Aquaporin-4 expression and modulation in a rat model of post-traumatic syringomyelia

Joel A. Berliner; Magdalena A. Lam; Elmira Najafi; Sarah J. Hemley; Lynne E. Bilston; Marcus A. Stoodley

doi:10.1038/s41598-023-36538-x

Aquaporin-4 expression and modulation in a rat model of post-traumatic syringomyelia

Joel A. Berliner^*, Magdalena A. Lam, Elmira Najafi, Sarah J. Hemley, Lynne E. Bilston, Marcus A. Stoodley

^*Corresponding author for this work

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Abstract

Aquaporin-4 (AQP4) has been implicated in post-traumatic syringomyelia (PTS), a disease characterised by the formation of fluid-filled cysts in the spinal cord. This study investigated the expression of AQP4 around a mature cyst (syrinx) and the effect of pharmacomodulation of AQP4 on syrinx size. PTS was induced in male Sprague–Dawley rats by computerized spinal cord impact and subarachnoid kaolin injection. Immunofluorescence of AQP4 was carried out on mature syrinx tissue 12 weeks post-surgery. Increased AQP4 expression corresponded to larger, multiloculated cysts (R² = 0.94), yet no localized changes to AQP4 expression in perivascular regions or the glia limitans were present. In a separate cohort of animals, at 6 weeks post-surgery, an AQP4 agonist (AqF026), antagonist (AqB050), or vehicle was administered daily over 4 days, with MRIs performed before and after the completion of treatment. Histological analysis was performed at 12 weeks post-surgery. Syrinx volume and length were not altered with AQP4 modulation. The correlation between increased AQP4 expression with syrinx area suggests that AQP4 or the glia expressing AQP4 are recruited to regulate water movement. Given this, further investigation should examine AQP4 modulation with dose regimens at earlier time-points after PTS induction, as these may alter the course of syrinx development.

Original language	English
Article number	9662
Pages (from-to)	1-14
Number of pages	14
Journal	Scientific Reports
Volume	13
Issue number	1
DOIs	https://doi.org/10.1038/s41598-023-36538-x
Publication status	Published - 14 Jun 2023

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Copyright the Author(s) 2023. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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abstract = "Aquaporin-4 (AQP4) has been implicated in post-traumatic syringomyelia (PTS), a disease characterised by the formation of fluid-filled cysts in the spinal cord. This study investigated the expression of AQP4 around a mature cyst (syrinx) and the effect of pharmacomodulation of AQP4 on syrinx size. PTS was induced in male Sprague–Dawley rats by computerized spinal cord impact and subarachnoid kaolin injection. Immunofluorescence of AQP4 was carried out on mature syrinx tissue 12 weeks post-surgery. Increased AQP4 expression corresponded to larger, multiloculated cysts (R2 = 0.94), yet no localized changes to AQP4 expression in perivascular regions or the glia limitans were present. In a separate cohort of animals, at 6 weeks post-surgery, an AQP4 agonist (AqF026), antagonist (AqB050), or vehicle was administered daily over 4 days, with MRIs performed before and after the completion of treatment. Histological analysis was performed at 12 weeks post-surgery. Syrinx volume and length were not altered with AQP4 modulation. The correlation between increased AQP4 expression with syrinx area suggests that AQP4 or the glia expressing AQP4 are recruited to regulate water movement. Given this, further investigation should examine AQP4 modulation with dose regimens at earlier time-points after PTS induction, as these may alter the course of syrinx development.",

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AU - Bilston, Lynne E.

AU - Stoodley, Marcus A.

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Aquaporin-4 expression and modulation in a rat model of post-traumatic syringomyelia

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