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

Dipak D Pukale; Kayla Adkins-Travis; Siddhartha R Aryal; Leah P Shriver; Gary J Patti; Nic D Leipzig

doi:10.1186/s12987-024-00514-y

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

Fluids Barriers CNS. 2024 Feb 26;21(1):19. doi: 10.1186/s12987-024-00514-y.

Authors

Dipak D Pukale¹, Kayla Adkins-Travis², Siddhartha R Aryal³, Leah P Shriver², Gary J Patti², Nic D Leipzig^{4

5}

Affiliations

¹ Department of Chemical, Biomolecular, and Corrosion Engineering, The University of Akron, Akron, OH, 44325, USA.
² Departments of Chemistry and Medicine, Center for Proteomics, Metabolomics, and Isotope Tracing, Washington University in St. Louis, St. Louis, MO, 63130, USA.
³ Department of Biomedical Engineering, The University of Akron, Akron, OH, 44325, USA.
⁴ Department of Chemical, Biomolecular, and Corrosion Engineering, The University of Akron, Akron, OH, 44325, USA. nl21@uakron.edu.
⁵ Department of Biomedical Engineering, The University of Akron, Akron, OH, 44325, USA. nl21@uakron.edu.

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.

Keywords: Fluid osmolality gradient; Osmoregulation; Post-traumatic syringomyelia; Syrinx.

MeSH terms

Animals
Betaine
Magnetic Resonance Imaging
Osmoregulation
Rats
Rats, Sprague-Dawley
Spinal Cord Injuries* / complications
Spinal Cord Injuries* / metabolism
Syringomyelia* / etiology

Substances

Betaine