Medical Student Johns Hopkins University School of Medicine Johns Hopkins School of Medicine
Introduction: Management of intramedullary spinal cord tumors (IMSCTs) poses a significant clinical challenge given the lack of adequate treatment options. The absence of appropriate animal models to test treatment responses further hinders the development of much-needed therapies. This study presents a novel rodent model that reliably and effectively mimics the pathophysiology of IMSCTs.
Methods: Four Spraque-Dawley rats received a 5 μl intramedullary injection of 9L gliosarcoma luciferase-expressing (9L-Luc) cells. The following concentrations of cells were given, respectively: 0, 500,000, 1,000,000, and 2,000,000. The intramedullary injection was performed by removing the T7 spinous process, resecting the underlying ligamentum flavum, and injecting a Hamilton syringe filled with cells into the exposed spinal cord. Every 3 days, tumor volume was measured using the IVIS imaging system and motor function tests were conducted using the Basso, Beattie, Bresnahan (BBB) Locomotor Rating Scale. All animals were euthanized when total hind limb paralysis was reached, and histopathological analysis was conducted on extracted cords.
Results: Intramedullary injection of 500,000 cells led to the onset of paraparesis on Day 4 and total paralysis on Day 12. Over this period, there was progressive tumor growth from 0—3.25 mm2. Injection of 1 million cells led to onset of paraparesis on Day 2 and total paralysis on Day 8, with tumor growth from 0—1.8 mm2. Injection of 2 million cells led to onset of paraparesis on Day 4, total paralysis on day 12, and tumor growth from 0—3.25 mm2. H&E staining of the spinal cord tumor site confirmed the presence of a highly cellular, circumscribed collection of 9L-Luc cells with fibrillary structures and alternating areas of angiogenesis and necrosis in the parenchyma. The control rat (no cells) did not experience tumor growth or motor function decline.
Conclusion : Intramedullary injection of 9L-Luc cells in rat spinal cords results in consistent tumor growth and motor function decline over time. This model can be used to investigate the underlying mechanisms of IMSCT progression, evaluate novel therapeutic approaches, and enhance our understanding of treatment responses.