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

Onur E Taparli; Pawan K Shahi; Nur Sena Cagatay; Nur Aycan; Burak Ozaydin; Sefer Yapici; Xinying Liu; Ulas Cikla; Dila Zafer; Jens C Eickhoff; Peter Ferrazzano; Bikash R Pattnaik; Pelin Cengiz

doi:10.1016/j.neuint.2022.105471

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

Neurochem Int. 2023 Feb:163:105471. doi: 10.1016/j.neuint.2022.105471. Epub 2022 Dec 30.

Authors

Affiliations

¹ Department of Pediatrics, University of Wisconsin-Madison, WI, USA; Department of Waisman Center, University of Wisconsin-Madison, WI, USA.
² Department of Pediatrics, University of Wisconsin-Madison, WI, USA; McPherson Eye Research Institute, University of Wisconsin-Madison, WI, USA.
³ Department of Pediatrics, University of Wisconsin-Madison, WI, USA.
⁴ Department of Neurological Surgery, University of Wisconsin-Madison, WI, USA.
⁵ Department of Pediatrics, University of Wisconsin-Madison, WI, USA; Department of Neurological Surgery, University of Wisconsin-Madison, WI, USA.
⁶ Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, WI, USA.
⁷ Department of Pediatrics, University of Wisconsin-Madison, WI, USA; McPherson Eye Research Institute, University of Wisconsin-Madison, WI, USA; Department of Ophthalmology and Visual Sciences, University of Wisconsin-Madison, WI, USA. Electronic address: bikashp@pediatrics.wisc.edu.
⁸ Department of Pediatrics, University of Wisconsin-Madison, WI, USA; Department of Waisman Center, University of Wisconsin-Madison, WI, USA. Electronic address: cengiz@pediatrics.wisc.edu.

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.

Keywords: 7,8-Dihydroxyflavone (7,8-DHF); Brain-derived neurotrophic factor (BDNF); Electroretinogram (ERG); Hypoxia-ischemia (HI); Tyrosine receptor kinase B (TrkB).

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Animals
Animals, Newborn
Brain Injuries* / pathology
Hypoxia
Hypoxia-Ischemia, Brain* / metabolism
Ischemia / pathology
Mice
Retina / metabolism

Abstract

Publication types

MeSH terms

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