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The objective was to investigate the prevalence of attention-deficit hyperactivity disorder (ADHD) in children with frontal lobe epilepsy and related factors. The medical records of 190 children diagnosed with frontal lobe epilepsy at Qilu Hospital of Shandong University between 2006 and 2011 were retrospectively collected, and a follow-up analysis of the prevalence of ADHD in these children was conducted. Of the 161 children with an effective follow-up, 59.0% (95/161) with frontal lobe epilepsy suffered from ADHD as well. Analysis of epilepsy and ADHD-related factors indicated that the incidence of ADHD was 89.4% (76/85) in children with abnormal electroencephalogram (EEG) discharges on the most recent EEG, which was significantly higher than the ADHD incidence of 25% (19/76) in children with normal readings on the most recent EEG (P < .01). Children with frontal lobe epilepsy have a high incidence of ADHD. Sustained abnormal discharge on the electroencephalogram is associated with increased comorbidity of ADHD with frontal lobe epilepsy. [ABSTRACT FROM AUTHOR]

The human neonate is at a higher risk for hypoglycemia-induced neuronal injury than other pediatric and adult patients. Repetitive and profound neonatal hypoglycemia can result in severe neurologic sequelae, of which the mechanisms was not elucidated by hitherto. Moreover, no reliable animal model of brain injury induced by neonatal hypoglycemia is available in order to carry out more research. Therefore, we tried to induce neonatal hypoglycemia in newborn rats by fasting and insulin injection, and then examined the neuronal degeneration after repetitive hypoglycemic insults by Fluoro-Jade B (FJB) staining. Experimental animals were randomly divided into four groups: insulin-treated rats with short hypoglycemia, insulin-treated rats with prolonged hypoglycemia, fasted rats, and control rats. Insulin injection and fasting both could induce consistent hypoglycemia in newborn rats. But from FJB staining results, only in insulin-treated rats with prolonged hypoglycemia could extensive neurodegeneration be detected. We can conclude that FJB staining is a useful method of marking neuronal degeneration in neonatal rats following hypoglycemic brain damage. Repetitive and profound neonatal hypoglycemia can result in extensive neurodegeneration, and it seems that neurons of the cortex, dentate gyrus of the hippocampus, the thalamus, and the hypothalamus are more vulnerable to hypoglycemic insult in newborn rats. Repetitive and profound insulin-induced hypoglycemia in newborn rats can establish a reliable animal model of brain injury resulting from neonatal hypoglycemia. [ABSTRACT FROM AUTHOR]

Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis is a type of newly recognized autoimmune encephalitis which is commonly seen in children, but its precise etiology is still uncertain. To reveal the etiology of anti-NMDAR encephalitis is very necessary for understanding its pathology, and for starting immune-related therapy as early as possible to improve its prognosis. In the initial literature, tumor, especially teratoma is more related with the anti-NMDAR encephalitis. In recent research, its etiology is related to infection and heredity. This article reviews the recognition and variation of the etiology of anti-NMDAR encephalitis.

Objective: To investigate the effect of ketogenic diet (KD) on the clinical and electroencephalogram features in children with pharmacoresistant epileptic encephalopathy., Method: Thirty-one children (19 boys, 12 girls) aged 7 months to 7 years (mean 2 years 5 month) with epilepsy refractory to conventional antiepileptic drugs (AEDs) were included in this study. In addition to their original AED treatment, the children were assigned to different ketogenic diets based on their age. The prospective electro-clinical assessment was performed prior to the KD and then one week, one month and again 3 months after the initiation of therapy, respectively., Result: The reduction of seizure frequency in 52%, 68% and 71% of all patients exceeded 50% one week, one month and three months after KD treatment respectively. KD is particularly effective in myoclonic astatic epilepsy (MAE; Doose Syndrome) and West syndrome with 100% and 81.25% of the patients having a greater than 50% seizure reduction, respectively. After 3 months of KD treatment, more than 2/3 patients experienced a reduction in interictal epileptiform discharges (IEDs) and improvement in EEG background., Conclusion: The clinical and electroencephalographic improvement confirms that KD is beneficial in children with refractory epilepsy.

Objective: Cleidocranial dysplasia (CCD) is a dominantly inherited skeletal dysplasia caused by mutations in the osteoblast-specific transcription factor-encoding gene, core binding factor α1 (CBFA1). Over 90 mutations in CBFA1 gene have been published to date in 500 independent cases of CCD, including missense mutations, deletions, insertions, frameshift, and splice mutations. However, mutational screening of the CBFA1 gene is still far from saturation, and more novel mutations will be identified to enrich the insights into the molecular basis for the pathogenesis of CCD. The aim of this study was to explore the clinical and image features and detect the mutations of CBFA1 gene in two CCD families., Method: In this study, the clinical features were investigated in two CCD families, radiological and CT examinations regarding osseous malformation were carried out over the entire body of these patients with CCD. Blood (2 ml) was drawn from all affected individuals, unaffected family members and one hundred unrelated normal controls, Genomic DNA was extracted from whole blood with PureGene DNA extraction kit and PCR was performed with eight pairs of PCR primers for exons 0 to 7 of the CBFA1 gene. The mutations of CBFA1 gene were screened in these two CCD families., Result: (1) The clinical features of patients with CCD include delayed closure of fontanelles, frontal bossing, dysplasia of clavicles, late tooth eruption, and other skeletal anomalies. X-ray and CT examination showed the bulging calvarium, patent fontanelles, wide cranial sutures, multiple Wormian bones, dental dysplasia or aplasia of clavicles. (2) Two mutations were identified, one is novel missense mutation (c.1259C > T[p.T420I]) in CBFA1 gene exon 7, other (c.577C > T[p.R193X]) was reported in Chinese cases with CCD for the first time., Conclusion: (1) The clinical and image features of patients in two CCD families include delayed closure of fontanelles, frontal bossing, dysplasia of clavicles, late tooth eruption, and other skeletal anomalies. (2) The T420I and R193X mutations of CBFA1 were reported, expanding the spectrum of CBFA1 mutations causing CCD.

Objectives: The effect of vascular active peptides on the development of pulmonary remodeling and pulmonary hypertension due to left to right shunt congenital heart diseases is the focus of today's studies. The present study was conducted to investigate the roles of adrenomedullin (ADM) and adrenotensin (ADT) in pulmonary remodeling due to left to right shunt in rat lungs., Methods: Twenty-one male Wistar rats were divided into two groups randomly. A right common carotid artery to external jugular vein shunt operation was performed on experimental rats (n = 9) to establish a left to right shunt animal model. Meanwhile, the common carotid artery and external jugular vein of the control group rats (n = 12) were just isolated without connection. Twelve weeks later, the mean pulmonary artery pressure (mPAP), the right ventricle to left ventricle plus septum ratio [weight, RV/(LV + SP)], the percentage of media wall thickness (MT%) were calculated. The distributions and relative protein contents of ADM and ADT in lungs were measured by immunohistochemical staining and Western blotting analysis. The relative gene expression for ADM, ADT, p46-p54 stress-actived protein kinase (SAPK) and p44 extracellular signal-regulated protein kinase 1 (ERK(1)) were investigated by RT-PCR., Results: The muscular and the tunica intimae layer of pulmonary artery were thicker in experiment group rats than those of control group, and the mPAP increased significantly in shunt group [(27.10 +/- 6.67) mm Hg (1 mm Hg = 0.133 kPa)] compared with that in control group [(14.32 +/- 3.14) mm Hg] (t = 5.5507, P < 0.001). The ratios of RV/(LV + SP) and MT% increased significantly in experimental group in contrast to the control group (P < 0.001). ADM and ADT positive granules distributed mainly over vascular smooth muscle cells, and Western blotting and integrated optical density analysis showed that the content of ADM increased in shunt group rats (P < 0.001), however, ADT content decreased (P < 0.001). The mRNA expression of ADM, SAPK and ERK(1) up-regulated in experiment group compared with the control group (P < 0.01, and P < 0.001 respectively), however, the ADT mRNA expression decreased in experimental rats in contrast to the control group (P < 0.001)., Conclusions: The phenomenon of intramolecular regulation of ADM and ADT, which both derived from proadrenomedullin, existed in the development of pulmonary remodeling and pulmonary hypertension due to left to right shunt. The mitogen-activated protein kinases (MAPKs) signal transduction pathway has been activated in the formation of left to right shunt pulmonary remodeling and pulmonary hypertension, and ADM may slow down the occurrence of pulmonary hypertension through cutting off MAPKs signaling pathway.

Objective: To construct the recombinant adenovirus containing rat insulin-like growth factor 1 (rIGF-1), and then infect to rat islet beta cells-RINm5F cells with the virus to investigate the role of rIGF-1 to streptozotocin-induced cell impairment in vitro., Methods: Recombinant adenovirus encoding rIGF-1 was constructed, and then infect to RINm5F cells. rIGF-1 protein was detected by Western blot analysis and ELISA method. Then streptozotocin was used to induce RINm5F cells impairment. The levels of nitric oxide were detected in cells culture supernatants. The cells function was evaluated by glucose-stimulated insulin production. The apoptosis was analyzed by flow cytometry. Thiaoollyl blue viability assay was applied to exam the number of viable cells., Results: The recombined adenovirus-rIGF-1 was constructed successfully and its titer was about 4.0x10(8) pfu/ml. The rIGF-1 was expressed in the RINm5F cells and cell culture supernatants. rIGF-1 expression could inhibit islet cells apoptosis, significantly decrease the level of NO induced by streptozotocin and significantly increase insulin secretion and cells viability., Conclusion: These results suggested that the high concentration of rIGF-1 in cultured islets may be beneficial in maintaining islet beta cells function and protecting islet beta cells from apoptosis-mediated factors. The apoptosis induced by STZ may be NO-dependent.

Objective: High pulmonary blood flow induced pulmonary hypertension (PH) is often associated with increased vasoconstriction and deteriorating pulmonary artery remodeling, of which the exact mechanism has not been completely elucidated. The involvement of RhoA/Rho-kinase pathway has been demonstrated in the pathogenesis of hypoxia and monocrotaline induced PH. Thus the purpose of this study was to test whether RhoA/Rho-kinase pathway is involved in the process of high pulmonary flow induced pulmonary artery remodeling in rats., Methods: Wistar rats aged 4 weeks in the shunt group underwent left common carotid artery-external jugular vein shunt operation, those in control group received sham-operation. At weeks 1, 2, 4 and 8 of the study, rats underwent right ventricular systolic pressure (RVSP) measurement; blood gases were analyzed to calculate Qp/Qs. The morphologic alterations of the pulmonary arteries were observed under optical microscope. The mean percentage of media wall thickness (%MT) was also measured to assess the extent of medial wall thickness of moderate size pulmonary arteries. Proliferating smooth muscle cells (SMCs) were evaluated by proliferating cell nuclear antigen (PCNA) immunohistochemical staining. Apoptotic SMCs were detected by TUNEL method. RhoA activity in pulmonary arteries was detected using pull down assay. Rho kinase activity was quantified by the extent of MYPT1 phosphorylation with Western blotting. The expression of RhoA and Rho kinase (ROCK2) was also detected with Western blotting., Results: Carotid artery-jugular vein shunt resulted in high pulmonary blood flow, of all rats in shunted groups, the mean Qp/Qs was 2.26 +/- 0.35, which were all considered large shunts. Compared with the control group, RVSP in shunt group increased significantly at both week 1 and week 8 (t = 8.799, t = 5.332, respectively, P < 0.01). Compared with the control group, moderate pulmonary artery medial wall thickening characterized by SMCs hyper-proliferation and hypertrophy in shunted group was firstly appeared at week 4 and became more significant at week 8, as indicated by MT% (t = 9.192, t = 11.185, respectively, P < 0.01). Compared with the control group, the percentage of PCNA-positive SMCs in shunted group increased significantly at week 1 (t = 2.438, P < 0.05), and reached the maximal level at week 2 (t = 7.213, P < 0.01), then, it decreased to a level significantly lower than that of the control group at week 4 (t = 4.183, P < 0.01), and continued to decrease to so low a level that proliferative SMCs was scarcely observed at week 8 (t = 6.152, P < 0.01). The percentage of TUNEL-positive SMCs decreased significantly compared with the control group at week 2 (t = 2.418, P < 0.05), and continued to decrease to a level that apoptotic SMCs was scarcely observed at week 8 (t = 4.582, P < 0.01). Compared with the control group, the expression of RhoA and ROCK2 increased significantly at week 1 (t = 6.056, t = 8.411, respectively, P < 0.01), and reached the maximal level at week 2 (t = 9.342, t = 10.437, respectively, P < 0.01), then began to decrease at week 4, however, both of them were still significantly higher than those of the control group at week 8 (t = 4.743, t = 4.455, respectively, P < 0.01). In line with the expression of RhoA and ROCK2, both RhoA and Rho kinase activity of shunted group increased significantly compared with the control group at week 1 (t = 10.246, t = 19.110, respectively, P < 0.01), and reached the maximal level at week 4 (t = 24.984, t = 16.124, respectively, P < 0.01), then decreased, however, both of them were still higher than those of the control group at week 8 (t = 4.934, t = 10.426, respectively, P < 0.01)., Conclusion: Activated RhoA/Rho-kinase pathway is associated with both high pulmonary blood flow induced acute pulmonary vasoconstriction and chronic pulmonary artery remodeling in rats.

Objective: To investigate the levels and roles of serum growth hormone (GH) and prolactin (PRL) in neonatal hypoxic-ischemic encephalopathy (HIE)., Methods: Serum GH and PRL levels were measured by radioimmunoassay in 54 neonates with HIE (20 mild, 19 moderate and 15 severe HIE) at the acute and convalescence stages. Twenty normal neonates were used as controls., Results: Serum GH levels were significantly lower, but PRL levels were significantly higher in moderate and severe HIE neonates at the acute stage compared with those of controls and mild HIE neonates (P < 0.01). There were noticeable differences in serum levels of GH and PRL between the moderate and severe HIE cases (P < 0.01). During the convalescence stage, serum GH levels increased and PRL levels decreased in moderate and severe HIE neonates compared with those at the acute stage (P < 0.01); serum GH and PRL levels in each sub-group of HIE restored to the levels of controls. There was a closely negative correlation between GH and PRL levels at the acute stage of HIE (r = -0.8759, P < 0.01)., Conclusions: GH and PRL might be involved in the pathophysiological process of HIE. The levels of GH and PRL closely relate to the severity of HIE at the acute stage.

Objective: Seizures occur more frequently in the neonatal period than at any other time in life. A controversy which has been debated for the recent years is whether recurrent neonatal seizures can lead to long-term adverse consequences or are simply a reflection of underlying brain dysfunction and are not intrinsically harmful. Despite numerous clinical observations showed that seizures may be detrimental to the developing brain, the pathological mechanism has not yet been completely understood. The goal of this study was to investigate what effect was induced by recurrent seizures in neonatal rats on dentate granule cell neurogenesis., Methods: Sixty-four neonatal Wistar rats were randomly divided into seizure group (n = 40) and control group (n = 24). The rats of seizure group were subjected to three times of pilocarpine injections intraperitonealy at postnatal day 1 (P1), 4 (P4) and 7 (P7). Neonatal rats of the control group were given saline injection (i.p.) at the same time points. The rat were sacrificed separately at the next four time points: immediately after the third seizure (P7), the fourth day after the seizure (P11), the fourteenth day (P21) and the forty fifth day (P52), corresponding control group rats were killed accordingly. The rats in both seizure and control groups were given bromodeoxyuridine (BrdU) injection 36 hours before sacrifice to indicate newly generated cells. Brain tissue sections were prepared and subjected to Nissl staining for neuronal loss, by BrdU labeling for cell proliferation and by BrdU + NF200 (neurofilament 200) double labeling for the identification of the newly formed cells., Results: The numbers of BrdU-labeled cells were age-dependent in the control group, decreased with age, and their morphorlogy and distribution changed (P < 0.01). BrdU-labeled cells decreased significantly in the seizure group compared with the matched controls at P7 and P11 (P < 0.01), while at P21 there was no significant difficence between the two groups. On the contrary, BrdU-labeled cells increased significantly in the seizure group compared with the matched controls at P52 (P < 0.01). Most BrdU-labeled cells in granular cell layer (GCL) of both seizure group and control group coexpressed NF200., Conclusion: Recurrent seizures during neonatal period lead to decreased neurogenesis at the early stage after the third seizure, and at later time points increase of neurogenesis. Most of newly generated cells can differentiate into neurons.

Objective: Ketogenic diet (KD) is a high fat, low protein, low carbohydrate diet. Its antiepileptic effect is certain but the underlying mechanism is unknown. The aim of the study was to reveal the possible mechanism from the view points of synaptic reorganization and GluR(5) expression in hippocampus., Methods: Epilepsy was induced in Sprague-Dawley rats by kainic acid at postnatal day 28, all control animals were fed with normal rodent chow, whereas experimental rats were fed with ketogenic feed for 8 weeks. Spontaneous recurrent seizures were recorded. Mossy fiber sprouting and neuron damage in hippocampus were investigated by Timm staining and Nissl staining. Western blot and RT-PCR methods were applied to detect the expression of GluR(5) and GluR(5) mRNA in hippocampus., Results: KD-fed rats (1.40 +/- 1.03) had significantly fewer spontaneous recurrent seizures than control diet-fed rats (7.36 +/- 3.75). The mean A of mossy fiber sprouting in the inner molecular layer of dentate gyrus was markedly higher in KA induced animals than that in saline control animals but it was similar in different diet fed groups. No significant differences were found in the mean A of Timm staining in CA(3) area and Nissl staining of neuron in hilus, CA(3) and CA(1) area. After KA kindling, KD-fed animals [(189.38 +/- 40.03)/mg pro] had significantly higher GluR(5) expression in hippocampus than control diet-fed animals [(128.79 +/- 46.51)/mg pro] although their GluR(5) mRNA was the same., Conclusion: Mossy fiber sprouting may be responsible for epileptogenesis in KA induced model and KD can suppress seizures in these animals. KD may upregulate young rat GluR(5) in inhibitory interneurons of CA(1) thus lead to an increased inhibition to prevent the propagation of seizure.

Objective: Refractory temporal lobe epilepsy (TCE) shows a unique type of hippocampal damage, referred to as hippocampal sclerosis. The mechanisms underlying drug-refractoriness in TCE are poorly understood, which may be connected with pharmacoresistance to antiepileptic drugs (AEDs). Some studies show that expression of the multidrug resistance gene (mdr1a and mdr1b) and p-glycoprotein encoded by mdr1a and mdr1b are high in the brain, especially in the hippocampus, and the expression may lead to reduction of AEDs concentration in the brain. But most of these studies focused on acute epileptic activity shortly after status epilepticus (SE), spontaneous seizures are seldom studied. The authors used a rat model of kainic acid induced spontaneous seizures to investigate expression of mdr1a and mdr1b mRNA, and explore whether topiramate (TPM) affects expression of mdr1a and mdr1b in the hippocampus., Methods: Seizures were induced by intraperitoneal injection of 10 mg/kg kainic acid at postnatal day 28. Control rats were injected with sodium chloride. All rats were divided into 4 groups 1 week after spontaneous seizures developed: status epilepticus complicated with spontaneous seizures (SE, n = 8) group, status epilepticus complicated with spontaneous seizures treated with TPM (SE + TPM, n = 9) group, spontaneous seizures without status epilepticus (N-SE, n = 7) group, spontaneous seizures without status epilepticus treated with TPM (N-SE + TPM, n = 8) group, control (n = 7) group and control treated with TPM (control + TPM, n = 7) group. The treated rats were given therapeutic dose of TPM (25 mg/kg). All the rats were killed on the 42nd day of administration. The mdr1a and mdr1b mRNAs in the hippocampus were measured by RT-PCR., Results: Expression of mdr1a and mdr1b mRNA in the hippocampus increased significantly in the SE + TPM group, SE group and N-SE + TPM group compared with control group (P < 0.001 or < 0.05). The mRNA in SE + TPM group increased significantly compared with the SE group, too (P < 0.01). The mdr1a and mdr1b mRNA expression in the hippocampus in control + TPM and N-SE groups did not change., Conclusion: Frequent seizures, especially status epilepticus resulted in overexpression of mdr1a and mdr1b mRNAs in the hippocampus. The drug-refractoriness mechanism in TCE may be related to overexpression of mdr1a and mdr1b mRNAs. TPM could enhance the expression of mdr1a and mdr1b mRNAs in the hippocampus. Seizure activity and TPM are likely to be the main determinant in enhancing mdr1a and mdr1b mRNA expression in epilepsy.