Acute Physiology and Neurologic Outcomes after Brain Injury in SCOP/PHLPP1 KO Mice

Abstract Suprachiasmatic nucleus circadian oscillatory protein (SCOP) (a.k.a. PHLPP1) regulates long-term memory consolidation in the brain. Using a mouse model of controlled cortical impact (CCI) we tested if (1) brain tissue levels of SCOP/PHLPP1 increase after a traumatic brain injury (TBI), and...

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Autores principales: Travis C. Jackson, C. Edward Dixon, Keri Janesko-Feldman, Vincent Vagni, Shawn E. Kotermanski, Edwin K. Jackson, Patrick M. Kochanek
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Publicado: Nature Portfolio 2018
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spelling oai:doaj.org-article:5d728bdcc90544d2bf5dd7ed474649772021-12-02T15:08:45ZAcute Physiology and Neurologic Outcomes after Brain Injury in SCOP/PHLPP1 KO Mice10.1038/s41598-018-25371-22045-2322https://doaj.org/article/5d728bdcc90544d2bf5dd7ed474649772018-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-018-25371-2https://doaj.org/toc/2045-2322Abstract Suprachiasmatic nucleus circadian oscillatory protein (SCOP) (a.k.a. PHLPP1) regulates long-term memory consolidation in the brain. Using a mouse model of controlled cortical impact (CCI) we tested if (1) brain tissue levels of SCOP/PHLPP1 increase after a traumatic brain injury (TBI), and (2) if SCOP/PHLPP1 gene knockout (KO) mice have improved (or worse) neurologic outcomes. Blood chemistry (pH, pCO2, pO2, pSO2, base excess, sodium bicarbonate, and osmolarity) and arterial pressure (MAP) differed in isoflurane anesthetized WT vs. KOs at baseline and up to 1 h post-injury. CCI injury increased cortical/hippocampal SCOP/PHLPP1 levels in WTs 7d and 14d post-injury. Injured KOs had higher brain tissue levels of phosphorylated AKT (pAKT) in cortex (14d post-injury), and higher levels of phosphorylated MEK (pMEK) in hippocampus (7d and 14d post-injury) and in cortex (7d post-injury). Consistent with an important role of SCOP/PHLPP1 on memory function, injured-KOs had near normal performance on the probe trial of the Morris water maze, whereas injured-WTs were impaired. CA1/CA3 hippocampal survival was lower in KOs vs. WTs 24 h post-injury but equivalent by 7d. No difference in 21d cortical lesion volume was detected. SCOP/PHLPP1 overexpression in cultured rat cortical neurons had no effect on 24 h cell death after a mechanical stretch-injury.Travis C. JacksonC. Edward DixonKeri Janesko-FeldmanVincent VagniShawn E. KotermanskiEdwin K. JacksonPatrick M. KochanekNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 8, Iss 1, Pp 1-14 (2018)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Travis C. Jackson
C. Edward Dixon
Keri Janesko-Feldman
Vincent Vagni
Shawn E. Kotermanski
Edwin K. Jackson
Patrick M. Kochanek
Acute Physiology and Neurologic Outcomes after Brain Injury in SCOP/PHLPP1 KO Mice
description Abstract Suprachiasmatic nucleus circadian oscillatory protein (SCOP) (a.k.a. PHLPP1) regulates long-term memory consolidation in the brain. Using a mouse model of controlled cortical impact (CCI) we tested if (1) brain tissue levels of SCOP/PHLPP1 increase after a traumatic brain injury (TBI), and (2) if SCOP/PHLPP1 gene knockout (KO) mice have improved (or worse) neurologic outcomes. Blood chemistry (pH, pCO2, pO2, pSO2, base excess, sodium bicarbonate, and osmolarity) and arterial pressure (MAP) differed in isoflurane anesthetized WT vs. KOs at baseline and up to 1 h post-injury. CCI injury increased cortical/hippocampal SCOP/PHLPP1 levels in WTs 7d and 14d post-injury. Injured KOs had higher brain tissue levels of phosphorylated AKT (pAKT) in cortex (14d post-injury), and higher levels of phosphorylated MEK (pMEK) in hippocampus (7d and 14d post-injury) and in cortex (7d post-injury). Consistent with an important role of SCOP/PHLPP1 on memory function, injured-KOs had near normal performance on the probe trial of the Morris water maze, whereas injured-WTs were impaired. CA1/CA3 hippocampal survival was lower in KOs vs. WTs 24 h post-injury but equivalent by 7d. No difference in 21d cortical lesion volume was detected. SCOP/PHLPP1 overexpression in cultured rat cortical neurons had no effect on 24 h cell death after a mechanical stretch-injury.
format article
author Travis C. Jackson
C. Edward Dixon
Keri Janesko-Feldman
Vincent Vagni
Shawn E. Kotermanski
Edwin K. Jackson
Patrick M. Kochanek
author_facet Travis C. Jackson
C. Edward Dixon
Keri Janesko-Feldman
Vincent Vagni
Shawn E. Kotermanski
Edwin K. Jackson
Patrick M. Kochanek
author_sort Travis C. Jackson
title Acute Physiology and Neurologic Outcomes after Brain Injury in SCOP/PHLPP1 KO Mice
title_short Acute Physiology and Neurologic Outcomes after Brain Injury in SCOP/PHLPP1 KO Mice
title_full Acute Physiology and Neurologic Outcomes after Brain Injury in SCOP/PHLPP1 KO Mice
title_fullStr Acute Physiology and Neurologic Outcomes after Brain Injury in SCOP/PHLPP1 KO Mice
title_full_unstemmed Acute Physiology and Neurologic Outcomes after Brain Injury in SCOP/PHLPP1 KO Mice
title_sort acute physiology and neurologic outcomes after brain injury in scop/phlpp1 ko mice
publisher Nature Portfolio
publishDate 2018
url https://doaj.org/article/5d728bdcc90544d2bf5dd7ed47464977
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