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2. Synergistic neuroprotection by a PAF antagonist plus a docosanoid in experimental ischemic stroke: Dose-response and therapeutic window

Author

Reid, Madigan M, Obenaus, Andre, Mukherjee, Pranab K, Khoutorova, Larissa, Roque, Cassia R, Petasis, Nicos A, Oria, Reinaldo B, Belayev, Ludmila, and Bazan, Nicolas G

Subjects
Pharmacology and Pharmaceutical Sciences, Biomedical and Clinical Sciences, Stroke, Brain Disorders, Neurosciences, Development of treatments and therapeutic interventions, 5.1 Pharmaceuticals, Animals, Aspirin, Infarction, Middle Cerebral Artery, Ischemic Stroke, Male, Neuroprotection, Neuroprotective Agents, Rats, Rats, Sprague-Dawley, LAU-0901, AT-NPD1, MRI, Penumbra, MCAo, Behavior, Clinical Sciences, Neurology & Neurosurgery, Clinical sciences
Abstract

ObjectiveWe tested the hypothesis that blocking pro-inflammatory platelet-activating factor receptor (PAFR) with LAU-0901 (LAU) plus administering a selected docosanoid, aspirin-triggered neuroprotectin D1 (AT-NPD1), which activates cell-survival pathways after middle cerebral artery occlusion (MCAo), would lead to neurological recovery. Dose-response and therapeutic window were investigated.Materials and methodsMale SD rats were subjected to 2 hours of MCAo. Behavior testing (days 1-7) and ex vivo MRI on day 7 were conducted. In dose-response, rats were treated with LAU (45 and 60 mg/kg; IP), AT-NPD1 (111, 222, 333 µg/kg; IV), LAU+AT-NPD1 (LAU at 3 hours and AT-NPD1 at 3.15 hours) or vehicle. In the therapeutic window, vehicle, LAU (60 mg/kg), AT-NPD1 (222 µg/kg), and LAU+AT-NPD1 were administered at 3, 4, 5, and 6 hours after onset of MCAo.ResultsLAU and AT-NPD1 treatments alone improved behavior by 40-42% and 20-30%, respectively, and LAU+AT-NPD1 by 40% compared to the vehicle group. T2-weighted imaging (T2WI) volumes were reduced with all doses of LAU and AT-NPD1 by 73-90% and 67-83% and LAU+AT-NPD1 by 94% compared to vehicle. In the therapeutic window, LAU+AT-NPD1, when administered at 3, 4, 5, and 6 hours, improved behavior by 50, 56, 33, and 26% and reduced T2WI volumes by 93, 90, 82, and 84% compared to vehicle.ConclusionsWe have shown here for the first time that LAU plus AT-NPD1 treatment affords high-grade neuroprotection in MCAo, equaling or exceeding that afforded by LAU or AT-NPD1 alone at considerably moderate doses. It has a broad therapeutic window extending to 6 hours after stroke onset.

Published
2022

6. Hair mercury is associated with dyslipidemia and cardiovascular risk: An anthropometric, biochemical and genetic cross-sectional study of Amazonian vulnerable populations.

Author

Lopes-Araújo, Amanda, Arrifano, Gabriela P., Macchi, Barbarella M., Augusto-Oliveira, Marcus, Santos-Sacramento, Letícia, Rodríguez Martín-Doimeadios, Rosa C., Jiménez-Moreno, María, Martins Filho, Arnaldo J., Alvarez-Leite, Jacqueline I., Oriá, Reinaldo B., do Nascimento, José Luiz M., and Crespo-Lopez, Maria Elena

Published
2023
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7. Methylmercury chronic exposure affects the expression of DNA single-strand break repair genes, induces oxidative stress, and chromosomal abnormalities in young dyslipidemic APOE knockout mice

Author

Roque, Cássia R., Sampaio, Letícia R., Ito, Mayumi N., Pinto, Daniel V., Caminha, Juan S.R., Nunes, Paulo I.G., Raposo, Ramon S., Santos, Flávia A., Windmöller, Cláudia C., Crespo-Lopez, Maria Elena, Alvarez-Leite, Jacqueline I., Oriá, Reinaldo B., and Pinheiro, Ronald F.

Published
2021
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9. Use of quantitative molecular diagnostic methods to assess the aetiology, burden, and clinical characteristics of diarrhoea in children in low-resource settings: a reanalysis of the MAL-ED cohort study

Author

Acosta, Angel Mendez, Rios de Burga, Rosa, Chavez, Cesar Banda, Flores, Julian Torres, Olotegui, Maribel Paredes, Pinedo, Silvia Rengifo, Trigoso, Dixner Rengifo, Vasquez, Angel Orbe, Ahmed, Imran, Alam, Didar, Ali, Asad, Rasheed, Muneera, Soofi, Sajid, Turab, Ali, Yousafzai, Aisha, Zaidi, Anita KM, Shrestha, Binob, Rayamajhi, Bishnu Bahadur, Strand, Tor, Ammu, Geetha, Babji, Sudhir, Bose, Anuradha, George, Ajila T, Hariraju, Dinesh, Jennifer, M. Steffi, John, Sushil, Kaki, Shiny, Karunakaran, Priyadarshani, Koshy, Beena, Lazarus, Robin P, Muliyil, Jayaprakash, Ragasudha, Preethi, Raghava, Mohan Venkata, Raju, Sophy, Ramachandran, Anup, Ramadas, Rakhi, Ramanujam, Karthikeyan, Rose, Anuradha, Roshan, Reeba, Sharma, Srujan L, Sundaram, Shanmuga, Thomas, Rahul J, Pan, William K, Ambikapathi, Ramya, Carreon, J Daniel, Doan, Viyada, Hoest, Christel, Knobler, Stacey, Miller, Mark A, Psaki, Stephanie, Rasmussen, Zeba, Richard, Stephanie A, Tountas, Karen H, Svensen, Erling, Amour, Caroline, Bayyo, Eliwaza, Mvungi, Regisiana, Pascal, John, Yarrot, Ladislaus, Barrett, Leah, Dillingham, Rebecca, Petri, William A, Scharf, Rebecca, Ahmed, AM Shamsir, Alam, Md Ashraful, Haque, Umma, Hossain, Md Iqbal, Islam, Munirul, Mahfuz, Mustafa, Mondal, Dinesh, Nahar, Baitun, Tofail, Fahmida, Chandyo, Ram Krishna, Shrestha, Prakash Sunder, Shrestha, Rita, Ulak, Manjeswori, Bauck, Aubrey, Black, Robert, Caulfield, Laura, Checkley, William, Lee, Gwenyth, Schulze, Kerry, Scott, Samuel, Murray-Kolb, Laura E, Ross, A Catharine, Schaefer, Barbara, Simons, Suzanne, Pendergast, Laura, Abreu, Cláudia B, Costa, Hilda, Di Moura, Alessandra, Filho, José Quirino, Leite, Álvaro M, Lima, Noélia L, Lima, Ila F, Maciel, Bruna LL, Medeiros, Pedro HQS, Moraes, Milena, Mota, Francisco S, Oriá, Reinaldo B, Quetz, Josiane, Soares, Alberto M, Mota, Rosa MS, Patil, Crystal L, Mahopo, Cloupas, Maphula, Angelina, Nyathi, Emanuel, Platts-Mills, James A, Liu, Jie, Rogawski, Elizabeth T, Kabir, Furqan, Lertsethtakarn, Paphavee, Siguas, Mery, Khan, Shaila S, Praharaj, Ira, Murei, Arinao, Nshama, Rosemary, Mujaga, Buliga, Havt, Alexandre, Maciel, Irene A, McMurry, Timothy L, Operario, Darwin J, Taniuchi, Mami, Gratz, Jean, Stroup, Suzanne E, Roberts, James H, Kalam, Adil, Aziz, Fatima, Qureshi, Shahida, Islam, M Ohedul, Sakpaisal, Pimmada, Silapong, Sasikorn, Yori, Pablo P, Rajendiran, Revathi, Benny, Blossom, McGrath, Monica, McCormick, Benjamin J J, Seidman, Jessica C, Lang, Dennis, Gottlieb, Michael, Guerrant, Richard L, Lima, Aldo A M, Leite, Jose Paulo, Samie, Amidou, Bessong, Pascal O, Page, Nicola, Bodhidatta, Ladaporn, Mason, Carl, Shrestha, Sanjaya, Kiwelu, Ireen, Mduma, Estomih R, Iqbal, Najeeha T, Bhutta, Zulfiqar A, Ahmed, Tahmeed, Haque, Rashidul, Kang, Gagandeep, Kosek, Margaret N, and Houpt, Eric R

Published
2018
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10. Use of quantitative molecular diagnostic methods to investigate the effect of enteropathogen infections on linear growth in children in low-resource settings: longitudinal analysis of results from the MAL-ED cohort study

Author

Acosta, Angel Mendez, Rios de Burga, Rosa, Chavez, Cesar Banda, Flores, Julian Torres, Olotegui, Maribel Paredes, Pinedo, Silvia Rengifo, Trigoso, Dixner Rengifo, Vasquez, Angel Orbe, Ahmed, Imran, Alam, Didar, Ali, Asad, Rasheed, Muneera, Soofi, Sajid, Turab, Ali, Yousafzai, Aisha, Zaidi, Anita KM, Shrestha, Binob, Rayamajhi, Bishnu Bahadur, Strand, Tor, Ammu, Geetha, Babji, Sudhir, Bose, Anuradha, George, Ajila T, Hariraju, Dinesh, Jennifer, M. Steffi, John, Sushil, Kaki, Shiny, Karunakaran, Priyadarshani, Koshy, Beena, Lazarus, Robin P, Muliyil, Jayaprakash, Ragasudha, Preethi, Raghava, Mohan Venkata, Raju, Sophy, Ramachandran, Anup, Ramadas, Rakhi, Ramanujam, Karthikeyan, Rose, Anuradha, Roshan, Reeba, Sharma, Srujan L, Sundaram, Shanmuga, Thomas, Rahul J, Pan, William K, Ambikapathi, Ramya, Carreon, J Daniel, Doan, Viyada, Hoest, Christel, Knobler, Stacey, Miller, Mark A, Psaki, Stephanie, Rasmussen, Zeba, Richard, Stephanie A, Tountas, Karen H, Svensen, Erling, Amour, Caroline, Bayyo, Eliwaza, Mvungi, Regisiana, Pascal, John, Yarrot, Ladislaus, Barrett, Leah, Dillingham, Rebecca, Petri, William A, Scharf, Rebecca, Ahmed, AM Shamsir, Alam, Md Ashraful, Haque, Umma, Hossain, Md Iqbal, Islam, Munirul, Mahfuz, Mustafa, Mondal, Dinesh, Nahar, Baitun, Tofail, Fahmida, Chandyo, Ram Krishna, Shrestha, Prakash Sunder, Shrestha, Rita, Ulak, Manjeswori, Bauck, Aubrey, Black, Robert, Caulfield, Laura, Checkley, William, Lee, Gwenyth, Schulze, Kerry, Scott, Samuel, Murray-Kolb, Laura E, Ross, A Catharine, Schaefer, Barbara, Simons, Suzanne, Pendergast, Laura, Abreu, Cláudia B, Costa, Hilda, Di Moura, Alessandra, Filho, José Quirino, Leite, Álvaro M, Lima, Noélia L, Lima, Ila F, Maciel, Bruna LL, Medeiros, Pedro HQS, Moraes, Milena, Mota, Francisco S, Oriá, Reinaldo B, Quetz, Josiane, Soares, Alberto M, Mota, Rosa MS, Patil, Crystal L, Mahopo, Cloupas, Maphula, Angelina, Nyathi, Emanuel, Rogawski, Elizabeth T, Liu, Jie, Platts-Mills, James A, Kabir, Furqan, Lertsethtakarn, Paphavee, Siguas, Mery, Khan, Shaila S, Praharaj, Ira, Murei, Arinao, Nshama, Rosemary, Mujaga, Buliga, Havt, Alexandre, Maciel, Irene A, Operario, Darwin J, Taniuchi, Mami, Gratz, Jean, Stroup, Suzanne E, Roberts, James H, Kalam, Adil, Aziz, Fatima, Qureshi, Shahida, Islam, M Ohedul, Sakpaisal, Pimmada, Silapong, Sasikorn, Yori, Pablo P, Rajendiran, Revathi, Benny, Blossom, McGrath, Monica, Seidman, Jessica C, Lang, Dennis, Gottlieb, Michael, Guerrant, Richard L, Lima, Aldo A M, Leite, Jose Paulo, Samie, Amidou, Bessong, Pascal O, Page, Nicola, Bodhidatta, Ladaporn, Mason, Carl, Shrestha, Sanjaya, Kiwelu, Ireen, Mduma, Estomih R, Iqbal, Najeeha T, Bhutta, Zulfiqar A, Ahmed, Tahmeed, Haque, Rashidul, Kang, Gagandeep, Kosek, Margaret N, and Houpt, Eric R

Published
2018
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12. Geography, Population, Demography, Socioeconomic, Anthropometry, and Environmental Status in the MAL-ED Cohort and Case-Control Study Sites in Fortaleza, Ceará, Brazil

Author

Lima, Aldo A. M., Oriá, Reinaldo B., Soares, Alberto M., Filho, José Q., de Sousa, Francisco, Abreu, Cláudia B., Bindá, Alexandre, Lima, Ila, Quetz, Josiane, Moraes, Milena, Maciel, Bruna, Costa, Hilda, Leite, Álvaro M., Lima, Noélia L., Mota, Francisco S., Di Moura, Alessandra, Scharf, Rebecca, Barrett, Leah, and Guerrant, Richard L.

Published
2014
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13. The MAL-ED Cohort Study: Methods and Lessons Learned When Assessing Early Child Development and Caregiving Mediators in Infants and Young Children in 8 Low- and Middle-Income Countries

Author

The MAL-ED Network Investigators, Murray-Kolb, Laura E., Rasmussen, Zeba A., Scharf, Rebecca J., Rasheed, Muneera A., Svensen, Erling, Seidman, Jessica C., Tofail, Fahmida, Koshy, Beena, Shrestha, Rita, Maphula, Angelina, Vasquez, Angel Orbe, da Costa, Hilda P., Yousafzai, Aisha K., Oria, Reinaldo B., Roshan, Reeba, Bayyo, Eliwasa B., Kosek, Margaret, Shrestha, Sanjaya, Schaefer, Barbara A., Bessong, Pascal, Ahmed, Tahmeed, and Lang, Dennis

Published
2014
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16. A global perspective on the influence of environmental exposures on the nervous system

Author

Tshala-Katumbay, Desire, Mwanza, Jean-Claude, Rohlman, Diane S., Maestre, Gladys, and Oria, Reinaldo B.

Subjects
Environmental health -- Research -- Analysis, Nervous system diseases -- Research, Environmental issues, Science and technology, Zoology and wildlife conservation
Abstract

Economic transitions in the era of globalization warrant a fresh look at the neurological risks associated with environmental change. These are driven by industrial expansion, transfer and mobility of goods, climate change and population growth. In these contexts, risk of infectious and non-infectious diseases are shared across geographical boundaries. In low- and middle-income countries, the risk of environmentally mediated brain disease is augmented several fold by lack of infrastructure, poor health and safety regulations, and limited measures for environmental protection. Neurological disorders may occur as a result of direct exposure to chemical and/or non-chemical stressors, including but not limited to, ultrafine particulate matters. Individual susceptibilities to exposure-related diseases are modified by genetic, epigenetic and metagenomic factors. The existence of several uniquely exposed populations, including those in the areas surrounding the Niger Delta or north western Amazon oil operations; those working in poorly regulated environments, such as artisanal mining industries; or those, mostly in sub-Saharan Africa, relying on cassava as a staple food, offers invaluable opportunities to advance the current understanding of brain responses to environmental challenges. Increased awareness of the brain disorders that are prevalent in low- and middle-income countries and investments in capacity for further environmental health-related research are positive steps towards improving human health. Nature 527, S187-S192 (19 November 2015), DOI: 10.1038/nature16034 This article has not been written or reviewed by Nature editors. Nature accepts no responsibility for the accuracy of the information provided., Reports from the World Health Organization (WHO) indicate that the global burden of disease is determined by patterns of disease and disability in low- and middle-income countries (LMICs), which, predictably, [...]

Published
2015
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20. Abstract WP235: Docosanoids Protect Inflammation-induced Brain Damage And Lead To Neurological Recovery In Experimental Stroke

Author

Bazan, Nicolas G, primary, Mukherjee, Pranab K, additional, Reid, Madigan M, additional, Obenaus, Andre, additional, Khoutorova, Larissa, additional, Roque, Cassia R, additional, Desai, Neehar N, additional, Simons, Tyler, additional, Ji, Jeff, additional, Oria, Reinaldo B, additional, and Belayev, Ludmila, additional

Published
2022
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23. The Role of Ruthenium Compounds in Neurological Diseases: A Minireview

Author

Justi, Fátima Virgínia Gama, primary, Matos, Gabriella Araújo, additional, Caminha, Juan de Sá Roriz, additional, Roque, Cássia Rodrigues, additional, Carvalho, Edinilton Muniz, additional, Campelo, Márcio Wilker Soares, additional, Belayev, Ludmila, additional, Lopes, Luiz Gonzaga de França, additional, and Oria, Reinaldo B., additional

Published
2021
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27. Malnutrition as an enteric infectious disease with long-term effects on child development

Author

Guerrant, Richard L., Oria, Reinaldo B., Moore, Sean R., Oria, Monica O.B., and Lima, Aldo A.M.

Subjects
Child development -- Research, Colorectal diseases -- Risk factors, Colorectal diseases -- Complications and side effects, Gastrointestinal diseases -- Risk factors, Gastrointestinal diseases -- Complications and side effects, Malnutrition -- Complications and side effects, Food/cooking/nutrition
Abstract

Malnutrition is a major contributor to mortality and is increasingly recognized as a cause of potentially lifelong functional disability. Yet, a rate-limiting step in achieving normal nutrition may be impaired absorptive function due to multiple repeated enteric infections. This is especially problematic in children whose diets are marginal. In malnourished individuals, the infections are even more devastating. This review documents the evidence that intestinal infections lead to malnutrition and that malnutrition worsens intestinal infections. The clinical data presented here derive largely from long-term cohort studies that are supported by controlled animal studies. Also reviewed are the mechanisms by which enteric infections lead to undernutrition and by which malnutrition worsens enteric infections, with implications for potential novel interventions. Further intervention studies are needed to document the relevance of these mechanisms and, most importantly, to interrupt the vicious diarrhea-malnutrition cycle so children may develop their full potential.

Published
2008

30. Cover Image

Author

Belayev, Ludmila, primary, Hong, Sung‐Ha, additional, Freitas, Raul S., additional, Menghani, Hemant, additional, Marcell, Shawn J., additional, Khoutorova, Larissa, additional, Mukherjee, Pranab K., additional, Reid, Madigan M., additional, Oria, Reinaldo B., additional, and Bazan, Nicolas G., additional

Published
2020
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31. List of contributors

Author

Abrantes, Margarida, Alves, Raquel, Anugula, Sharath, Aran, Veronica, Badimon, Lina, Barreto, Jorge N., Bartosz, Grzegorz, Borges, Fernanda, Borrás, Consuelo, Botelho, Maria Filomena, Bousquet, Jean, Brehm, António M.D., Brito, Gerly A.C., Bultje, Daan, Cabral, Ana Cristina, Caetano, André, Canhão, Helena, Carreira, Isabel Marques, Carriazo, Ana Maria, Carvalho, Cristina, Carvalho, Eugenia, Castel-Branco, Margarida, Chen, Yaohua, Coelho-Filho, João M., Constâncio, Vera, Correia e Silva, António, Costa, Deiziane V.S., Costa, Elísio, Costa, Inês, Cunha-Oliveira, Teresa, de Carvalho, Paulo, De Luca, Vicenzo, de Natale, Edoardo R., Dias, Jorge, Dias, Ronaldo P., Duarte, Ana I., Farrel, John, Fernandez-Llimos, Fernando, Ferreira, Lino, Ferrucci, Luigi, Figueiredo, Isabel Vitoria, Ford, Jamie K., Franceschi, Claudio, Freitas, Alex A., Furlan de Brito, Maja, Giacomin, Karla C., Girao, Henrique, Gkikas, Ilias, Gomes, Bárbara, Gomes, Rodrigo M., Gonçalves, Ana Cristina, Goulden, Peter, Grant, Marcus, Grilo, Luís F., Guldemond, Nick, Henriques, Jorge, Heringer, Manoela, Illario, Maddalena, Jerónimo, Carmen, Jones, John G., Jorge, Joana, Kabiri, Yaschar, Karkucinska-Wieckowska, Agnieszka, Kelly, George, Kirkland, James L., Kitaeva, Kristina, Kiyasov, Andrey, Korolchuk, Viktor I., Laranjo, Mafalda, LaRocca, Thomas J., Lavrador, Marta, Lebiedzinska-Arciszewska, Magdalena, Li, Zhiquan, Liu, Yuezhong, Lourenço, Alexandre, Ma, Lina, Malva, João O., Martens, Christopher R., Mas-Bargues, Cristina, Matafome, Paulo, Melo, Joana Barbosa, Mendonça, Maria L. Lima, Metaxakis, Athanasios, Middleton, Lefkos T., Moreira, Paula I., Nascimento, Judite M., Neto, Vivaldo M., Oliveira, Paulo J., Ori, Alessandro, Oriá, Reinaldo B., Ozanne, Susan E., Padeiro, Miguel, Padro, Teresa, Palmeira, Carlos M., Pan, Yiming, Paredes, Simão, Passos, João F., Pereira, Edith, Pereira, Francisco B., Pereira, Susana P., Pinton, Paolo, Pires, Joana F., Pires, Salomé, Polidori, M. Cristina, Politis, Marios, Raimundo, Nuno, Ramalho-Santos, João, Rasmussen, Lene Juel, Regateiro, Fernando J., Reis, Dario D., Ribeiro, Caio, Ribeiro, Ilda Patrícia, Ribeiro-Rodrigues, Teresa M., Rizvanov, Albert, Rocha, Teresa, Röhr, Susanne, Rolo, Anabela P., Román-Domínguez, Aurora, Romero-Ortuno, Roman, Rosa, Manuel Santos, Rutland, Catrin, Sadowska-Bartosz, Izabela, Santana, Paula, Santinha, Deolinda, Santos, Marcos, Sarmento Ribeiro, Ana Bela, Semedo, Deisa S.R.C., Sequeira, João, Sierra, Felipe, Silva, Maria Natalina L., Solana, Rafael, Solovyeva, Valeriya, Spínola, Hélder, Tavares, Renata S., Tavernarakis, Nektarios, Tchkonia, Tamar, Theng, Yin-Leng, Traver-Salcedo, Vicente, Udeh-Momoh, Chi, Verma, Rakhi, Victorelli, Stella, Vilaça, Andreia, Vilahur, Gemma, Viña, José, von Zglinicki, Thomas, Wahl, Devin, Werle, Berenice Maria, Wieckowski, Mariusz R., Wilson, Heather, Wissler Gerdes, Erin O., Wozniak, Lucyna A., Zavan, Barbara, Zhu, Yi, and Zischka, Hans

Published
2023
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33. DHA modulates MANF and TREM2 abundance, enhances neurogenesis, reduces infarct size, and improves neurological function after experimental ischemic stroke

Author

Belayev, Ludmila, primary, Hong, Sung‐Ha, additional, Freitas, Raul S., additional, Menghani, Hemant, additional, Marcell, Shawn J., additional, Khoutorova, Larissa, additional, Mukherjee, Pranab K., additional, Reid, Madigan M., additional, Oria, Reinaldo B., additional, and Bazan, Nicolas G., additional

Published
2020
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35. Blocking pro-inflammatory platelet-activating factor receptors and activating cell survival pathways: A novel therapeutic strategy in experimental ischemic stroke.

Author

Belayev, Ludmila, Obenaus, Andre, Mukherjee, Pranab K., Knott, Eric J., Khoutorova, Larissa, Reid, Madigan M., Roque, Cassia R., Nguyen, Lawrence, Jeong Bin Lee, Petasis, Nicos A., Oria, Reinaldo B., and Bazan, Nicolas G.

Subjects
ISCHEMIC stroke, PLATELET activating factor receptors, DOCOSAHEXAENOIC acid, NEUROINFLAMMATION, SMALL molecules
Abstract

OBJECTIVE: Acute ischemic stroke triggers complex neurovascular, neuroinflammatory, and synaptic alterations. This study explores whether blocking pro-inflammatory platelet-activating factor receptor (PAF-R) plus selected docosanoids after middle cerebral artery occlusion (MCAo) would lead to neurological recovery. The following small molecules were investigated: (a) LAU-0901, a PAF-R antagonist that blocks pro-inflammatory signaling; and (b) derivatives of docosahexaenoic acid (DHA), neuroprotectin D1 (NPD1), and aspirin-triggered NPD1 (AT-NPD1), which activates cell survival pathways and are exert potent anti-inflammatory activity in the brain. MATERIALS AND METHODS: Sprague-Dawley rats received 2 h MCAo and LAU-0901 (30 or 60 mg/kg, 2 h after stroke), NPD1, and AT-NPD1 (333 µg/kg), DHA (5 mg/kg), and their combination were administered intravenous at 3 h after stroke. Behavior testing and ex vivo magnetic resonance imaging were conducted on day 3 or 14 to assess lesion characteristics and lipidomic analysis on day 1. Series 1 (LAU-0901 + NPD1, 14d), Series 2 (LAU-0901 + AT-NPD1, 3d), and Series 3 (LAU-0901 + DHA, 1d). RESULTS: All combinatory groups improved behavior compared to NPD1, AT-NPD1, or DHA treatments alone. Total lesion volumes were reduced with LAU-0901 + NPD1 by 62% and LAU-0901 + AT-NPD1 by 90% treatments versus vehicle groups. LAU-0901 and LAU-0901 + DHA increased the production of vasoactive lipid mediators (prostaglandins: PGE2, PGF2-α, 6-keto-PGF1-α, and PGD2) as well an inflammatory regulating mediator hydroxyoctadecadienoic acid. In contrast, LAU-0901 and LAU-0901 + DHA decreased the production of 12-hydroxyeicosatetraenoic acid, a pro-inflammatory mediator. CONCLUSION: Combination therapy with LAU-0901 and selected docosanoids is more effective than the single therapy, affording synergistic neuroprotection, with restored pro-homeostatic lipid mediators and improved neurological recovery. Altogether, our findings support the combinatory therapy as the basis for future therapeutics for ischemic stroke. [ABSTRACT FROM AUTHOR]

Published
2020
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36. The MAL-ED Cohort Study: Methods and Lessons Learned When Assessing Early Child Development and Caregiving Mediators in Infants and Young Children in 8 Low- and Middle-Income Countries.

Author

Murray-Kolb, Laura E., Rasmussen, Zeba A., Scharf, Rebecca J., Rasheed, Muneera A., Svensen, Erling, Seidman, Jessica C., Tofail, Fahmida, Koshy, Beena, Shrestha, Rita, Maphula, Angelina, Vasquez, Angel Orbe, da Costa, Hilda P., Yousafzai, Aisha K., Oria, Reinaldo B., Roshan, Reeba, Bayyo, Eliwasa B., Kosek, Margaret, Shrestha, Sanjaya, Schaefer, Barbara A., and Bessong, Pascal

Subjects
CHILD development, CHILD psychology, JUVENILE diseases, ETIOLOGY of diseases, MALNUTRITION, PSYCHOLOGY
Abstract

More epidemiological data are needed on risk and protective factors for child development. In The Etiology, Risk Factors and Interactions of Enteric Infections and Malnutrition and the Consequences for Child Health and Development (MAL-ED) cohort study, we assessed child development in a harmonious manner across 8 sites in Bangladesh, Brazil, India, Nepal, Pakistan, Peru, South Africa, and Tanzania. From birth to 24 months, development and language acquisition were assessed via the Bayley Scales of Infant and Toddler Development and a modified MacArthur Communicative Development Inventory. Other measures were infant temperament, the child's environment, maternal psychological adjustment, and maternal reasoning abilities. We developed standard operating procedures and used multiple techniques to ensure appropriate adaptation and quality assurance across the sites. Test adaptation required significant time and human resources but is essential for data quality; funders should support this step in future studies. At the end of this study, we will have a portfolio of culturally adapted instruments for child development studies with examination of psychometric properties of each tool used. [ABSTRACT FROM AUTHOR]

Published
2014

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