Migraine inhibitor olcegepant reduces weight loss and IL-6 release in SARS-CoV-2 infected older mice with neurological signs

Abstract

COVID-19 can result in neurological symptoms such as fever, headache, dizziness, and nausea. We evaluated whether the Calcitonin Gene-Related Peptide (CGRP) receptor antagonist, olcegepant, used in migraine treatment could mitigate acute neuroinflammatory and neurological responses to SARS-COV-2 infection. We infected wildtype C57BL/6J and 129/SvEv mice, and a 129 αCGRP-null mouse line with a mouse-adapted SARS-CoV-2 virus, and evaluated the effect of CGRP receptor antagonism on the outcome of that infection. We determined that CGRP receptor antagonism provided protection from permanent weight loss in older (>12 m) C57BL/6J and 129 SvEv mice. We also observed acute fever and motion-induced dizziness in all older mice, regardless of treatment. However, in both wildtype mouse lines, CGRP antagonism reduced acute interleukin 6 (IL-6) levels by half, with virtually no IL-6 release in mice lacking αCGRP. These findings suggest that blockage of CGRP signaling protects against acute IL-6 release and subsequent inflammatory events after SARS-CoV-2 infection.

Effects of perioperative low-dose naloxone on the immune system in patients undergoing laparoscopic assisted total gastrectomy: a randomized controlled trial

“…It can regulate the metabolism of calcium and phosphorus in the body and participate in the balance of calcium and phosphorus in the body. High levels of calcitonin may be caused by diseases such as medullary thyroid cancer, small cell lung cancer, and medullary thyroid cancer, as well as by bacterial or fungal infections, allergies, and other reasons [30].Our research results indicate that the 2 groups showed a signi cant increase in IL-6(P < 0.01)(Table 4) and Calcitonin(P < 0.01)(Table 4) at 24 h after surgery, 96 h after surgery(P < 0.01)(Table 4) and 144 h after surgery.The levels of IL-6(P < 0.05)(Table 4)and Calcitonin in the Non-naloxone group were signi cantly higher at 24 h after surgery in Table 4.These results indicate that perioperative naloxone use can delay the rise rate of IL-6 and calcitonin in postoperative gastric cancer patients.…”

Loss of calcitonin gene-related peptide (αCGRP) and use of a vestibular challenge highlight balance deficiencies in aging mice

“…CGRP’s role in inflammation, pain transmission, and in evoking sensory hypersensitivities has supported therapeutic efforts to block CGRP signaling for migraine [ 58 ] and COVID therapy [ 59 ]. Yet others have found CGRP to act as a neuromodulator with neuroprotective effects [ 60 ].…”