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Sci Rep. 2018 May 8;8(1):7158. doi: 10.1038/s41598-018-25371-2.

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

Author information

1
University of Pittsburgh School of Medicine, Safar Center for Resuscitation Research, Children's Hospital of Pittsburgh of UPMC, John G. Rangos Research Center - 6th Floor 4401 Penn Avenue, Pittsburgh, PA, 15224, USA. jacksontc@upmc.edu.
2
University of Pittsburgh School of Medicine, Department of Critical Care Medicine, Scaife Hall, 3550 Terrace Street, Pittsburgh, USA. jacksontc@upmc.edu.
3
University of Pittsburgh School of Medicine, Safar Center for Resuscitation Research, Children's Hospital of Pittsburgh of UPMC, John G. Rangos Research Center - 6th Floor 4401 Penn Avenue, Pittsburgh, PA, 15224, USA.
4
University of Pittsburgh School of Medicine, Department of Neurology, 811 Kaufmann Medical Building, 3471 Fifth Avenue, Pittsburgh, USA.
5
University of Pittsburgh School of Medicine, Department of Critical Care Medicine, Scaife Hall, 3550 Terrace Street, Pittsburgh, USA.
6
University of Pittsburgh School of Medicine, Department of Pharmacology and Chemical Biology, Bridgeside Point Building 1, 100 Technology Drive, Pittsburgh, USA.

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.

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