AUTHOR=Qiu Han , Qian Tianyang , Wu Tong , Gao Ting , Xing Qinghe , Wang Laishuan 

TITLE=Src Family Kinases Inhibition Ameliorates Hypoxic-Ischemic Brain Injury in Immature Rats

JOURNAL=Frontiers in Cellular Neuroscience

VOLUME=Volume 15 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/cellular-neuroscience/articles/10.3389/fncel.2021.746130

DOI=10.3389/fncel.2021.746130

ISSN=1662-5102

ABSTRACT=Hypoxic-ischemic (HI) injury is one of the initial factors contributing to neonatal brain injury. Src family kinases (SFKs) are considered to act as molecular hubs for N-methyl-D-aspartate receptor (NMDAR) regulation and participate in the HI injury process. The objectives of the present study were to evaluate the levels of phospho-Src, the relationship between NMDARs and SFKs, and the effects of SFK inhibition on an immature rat HI brain injury model. The model was induced in three-day-old Sprague–Dawley rats using the Rice-Vannucci model operation. The level of phospho-Src was evaluated using western blotting. The association of NMDARs with SFKs was detected using western blotting and coimmunoprecipitation. After intraperitoneal injection of PP2, an SFK-selective inhibitor, neuropathological changes were observed by performing H-E and immunofluorescence staining, and the neurological functions were assessed using the following behavioral tests: modified neurological severity score (mNSS), open field test, and Morris water maze test. Levels of phospho-Src first decreased at 0 h after injury, increased at 2 h after injury, and continuously decreased from 6 h to 3 d. Along with the increased phospho-Src levels observed at 2 h after injury, the phosphorylation of NMDAR subunit NR2B at tyrosine 1472 was increased. Following the administration of PP2, the increased phospho-Src and NMDAR-2B levels detected at 2 h after injury were decreased, and tissue injury and myelin basic protein expression were improved at 7 days after injury. The PP2 intervention improved the performance of injured rats on behavioral tests. In conclusion, we determined the patterns of phospho-Src expression after HI brain injury in immature rats and showed a relationship with the activated NMDA receptor. Inhibition of phospho-Src ameliorates neuropathological changes and damaged neurological functions induced by HI injury.