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Neuroprotective Effects of a Cardioplegic Combination (Adenosine, Lidocaine, and Magnesium) in an Ischemic Stroke Model

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Abstract

Adenosine, lidocaine, and magnesium (ALM) are clinically available cardioplegic solutions. We examined the effects of low-dose ALM on ischemic stroke in cell and animal models. Cobalt chloride (CoCl2)–treated SH-SY5Y cells were used as a surrogate model to mimic oxygen–glucose deprivation conditions. The cells were incubated with different dilutions of ALM authentic solution (1.0 mM adenosine, 2.0 mM lidocaine, and5 mM MgSO4 in Earle’s balanced salt solution). At a concentration of 2.5%, ALM significantly reduced CoCl2-induced cell loss. This protective effect persisted even when ALM was administered 1 h after the insult. We used transient middle cerebral artery occlusion to investigate the therapeutic effects of ALM in vivo. Rats were randomly assigned to two groups—the experimental (ALM) and control (saline) groups—and infusion was administered during the ischemia for 1 h. The infarction area was significantly reduced in the ALM group compared with the control group (5.0% ± 2.0% vs. 23.5% ± 5.5%, p = 0.013). Neurological deficits were reduced in the ALM group compared with the control group (modified Longa score: 0 [0–1] vs. 2 [1–2], p = 0.047). This neuroprotective effect was substantiated by a reduction in the levels of various neuronal injury markers in plasma. These results demonstrate the neuroprotective effects of ALM and may provide a new therapeutic strategy for ischemic stroke.

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Data Availability

The datasets generated and analyzed during the current study are available from the corresponding author upon reasonable request.

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Acknowledgements

We would like to express our thanks to Prof. Thomas Toung who helped us with the rat ischemic model; Dr.Ti-Yen Yeh, for rat randomization and plasma preparation; and Dr. John-Chun Ho, for cell model establishment.

Funding

This work was supported by the Ministry of Science and Technology in Taiwan (grant numbers 109–2314-B-002–243 and 107–2314-B-002–043-MY3).

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Authors and Affiliations

  1. Department of Anesthesiology, National Taiwan University College of Medicine and National University Hospital, Taipei, Taiwan

    Yi-Chia Wang

  2. Graduate Institutes of Anatomy and Cell Biology, National Taiwan University College of Medicine, 1 Jen-Ai Road, Section 1, Taipei, 100233, Taiwan

    Yi-Chia Wang & Sung-Tsang Hsieh

  3. Department of Surgery, National Taiwan University College of Medicine and National University Hospital, Taipei, Taiwan

    Yih-Sharng Chen

  4. Department of Neurology, National Taiwan University College of Medicine and National University Hospital, Taipei, Taiwan

    Sung-Tsang Hsieh

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  1. Yi-Chia Wang
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Contributions

All authors contributed to the study conception and design. Yi-Chia Wang performed the experiments and wrote the manuscript with support from Sung-Tsang Hsieh. Chen designed and directed the project of the oxygen–glucose deprivation model and aided in the interpretation of the results. The first draft of the manuscript was written by Yi-Chia Wang, and all authors commented on the previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Sung-Tsang Hsieh.

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All animal experiments were performed in accordance with the animal protocol approved by the National Taiwan University College of Medicine and College of Public Health Institutional Animal Care and Use Committee (IACUC No. 20180302).

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Wang, YC., Chen, YS. & Hsieh, ST. Neuroprotective Effects of a Cardioplegic Combination (Adenosine, Lidocaine, and Magnesium) in an Ischemic Stroke Model. Mol Neurobiol 59, 7045–7055 (2022). https://doi.org/10.1007/s12035-022-03020-0

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