Selectively compromised inner retina function following hypoxic-ischemic encephalopathy in mice: A noninvasive measure of severity of the injury. (February 2023)

• Record Type: Journal Article
• Authors: Taparli, Onur E.; Shahi, Pawan K.; Cagatay, Nur Sena; Aycan, Nur; Ozaydin, Burak; Yapici, Sefer; Liu, Xinying; Cikla, Ulas; Zafer, Dila; Eickhoff, Jens C.; Ferrazzano, Peter; Pattnaik, Bikash R.; Cengiz, Pelin
• Is Part Of: Neurochemistry international. Volume 163(2023)
• Publication Date: 2023-02
• Subjects: Electroretinogram (ERG) -- Hypoxia-ischemia (HI) -- Brain-derived neurotrophic factor (BDNF) -- Tyrosine receptor kinase B (TrkB) -- 7, 8-Dihydroxyflavone (7, 8-DHF); Neurochemistry -- Periodicals; Neurochemistry -- Periodicals; Neurochimie -- Périodiques; Neurochemistry; Periodicals; 612.804205
• DOI: 10.1016/j.neuint.2022.105471
• Languages: English
• ISSNs: 0197-0186

Abstract

Abstract: The intricate system of connections between the eye and the brain implies that there are common pathways for the eye and brain that get activated following injury. Hypoxia-ischemia (HI) related encephalopathy is a consequence of brain injury caused by oxygen and blood flow deprivation that may result in visual disturbances and neurodevelopmental disorders in surviving neonates. We have previously shown that the tyrosine receptor kinase B (TrkB) agonist/modulator improves neuronal survival and long-term neuroprotection in a sexually differential way. In this study, we tested the hypotheses that; 1) TrkB agonist therapy improves the visual function in a sexually differential way; 2) Visual function detected by electroretinogram (ERG) correlates with severity of brain injury detected by magnetic resonance (MRI) imaging following neonatal HI in mice. To test our hypotheses, we used C57/BL6 mice at postnatal day (P) 9 and subjected them to either Vannucci's rodent model of neonatal HI or sham surgery. ERG was performed at P 30, 60, and 90. MRI was performed following the completion of the ERG. ERG in these mice showed that the a-wave is normal, but the b-wave amplitude is severely abnormal, reducing the b/a wave amplitude ratio. Inner retina function was found to be perturbed as we detected severely attenuated oscillatory potential after HI. No sex differences were detected in the injury and severity pattern to the retina as well as in response to 7, 8-DHF therapy. Strong correlations were detected between the percent change in b/a ratio and percent hemispheric/hippocampal tissue loss obtained by MRI, suggesting that ERG is a valuable noninvasive tool that can predict the long-term severity of brain injury. Highlights: Neonatal hypoxia-ischemia (HI) results in severe inner retina function in mice. The loss of inner retinal function detected post-HI in mice is sex-independent. A mild protective effect of TrkB agonist/modulator therapy on inner retina functions was found. ERG can be a non-invasive assessment method for predicting long-term imaging outcomes.