Preclinical randomized controlled multicenter trials in translational stroke research

Natalizumab is a humanized monoclonal antibody against alpha-4 integrin (CD49d) that reduces the incursion of circulating leukocytes into the central nervous system across the endothelium (1). As widely shown in experimental models of brain ischemia and in clinical studies, the infiltration of leukocytes across the blood-brain barrier is a well-known mechanism implicated in the progression of ischemic damage. One of the endothelial receptors involved in the transmigration of leukocytes is the alpha-4 integrin (CD49d). The inhibition of this receptor may modulate the invasion of leukocytes into the ischemic brain and it has been considered as a promising therapeutic target for neuroprotection (2). However, a number of single center experimental studies have evaluated the neuroprotective efficacy of antagonizing that receptor with mixed results (1)