Diverse pharmacological, molecular, and

physiological approaches are being examined for modulating neural plasticity and to treat neurological and psychiatric diseases. Targets of Afatinib price modulation include neuromodulatory systems, cortical inhibition, as well as molecules that may actively promote or inhibit plasticity (Barbay and Nudo, 2009, Bavelier et al., 2010 and Cramer, 2008). Examples include improving function in animal models of neurodevelopmental disorders (Ebert and Greenberg, 2013), neuropsychiatric disorders (Lakhan et al., 2013 and Stephan et al., 2006), and stroke (Cramer et al., 2011 and Overman et al., 2012). While some are highly targeted (e.g., specific pharmacological blockade of inhibition), others likely recruit multiple cellular processes and neural circuits (e.g., cell-based therapies and noninvasive stimulation). The noradrenergic system has been extensively studied for neural repair after brain injury (Barbay and Nudo, 2009 and Walker-Batson, 2013). D-amphetamine has been shown to improve functional recovery in both rodents and nonhuman primates (Barbay and Nudo, 2009 and Feeney et al., 1982), possibly through augmentation of neural plasticity. However, d-amphetamine

treatment of stroke patients with motor and language deficits has yielded mixed outcomes (Walker-Batson, 2013). This highlights the challenge associated with translation from animal models to patient care. Moreover, CP-868596 mw the selective serotonin reuptake inhibitor (SSRI) fluoxetine, which is used widely for depression and other psychiatric illness, has effects on synaptic plasticity, neurogenesis, and the BDNF level in

the brain (Pilar-Cuéllar et al., 2013). It has been demonstrated to improve motor recovery after stroke in a recent clinical trial (Chollet et al., 2011) and is a promising drug for patients with amblyopia (Maya Vetencourt et al., 2008), presumably through modulation of cortical inhibition (Espinosa and Stryker, 2012). Since inhibitory interneurons play a key role in shaping cortical function and plasticity, modulation of cortical inhibition offers a general mechanism of enhancing recovery by engaging neural plasticity (Ramamoorthi and Lin, 2011). Reduction of inhibition in the visual system, for example, can restore a juvenile state of plasticity in the adult Levetiracetam rodent brain (Espinosa and Stryker, 2012 and Maya Vetencourt et al., 2008). Many genetic disorders with cognitive deficits, such as autism and Down syndrome, are also associated with excessive inhibition (Ramamoorthi and Lin, 2011 and Wetmore and Garner, 2010). In the case of Down syndrome, reducing inhibition in a genetic model was found to improve cognitive function (Fernandez et al., 2007). Reduction of extrasynaptic GABAergic currents has also improved motor recovery in animal models of focal stroke (Clarkson et al., 2010). Cell-based therapies also have a great potential to result in novel treatments (Leong et al., 2013, Sanberg et al.