animal models of stroke and traumatic brain injury (Kaminska et al., 2004). The drugs are now being tested in animals with spinal cord injuries (Madsen et al., 1998; Bavetta et al., 1999; Diaz-Ruiz et al., 1999, 2000; Nottingham et al., 2002; Akgun et al., 2004). Although their mechanisms of action are not fully known, they may reduce glial cell responses and inflammation (Kaminska et al., 2004).
One promising therapy is based on a set of experiments designed to decrease the infiltration of neutrophils and to delay the entry of monocytes into the spinal cord after an injury (Gris et al., 2004). After a spinal cord injury, monocytes and neutrophils bind to a specific protein, VCAM-1, or the CD11d subunit of the CD11d/CD18 integrin on the interior of blood vessels and then egress into the spinal cord. These actions contribute to the inflammatory response and cause considerable secondary damage. Antibodies to VCAM-1 have been developed (Mabon et al., 2000) and have been found to significantly reduce the numbers of macrophages and neutrophils at the site of injury when they are administered to rodents after a spinal cord injury. Rats that received this antibody also showed improved proprioception and locomotion, significant decreases in autonomic dysreflexia, and less pain (Mabon et al., 2000; Bao et al., 2004). If the results of these experiments are validated, this therapy could be successfully translated into a clinical trial.
Researchers and clinicians have also explored the possibility of cooling the spinal cord. The purpose of this treatment is to minimize the damage caused by apoptosis and the secondary effects of inflammation (Dimar et al., 1999). This approach, which uses extreme levels of total body hypothermia, was extensively studied in the 1960s and 1970s but lost favor in the 1980s because of potential adverse effects, including kidney failure (Inamasu et al., 2003). However, new methods of introducing mild hypothermia have been developed, and hypothermia treatment is once again being considered as a potential treatment for traumatic brain injuries and spinal cord injuries (Dietrich et al., 1994; Yu et al., 2000). Of particular interest are techniques that are under development to precisely control hypothermia to the area of injury beyond several hours (Robertson et al., 1986; Kida et al., 1994; Marsala et al., 1997; Dimar et al., 2000).
In patients with cardiovascular and traumatic brain injuries, mild to moderate hypothermia has been reported to improve outcomes (Marion et al., 1997; Jiang et al., 2000; Hypothermia After Cardiac Arrest Study Group, 2002; Bernard et al., 2002). Two studies have examined the efficacy of spinal cord cooling in 18 patients with complete spinal cord injuries (Bricolo et al., 1976; Hansebout et al., 1984). Each of those studies demonstrated that the patients had rates of recovery of sensory and motor functions that were better than expected (Koons et al., 1972; Tator and Deecke, 1973; Negrin, 1975); however, in the 20 years that have followed there has