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

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.

Comparison of Cortical and Cutaneous Vascular Hemodynamic Changes in Hypoxia by Usingin VivoSkull and Skin Optical Clearing Techniques

“…Similar with other study, the cerebral blood oxygen decreased during the hypoxia [53]. Besides, our results showed that the cortical arteriovenous blood flow also decreased after hypoxia, which was consistent with René Schiffner et al's findings [54]. Ashley D. Harris' research found that across the grey matter, cerebral blood flow increased by approximately 15% over the course of hypoxia [55].…”

“…Ashley D. Harris' research found that across the grey matter, cerebral blood flow increased by approximately 15% over the course of hypoxia [55]. But the latest study reported that the subcortical blood flow increased, whereas the cortical blood flow decreased in comparison to baseline values during hypoxia [54]. These findings suggest that there may be differences in cerebral blood flow response in different brain regions to hypoxia.…”