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0005 The causes of cerebral palsy: Intrauterine exposure to infection and risk of cerebral palsy
N[ ELSEVIER
Journalof lbe
Ne o!ogical clences Journal of the Neurological Sciences 238 (2005) S101-S196 www.elsevier, com/locate/jns
Poster Abstracts
7 November 2005 0001 Regulation of Ca2+-activated K + dmnnels by purine~gic P2Y receptors Novak, I ~, Hede, SE 1, Aznstrup, J~, Klaerke, DA 2. ~Institute of
Molecular Biology and Physiology, The August Krogh Building, University of Copenhagen, Denmark; 2Sectionfor Physiology and Biochemistry, The Royal Veterinary and Agrieulturd University, Denmark Background: ATP and other nucleotides are co-released with other transmitters in CNS. They are also released during ischemJa and cell damage. ATP interacts with ionotrophic P2X receptors or metabotrophic P2Y receptors. Thus P2 receptors can regulate neurotransmission and also exert long-term effects. Their action can be mediated through Ca a+- activated K + channels of intermediate conductance ([K) and big conductance (BK), both expressed in CNS. The aim of our studies is to elucidate how P2Y.~ and P2Y4 receptors regulate BK and [K channels. Method: Human P2 receptors and K + channels were co-expressed in Xenopus laevis oocytes and K + channel activity was measured electrophysiologically in oocytes stimulated with UTP (0.1 mM). Results: UTP stimulation of oocytes co-expressing IK channels with P2Y4 and P2Y.~ receptors resulted in a large hyperpolarization and 22-fold and 5-fold activation of currents, respectively. In oocytes expressing P2Y4 receptors and BK channels UTP resulted in a 30% increase in the current through the expressed channels. In contrast, stinmlation of P2Y2 receptors led to a 20"/0 inlffbition of co-expressed BK channel activity that was sensitive to TEA. Conclusion: Tiffs study shows that there is a differential interaction between the subtypes of P2Y receptors and Caa+-acdvated K + channels. Thus ATP or UTP release may lead to hyperpolarization or depolarization of membrane potential in cells where P Y receptors and K + channels are co-expressed. Future aims are to investigate co-expression of P2Y receptors and corresponding K + channels in manmtalian CNN, and to understand their regulation of menlbrane excitability, cell volume and cell survival. 0002 EIti~ets of ropivaeaine and bupivacaine on glutamate-evoked o~r~ents in culluted rat Idppocampus neu]fons
Xu, L, Jiang, Y, Xue, Y, Zhang, H. PLA General Hospital, Beijing,
Beijing, China Aim: To observe the effects o f ropivacaine and bupivacaine on glutamate-evoked currents in cultured rat lffppocampus neurons. Methods: Rat hippocampus neurons were dissected and cultured. Ghitamate-evoked currents were recorded by whole cell recording of patch clamp. Effects o f ropivacaine and bupivacaine on glutamateevoked currents were observed. Drugs were given by pressure ejection or bath injection.
Results: Glutamate(100mmol.L 1)can elicit inward currents in cultured rat lffppocampus neurons and this currents can be locked by n o n - N M D A antagonists DNQX. At the concentration of 10,50,100m_mol.L-~,bupivacaine and ropivacaine all can obviously decrease glutamate-evoked currents in cultured rat hippocampus neurons. At higher concentration of 50 and 100mmol.L -1, the reduced amplitude of glutamate-evoked currents by ropivacaine was larger than that of by bupivacaine (P < 0.01). Conclusion: Ropivacaine and bupivacaine have obviously inhibition effect on glutamate-evoked currents in cultured rat hippocampus neurons. The inhibition effect of ropivacaine on glutamate-evoked currents was stronger than that of bupivacaine.
0003 Neuxoendocxine Changes after C~atdal Radiotherapy in Chihlxen
Ragab, M 1, Abdou, A 2. ~Pediatrics dept., Faculty o/medicine, Alexandria Univ, Alexandria, Egypt; 2Neuropsychiatry dept., Faculty of medicine, Alexandria Univ, Alexandria, Eg>Tt Background: When the hypothalamic-pituitary axis (HPA) is included field of cranial irradiation, a variety of neuroendocrine disturbances occur especially in clffldren. We evaluated growth hormone secretion and the hypothalamic-pituitary-thyroid taxis function in children after cranial radiotherapy. Methods: Twenty children (112 boys and 8 girls) who received cranial/ craniospinal radiation therapy were included in tiffs study. The serum concentrations of the basal and peak growth hormone [GH], total and free T4, total T3, and basal and peak thyroid stinmlating hormone [TSH] were measured by radioimmunoassay. Twelve age-matched healthy children served as controls. Results: The mean serum basal and peak GH concentrations after stimulation with clonidine were significantly lower lweor in patients. Forty-five percent and 65% of the patients had below-normal basal and peak GH secretion respectively. There was a sigtffficant inverse correlation between the serum peak GH concentration and both the dose of radiation and the interval between therapy and testing. The mean serum total T4, free ]'4, and total T3 concentrations were sigtffficantly lower in patients. Thirty-five percent, 45"/o, and 25"/o of the patients had below-normal serum total T4, free T4, and total T3 respectively. Negative significant correlation was found between the dose of radiation and all the thyroid hormones, while inverse significant correlation was observed between the intervals between radiations and testing and serum free ]'4 concentration only. Conclusion: A large percentage of clffldren develop growth hormone deficiency (GHD) and hypothyroidism witlffn 2 years after receiving doses of cranial radiation.
0004 Predisposing factoxs for the development of ce~ebrovasculax accidents (CVAs) in young Sudanese patients
S102
Monday, November 7, 2005
Abd Gadir H. Elagib ~, Abbashar Hussein2, Ammar Eltahir Ahmed3, Ahmed M. Musa 1, Eltahir Awad G. Khalil ~, Ahmed M. Elhassan ~.
Leishmaniasis Research Group/Sudan: ;Institute of Endemic Diseases, University of Kkartoum; 2Department of Medicine, Faculty of Medicine, University of Kkartoum; 3Department of Physiology, Faculty of Medicine, University of Kkartoum Cerebrovascular accidents (CVAs) a represent major cause of death and disability among middle-aged people. Cigarette smoking, alcohol intake, hypertension, diabetes mellitus, hyperlipidemia and heart disease are known predisposing factors. In industrialized countries, one in six patients die in the first months following ischaemic stroke, and half of survivors are permanently disabled despite best efforts of rehabilitation. Optimization of the early and ongoing management of patients with acute ischaemic stroke is pivotal to the reduction of case fatality and long-term disability. The objective of tiffs study was to determine other predisposing factors to the development CVAs among young Sudanese patients. Early detection of predisposing factors of CVA through regular screening of patients at risk can reduce morbidity and improve management. Following informed consent, sixty five patients of both sexes and with an age of < 50 years with confirmed CVA due to thrombosis were enrolled in the study. Patients who had malaria were excluded from the study. Comparable healthy controls (in - 130) were selected from medical staff and students. Full blood counts, PT, APTT, TT, Protein C., Protein S, ATIII levels were conducted for patients and controls. Screening for anticardiolipin and mixing coagulation test were also conducted (antipho spholipids screening). Females were affected more than males in the study sample (F/M was 40/25). Haematological and coagulation findings of patients and the controls were comparable. ATIII, although within the normal range it was significantly lower in patients compared to controls (p - 0.001) In conclusion, ATIII relative deficiency could be a possible cause of increased incidence o f thrombotic CWA among young Sudanese patients. The predominance of females in the study group could not be explained. Further studies are needed to verify our suggested explanation. 0005 Tile cauSes of cerebral palsy: hdrauteritm exposure to infection and risk of cerebral palsy Akbarzadeh, Marjaneh 1, Akbarzadeh, Reza 2, Akbarzadeh, Reyhaneh 1.
1Department of Psychology, Pa~ssian University of Economies and Culture, Moscow, Russia; 2Mashhad University of Medical Sciences, Mashhad, .[ran Background anti Aims: Cerebral palsy (CP) is a major neurodevelopmental disability in childhood. Exposure to maternal or placental infection is related to risk of preterm birth and, in premature infants, of brain lesions predictive of cerebral palsy (CP). The aim of this study was to analyze infection-related risk factors for spastic (CP) in infants. Method: In tiffs review we presented investigation exposure to intrauterine infection as an independent risk factor for spastic (CP) in infants. Results: There are many known risk factors for cerebral palsy, including multiple gestation, prematurity and low birth weight. Recently, intrauterine infection, maternal pyrexia, and the presence of thromboplfflic disorders have been identified as major risk factors for subsequent cerebral palsy. Intrauterine exposure to maternal infection was associated with a marked increase in risk of CP in infants. Among children with C.P, those born to infected women were more often hypertensive, low Apgar scores, needed intubafions, had neonatal seizures, and received a clinical diagnosis of hypoxic-ischemic encephalopathy. The hypothesis under exanffnation is that inflannnatory cytokines released during the course of intrauterine infection play a central role in the genesis o f pretetm parturition, and cerebral palsy.
Poster Abstracts Conclusion: Cerebral palsy is a serious motor disorder that appears in early life. The interactions of viral or bacterial infections during pregnancy, normal or abnormal fetal cytokine responses, and hereditary fetal thromboptfilia as antenatal causes of the neuropathology of cerebral palsy are now areas of research priority. These data suggest that factors related to the fetal inflammatory response, including cytokines, may be causal agents in brain damage and neurodevelopmental disability associated with intrauterine infection. 0006 Gila and Fetal Alcohol Syndronle: Ethanol-induced disturbances of gliogenesis anti nemogenesis in tile brain developnlent Akbaxzadeh, Maxjaneh l, Akb arzadeh, Reza ~, Akbarzadeh, Reyhaneh ~.
1Department of Psychology, Russian University of Economies and Culture, Moscow, Russia; 2Mashhad University of Medical Sciences, Mashhad, .[ran Inlxoduelion: The central nervous system is particularly susceptible to alcohol effects and toxicity. Alcohol intake during pregnancy can cause mental retardation and neurobehavioral disorders as well as fetal alcohol syndrome (FAS). Clinical and experimental evidence indicate that in uterus alcohol exposure induces structural and functional abnormalities in gliogenesis and in glial-neuronal interactions, suggesting a potential role of glial cells on ethanol-induced developmental brain abnormalities. Aims and Method: This review summarizes available information regarding the effects of consumption of ethanol on the developing nervous systems in children are among the uterus exposure to ethanol. Results: Glial cells constitute the most common cell type in the brain and play critical roles in normal brain function and during infection and injury. Prenatal exposure to ethanol affects many crucial neurochemical and cellular components of the developing brain. Ethanol has been shown to cause alterations of both neuronal and glial cells, including cell loss, and changes in their migration and maturation. One of the most severe consequences of maternal ethanol consumption is the damage to the developing central nervous system, wlffch is manifested by long-term cognitive and behavioral deficits in the offspring. Ethanol interferes with all of the stages of brain development, and the severity of the damage depends on the amount of ethanol intake and level of exposure. Conclusion: In uterus exposure to ethanol is deleterious to fetal brain development. Children born with the fetal alcohol syndrome (FAS) display a number of abnormalities, the most significant of which are central nervous system (CNS) dysfunctions, such as microencephaly and mental retardation. A n interaction of ethanol with glial cells, particularly astrocytes, has been suggested to contribute to the developmental neurotoxidty of tiffs alcohol. 0007 Antenatal causes of cerebral palsy: associations between viral and bacterial infection, and the development of cerebral palsy
Akbarzadeb, Reybaneh1, Akbarzadeh, Reza 2, Akbarzadeh, Matjanell 1.
1 Department of Psychology, Russian University of Economics and Culture, Moscow, Russia; 2 Mashhad University of Medical Sciences, Mashhad, Iran Background and Aims: Cerebral palsy is the most common neuromotor developmental disability o f clffldhood. A n association between intrauterine infection and CP has been reported. Infection in pregnancy may be an important cause of the disorder. The purpose of tiffs study was to analyze associations between prenatal factors and cerebral palsy in neonate and infant. Method: This review will attempt to establish the link between prenatal infection and brain damage in infants. The potential mechanisms of brain injury associated with infection will be discussed. Results: Much of the current research into the causes of cerebral palsy in infants has focused on two potential mechanisms of brain damage.
Journalof lbe
Ne o!ogical clences Journal of the Neurological Sciences 238 (2005) S101-S196 www.elsevier, com/locate/jns
Poster Abstracts
7 November 2005 0001 Regulation of Ca2+-activated K + dmnnels by purine~gic P2Y receptors Novak, I ~, Hede, SE 1, Aznstrup, J~, Klaerke, DA 2. ~Institute of
Molecular Biology and Physiology, The August Krogh Building, University of Copenhagen, Denmark; 2Sectionfor Physiology and Biochemistry, The Royal Veterinary and Agrieulturd University, Denmark Background: ATP and other nucleotides are co-released with other transmitters in CNS. They are also released during ischemJa and cell damage. ATP interacts with ionotrophic P2X receptors or metabotrophic P2Y receptors. Thus P2 receptors can regulate neurotransmission and also exert long-term effects. Their action can be mediated through Ca a+- activated K + channels of intermediate conductance ([K) and big conductance (BK), both expressed in CNS. The aim of our studies is to elucidate how P2Y.~ and P2Y4 receptors regulate BK and [K channels. Method: Human P2 receptors and K + channels were co-expressed in Xenopus laevis oocytes and K + channel activity was measured electrophysiologically in oocytes stimulated with UTP (0.1 mM). Results: UTP stimulation of oocytes co-expressing IK channels with P2Y4 and P2Y.~ receptors resulted in a large hyperpolarization and 22-fold and 5-fold activation of currents, respectively. In oocytes expressing P2Y4 receptors and BK channels UTP resulted in a 30% increase in the current through the expressed channels. In contrast, stinmlation of P2Y2 receptors led to a 20"/0 inlffbition of co-expressed BK channel activity that was sensitive to TEA. Conclusion: Tiffs study shows that there is a differential interaction between the subtypes of P2Y receptors and Caa+-acdvated K + channels. Thus ATP or UTP release may lead to hyperpolarization or depolarization of membrane potential in cells where P Y receptors and K + channels are co-expressed. Future aims are to investigate co-expression of P2Y receptors and corresponding K + channels in manmtalian CNN, and to understand their regulation of menlbrane excitability, cell volume and cell survival. 0002 EIti~ets of ropivaeaine and bupivacaine on glutamate-evoked o~r~ents in culluted rat Idppocampus neu]fons
Xu, L, Jiang, Y, Xue, Y, Zhang, H. PLA General Hospital, Beijing,
Beijing, China Aim: To observe the effects o f ropivacaine and bupivacaine on glutamate-evoked currents in cultured rat lffppocampus neurons. Methods: Rat hippocampus neurons were dissected and cultured. Ghitamate-evoked currents were recorded by whole cell recording of patch clamp. Effects o f ropivacaine and bupivacaine on glutamateevoked currents were observed. Drugs were given by pressure ejection or bath injection.
Results: Glutamate(100mmol.L 1)can elicit inward currents in cultured rat lffppocampus neurons and this currents can be locked by n o n - N M D A antagonists DNQX. At the concentration of 10,50,100m_mol.L-~,bupivacaine and ropivacaine all can obviously decrease glutamate-evoked currents in cultured rat hippocampus neurons. At higher concentration of 50 and 100mmol.L -1, the reduced amplitude of glutamate-evoked currents by ropivacaine was larger than that of by bupivacaine (P < 0.01). Conclusion: Ropivacaine and bupivacaine have obviously inhibition effect on glutamate-evoked currents in cultured rat hippocampus neurons. The inhibition effect of ropivacaine on glutamate-evoked currents was stronger than that of bupivacaine.
0003 Neuxoendocxine Changes after C~atdal Radiotherapy in Chihlxen
Ragab, M 1, Abdou, A 2. ~Pediatrics dept., Faculty o/medicine, Alexandria Univ, Alexandria, Egypt; 2Neuropsychiatry dept., Faculty of medicine, Alexandria Univ, Alexandria, Eg>Tt Background: When the hypothalamic-pituitary axis (HPA) is included field of cranial irradiation, a variety of neuroendocrine disturbances occur especially in clffldren. We evaluated growth hormone secretion and the hypothalamic-pituitary-thyroid taxis function in children after cranial radiotherapy. Methods: Twenty children (112 boys and 8 girls) who received cranial/ craniospinal radiation therapy were included in tiffs study. The serum concentrations of the basal and peak growth hormone [GH], total and free T4, total T3, and basal and peak thyroid stinmlating hormone [TSH] were measured by radioimmunoassay. Twelve age-matched healthy children served as controls. Results: The mean serum basal and peak GH concentrations after stimulation with clonidine were significantly lower lweor in patients. Forty-five percent and 65% of the patients had below-normal basal and peak GH secretion respectively. There was a sigtffficant inverse correlation between the serum peak GH concentration and both the dose of radiation and the interval between therapy and testing. The mean serum total T4, free ]'4, and total T3 concentrations were sigtffficantly lower in patients. Thirty-five percent, 45"/o, and 25"/o of the patients had below-normal serum total T4, free T4, and total T3 respectively. Negative significant correlation was found between the dose of radiation and all the thyroid hormones, while inverse significant correlation was observed between the intervals between radiations and testing and serum free ]'4 concentration only. Conclusion: A large percentage of clffldren develop growth hormone deficiency (GHD) and hypothyroidism witlffn 2 years after receiving doses of cranial radiation.
0004 Predisposing factoxs for the development of ce~ebrovasculax accidents (CVAs) in young Sudanese patients
S102
Monday, November 7, 2005
Abd Gadir H. Elagib ~, Abbashar Hussein2, Ammar Eltahir Ahmed3, Ahmed M. Musa 1, Eltahir Awad G. Khalil ~, Ahmed M. Elhassan ~.
Leishmaniasis Research Group/Sudan: ;Institute of Endemic Diseases, University of Kkartoum; 2Department of Medicine, Faculty of Medicine, University of Kkartoum; 3Department of Physiology, Faculty of Medicine, University of Kkartoum Cerebrovascular accidents (CVAs) a represent major cause of death and disability among middle-aged people. Cigarette smoking, alcohol intake, hypertension, diabetes mellitus, hyperlipidemia and heart disease are known predisposing factors. In industrialized countries, one in six patients die in the first months following ischaemic stroke, and half of survivors are permanently disabled despite best efforts of rehabilitation. Optimization of the early and ongoing management of patients with acute ischaemic stroke is pivotal to the reduction of case fatality and long-term disability. The objective of tiffs study was to determine other predisposing factors to the development CVAs among young Sudanese patients. Early detection of predisposing factors of CVA through regular screening of patients at risk can reduce morbidity and improve management. Following informed consent, sixty five patients of both sexes and with an age of < 50 years with confirmed CVA due to thrombosis were enrolled in the study. Patients who had malaria were excluded from the study. Comparable healthy controls (in - 130) were selected from medical staff and students. Full blood counts, PT, APTT, TT, Protein C., Protein S, ATIII levels were conducted for patients and controls. Screening for anticardiolipin and mixing coagulation test were also conducted (antipho spholipids screening). Females were affected more than males in the study sample (F/M was 40/25). Haematological and coagulation findings of patients and the controls were comparable. ATIII, although within the normal range it was significantly lower in patients compared to controls (p - 0.001) In conclusion, ATIII relative deficiency could be a possible cause of increased incidence o f thrombotic CWA among young Sudanese patients. The predominance of females in the study group could not be explained. Further studies are needed to verify our suggested explanation. 0005 Tile cauSes of cerebral palsy: hdrauteritm exposure to infection and risk of cerebral palsy Akbarzadeh, Marjaneh 1, Akbarzadeh, Reza 2, Akbarzadeh, Reyhaneh 1.
1Department of Psychology, Pa~ssian University of Economies and Culture, Moscow, Russia; 2Mashhad University of Medical Sciences, Mashhad, .[ran Background anti Aims: Cerebral palsy (CP) is a major neurodevelopmental disability in childhood. Exposure to maternal or placental infection is related to risk of preterm birth and, in premature infants, of brain lesions predictive of cerebral palsy (CP). The aim of this study was to analyze infection-related risk factors for spastic (CP) in infants. Method: In tiffs review we presented investigation exposure to intrauterine infection as an independent risk factor for spastic (CP) in infants. Results: There are many known risk factors for cerebral palsy, including multiple gestation, prematurity and low birth weight. Recently, intrauterine infection, maternal pyrexia, and the presence of thromboplfflic disorders have been identified as major risk factors for subsequent cerebral palsy. Intrauterine exposure to maternal infection was associated with a marked increase in risk of CP in infants. Among children with C.P, those born to infected women were more often hypertensive, low Apgar scores, needed intubafions, had neonatal seizures, and received a clinical diagnosis of hypoxic-ischemic encephalopathy. The hypothesis under exanffnation is that inflannnatory cytokines released during the course of intrauterine infection play a central role in the genesis o f pretetm parturition, and cerebral palsy.
Poster Abstracts Conclusion: Cerebral palsy is a serious motor disorder that appears in early life. The interactions of viral or bacterial infections during pregnancy, normal or abnormal fetal cytokine responses, and hereditary fetal thromboptfilia as antenatal causes of the neuropathology of cerebral palsy are now areas of research priority. These data suggest that factors related to the fetal inflammatory response, including cytokines, may be causal agents in brain damage and neurodevelopmental disability associated with intrauterine infection. 0006 Gila and Fetal Alcohol Syndronle: Ethanol-induced disturbances of gliogenesis anti nemogenesis in tile brain developnlent Akbaxzadeh, Maxjaneh l, Akb arzadeh, Reza ~, Akbarzadeh, Reyhaneh ~.
1Department of Psychology, Russian University of Economies and Culture, Moscow, Russia; 2Mashhad University of Medical Sciences, Mashhad, .[ran Inlxoduelion: The central nervous system is particularly susceptible to alcohol effects and toxicity. Alcohol intake during pregnancy can cause mental retardation and neurobehavioral disorders as well as fetal alcohol syndrome (FAS). Clinical and experimental evidence indicate that in uterus alcohol exposure induces structural and functional abnormalities in gliogenesis and in glial-neuronal interactions, suggesting a potential role of glial cells on ethanol-induced developmental brain abnormalities. Aims and Method: This review summarizes available information regarding the effects of consumption of ethanol on the developing nervous systems in children are among the uterus exposure to ethanol. Results: Glial cells constitute the most common cell type in the brain and play critical roles in normal brain function and during infection and injury. Prenatal exposure to ethanol affects many crucial neurochemical and cellular components of the developing brain. Ethanol has been shown to cause alterations of both neuronal and glial cells, including cell loss, and changes in their migration and maturation. One of the most severe consequences of maternal ethanol consumption is the damage to the developing central nervous system, wlffch is manifested by long-term cognitive and behavioral deficits in the offspring. Ethanol interferes with all of the stages of brain development, and the severity of the damage depends on the amount of ethanol intake and level of exposure. Conclusion: In uterus exposure to ethanol is deleterious to fetal brain development. Children born with the fetal alcohol syndrome (FAS) display a number of abnormalities, the most significant of which are central nervous system (CNS) dysfunctions, such as microencephaly and mental retardation. A n interaction of ethanol with glial cells, particularly astrocytes, has been suggested to contribute to the developmental neurotoxidty of tiffs alcohol. 0007 Antenatal causes of cerebral palsy: associations between viral and bacterial infection, and the development of cerebral palsy
Akbarzadeb, Reybaneh1, Akbarzadeh, Reza 2, Akbarzadeh, Matjanell 1.
1 Department of Psychology, Russian University of Economics and Culture, Moscow, Russia; 2 Mashhad University of Medical Sciences, Mashhad, Iran Background and Aims: Cerebral palsy is the most common neuromotor developmental disability o f clffldhood. A n association between intrauterine infection and CP has been reported. Infection in pregnancy may be an important cause of the disorder. The purpose of tiffs study was to analyze associations between prenatal factors and cerebral palsy in neonate and infant. Method: This review will attempt to establish the link between prenatal infection and brain damage in infants. The potential mechanisms of brain injury associated with infection will be discussed. Results: Much of the current research into the causes of cerebral palsy in infants has focused on two potential mechanisms of brain damage.