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Real-time Monitoring of Hypoxic-Ischemic Brain Damage in Neonatal Rats Using Diffuse Light Reflectance Spectroscopy

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Abstract

Obstetric management to prevent hypoxic ischemic encephalopathy (HIE) during labor is important to reduce the cerebral palsy incidence in neonates. A novel approach to monitor or predict fetal brain damage during labor is required. Diffuse reflectance spectroscopy is a noninvasive method routinely used to assess the intrinsic characteristics of tissues. This study investigated the time course of diffuse reflectance signals during an early stage of cerebral cortical damage in a neonatal rat HIE model (Vannucci’s model). In the model, an HIE lesion was induced by hypoxic exposure following ligation of the left common carotid artery. Using this model, we established an experimental system to detect diffuse light reflectance signals at time points of interest. Quantitative monitoring of total hemoglobin, oxygen saturation, and scattering amplitude was conducted to examine the basis of the diffused reflectance signals. During hypoxic exposure, which induced HIE damage in the left hemisphere after ligation, the oxygen saturation level decreased, but the difference between the two hemispheres was relatively small. During this period, total hemoglobin was increased in both hemispheres, but the change in the left hemisphere was significantly greater than that in the right, which is attributable to a vigorous compensation response. During hypoxia, scattering amplitude, which reflects cellular/subcellular morphology, revealed a remarkable difference between the two hemispheres. We confirmed that scattering amplitude levels negatively correlated with the extent of edema. These findings suggest that simultaneous monitoring of the scattering amplitude, in addition to hemodynamic parameters, is useful for detecting brain tissue alterations leading to HIE.

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Acknowledgments

We thank Mai Miyaki and Keiichiro Yoshida for technical assistance and optical data analysis.

Funding

This work was supported by JSPS KAKENHI (Grant Number 15K15595).

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Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo, 113-0033, Japan

    Sakiko Kinoshita, Takeshi Nagamatsu & Tomoyuki Fujii

  2. Division of Biomedical Information Sciences, National Defense Medical College Research Institute, Saitama, Japan

    Satoko Kawauchi & Shunichi Sato

  3. Graduate School of Bio-Application and Systems Engineering, Tokyo University of Agriculture and Technology, Tokyo, Japan

    Izumi Nishidate

Authors
  1. Sakiko Kinoshita
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  2. Satoko Kawauchi
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  3. Takeshi Nagamatsu
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  4. Izumi Nishidate
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  5. Tomoyuki Fujii
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  6. Shunichi Sato
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Correspondence to Takeshi Nagamatsu.

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All procedures were approved by the ethics committee of the National Defense Medical College of Japan (No. 17022).

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The authors declare that they have no conflict of interest.

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Kinoshita, S., Kawauchi, S., Nagamatsu, T. et al. Real-time Monitoring of Hypoxic-Ischemic Brain Damage in Neonatal Rats Using Diffuse Light Reflectance Spectroscopy. Reprod. Sci. 27, 172–181 (2020). https://doi.org/10.1007/s43032-019-00020-9

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  • DOI: https://doi.org/10.1007/s43032-019-00020-9

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