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Cellular recovery after prolonged warm ischaemia of the whole body.

ABSTRACT: After cessation of blood flow or similar ischaemic exposures, deleterious molecular cascades commence in mammalian cells, eventually leading to their death^1,2. Yet with targeted interventions, these processes can be mitigated or reversed, even minutes or hours post mortem, as also reported in the isolated porcine brain using BrainEx technology³. To date, translating single-organ interventions to intact, whole-body applications remains hampered by circulatory and multisystem physiological challenges. Here we describe OrganEx, an adaptation of the BrainEx extracorporeal pulsatile-perfusion system and cytoprotective perfusate for porcine whole-body settings. After 1 h of warm ischaemia, OrganEx application preserved tissue integrity, decreased cell death and restored selected molecular and cellular processes across multiple vital organs. Commensurately, single-nucleus transcriptomic analysis revealed organ- and cell-type-specific gene expression patterns that are reflective of specific molecular and cellular repair processes. Our analysis comprises a comprehensive resource of cell-type-specific changes during defined ischaemic intervals and perfusion interventions spanning multiple organs, and it reveals an underappreciated potential for cellular recovery after prolonged whole-body warm ischaemia in a large mammal.

SUBMITTER: Andrijevic D

PROVIDER: S-EPMC9518831 | biostudies-literature | 2022 Aug

REPOSITORIES: biostudies-literature

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Cellular recovery after prolonged warm ischaemia of the whole body.

Andrijevic David D Vrselja Zvonimir Z Lysyy Taras T Zhang Shupei S Skarica Mario M Spajic Ana A Dellal David D Thorn Stephanie L SL Duckrow Robert B RB Ma Shaojie S Duy Phan Q PQ Isiktas Atagun U AU Liang Dan D Li Mingfeng M Kim Suel-Kee SK Daniele Stefano G SG Banu Khadija K Perincheri Sudhir S Menon Madhav C MC Huttner Anita A Sheth Kevin N KN Gobeske Kevin T KT Tietjen Gregory T GT Zaveri Hitten P HP Latham Stephen R SR Sinusas Albert J AJ Sestan Nenad N

Nature 20220803 7922

After cessation of blood flow or similar ischaemic exposures, deleterious molecular cascades commence in mammalian cells, eventually leading to their death<sup>1,2</sup>. Yet with targeted interventions, these processes can be mitigated or reversed, even minutes or hours post mortem, as also reported in the isolated porcine brain using BrainEx technology<sup>3</sup>. To date, translating single-organ interventions to intact, whole-body applications remains hampered by circulatory and multisystem ...[more]

PMID: 35922506

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Project description:Although exercise is usually associated with beneficial effects on physical and mental health, patients recovering from surgery may be hampered to perform active exercise. Whole body vibration (WBV) is suggested a passive alternative for physical training. Aim of the present study was to explore the therapeutic potential of WBV compared to physical exercise during early post-surgery recovery. Male three months old Wistar rats underwent major abdominal surgery. Starting the day after surgery, rats were subjected to either daily WBV or exercise (treadmill running) for 15 consecutive days. Control rats underwent pseudo treatment. During the first week after surgery, effects of interventions were obtained from continuous recording of hemodynamic parameters, body temperature and activity (via an implanted transducer). Behavioral tests were performed during the second post-surgical week to evaluate anxiety-like behavior, short and long-term memory functions, cognitive flexibility and motor performance. Animals were sacrificed 15 days after surgery and brain tissue was collected for analysis of hippocampal neuroinflammation and neurogenesis. Surgery significantly impacted all parameters measured during the first post-surgery week, irrespective of the type of surgery. Effect on cognitive performance was limited to cognitive flexibility; both WBV and exercise prevented the surgery-induced decline. Exercise, but not WBV increased anxiety-like behavior and grip strength. WBV as well as exercise prevented the surgery-induced declined neurogenesis, but surgery-associated hippocampal neuroinflammation was not affected. Our results indicated that active exercise and WBV share similar therapeutic potentials in the prevention of surgery induced decline in cognitive flexibility and hippocampal neurogenesis. In contrast to exercise, WBV did not increase anxiety-like behavior. Since neither intervention affected hippocampal neuroinflammation, other mechanisms and/or brain areas may be involved in the behavioral effects. Taken together, we conclude that WBV may provide a relevant alternative to active exercise during the early stage of post-operative recovery.

Dataset Information

Cellular recovery after prolonged warm ischaemia of the whole body.

Publications

Cellular recovery after prolonged warm ischaemia of the whole body.

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