C Mari1, F K Odorcyk2, E F Sanches3, K M Wartchow4, A P Martini5, F Nicola5, C Zanotto3, A T Wyse6, C A Gonçalves6, C A Netto6. 1. Post-graduation Program of Neuroscience, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. 2. Post-graduation Program of Physiology, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Post-graduation Program of Biochemistry, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. Electronic address: felipe.odorcyk@gmail.com. 3. Department of Biochemistry, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. 4. Post-graduation Program of Physiology, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Post-graduation Program of Biochemistry, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Department of Biochemistry, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. 5. Post-graduation Program of Neuroscience, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Department of Biochemistry, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. 6. Post-graduation Program of Neuroscience, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Post-graduation Program of Physiology, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Post-graduation Program of Biochemistry, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Department of Biochemistry, Instituto de Ciências Básicas da Saúde (ICBS), Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil.
Abstract
INTRODUCTION: Perinatal hypoxia-ischemia (HI) is one of the main causes of mortality and chronic neurological morbidity in infants and children. Astrocytes play a key role in HI progression, becoming reactive in response to the injury, releasing S100 calcium binding protein B (S100B). Since S100B inhibition seems to have neuroprotective effects on central nervous system injury models, here we evaluated the neuroprotective effects of an S100B inhibitor, arundic acid (AA) in a HI model. METHODS: On the 7th postnatal day, animals were submitted to the combination of common carotid artery occlusion and hypoxic atmosphere (8% O2) for 60 min. Three experiments were performed in order to: (1) define AA dose (0.1, 1 or 10 mg/kg, pre-hypoxia i.p. injection), (2) test if repeated AA administrations (10 mg/kg at 3 time points: Pre-hypoxia, 24 h and 48 h after HI) would improve the response and (3) investigate biochemical mechanisms involved in AA protection two days after HI. RESULTS: AA at a dose of 10 mg/kg applied before and after hypoxia, was the only treatment protocol that was able to improve HI-induced memory deficits, to reduce tissue damage, to promote astrocytic survival in the hippocampus and to reduced extracellular release of S100B in the cerebrospinal fluid. CONCLUSION: Overall, AA treatment showed beneficial effects on memory deficits, tissue damage, promoting astrocyte survival likely by reducing S100B release. Protection aided to astrocytes by AA treatment against HI lesion may lead to development of new therapeutic strategies that target these particular cells.
INTRODUCTION: Perinatal hypoxia-ischemia (HI) is one of the main causes of mortality and chronic neurological morbidity in infants and children. Astrocytes play a key role in HI progression, becoming reactive in response to the injury, releasing S100 calcium binding protein B (S100B). Since S100B inhibition seems to have neuroprotective effects on central nervous system injury models, here we evaluated the neuroprotective effects of an S100B inhibitor, arundic acid (AA) in a HI model. METHODS: On the 7th postnatal day, animals were submitted to the combination of common carotid artery occlusion and hypoxic atmosphere (8% O2) for 60 min. Three experiments were performed in order to: (1) define AA dose (0.1, 1 or 10 mg/kg, pre-hypoxia i.p. injection), (2) test if repeated AA administrations (10 mg/kg at 3 time points: Pre-hypoxia, 24 h and 48 h after HI) would improve the response and (3) investigate biochemical mechanisms involved in AA protection two days after HI. RESULTS: AA at a dose of 10 mg/kg applied before and after hypoxia, was the only treatment protocol that was able to improve HI-induced memory deficits, to reduce tissue damage, to promote astrocytic survival in the hippocampus and to reduced extracellular release of S100B in the cerebrospinal fluid. CONCLUSION: Overall, AA treatment showed beneficial effects on memory deficits, tissue damage, promoting astrocyte survival likely by reducing S100B release. Protection aided to astrocytes by AA treatment against HI lesion may lead to development of new therapeutic strategies that target these particular cells.
Authors: Daan R M G Ophelders; Ruth Gussenhoven; Luise Klein; Reint K Jellema; Rob J J Westerlaken; Matthias C Hütten; Jeroen Vermeulen; Guido Wassink; Alistair J Gunn; Tim G A M Wolfs Journal: Cells Date: 2020-08-10 Impact factor: 6.600
Authors: Chiara Camponeschi; Maria De Carluccio; Susanna Amadio; Maria Elisabetta Clementi; Beatrice Sampaolese; Cinzia Volonté; Maria Tredicine; Vincenzo Romano Spica; Rosa Di Liddo; Francesco Ria; Fabrizio Michetti; Gabriele Di Sante Journal: Int J Mol Sci Date: 2021-12-17 Impact factor: 5.923