Selective serotonin reuptake inhibitors for functional recovery after stroke: similarities with the critical period and the role of experience-dependent plasticity.

There has been a growing interest in the potential for plasticity-inducing pharmacological interventions to enhance post-stroke recovery. One group of drugs that continues to garner a great deal of attention in this regard is a class of antidepressants called the selective serotonin reuptake inhibitors. Here we propose a model for the mechanism by which these drugs may enhance plasticity after ischemic brain injury. First, we review the research in animal models demonstrating how selective serotonin reuptake inhibitors reopen the critical period for ocular dominance plasticity in adulthood. We then compare this period of heightened plasticity to the cellular and biochemical milieu of perilesional tissue after an ischemic event in the adult brain. We argue that selective serotonin reuptake inhibitors administered acutely after an ischemic stroke alter excitatory-inhibitory balance in perilesional tissue and reinstate a type of plasticity reminiscent of the critical period in development. Finally, we discuss opportunities for future research in this area in both the preclinical and clinical realms.