Xiaogang Zhang

The Third People's Hospital, Shen-ch’üan-shih, Zhejiang Sheng, China

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Publications (11)30.24 Total impact

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    ABSTRACT: Leucine zipper-EF-hand containing transmembrane protein 1 (Letm1) is a mitochondrial protein that is associated with seizure attacks in Wolf-Hirschhorn syndrome. This study aimed to investigate the expression pattern of Letm1 in patients with temporal lobe epilepsy (TLE) and pilocarpine-induced rat model of epilepsy, and to determine if altered Letm1 leads to mitochondrial dysfunction and increased susceptibility to seizures. Using immunohistochemical, immunofluorescent, western blotting, and transmission electron microscopic methods, we have found that Letm1 was significantly decreased in TLE patients, and gradually decreased in experimental rats from 1 to 7 days after onset of seizures. Letm1 knock-down by a lentivirus bearing LV-Letm1-sh resulted in mitochondrial swelling and decreased expression of Letm1 target protein mitochondrially encoded cytochrome B (MT-CYB). Behavioral study revealed that inhibition of Letm1 caused early onset of the first seizure, increased seizure frequency, and duration. However, administration of Letm1 homolog nigericin failed to prevent epilepsy. These results indicate that inhibition of Letm1 and mitochondrial dysfunctions contributes to the development of epileptic seizures. Appropriate Letm1 level may be critical for maintaining normal neuronal functions.
    Cerebral Cortex 05/2013; · 6.83 Impact Factor
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    ABSTRACT: Ras-guanine nucleotide-releasing factor 1 (Ras-GRF1) is present mainly at synaptosome and its expression after birth increases in parallel with the development of neuronal circuitry. Evidences suggested that Ras-GRF1 could mediate forms of synaptic plasticity and might participate in the regulation of neuronal excitability and neurite outgrowth though various signal transduction pathway. The aim of this study was to measure Ras-GRF1 expression in brain tissue of patients with drug-refractory temporal lobe epilepsy (TLE) and lithium chloride-pilocarprine kindled rats using double-label immunofluorescence, immunohistochemistry and Western blotting and to discuss the possible role of Ras-GRF1 in TLE. We randomly selected 30 temporal neocortices tissues from patients with TLE and 9 histologically normal temporal neocortices samples from controls. Meanwhile, we investigated the distribution and level of Ras-GRF1 protein expression during the different phases (the acute period, the latent period and the chronic phase) in the epileptic and control rats. Ras-GRF1 was mainly expressed in the plasma membrane and dendrite of neurons, but it was not co-expressed with GFAP-positive astrocytes in the brain tissue of patients and epileptic rats. Compared with controls, Ras-GRF1 expression was significantly decreased in TLE patients. Ras-GRF1 expression in epileptic rats was already reduced at 1 day post-seizures, then gradually decreased during the latent period and reached a minimum level during the chronic phase. These results demonstrated that the decreased expression of Ras-GRF1 could be involved in the pathogenesis of human TLE.
    Brain research 11/2012; · 2.46 Impact Factor
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    ABSTRACT: Microtubule dynamics have been shown to contribute to neurite outgrowth, branching, and guidance. Stathmin 1 is a potent microtubule-destabilizing factor that is involved in the regulation of microtubule dynamics and plays an essential role in neurite elongation and synaptic plasticity. Here, we investigate the expression of stathmin 1 in the brain tissues of patients with intractable temporal lobe epilepsy (TLE) and experimental animals using immunohistochemistry, immunofluorescence and western blotting. We obtained 32 temporal neocortex tissue samples from patients with intractable TLE and 12 histologically normal temporal lobe tissues as controls. In addition, 48 Sprague Dawley rats were randomly divided into six groups, including one control group and five groups with epilepsy induced by lithium chloride-pilocarpine. Hippocampal and temporal lobe tissues were obtained from control and epileptic rats on Days 1, 7, 14, 30, and 60 after kindling. Stathmin 1 was mainly expressed in the neuronal membrane and cytoplasm in the human controls, and its expression levels were significantly higher in patients with intractable TLE. Moreover, stathmin 1 was also expressed in the neurons of both the control and the experimental rats. Stathmin 1 expression was decreased in the experimental animals from 1 to 14 days postseizure and then significantly increased at Days 30 and 60 compared with the control group. Many protruding neuronal processes were observed in the TLE patients and in the chronic stage epileptic rats. These data suggest that stathmin 1 may participate in the abnormal network reorganization of synapses and contribute to the pathogenesis of TLE.
    Synapse 04/2012; 66(9):781-91. · 2.31 Impact Factor
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    ABSTRACT: The Collapsin Response Mediator Protein-1 (CRMP-1) is a brain specific protein identified as a signaling molecule of Semaphorin-3A and act as axon repellent guidance factor in nervous system. Recent studies indicated that axon guidance molecules may play a role in synaptic reorganization in the adult brain and thereby promote epileptogenesis. This study aimed to investigate expression pattern of CRMP-1 in epileptogenesis. Using double immunofluorescence labeling, immunohistochemistry and western blot analysis, we looked into the CRMP-1 expression in temporal neocortex from patients with temporal lobe epilepsy (TLE) and histological normal temporal neocortex from the controls. We also studied the expression pattern of CRMP-1 in hippocampus and adjacent cortex of a TLE rat model on 6, 24, 72 h, 1, 2 weeks, 1 month, and 2 months post-seizure, and from control rats. CRMP-1 was mainly expressed in the neuronal cytoplasm in the temporal lobe of intractable TLE patients, which was co-expressed with -2. CRMP-1 expression was downregulated in temporal neocortical of TLE patients. In addition, in pilocarpine-induced animal model of epilepsy, CRMP-1 dynamically decreased in a range of 2 months. Thus, our results indicate that CRMP-1 may be involved in the development of TLE.
    Neurochemical Research 02/2012; 37(7):1381-91. · 2.13 Impact Factor
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    ABSTRACT: The gene encoding dystrobrevin-binding-protein-1 (dysbindin) is expressed in many areas of the central nervous system and plays a role in intracellular vesicle trafficking, synaptic vesicle trafficking, and neurotransmitter release. At a cellular level, dysbindin is thought to mediate presynaptic glutamatergic transmission. Using Western blotting and immunofluorescence, we investigated dysbindin expression in brain tissues of the patients with temporal lobe epilepsy (TLE) and rats with TLE (lithium chloride pilocarpine model) to explore its possible role in epileptogenesis. Twenty-five samples of temporal neocortex from patients undergoing surgery for drug-refractory TLE epilepsy and 10 histologically normal temporal lobes tissues from control subjects were used in our study. We also examined dysbindin expression in the hippocampus and adjacent cortex from experimental Sprague-Dawley rats. Dysbindin was expressed in the cytoplasm of neurons from epileptic specimens, and levels of dysbindin proteins were significantly increased in patients with TLE. Dysbindin was also expressed in the neurons of the hippocampus and adjacent cortex from experimental and control rats. Western blotting of rat brain tissue showed that dysbindin was upregulated gradually from 6 h after kindling. Maximal expression was seen around 2 months in chronic epileptic phase. These results demonstrated that the increased expression of dysbindin might play a role in the pathogenesis of drug-refractory TLE.
    Synapse 02/2012; 66(7):622-9. · 2.31 Impact Factor
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    ABSTRACT: Inositol polyphosphate phosphatase 4 A (INPP4A), a phosphoinositides phosphatase, is highly expressed in the central nervous system and plays a role in glutamate excitotoxicity and cell proliferation. Our aim was to investigate the expression of INPP4A in patients with temporal lobe epilepsy (TLE) and in a rat model of epilepsy. We assessed the expression of INPP4A in the temporal neocortex from 20 TLE patients. The result showed that INPP4A expression was significantly lower in TLE patients than in controls. To validate the results found in TLE patients, we assessed the expression of INPP4A in rat model. Rat epilepsy was induced by lithium-pilocarpine. Expression of INPP4A of rat models was assessed by immunohistochemistry, immunofluorescence, and Western blotting. INPP4A was expressed in the membrane and cytoplasm of neurons. In the hippocampus and neocortex of epileptic rats, INPP4A expression was first downregulated at the 24 h after seizures and maintained decreased levels at 72 h, 7 days, 14 days, 30 days, and 60 days, respectively. These results suggest that a decreased expression of INPP4A in the brain may be associated with TLE.
    Synapse 01/2012; 66(6):533-41. · 2.31 Impact Factor
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    ABSTRACT: Recent studies suggest that angiogenesis and vascular endothelial growth factor (VEGF) are involved in the pathophysiology of epilepsy. However, relatively little data are available linking placenta growth factor (PIGF) with epilepsy. In this study, we assessed concentrations of PIGF in cerebrospinal fluid (CSF) of 60 epileptic patients and 24 non-seizure subjects using sandwich enzyme-linked immunosorbent assays. Epileptic patients in general had higher concentration of CSF-PIGF than controls (7.95 ± 0.88 ng/l vs. 5.87 ± 0.79 ng/l, P < 0.01). CSF-PIGF level in secondary epileptic patients (8.59 ± 1.26 ng/l) was higher than that in idiopathic epileptic patients (7.62 ± 0.20 ng/l) (P < 0.05). In idiopathic epilepsy, CSF-PIGF level in patients with high seizure frequency was higher than those in patients with low seizure frequency and seizure-free in recent 3 years (7.78 ± 0.23 ng/l vs. 7.49 ± 0.09 ng/l and 7.59 ± 0.10 ng/l, P < 0.05). Concentration of CSF-PIGF in patients with a disease duration of > 5 years was higher than those in patients with durations of 1-5 years and <1 year (7.72 ± 0.20 ng/l vs. 7.52 ± 0.09 ng/l and 7.41 ± 0.07 ng/l, P < 0.05). These results indicate that preexisting brain damage, seizure frequency and disease duration are important factors contributing to elevated PIGF.
    Neurochemical Research 12/2011; 37(3):665-70. · 2.13 Impact Factor
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    ABSTRACT: Placental growth factor (PIGF) plays a role in angiogenesis and neuroprotection. It has been suggested that angiogenesis and blood-brain barrier damage are involved in the pathophysiology of epilepsy. In this study, we investigated the PIGF expression in the temporal neocortices of 11 patients with pharmaco-resistant temporal lobe epilepsy (TLE) and 6 non-epileptic controls, using double immunofluorescence labeling, immunohistochemistry and Western blotting. We also assessed PIGF expression pattern in a rat model of TLE induced by lithium chloride-pilocarpine. We found that PIGF expression was significantly elevated in patients with TLE than in control. TLE patients with initial injuries had significantly higher PIGF level than those without initial injuries. In the TLE rat model, PIGF upregulation started at 6h after status epilepticus and maintained at significant high level for up to 60 days. These results suggest that the augmentation of brain PIGF is associated with development of epilepsy.
    Brain research 10/2011; 1429:124-33. · 2.46 Impact Factor
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    ABSTRACT: Prolonged epileptic seizures or SE can cause neuronal cell death. However, the exact role of neuroprotectant against brain injury during epileptic seizure needs to be further elucidated. The aim of this study was to investigate the expression of the apelin, a novel neuroprotective peptide, in brain tissues of the patients with temporal lobe epilepsy (TLE) and experimental rats using immunohistochemistry, immunofluorescence and Western blotting analysis and to discuss the possible role of apelin in TLE. Thirty temporal neocortical tissue samples from the patients with drug-refractory TLE underwent surgical therapy and nine histologically normal temporal lobes tissues as controls were used in our study. Fifty-six Sprague-Dawley rats were randomly divided into seven groups, including one control group and six groups with epilepsy induced by lithium-pilocarpine. Hippocampus and adjacent cortex were taken from the controls and epileptic rats at 1, 3, 7, 14, 30, and 60 days after onset of seizures. Apelin was mainly expressed in the neurons of TLE patients and controls, and was significantly increased in TLE patients compared with the controls. Apelin was also expressed in the neurons of experimental and control rats, it was gradually increased in the experimental rat post-seizure and reached a stable high level in chronic epileptic phase. Our results demonstrated that the increased expression of apelin in the brain may be involved in human TLE.
    Peptides 08/2011; 32(9):1793-9. · 2.52 Impact Factor
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    ABSTRACT: Gelsolin is an actin regulatory protein that generally distributed in a wide variety of body tissues, especially the brain tissues and cerebrospinal fluid. In this study we found that lumbar CSF-gelsolin concentrations markedly decreased in epileptic patients by enzyme linked immunosorbent assay. In order to help judge the result, we determined gelsolin expression in temporal lobe tissues of patients with temporal lobe epilepsy using double-label immunofluorescence to location and using western blot to quantitation. Then we observed that gelsolin was co-expressed with microtubule-associated protein-2 in axons and cytoplasms of neurons and gelsolin protein level was also down-regulated in temporal lobe tissues of epileptic patients. Our findings suggested that CSF-gelsolin level might reflect the alteration of gelsolin in brain tissue of epileptic patients and CSF-gelsolin seems to be a potential biomarker for epilepsy.
    Neurochemical Research 07/2011; 36(12):2250-8. · 2.13 Impact Factor
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    ABSTRACT: Several studies have shown that serum- and glucocorticoid-induced protein kinase 1(SGK1) can regulate both glutamate receptors and glutamate transporters and may participate in the regulation of neuroexcitability in neuronal diseases. In our previous study, we analyzed differential gene expression in the anterior temporal neocortex of drug-refractory epilepsy patients relative to control patients using a complementary DNA microarray and found that the SGK1 gene was up-regulated more than twofold in the brain tissues of epileptic patients. In the current study, we measured SGK1 expression in the brain tissues of humans and in an experimental model of rat epilepsy in order to explore the relationship between SGK1 expression and epilepsy. The SGK1 expression was detected in thirty human brain tissues derived from patients undergoing operation for drug-refractory epilepsy and was also detected in eight samples from autopsies. Meanwhile, we investigated SGK1 expression during the epileptic process in rats using immunofluorescence, RT-PCR and western blot analysis. SGK1 expression was enhanced in the temporal neocortex of patients with drug-refractory epilepsy and was also highly expressed in the rat brain during different phases of the epileptic process. SGK1 expression was also related with the elevation of EAAT3, which expression reduced after knockdown SGK1. These results provide new insight into the potential role of SGK1 in the pathophysiology of epilepsy.
    Neurochemistry International 10/2010; 57(8):899-905. · 2.66 Impact Factor