Altered hypoxic and hypercapnic ventilatory response following neonatal chronic intermittent hypoxia is associated with changes in serum and brainstem neuroglobin levels

Neuroglobin is an oxygen binding heme protein abundantly expressed in neurons (Burmeister et al.2000). It is thought to be neuroprotective, and involved in hypoxia mediated intracellular signaling (Fago et al 2006). It has been shown to have altered expression in adult rats in response to hypoxic-ischemic insults (Sun et al 2001) as well as sustained and chronic intermittent hypoxia (CIH) (Li et al 2006). Prenatal infants frequently experience apnea of prematurity, and undergo frequent hypoxic episodes. Additionally, the hypoxic ventilatory response (HVR) is increased in preterm infants that experience frequent hypoxic episodes (Nock et el 2004). We therefore hypothesized that CIH exposure would increase HVR and alter neuroglobin expression in neonatal rat pups. Neonatal Sprague Dawley rat pups were exposed to CIH (5% 02 at 5min intervals, 24 hrs per day) for the first 10 days of life. Age matched, normoxic (NX) reared pups were used as control. Plethysmography was then performed on postnatal day (P)11 to assess HVR and the hypercapnic ventilatory response (HCVR), and serum and brain samples harvested to assess neuroglobin expression via ELISA. Ten days of CIH resulted in an increased HVR on postnatal day 11, whereas the HCVR was not affected. Neuroglobin was undetected in the serum of NX rats, but was increased following CIH (0.00ng/ml NX vs 0.31ng/ml, CIH). The augmented HVR was associated with decreased brainstem (0.0046ng/ug, NX vs 0.0020ng/ug, CIH) neuroglobin levels. Neuroglobin remained unchanged in the cerebellum and hippocampus. The augmented HVR following CIH is consistent with other studies, but corresponding decreased brainstem neuroglobin levels could be an indicator of disrupted neuroprotection. It is unclear why CIH affects neuroglobin uniquely in the brainstem, but this may have significant implications for respiratory control abnormalities associated with prematurity. We believe that elevated serum neuroglobin levels could be an important biomarker of apnea and IH in preterm infants. Funding: NIH-5R01HD111415 to Peter M. MacFarlane This abstract was presented at the American Physiology Summit 2026 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.