Etiology of anti-N-methyl-D-aspartate receptor encephalitis / 中国当代儿科杂志

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.

Influence of ketogenic diet on the clinical effects and electroencephalogram features in 31 children with pharmacoresistant epileptic encephalopathy / 中华儿科杂志

<p><b>OBJECTIVE</b>To investigate the effect of ketogenic diet (KD) on the clinical and electroencephalogram features in children with pharmacoresistant epileptic encephalopathy.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>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.</p><p><b>CONCLUSION</b>The clinical and electroencephalographic improvement confirms that KD is beneficial in children with refractory epilepsy.</p>

Clinical and image features, and identification of pathogenic gene mutation of two cleidocranial dysplasia families / 中华儿科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHOD</b>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.</p><p><b>RESULT</b>(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.</p><p><b>CONCLUSION</b>(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.</p>

Prevention of beta cell dysfunction and apoptosis by adenoviral gene transfer of rat insulin-like growth factor 1 / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Islet beta-cells are almost completely destroyed when patients with type 1 diabete are diagnosed. To date, insulin substitute therapy is still one of the main treatments. The cure of type 1 diabetes requires beta-cell regeneration from islet cell precursors and prevention of recurring autoimmunity. Therefore, beta-cell regeneration and proliferation emerge as a new research focus on therapy for type 1 diabetes. Islet beta-cell regeneration and development are controlled by many growth factors, especially insulin-like growth factor-1 (IGF-1).</p><p><b>METHODS</b>Recombinant adenovirus encoding rat IGF-1 (rIGF-1) was constructed and transduced into rat beta-cells, RINm5F cells. Western blotting analysis and ELISA were used to detect rIGF-1 protein. Streptozotocin (STZ) was used to induce RINm5F cell destruction. The level of nitric oxide (NO) was detected in cell culture supernatants by the Griess reaction. Islet cell function was evaluated by glucose-stimulated insulin production. Flow cytometry analysis was further used to investigate the apoptosis of RINm5F cells. Thiaoollyl blue viability assay was applied to determine cell viability.</p><p><b>RESULTS</b>The recombined adenovirus-rIGF-1 was successfully constructed and the titer was 4.0 x 10(8) pfu/ml. The rIGF-1 protein was effectively expressed in the RINm5F cells and cell culture supernatants. rIGF-1 expression remarkably inhibited STZ-induced islet cell apoptosis and significantly decreased the level of NO. Furthermore, IGF-1 expression also significantly protected insulin secretion and cell proliferation in a time-dependent manner.</p><p><b>CONCLUSIONS</b>Our study suggests that locally produced rIGF-I from RINm5F cells may be beneficial in maintaining beta-cell function, protecting beta-cells from the destruction of apoptosis factors and promoting beta-cell survival and proliferation. IGF-I might be considered as a candidate gene in gene therapy for type 1 diabetes. In addition, it appears that the apoptosis induced by STZ may be NO-dependent.</p>

Roles and signal pathways of adrenomedullin and adrenotensin in pulmonary remodeling due to left to right shunt in rats / 中华儿科杂志

<p><b>OBJECTIVES</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Prevalence of dental caries among preschool children in Shanghe County of Shandong Province and relevant prevention and treatment strategies / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Decayed teeth are harmful to children's growth and development and can severely jeopardize their health. This study was set out to investigate and analyze the prevalence of dental caries in preschool children in Shanghe County in Shandong Province, China, and provide new insights into potential prevention and treatment strategies.</p><p><b>METHODS</b>Based on the random sampling method, we performed dental examinations of children aged 2 to 6 years in kindergartens of Shanghe County. The prevalence of caries, the average number of decayed teeth per capita as well as the constituent rates of decayed, missing and filled teeth were determined retrospectively. SPSS software was used for data analysis.</p><p><b>RESULTS</b>Dental caries were found in 1088 out of 2052 children from 56 kindergartens. The total number of decayed teeth was 4487 with a prevalence of 53.02%. The average number of decayed teeth per capita was 2.187, and the filling rate was 0.29%. There was no statistical difference in the prevalence of caries between boys and girls though there were significant differences between different age groups. The prevalence of decayed teeth as well as the mean number of decayed teeth infected per capita increased with age. In addition, urban children had a higher prevalence than those from rural areas (P < 0.01).</p><p><b>CONCLUSIONS</b>The prevalence of decayed caries among kindergarten children in Shanghe County was high, suggesting that more emphasis should be put on improving oral health education with priority given to prevention. Further efforts should be made to increase the decayed caries filling rate.</p>

Cyclooxygenase-2 inhibitor inhibits hippocampal synaptic reorganization in pilocarpine-induced status epilepticus rats / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To examine modulations caused by cyclooxygenase-2 (COX-2) inhibitors on altered microenvironments and overbalanced neurotransmitters in pilocarpine-induced epileptic status rats and to investigate possible mechanisms.</p><p><b>METHODS</b>Celecoxib (a COX-2 inhibitor) was administered 45 min prior to pilocarpine administration. The effects of COX-2 inhibitors on mIPSCs (miniature GABAergic inhibitory postsynaptic currents) of CA3 pyramidal cells in the hippocampus were recorded. Expressions of COX-2, c-Fos, newly generated neurons, and activated microgliosis were analyzed by immunohistochemistry, and expressions of alpha-subunit of gamma-amino butyric acid (GABA(A)) receptors and mitogen-activated protein kinase/extracellular signal-regulated protein kinase (MAPK/ERK) activity were detected by Western blotting.</p><p><b>RESULTS</b>Pretreatment with celecoxib showed protection against pilocarpine-induced seizures. Celecoxib prevented microglia activation in the hilus and inhibited the abnormal neurogenesis and astrogliosis in the hippocampus by inhibiting MAPK/ERK activity and c-Fos transcription. Celecoxib also up-regulated the expression of GABA(A) receptors. NS-398 (N-2-cyclohexyloxy-4-nitrophenyl-methanesulfonamide), another COX-2 inhibitor, enhanced the frequency and decay time of mIPSCs.</p><p><b>CONCLUSION</b>The COX-2 inhibitor celecoxib decreased neuronal excitability and prevented epileptogenesis in pilocarpine-induced status epilepticus rats. Celecoxib regulates synaptic reorganization by inhibiting astrogliosis and ectopic neurogenesis by attenuating MAPK/ERK signal activity, mediated by a GABAergic mechanism.</p>

Inhibition of rho kinase attenuates high flow induced pulmonary hypertension in rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The RhoA/Rho kinase pathway may participate in the pathogenesis of hypoxia and monocrotaline induced pulmonary hypertension. This study tested whether RhoA/Rho kinase pathway is involved in the pathogenesis of high flow induced pulmonary hypertension in rats.</p><p><b>METHODS</b>Male Wistar rats (4 weeks) were randomly divided into 4 shunt groups, 4 treated groups and 4 control groups. Shunt and treated groups underwent left common carotid artery/external jugular vein shunt operation. Control groups underwent sham operation. Treated groups received fasudil treatment and the others received same dose of saline. At weeks 1, 2, 4 and 8 of the study, right ventricular systolic pressure was measured and blood gases were analysed to calculate Qp/Qs. The weight ratio of right ventricle to left ventricle plus septum and the mean percentage of medial wall thickness in moderate sized pulmonary arteries were obtained. RhoA activity in pulmonary arteries was detected using Rho activity assay reagent. Rho kinase activity was quantified by the extent of MYPT1 phosphorylation with Western blot. Proliferating cells were evaluated using proliferating cell nuclear antigen immunohistological staining.</p><p><b>RESULTS</b>Carotid artery/jugular vein shunt resulted in high pulmonary blood flow, both an acute and a chronic elevation of right ventricular systolic pressure, significant medial wall thickening characterized by smooth muscle cells proliferation, right ventricular hypertrophy and increased activation of RhoA and Rho kinase. Fasudil treatment lowered pulmonary artery systolic pressure, suppressed pulmonary artery smooth muscle cells proliferation, attenuated pulmonary artery medial wall thickening and inhibited right ventricular hypertrophy together with significant suppression of Rho kinase activity but not Rho activity.</p><p><b>CONCLUSIONS</b>Activated RhoA/Rho kinase pathway is associated with both the acute pulmonary vasoconstriction and the chronic pulmonary artery remodelling of high flow induced pulmonary hypertension. Fasudil treatment could improve pulmonary hypertension by inhibiting Rho kinase activity.</p>

Protective effect of recombinant adenovirus carrying rat insulin-like growth factor 1 on rat islet beta-cell against strepozotocin-induced impairment in vitro / 中华实验和临床病毒学杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Morphological and behavioral consequences of recurrent seizures in neonatal rats are associated with glucocorticoid levels / 神经科学通报·英文版

<p><b>OBJECTIVE</b>It is well documented that epilepsy can increase neurogenesis in certain brain regions and cause behavioral alternations in patients and different epileptic animal models. A series of experimental studies have demonstrated that neurogenesis is regulated by various factors including glucocorticoid (CORT), which can reduce neurogenesis. Most of studies in animal have been focused on adulthood stage, while the effect of recurrent seizures to immature brain in neonatal period has not been well established. This study was designed to investigate how the recurrent seizures occurred in the neonatal period affected the immature brain and how CORT regulated neurogenesis in immature animals.</p><p><b>METHODS</b>Neonatal rats were subjected to 3 pilocarpine-induced seizures from postnatal day 1 to day 7. Then neurogenesis at different postnatal ages (i.e. P8, P12, P22, P50) was observed. Behavioral performance was tested when the rats were mature (P40), and plasma CORT levels following recurrent seizures were simultaneously monitored.</p><p><b>RESULTS</b>Rats with neonatal seizures had a significant reduction in the number of Bromodeoxyuridine (BrdU) labeled cells in the dentate gyrus compared with the control groups when the animals were euthanized on P8 or P12 (P<0.05); whereas there was no difference between the two groups on P22. Until P50, rats with neonatal seizures had increased number of BrdU-labeled cells compared with the control group (P<0.05). In Morris water maze task, pilocarpine-treated rats were significantly slower than the control rats at the first and second day, and there were no differences at other days. In probe trial, there was no significant difference in time spent in the goal quadrant between the two groups. Endocrine studies showed a correlation between the number of BrdU positive cells and the CORT level. Sustained increase in circulating CORT levels was observed following neonatal seizures on P8 and P12.</p><p><b>CONCLUSION</b>Neonatal recurrent seizures can biphasely modulate neurogenesis over different time windows with a down-regulation at early time and up-regulation afterwards, cause persistent deficits in cognitive functions of adults, and increase the circulating CORT levels. CORT levels are related with the morphological and behavioral consequences of recurrent seizures.</p>

Expression and activity of RhoA/Rho kinase in remodeling of high blood flow pulmonary vessels / 中华儿科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSION</b>Activated RhoA/Rho-kinase pathway is associated with both high pulmonary blood flow induced acute pulmonary vasoconstriction and chronic pulmonary artery remodeling in rats.</p>

Correlation between Pulmonary Hypertension Induced by High Blood Flow and Nuclear Factor-?B / 实用儿科临床杂志

Congenital heart disease with left-to-right shunt easily lead to pulmonary hypertension.Currently agreed about its mechanism:shear stress induced by high pulmonary blood flow stimulus pulmonary endothelium,to start regulation of genetic transcription,to initiate a series of molecular biology and pathophysiology changes,and finally to lead to pulmonary vascular pathologic remolding.Nuclear factor(NF)-?B is a kind of nuclear factor with multiple biological effect and play an important role in pulmonary vascular remolding.NF-?B signal can be actiacted by high blood flow.Its target gene products,for example,vasoactive mediators,cytokines,make pulmonary vessels difficulty to maintain the normal structure and cause pulmonary vascular contraction and remolding,thus,pulmonary arterial pressure increases.

Effects and consequence of recurrent seizures of neonatal rat on the hippocampal neurogenesis / 中华儿科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Serum growth hormone and prolactin levels in neonates with hypoxic-ischemic encephalopathy / 中国当代儿科杂志

<p><b>OBJECTIVE</b>To investigate the levels and roles of serum growth hormone (GH) and prolactin (PRL) in neonatal hypoxic-ischemic encephalopathy (HIE).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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).</p><p><b>CONCLUSIONS</b>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.</p>

Effect of ketogenic diet on hippocampus synaptic reorganization and GluR5 expression in kainic acid induced rat model of epilepsy / 中华儿科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Expression of multidrug resistance gene and topiramate affect expression of multidrug resistance gene in the hippocampus of spontaneous epileptic rats / 中华儿科杂志

<p><b>OBJECTIVE</b>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.</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Diagnostic Value of Neuron-Specific Enolase in Children with Meningitis / 实用儿科临床杂志

Objective To explore the diagnostic value of neuron-specific enolase(NSE) in cerebrospinal fluid(CSF) in children with meningitis.Methods NSE levels in CSF of 18 children with purulent meningitis,13 children with tuberculous meningitis and 25 children with viral meningitis were determined by enzyme-linked immunosorbent assay(ELISA).Results CSF-NSE levels increased significantly in children with purulent meningitis and tuberculous meningitis compared with that of control group(P0.05);CSF-NSE levels increased significantly in children with purulent meningitis and tuberculous meningitis,compared with that of viral meningitis group(P0.05).Conclusions The determination of the neuron-specific enolase in cerebrospinal fluid can be used as an important parameter for identifying bacterial meningitis from viral meningitis.It also can be used to estimate the severity and prognosis of meningitis in children.

Relationship between Prognosis of Cyclic Vomiting Syndrome and Migraine / 实用儿科临床杂志

Objective To study the proportion of cyclic vomiting syndrome(CVS) developing to migraine by the medium term prognosis,and explore the relationship between CVS and migraine.Methods Twenty-eight of 38 cases who had identified in our clinical records were traced ,each child was matched to a control,and they all conducted a telephone interview by a standardized question.Results Ninteen(46%) of the subject had continued CVS and(or) migraine,the prevalence of past or present migraine in subjects(46%)was significantly higher than that in control group(10.7%)(P=0.003).Conclusion The progonosis of CVS is closely related to migraine,many of the suffers of CVS tend to develop migraine.

Neurogenesis of dentate granule cells following kainic acid induced seizures in immature rats / 中华儿科杂志

<p><b>OBJECTIVE</b>Data accumulated over the past years have led to widespread recognition that neurogenesis, the emergence of new neurons, persists in the hippocampal dentate gyrus of the adult mammalian brain, and can be increased by seizures in multiple models. Also, aberrant reorganization of dentate granule cell axons, the mossy fiber sprouting, occurs in human temporal lobe epilepsy and rodent epilepsy models. However a number of studies suggest that the immature brain is less vulnerable to the morphologic alteration of hippocampus after seizures. The goal of this study was to determine whether the seizures can induce dentate granule cell neurogenesis and mossy fiber sprouting in the immature rat.</p><p><b>METHODS</b>Seizures was elicited by unilateral microinfusion of kainic acid (KA, 1 micro g) into the amygdula at postnatal day 15 (P15). Rat pups were given bromodeoxyuridine (BrdU) intraperitoneally on day 5 after KA administration and killed 7 d or 21 d later. The brains were processed for BrdU mitotic labeling combined with double-label immunohistochemistry using neuron-specific, early differentiation marker TuJ1 (betaIII tubulin) or granule-specific marker CaBP (calcium-binding protein calbindin D28k) as well as glia-specific marker GFAP (glial fibrillary acidic protein). Mossy fiber sprouting in intermolecular layer and CA3 subfield was assessed in Timm-stained sections both 1 month and 3 months after KA administration by using a rating scale and density measurement.</p><p><b>RESULTS</b>The dentate BrdU-immunoreactive cells of the KA-treated rats increased significantly compared with those of control rats on day 7 and 21 after BrdU administration (7 d: 244 +/- 15 vs. 190 +/- 10; 21 d: 218 +/- 19 vs. 133 +/- 12, P < 0.05). Approximately 80.2% and 78.7% of BrdU-labeled cells coexpressed TuJ1 in KA-treated rats and control rats on day 7 after BrdU respectively (P > 0.05). On 21 d after BrdU, 60.2% and 58.2% of dentate BrdU-labeled cells coexpressed GaBP in KA-treated rats and control rats respectively (P > 0.05). GFAP colocalized with 3%-5% dentate BrdU-labeled cells in the rats of both groups on day 7 and 21 after BrdU. It was also demonstrated that status epilepticus at P15 did not result in any detectable mossy fiber sprouting within the hippocampus both 1 month and 3 months after KA administration.</p><p><b>CONCLUSIONS</b>KA induced seizures can increase granule cell neurogenesis in the immature rat. Most of newly appeared cells migrate from subgranular proliferation zone (SGZ) into granule cell layer, the hilus as well as the molecular layer, and there they can differentiate into granule neurons. These observations also indicate that there is an early developmental resistance to seizure-induced mossy fiber sprouting in the immature brain.</p>

Malnutrition increases hippocampal neurogenesis in the immature rat after status epilepticus / 中华儿科杂志

<p><b>OBJECTIVE</b>Neurogenesis in the dentate gyrus of hippocampus persists in brain of the immature and adult mammalian including human and it can be regulated by physiological and pathological events including nutritional status and seizures. The present study was designed to investigate the potential effects of malnutrition followed by status epileptics on hippocampal neurogenesis in the immature rat.</p><p><b>METHODS</b>Rat pups were divided into 4 groups: malnourished (M), nourished (N), malnourished plus seizures (MS) and nourished plus seizures (NS). The rat pups of group M and group MS were maintained on a starvation regimen from postnatal day 2 (P2) to P18. The status epilepticus of the rat pups in group MS and group NS was elicited by unilateral microinfusion of kainic acid (KA) into the amygdula at P15. Rat pups of the 4 groups were given bromodeoxyuridine (BrdU) intraperitoneally twice daily for 2 days beginning at P17. At P19, the rat pups were killed and the brains were processed for BrdU mitotic labeling combined with double-label immunohistochemistry using early neuron- or glia-specific markers TuJ1 (beta III tubulin) or GFAP (glial fibrillary acidic protein).</p><p><b>RESULTS</b>There were no significant differences in the latent time of seizure between group M and group N [(12.4 +/- 2.6) min vs. (12.1 +/- 2.9) min, P < 0.05]. Histological assessment did not reveal any evidence of hippocampal cell loss after status epilepticus in either group. BrdU-labeled cells were significantly higher in the rats of group MS (374 +/- 18) than group M (303 +/- 20), group NS (312 +/- 24) than group N (269 +/- 18), respectively (P < 0.01). There was also significant difference between group M and group N, group MS and group NS, respectively (P < 0.01). No significant difference was seen between the rats of group NS and group M (P > 0.05). Approximately 60% of BrdU-labeled cells coexpressed TuJ1, and 5% approximately 10% of those co-expressed GFAP.</p><p><b>CONCLUSION</b>Early malnutrition do not alter KA seizure susceptibility and the behavioral manifestations of seizures at P15. Although malnutrition and status epilepticus can increase the proliferation of newly developed cells in the immature rat respectively, malnutrition followed by status epilepticus further increases this proliferation. Furthermore, most of newly developed cells differentiate into early neurons.</p>