Normobaric oxygen treatment improves neuronal survival functional recovery and axonal plasticity after newborn hypoxia-ischemia

• Published in: Behavioural brain research Vol. 379; p. 112338
• Main Authors: Kelestemur, Taha, Beker, Mustafa C., Caglayan, Ahmet B., Caglayan, Berrak, Altunay, Serdar, Kutlu, Selim, Kilic, Ertugrul
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 03-02-2020
• Subjects: Animals; Animals, Newborn; Behavior, Animal - physiology; Cell Survival - physiology; Disease Models, Animal; Functional Recovery; Humans; Hypoxia-Ischemia, Brain - metabolism; Hypoxia-Ischemia, Brain - therapy; Infant, Newborn; Infant, Newborn, Diseases - therapy; Matrix Metalloproteinase 9 - metabolism; MMP-9; Motor Activity - physiology; Neuronal Plasticity - physiology; Neurons - physiology; Newborn Hypoxia Ischemia; Normobaric Oxygen; Oxygen Inhalation Therapy - methods; Plasticity; PTEN; PTEN Phosphohydrolase - metabolism; Rats; Rats, Sprague-Dawley; Recovery of Function - physiology; Spatial Learning - physiology; PTEN; Newborn Hypoxia Ischemia; MMP-9; Functional Recovery; Normobaric Oxygen; Plasticity
• ISSN: 0166-4328; 1872-7549
• DOI: 10.1016/j.bbr.2019.112338

•NBO is an easy-to-access strategy that allows to enhance tissue re-oxygenation even in the hands of paramedics.•Hyperoxia promotes axonal reorganization, which was revealed for the first time after newborn HI.•Different dose of NBO were compared in the context of cell survival and functional recovery.•Hyperoxic NBO reduces infarct development and promotes neuronal survival.•NBO is a promising approach for the treatment of newborn HI, which encourage proof-of-concept studies in newborn.
Newborn hypoxia ischemia (HI) is one of the most prevalent cases in the emergency and can result from fetal hypoxia during delivery. In HI, restricted blood supply to the fetal brain may cause epilepsy or mental disorders.
In the present study, seven-day-old pups were subjected HI and treated with different normobaric oxygen (NBO) concentrations (21%, 70% or 100%). In the acute phase, we analyzed infarct area, disseminate neuronal injury and surviving neurons. In addition, we studied the regulation of PTEN and MMP-9 proteins which were suggested to be activated by HI in the ischemic tissue. Moreover, long-term effects of NBO treatments were evaluated with open field, rotarod and Barnes maze tests. We also examined axonal plasticity with EGFP-AAV injection.
Here, we demonstrate that hyperoxic NBO concentration causes an increase in cellular survival and a decrease in the number of apoptotic cells, meanwhile inhibiting the proteins involved in cellular death mechanisms. Moreover, we found that hyperoxia decreases anxiety, promotes motor coordination and improve spatial learning and memory. Notably that axonal sprouting was promoted by hyperoxia.
Our data suggest that NBO is a promising approach for the treatment of newborn HI, which encourage proof-of-concept studies in newborn.