Low oxygen in inspired air causes severe cerebrocortical hypoxia and cell death in the cerebral cortex of awake rats

• Published in: Neuroscience letters Vol. 818; p. 137515
• Main Authors: Barakat, Rawan M., Turcani, Marian, Al-Khaledi, Ghanim, Kilarkaje, Narayana, Al-Sarraf, Hameed, Sayed, Zeinab, Redzic, Zoran
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier B.V 01.01.2024
• Subjects: Cell death; Cerebral blood flow; Cerebral cortex; Hypoxia; Lactate; Type 1 respiratory failure; Hypoxia; Cerebral cortex; Lactate; Cell death; Cerebral blood flow; Type 1 respiratory failure
• ISSN: 0304-3940; 1872-7972
• DOI: 10.1016/j.neulet.2023.137515

•Low inspired partial pressure of oxygen (PiO2) (7.5–8 % O2) for 48 h was used to mimick conditions that occur during severe type 1 respiratory failure.•During these conditions hypoxia and massive cell death occurred in the cerebral cortices of conscious, freely moving rats.•Surprisingly, these conditions did not change blood flow in the pial vessels during 48 h. Type 1 respiratory failure (T1RF) is associated with secondary acute brain injury (sABI). The underlying mechanisms of sABI could include injury to brain cells mediated either by hypoxia or by lung injury-triggered inflammation. To elucidate to what extent T1RF causes hypoxia and a consequent hypoxic injury in the brain in the absence of lung injury, we exposed healthy, conscious Sprague-Dawley rats to 48 h long low partial pressure of O2 in inspired air (PiO2) (7.5–8 % O2 in N2, CO2 < 0.5 %, normal barometric pressure) and measured the partial pressure of oxygen in the premotor cortex (PtO2), cerebral blood flow (CBF), lactate concentrations, and cell death. Low PiO2 significantly affected PtO2, which was 52.3 (SD 2.1) mmHg when PiO2 was normal but declined to 6.4 (SD 3.8) mmHg when PiO2 was low for 1 h. This was accompanied by increased lactate concentrations in plasma, CSF, and premotor cortex. Low PiO2 elevated the number of dead cells in the cerebral cortex from 5.6 (SD 4.8) % (when PiO2 was normal) to 20.5 (SD 4.1) % and 32.37 (SD 6.5) % after 24 h and 48 h exposure to low PiO2, respectively. The Mann-Kendall test could not detect any monotonic increase or decrease in pial blood flow during the 48 h exposure to low PiO2. In summary, our findings suggest that exposure to low PiO2 caused a severe hypoxia in the cerebral cortex, which triggers a massive cell death. Since these conditions mimic T1RF, hypoxic injury could be an important underlying cause of T1RF-induced sABI.