The duration of hypothermia affects short-term neuroprotection in a mouse model of neonatal hypoxic ischaemic injury
Autor: | Rocha-Ferreira, Eridan, Vincent, Amy, Bright, Sarah, Peebles, Donald M., Hristova, Mariya |
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Jazyk: | angličtina |
Rok vydání: | 2018 |
Předmět: |
Male
Integrins Time Factors Physiology Science Mouse Models Hypothermia Pathology and Laboratory Medicine Research and Analysis Methods Hippocampus Body Temperature Mice Signs and Symptoms Model Organisms Diagnostic Medicine Hypothermia Induced Medicine and Health Sciences Cell Adhesion Animals Brain Damage Cell Death Behavior Animal Biology and Life Sciences Brain Animal Models Cell Biology Neuroprotection Extracellular Matrix Neostriatum Mice Inbred C57BL Disease Models Animal Neuroprotective Agents Neurology Experimental Organism Systems Physiological Parameters Animals Newborn Cell Processes Hypoxia-Ischemia Brain Medicine Female Cellular Structures and Organelles Anatomy Research Article |
Zdroj: | PLoS ONE PLoS ONE, Vol 13, Iss 7, p e0199890 (2018) |
ISSN: | 1932-6203 |
Popis: | Neonatal hypoxic-ischaemic encephalopathy (HIE) is major cause of neonatal mortality and morbidity. Therapeutic hypothermia is standard clinical care for moderate hypoxic-ischaemic (HI) brain injury, however it reduces the risk of death and disability only by 11% and 40% of the treated infants still develop disabilities. Thus it is necessary to develop supplementary therapies to complement therapeutic hypothermia in the treatment of neonatal HIE. The modified Rice-Vannucci model of HI in the neonatal mouse is well developed and widely applied with different periods of hypothermia used as neuroprotective strategy in combination with other agents. However, different studies use different periods, time of initiation and duration of hypothermia following HI, with subsequent varying degrees of neuroprotection. So far most rodent data is obtained using exposure to 5-6h of therapeutic hypothermia. Our aim was to compare the effect of exposure to three different short periods of hypothermia (1h, 1.5h and 2h) following HI insult in the postnatal day 7 C57/Bl6 mouse, and to determine the shortest period providing neuroprotection. Our data suggests that 1h and 1.5h of hypothermia delayed by 20min following a 60min exposure to 8%O2 do not prove neuroprotective. However, 2h of hypothermia significantly reduced tissue loss, TUNEL+ cell death and microglia and astroglia activation. We also observed improved functional outcome 7 days after HI. We suggest that the minimal period of cooling necessary to provide moderate short term neuroprotection and appropriate for the development and testing of combined treatment is 2h. |
Databáze: | OpenAIRE |
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