Chronic intrathecal infusions after spinal cord injury cause scarring and compression

Intrathecal infusions are used in a number of rodent studies to deliver sub stances to the injured spinal cord. Whereas this method has been successful in certain paradigms, two potential limitations of this model have not bee n extensively reported: (1) scar formation at the catheter tip, which can l ead to infusion failure, and (2) damage to the spinal cord caused by the ca theter itself. Thus, the purpose of the present study was threefold: (1) to determine intrathecal infusion efficiency over 14 days following spinal co rd injury; (2) to examine possible secondary damage caused by intrathecal t ubing; and (3) to explore whether alternative protocols that avoid such dam age are effective. Adult Fischer 344 rats were subjected to spinal cord les ions at T7, followed by placement of an intrathecal catheter attached to an Alzet minipump. Seven or 14 days following injury and catheter placement, tube patency was evaluated by diffusion of Evans Blue dye from the minipump . Results indicate that infusion was efficient 7 days following injury but was markedly reduced after 14 days. Further, histology and immunocytochemis try 14 days after injury demonstrated compression damage to the cord where the tubing rested. Alternative protocols, including intrathecal infusions t hrough metal cannulae, or "drip" infusions directly over the lesion, did no t improve delivery. These data suggest that results from rodent studies usi ng infusion from catheters placed adjacent to lesion sites may be attributa ble to acute or subacute effects of the delivered substance. Future rodent studies using intrathecal infusions should include rigorous evaluation of i nfusion efficiency and possible secondary tissue damage. Microsc. Res. Tech . 54: 317-324, 2001. (C) 2001 Wiley-Liss, Inc.