Regeneration of the Adult Rat Spinal Cord in Response to Ensheathing Cells and Methylprednisolone

摘要

Axons fail to regenerate after spinal cord injury (SCI) in adult mammals, leading to permanent loss of function. Following SCI, ensheathing cells promote recovery in animal models, whereas methylprednisolone promotes neurological recovery in humans. The aim of this research was to explore the effectiveness of ensheathing cells and methylprednisolone after acute SCI in the adult rat. Three studies were conducted to accomplish this goal. In the first study, a new method of purifying ensheathing cells was developed, resulting in a final population of ensheathing cells that were 93% pure. In the second study, the ability of a modified directed forepaw reaching (DFR) apparatus to accurately assess function of the corticospinal tract (CST) was examined. The data demonstrated that the modified apparatus prevented extinguishing of DFR behavior after SCI. In addition, the modified apparatus allowed for the collection of quantitative data to accurately assess CST function after bilateral, cervical spinal cord lesions. In the third study, the effectiveness of combining ensheathing cells and methylprednisolone after SCI was investigated. After lesioning the CST in adult rats, a purified population of ensheathing cells was transplanted into the lesion, and methylprednisolone was administered for 24 hours. At six weeks post injury, functional recovery was assessed by measuring successful DFR performance. Axonal regeneration was analyzed by counting the number of anterogradely labeled CST axons caudal to the lesion. Lesioned control rats, receiving either no treatment or vehicle, had abortive axonal regrowth (1 mm) and poor DFR success (38% and 42%, respectively) . Compared to controls, rats treated with methylprednisolone for 24 hours had significantly more axons at 7 mm caudal to the lesion, and DFR performance was significantly improved (57%). Rats that received ensheathi.