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Fluids and Barriers of the CNS

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Open Access 01-12-2024 | Syringomyelia | Research

Investigating post-traumatic syringomyelia and local fluid osmoregulation via a rat model

Authors: Dipak D. Pukale, Kayla Adkins-Travis, Siddhartha R. Aryal, Leah P. Shriver, Gary J. Patti, Nic D. Leipzig

Published in: Fluids and Barriers of the CNS | Issue 1/2024

Abstract

Background

Syringomyelia (SM) is characterized by the development of fluid-filled cavities, referred to as syrinxes, within the spinal cord tissue. The molecular etiology of SM post-spinal cord injury (SCI) is not well understood and only invasive surgical based treatments are available to treat SM clinically. This study builds upon our previous omics studies and in vitro cellular investigations to further understand local fluid osmoregulation in post-traumatic SM (PTSM) to highlight important pathways for future molecular interventions.

Methods

A rat PTSM model consisting of a laminectomy at the C7 to T1 level followed by a parenchymal injection of 2 μL quisqualic acid (QA) and an injection of 5 μL kaolin in the subarachnoid space was utilized 6 weeks after initial surgery, parenchymal fluid and cerebrospinal fluid (CSF) were collected, and the osmolality of fluids were analyzed. Immunohistochemistry (IHC), metabolomics analysis using LC–MS, and mass spectrometry-based imaging (MSI) were performed on injured and laminectomy-only control spinal cords.

Results

We demonstrated that the osmolality of the local parenchymal fluid encompassing syrinxes was higher compared to control spinal cords after laminectomy, indicating a local osmotic imbalance due to SM injury. Moreover, we also found that parenchymal fluid is more hypertonic than CSF, indicating establishment of a local osmotic gradient in the PTSM injured spinal cord (syrinx site) forcing fluid into the spinal cord parenchyma to form and/or expand syrinxes. IHC results demonstrated upregulation of betaine, ions, water channels/transporters, and enzymes (BGT1, AQP1, AQP4, CHDH) at the syrinx site as compared to caudal and rostral sites to the injury, implying extensive local osmoregulation activities at the syrinx site. Further, metabolomics analysis corroborated alterations in osmolality at the syrinx site by upregulation of small molecule osmolytes including betaine, carnitine, glycerophosphocholine, arginine, creatine, guanidinoacetate, and spermidine.

Conclusions

In summary, PTSM results in local osmotic disturbance that propagates at 6 weeks following initial injury. This coincides with and may contribute to syrinx formation/expansion.

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Title: Investigating post-traumatic syringomyelia and local fluid osmoregulation via a rat model
Authors: Dipak D. Pukale
Kayla Adkins-Travis
Siddhartha R. Aryal
Leah P. Shriver
Gary J. Patti
Nic D. Leipzig
Publication date: 01-12-2024
Publisher: BioMed Central
Keywords: Syringomyelia
Laminectomy
Published in: Fluids and Barriers of the CNS / Issue 1/2024
Electronic ISSN: 2045-8118
DOI: https://doi.org/10.1186/s12987-024-00514-y

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Investigating post-traumatic syringomyelia and local fluid osmoregulation via a rat model

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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