET and MRI imaging within one month of the seizure. In this study, head MRI was performed using a 3.0 T magnetic resonance scanner (Philips) to obtain 3D T1WI images. The Siemens Biograph 16 scanner was used for a routine scanning of the head to obtain PET images. BrainLAB's iPlan software was used to fuse 3D T1 images with PET images to obtain PET/MRI images. RESULTS: Focal cortical dysplasia was divided into three types according to ILAE: three patients were classified as type I, twenty-five patients as type II, and forty-one patients as type III. Patients age of onset under 18 and age of operation over 18 had a longer duration (p = 0.036, p = 0.021). MRI had a high lesion detection sensitivity of type III focal cortical dysplasia (p = 0.003). Simultaneous Hybrid PET/MRI showed high sensitivity in detecting type II and III focal cortical dysplasia lesions (p = 0.037). The lesions in Simultaneous Hybrid PET/MRI-positive focal cortical dysplasia patients were mostly located in the temporal and multilobar (p = 0.005, 0.040). CONCLUSION: Simultaneous Hybrid PET/MRI has a high accuracy in detecting the classification of focal cortical dysplasia. The results of this study indicate that patients with focal cortical dysplasia with positive Simultaneous Hybrid PET/MRI have better postoperative prognoses.

SSa ameliorates the Glu uptaking capacity of astrocytes in epilepsy via AP-1/miR-155/GLAST.

BACKGROUND: Neuronal glutamate (Glu) release has been reported to mediate the neuronal injury of epilepsy, while Saikosaponin a (Ssa) was shown to ameliorate the epilepsy that induced by pentylenetetrazol (PTZ). However, potential interactions between glutamate release and Ssa has not been fully identified. METHODS: Herein, PTZ-induced rat model were established to evaluate the neuron injury, while Ssa was used to treat the model rat. Rat astrocytes were isolated and induced by PTZ to construct cell models of epilepsy, real-time PCR and western blot were used to determine genes' expression. Luciferase reporter assay were performed to validate the relationship between miR-155-5p and glutamate aspartate transporter (GLAST). The level of Glu was sampled for HPLC measurement. RESULTS: Ssa treatment could decrease the level of Glu in hippocampus of rat. PTZ-induced astrocytes pretreated with Ssa significantly decreased the expression of AP-1 and miR-155, but increased the expression of GLAST, furthermore, PTZ stimulation enables astrocytes to uptake large amount of extracellular Glu. AP-1 could bind with the promoter of miR-155 to promote its transcription. MiR-155 tragets GLAST to govern its expression. CONCLUSION: Ssa treatment played pivotal roles in PTZ-induced epilepsy by promoting the expression of GLAT1 and uptaking of Glu, which was mediated by the expression of AP-1 and miR-155.

Saikosaponin a functions as anti-epileptic effect in pentylenetetrazol induced rats through inhibiting mTOR signaling pathway.

OBJECTIVE: Saikosaponin a (SSa), which is one major bioactive compound isolated from radix bupleuri, has been demonstrated to exhibit the properties of anticonvulsant and antiepileptic in few reports. This study aims to clarify the molecular mechanism by which SSa protects against pentylenetetrazol (PTZ) induced epileptic seizure. METHODS: PTZ induced rat and hippocampal neuron were established. Treated rats or hippocampal neuron with SSa, and mTOR, P70S6K, IL-1ß and TNF-α were then determined. RESULTS: In PTZ induced rat, SSa significantly reduced seizure severity and duration while markedly elevated seizure latency, and it also down-regulated hippocampal p-mTOR, p-70S6K, L-1ß and TNF-α expression. In hippocampal neurons exposed to PTZ, p-mTOR and p-70S6K expression levels were also decreased by SSa. Pre-incubated hippocampal neurons with leucine, an mTOR agonist, reversed the effects of SSa on decreasing cytokines expression and inhibiting cell apoptosis. The treatment of mTOR inhibitor rapamycin prevented against the increase of cytokines expression and hippocampal neuron apoptosis induced by PTZ. Leucine also canceled the alleviation of seizures and induction of hippocampal caspase-3 activity in PTZ induced rat with the treatment of SSa. CONCLUSION: SSa protects against PTZ induced epileptic seizure and hippocampal neuron apoptosis through inhibiting mTOR signaling pathway.

Upregulated expression of NF-YC contributes to neuronal apoptosis via proapoptotic protein bim in rats' brain hippocampus following middle cerebral artery occlusion (MCAO).

Cerebral ischemia represents a severe brain injury that could lead to significant neuronal damage and death. In this study, we performed a middle cerebral artery occlusion (MCAO) in adult rats and observed that a subunit of nuclear factor-Y (NF-Y) transcriptional factor, NF-YC, was accumulated in rat hippocampal CA1 neurons. Immunochemistrical and immunofluorescent analysis revealed that NF-YC was primarily expressed in the nucleus of neurons. Meanwhile, we found that the changes of bim, one of the target genes of NF-Y, were consistent with the expression of NF-YC and Bim was mainly located in the NF-YC positive cells. Moreover, there was a concomitant upregulation of active caspase-3 and TUNEL positive cells. Taken together, these results suggested that the upregulation of NF-YC might play an important role in the pathophysiology via proapoptotic protein Bim after MCAO and further research is needed to have a better understanding of its function and mechanism.

High-frequency electrical stimulation in the nucleus accumbens of morphine-treated rats suppresses neuronal firing in reward-related brain regions.

BACKGROUND: Previous studies have reported that high-frequency stimulation (HFS) in the nucleus accumbens (NAc) is a potential treatment modality for drug craving and relapse. We aimed to explore the electrophysiological changes in reward-related brain regions during NAc stimulation and reveal the effects of stimulation frequency and target changes on NAc neuronal activities. MATERIAL/METHODS: Twenty-eight rats were randomized into saline (n=8) and morphine (n=20) groups. The morphine group was further divided into core (n=10, only the core of the NAc was stimulated) and shell (n=10, only the shell of the NAc was stimulated) subgroups. Conditioned place preference (CPP) behavior of the rats was evaluated to confirm morphine preference after morphine injection and CPP training for 10 days. We recorded NAc neuronal responses to NAc core stimulation at different frequencies, as well as changes in VP and VTA neuronal firing during NAc core stimulation, and changes in NAc neuronal firing during NAc shell stimulation. RESULTS: The results indicate that high frequency stimulation was more effective in suppressing NAc neuronal activities than low frequency stimulation and that core stimulation was more effective than shell stimulation. Most VP neurons were inhibited by NAc core stimulation, while VTA neurons were not. CONCLUSIONS: The results suggest that electrical stimulation in the NAc can suppress neuronal firing in reward-related brain regions. The stimulation might be frequency- dependent in suppressing neuronal firing. The core and shell of the NAc play different roles in suppressing NAc neuronal firing as 2 stimulating targets.