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088 — (ZAN0025) Transplantation of bone marrow mononuclear cells modulates expression of growth factors in chronic pilocarpine-treated epileptic rats
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Abstracts
STY decreased the content of aspartic acid in the lowest dose (STY-1: 0.15 ± 0.0) and increased in the highest dose (STY-20: 0.49 ± 0.03) when compared with control (0.46 ± 0.0) [F(3,25) = 14.81; p b 0.0001]. The content of GLU increased in the lowest dose (STY-1: 0.16 ± 0.0). In addition, STY 1-mg/kg dose increased the content of GLY (0.03 ± 0.0) relative to control (0.0 ± 0.0) [F(3,24) = 5.99; p b 0.0041]. There was no variance on the level of TAU [F(3,26) = 1.847; p b 0.597]. The content of GABA increased in STY 1-mg/kg dose (STY-1: 0.12 ± 0.0) relative to control (0.05 ± 0.0) [F(3,25) = 9.426; p b 0.0003]. Discussion/conclusions: There was modulation of the levels of GLU, GABA, GLY, and ASP with the STY lowest dose in the PFC. Pilocarpine was able to modify the content of inhibitory and excitatory amino acids. 6Styryl-2-pyrone decreased the excitatory activity mediated, perhaps, by the modulation of glycine content and increased the inhibitory activity by GABAergic pathways on the prefrontal cortex. These effects are similar to the action of anticonvulsant drugs. Keywords: Medicinal plants, 6-Styryl-2-pyrone, Pyrones, Amino acids, Prefrontal cortex. Acknowledgments/financial support: CAPES, CNPq, and FUNCAP. doi:10.1016/j.yebeh.2014.08.120
088 — (ZAN0025) Transplantation of bone marrow mononuclear cells modulates expression of growth factors in chronic pilocarpine-treated epileptic rats G. Zaniratia,b, F. Simãoa,b, G.T. Venturina, S. Greggioa, D. Marinowika,b, F. Rodriguesc, J.C. DaCostaa,b a Instituto do Cérebro do Rio Grande do Sul (InsCer), Instituto de Pesquisas Biomédicas (IPB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil b Programa de Pós-Graduação em Medicina e Ciências da Saúde, Brazil c Faculdade de Biomedicina, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil Rationale: Epilepsy affects 1% of the world population, and seizures in 30% of these patients are refractory to available medication. Stem cells offer hope in the treatment of epilepsy since they can proliferate, differentiate, and produce factors which may activate endogenous mechanisms to restore the injured brain. Knowing that the administration of bone marrow mononuclear cells (BMMCs) has therapeutic potential in an experimental model of epilepsy, the aim of this study is to investigate the mechanisms by which administered cells exert their beneficial effect. Thus, a comparative study was done to detect the expression of trophic factors such as brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF), transforming growth factor-beta (TGF-beta), and vascular endothelial growth factor (VEGF) in the hippocampi of untreated or BMMC-transplanted epileptic animals by ELISA. Methods: Epilepsy was induced by pilocarpine injection (320 mg/kg; ip). Seizures were scored by the Racine scale (Racine R.J., Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):281–94). The duration of status epilepticus was controlled with diazepam (10 mg/kg; ip; 90 min after SE onset). Twenty-two days after SE, rats were treated with either saline or BMMC and randomly assigned into groups: Control, Pilo, and Pilo + BMMC. The BMMC groups received cell transplantation (EGFP C57BL/6 mice) via tail vein (1 × 107 cells, 100 mL). The hippocampi were collected 3, 7, and 14 days after transplantation, and the levels of BDNF, GDNF, NGF, VEGF, and TGF-beta were analyzed by ELISA. Pilocarpinetreated animals were monitored for the presence of spontaneous seizures for 7 days prior to transplant. Results: Our results showed that there was a change in the protein expression of BDNF, GDNF, NGF, TGF-beta, and VEGF in the hippocampus
of epileptic animals treated with BMMCs compared with untreated epileptic animals and controls, with variations in the expression of each factor at different times after transplantation. The expression of BDNF, GDNF, NGF, and VEGF was increased, while TGF-beta1 levels were reduced after BMMC transplantation compared with untreated epileptic animals. However, there was no difference in the expression of these factors in untreated epileptic animals compared with control animals, except for TGF-beta1, which was increased in the group of epileptic animals compared with control animals. Discussion/conclusions: Studies show an increased expression of trophic factors in epileptic rats during the acute period of epilepsy. However, in our study, during chronic epilepsy, the levels of these factors did not seem to be affected. Trophic factors appear to play important roles in pathophysiological conditions, such as in epileptic seizures. Some trophic factors have been shown to be involved in the beneficial effects after transplantation of BMMCs in epilepsy. Some of them may have therapeutic potential in this disease, exerting their effect by decreasing the frequency of seizures, inflammation, and excitability and increasing neuronal survival, synaptic plasticity, and cell differentiation in animal models of epilepsy. The results of our study provide additional data on the potential benefit of BMMC transplantation in epilepsy as well as provide an insight into the mechanisms by which BMMCs promote functional recovery in epileptic rats. Acknowledgments/financial support: This work was supported by research grants from the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS; PQG-11/1546-1 to J.C.C. and ARD-11/16780 to F.S.). The authors received fellowships from Coordenação de Aperfeiçoamento Pessoal de Nível Superior (CAPES) or Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). We acknowledge the help of Dr. Denise Cantarelli Machado for her support in bone marrow mononuclear cell processing. doi:10.1016/j.yebeh.2014.08.121
089 — (ZAN0154) Developing a serious computer game to promote self-management and knowledge among children with epilepsy K.P. Zanni Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil Rationale: The traditional methods of education about chronic conditions are changing, and new media are being adopted to improve learning. One of these new media is the so-called “serious games”, which can be a tool to reach out to young people and teach them notions of health care and self-efficacy. With this scenario, we proposed to design a health educational serious game about epilepsy for children aged between 8 and 12 years, with the main goal of helping the player to be conscious about this condition and preparing him/her to deal with situations related to seizures, treatment, and activities of daily living. Methods: The game was developed as a cognitive, motivational, and self-regulatory model for promoting self-management behaviors and knowledge in children with epilepsy. Formative work must be conducted prior to constructing the video game to ensure that the characters and storyline, including situations in which characters find themselves, problems encountered, and solutions, are realistic and appeal to the intended audience such as children with epilepsy. Character modeling and dialogue can convey knowledge, demonstrate skills, and enhance self-efficacy. Modeling a coping style in which characters model imperfect performance initially but persevere and gradually improve through personal effort and skill refinement, emphasizing the importance of using strategies and verbalizing and/or demonstrating how
Abstracts
STY decreased the content of aspartic acid in the lowest dose (STY-1: 0.15 ± 0.0) and increased in the highest dose (STY-20: 0.49 ± 0.03) when compared with control (0.46 ± 0.0) [F(3,25) = 14.81; p b 0.0001]. The content of GLU increased in the lowest dose (STY-1: 0.16 ± 0.0). In addition, STY 1-mg/kg dose increased the content of GLY (0.03 ± 0.0) relative to control (0.0 ± 0.0) [F(3,24) = 5.99; p b 0.0041]. There was no variance on the level of TAU [F(3,26) = 1.847; p b 0.597]. The content of GABA increased in STY 1-mg/kg dose (STY-1: 0.12 ± 0.0) relative to control (0.05 ± 0.0) [F(3,25) = 9.426; p b 0.0003]. Discussion/conclusions: There was modulation of the levels of GLU, GABA, GLY, and ASP with the STY lowest dose in the PFC. Pilocarpine was able to modify the content of inhibitory and excitatory amino acids. 6Styryl-2-pyrone decreased the excitatory activity mediated, perhaps, by the modulation of glycine content and increased the inhibitory activity by GABAergic pathways on the prefrontal cortex. These effects are similar to the action of anticonvulsant drugs. Keywords: Medicinal plants, 6-Styryl-2-pyrone, Pyrones, Amino acids, Prefrontal cortex. Acknowledgments/financial support: CAPES, CNPq, and FUNCAP. doi:10.1016/j.yebeh.2014.08.120
088 — (ZAN0025) Transplantation of bone marrow mononuclear cells modulates expression of growth factors in chronic pilocarpine-treated epileptic rats G. Zaniratia,b, F. Simãoa,b, G.T. Venturina, S. Greggioa, D. Marinowika,b, F. Rodriguesc, J.C. DaCostaa,b a Instituto do Cérebro do Rio Grande do Sul (InsCer), Instituto de Pesquisas Biomédicas (IPB), Pontifícia Universidade Católica do Rio Grande do Sul (PUCRS), Brazil b Programa de Pós-Graduação em Medicina e Ciências da Saúde, Brazil c Faculdade de Biomedicina, Universidade Federal do Rio Grande do Sul (UFRGS), Brazil Rationale: Epilepsy affects 1% of the world population, and seizures in 30% of these patients are refractory to available medication. Stem cells offer hope in the treatment of epilepsy since they can proliferate, differentiate, and produce factors which may activate endogenous mechanisms to restore the injured brain. Knowing that the administration of bone marrow mononuclear cells (BMMCs) has therapeutic potential in an experimental model of epilepsy, the aim of this study is to investigate the mechanisms by which administered cells exert their beneficial effect. Thus, a comparative study was done to detect the expression of trophic factors such as brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF), transforming growth factor-beta (TGF-beta), and vascular endothelial growth factor (VEGF) in the hippocampi of untreated or BMMC-transplanted epileptic animals by ELISA. Methods: Epilepsy was induced by pilocarpine injection (320 mg/kg; ip). Seizures were scored by the Racine scale (Racine R.J., Electroencephalogr Clin Neurophysiol. 1972 Mar;32(3):281–94). The duration of status epilepticus was controlled with diazepam (10 mg/kg; ip; 90 min after SE onset). Twenty-two days after SE, rats were treated with either saline or BMMC and randomly assigned into groups: Control, Pilo, and Pilo + BMMC. The BMMC groups received cell transplantation (EGFP C57BL/6 mice) via tail vein (1 × 107 cells, 100 mL). The hippocampi were collected 3, 7, and 14 days after transplantation, and the levels of BDNF, GDNF, NGF, VEGF, and TGF-beta were analyzed by ELISA. Pilocarpinetreated animals were monitored for the presence of spontaneous seizures for 7 days prior to transplant. Results: Our results showed that there was a change in the protein expression of BDNF, GDNF, NGF, TGF-beta, and VEGF in the hippocampus
of epileptic animals treated with BMMCs compared with untreated epileptic animals and controls, with variations in the expression of each factor at different times after transplantation. The expression of BDNF, GDNF, NGF, and VEGF was increased, while TGF-beta1 levels were reduced after BMMC transplantation compared with untreated epileptic animals. However, there was no difference in the expression of these factors in untreated epileptic animals compared with control animals, except for TGF-beta1, which was increased in the group of epileptic animals compared with control animals. Discussion/conclusions: Studies show an increased expression of trophic factors in epileptic rats during the acute period of epilepsy. However, in our study, during chronic epilepsy, the levels of these factors did not seem to be affected. Trophic factors appear to play important roles in pathophysiological conditions, such as in epileptic seizures. Some trophic factors have been shown to be involved in the beneficial effects after transplantation of BMMCs in epilepsy. Some of them may have therapeutic potential in this disease, exerting their effect by decreasing the frequency of seizures, inflammation, and excitability and increasing neuronal survival, synaptic plasticity, and cell differentiation in animal models of epilepsy. The results of our study provide additional data on the potential benefit of BMMC transplantation in epilepsy as well as provide an insight into the mechanisms by which BMMCs promote functional recovery in epileptic rats. Acknowledgments/financial support: This work was supported by research grants from the Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul (FAPERGS; PQG-11/1546-1 to J.C.C. and ARD-11/16780 to F.S.). The authors received fellowships from Coordenação de Aperfeiçoamento Pessoal de Nível Superior (CAPES) or Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq). We acknowledge the help of Dr. Denise Cantarelli Machado for her support in bone marrow mononuclear cell processing. doi:10.1016/j.yebeh.2014.08.121
089 — (ZAN0154) Developing a serious computer game to promote self-management and knowledge among children with epilepsy K.P. Zanni Departamento de Neurociências e Ciências do Comportamento, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil Rationale: The traditional methods of education about chronic conditions are changing, and new media are being adopted to improve learning. One of these new media is the so-called “serious games”, which can be a tool to reach out to young people and teach them notions of health care and self-efficacy. With this scenario, we proposed to design a health educational serious game about epilepsy for children aged between 8 and 12 years, with the main goal of helping the player to be conscious about this condition and preparing him/her to deal with situations related to seizures, treatment, and activities of daily living. Methods: The game was developed as a cognitive, motivational, and self-regulatory model for promoting self-management behaviors and knowledge in children with epilepsy. Formative work must be conducted prior to constructing the video game to ensure that the characters and storyline, including situations in which characters find themselves, problems encountered, and solutions, are realistic and appeal to the intended audience such as children with epilepsy. Character modeling and dialogue can convey knowledge, demonstrate skills, and enhance self-efficacy. Modeling a coping style in which characters model imperfect performance initially but persevere and gradually improve through personal effort and skill refinement, emphasizing the importance of using strategies and verbalizing and/or demonstrating how