Intrathecal epidermal growth factor and fibroblast growth factor-2 exacerbate meningeal proliferative lesions associated with intrathecal catheters

OBJECTIVE: There is evidence that promoting the proliferation of endogenous neural stem cells in the spinal cord could be an effective strategy in the treatment of spinal cord injury. We studied this proliferation in a minimal injury rat model in the presence of epidermal growth factor and fibroblast growth factor-2. METHODS: Adult female Sprague Dawley rats were minimally injured at T8 and received the growth factors intrathecally by osmotic pump for either 3, 7, or 14 days beginning immediately after spinal cord injury. The infusions were made through a subarachnoid catheter connected to an osmotic minipump. Beginning at the time of injury, the rats received daily bromodeoxyuridine to label proliferating cells for determination of the labeling index. RESULTS: Significant differences were found in the labeling index between injured and non-injured rats. We concluded that minimal spinal cord injury from the stab injury and from the catheter itself increased the proliferation of ependymal region stem/progenitor cells. A minority (23.3%) of the rats developed proliferative lesions in association with the catheters alone, but the lesions were significantly larger and occurred in almost all (93.8%) rats receiving the mitogens, resulting in marked spinal cord compression. CONCLUSION: The large proliferative growths in the epidermal growth factor and fibroblast growth factor-2-treated rats were unexpected and are indicative of the major effects of these mitogens. This suggests that considerable caution is required in devising therapeutic strategies directed toward mitogenic stimulation by growth factors delivered into the subarachnoid space. Further study is required to determine the appropriate and safe dosage of mitogens for potential use in spinal cord repair.