Local Cooling: Limits on Secondary Injury and Neuronal Death Following Spinal Cord Injury

This study evaluates the effects of local cooling by irrigating artificial cerebrospinal fluid for mild hypothermia to spinal cord injury in rats. Crush injuries were produced at the T8 level using an extradural approach. Local hypothermia was established immediately after crush and maintained under several conditions (irrigation temperature, velocity, duration). Animals were allowed to survive 24 h and 1, 3, and 8 weeks postinjury, and spinal cords were prepared for histological evaluation using hematoxylin-eosin staining for general histopathology. DNA fragmentation following spinal cord crush were evaluated using TUNEL staining. The evolution of secondary injury following crush injury with local mild hypothermia decreased dramatically compared with that in rats treated without hypothermia, even though the primary lesions were statistically the same size. In particular, although there was complete destruction of neural tissue at the crush site, the area was filled in by other cells including neutrophils and connective tissue elements in both the hypothermia-treated and the untreated groups. These was a striking reduction in the progressive necrosis and cavitation that is characteristic of the response to spinal cord injury in the normothermic condition. Control and treated animals differed in terms of the appearance of the TUNEL-positive cell response to injury. In control animals, increases in TUNEL-positive cells 24 h after crush were most pronounced not at the crush site but in an area several millimeters distant from the crush edge. The control and hypothermia-treated animals did not differ in this regard. There were substantial increases in TUNEL-positive cells at the crush site and for some distance rostral and caudal to the injury, especially within the areas containing the long ascending and descending tracts that would contain myelinated axons undergoing Wallerian degeneration and the gray matter. In animals treated with hypothermia, however, there was little increase in TUNEL- positive cells at 24 h after crush, and the increase that was seen occurred primarily in the area immediately surrounding the wound cavity where the tissue had been damaged directly. Increases in apoptotic cells did not become prominent at the site of the crush and for some distance both rostral and caudal to the injury in animals treated with and without hypothermia until 24 h after injury. These results indicate that decreases in secondary injury comes not from suppression of apoptosis but from necrosis, especially at sites some distance rostral and caudal to the injury.