Altered Cerebral Blood Flow and Potential Neuroprotective Effect of Human Relaxin-2 (Serelaxin) During Hypoxia or Severe Hypovolemia in a Sheep Model

Schiffner, René; Bischoff, Sabine J.; Lehmann, Thomas; Irintchev, Andrey; Nistor, Marius; Lemke, Cornelius; Schmidt, Martin

doi:10.3390/ijms21051632

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Altered Cerebral Blood Flow and Potential Neuroprotective Effect of Human Relaxin-2 (Serelaxin) During Hypoxia or Severe Hypovolemia in a Sheep Model

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Zentrale Notaufnahme, Otto-von-Guericke University Magdeburg, 39120 Magdeburg, Germany

Orthopedic Department, Jena University Hospital, Friedrich Schiller University, 07743 Jena, Germany

Institute for Laboratory Animal Science and Welfare, Jena University Hospital, Friedrich Schiller University, 07743 Jena, Germany

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Institute of Medical Statistics, Computer Sciences and Documentation Science, Jena University Hospital, Friedrich Schiller University, 07743 Jena, Germany

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Department of Otorhinolaryngology, Jena University Hospital, Friedrich Schiller University, 07747 Jena, Germany

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Institute for Anatomy I, Jena University Hospital, Friedrich Schiller University, 07743 Jena, Germany

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Institute for Biochemistry II, Jena University Hospital, Friedrich Schiller University, 07743 Jena, Germany

Author to whom correspondence should be addressed.

Int. J. Mol. Sci. 2020, 21(5), 1632; https://doi.org/10.3390/ijms21051632

Received: 23 January 2020 / Revised: 21 February 2020 / Accepted: 25 February 2020 / Published: 27 February 2020

(This article belongs to the Collection Neuroprotective Strategies)

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Abstract

Specific neuroprotective strategies to minimize cerebral damage caused by severe hypoxia or hypovolemia are lacking. Based on previous studies showing that relaxin-2/serelaxin increases cortical cerebral blood flow, we postulated that serelaxin might provide a neuroprotective effect. Therefore, we tested serelaxin in two emergency models: hypoxia was induced via inhalation of 5% oxygen and 95% nitrogen for 12 min; thereafter, the animals were reoxygenated. Hypovolemia was induced and maintained for 20 min by removal of 50% of the total blood volume; thereafter, the animals were retransfused. In each damage model, the serelaxin group received an intravenous injection of 30 µg/kg of serelaxin in saline, while control animals received saline only. Blood gases, shock index values, heart frequency, blood pressure, and renal blood flow showed almost no significant differences between control and treatment groups in both settings. However, serelaxin significantly blunted the increase of lactate during hypovolemia. Serelaxin treatment resulted in significantly elevated cortical cerebral blood flow (CBF) in both damage models, compared with the respective control groups. Measurements of the neuroproteins S100B and neuron-specific enolase in cerebrospinal fluid revealed a neuroprotective effect of serelaxin treatment in both hypoxic and hypovolemic animals, whereas in control animals, neuroproteins increased during the experiment. Western blotting showed the expression of relaxin receptors and indicated region-specific differences in relaxin receptor-mediated signaling in cortical and subcortical brain arterioles, respectively. Our findings support the hypothesis that serelaxin is a potential neuroprotectant during hypoxia and hypovolemia. Due to its preferential improvement of cortical CBF, serelaxin might reduce cognitive impairments associated with these emergencies. View Full-Text

Keywords: neuroprotection; cerebral blood flow; relaxin-2; relaxin receptors; sheep model; hypoxia; shock

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Schiffner, R.; Bischoff, S.J.; Lehmann, T.; Irintchev, A.; Nistor, M.; Lemke, C.; Schmidt, M. Altered Cerebral Blood Flow and Potential Neuroprotective Effect of Human Relaxin-2 (Serelaxin) During Hypoxia or Severe Hypovolemia in a Sheep Model. Int. J. Mol. Sci. 2020, 21, 1632. https://doi.org/10.3390/ijms21051632

AMA Style

Schiffner R, Bischoff SJ, Lehmann T, Irintchev A, Nistor M, Lemke C, Schmidt M. Altered Cerebral Blood Flow and Potential Neuroprotective Effect of Human Relaxin-2 (Serelaxin) During Hypoxia or Severe Hypovolemia in a Sheep Model. International Journal of Molecular Sciences. 2020; 21(5):1632. https://doi.org/10.3390/ijms21051632

Chicago/Turabian Style

Schiffner, René, Sabine J. Bischoff, Thomas Lehmann, Andrey Irintchev, Marius Nistor, Cornelius Lemke, and Martin Schmidt. 2020. "Altered Cerebral Blood Flow and Potential Neuroprotective Effect of Human Relaxin-2 (Serelaxin) During Hypoxia or Severe Hypovolemia in a Sheep Model" International Journal of Molecular Sciences 21, no. 5: 1632. https://doi.org/10.3390/ijms21051632

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Altered Cerebral Blood Flow and Potential Neuroprotective Effect of Human Relaxin-2 (Serelaxin) During Hypoxia or Severe Hypovolemia in a Sheep Model

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