Acoustic trauma and other insults to the inner ear may trigger increased levels of extra-cellular glutamate, which in turn cause excessive activation of cochlear NMDA receptors. This process results in damage or killing of sensory cells and is thought to be responsible for abnormal spontaneous "firing" of auditory nerves, which may be perceived as tinnitus. Under normal circumstances, the NMDA receptors are thought to play no role in fast excitatory neurotransmission, respectively normal hearing. Keyzilen ® is blocking cochlear NMDA receptors to suppress the aberrant excitation of the auditory nerve that is perceived as tinnitus.
Since NMDA receptor overactivation is implicated in excitotoxicity , NMDA receptor antagonists have held much promise for the treatment of conditions that involve excitotoxicity, including benzodiazepine withdrawal, traumatic brain injury , stroke , and neurodegenerative diseases such as Alzheimer's , Parkinson's , and Huntington's . This is counterbalanced by the risk of developing Olney's lesions ,  which have only ever been observed in rodents, and studies have started to find agents that prevent this neurotoxicity.   Most clinical trials involving NMDA receptor antagonists have failed due to unwanted side effects of the drugs; since the receptors also play an important role in normal glutamatergic neurotransmission, blocking them causes side-effects. These results have not yet been reproduced in humans, however.  Mild NMDA receptor antagonists like amitriptyline have been found to be helpful in benzodiazepine withdrawal. 
Abstract: The blood-brain barrier (BBB) plays an important role in maintaining brain health and is often compromised in disease. Moreover, as a result of its significant barrier properties, this endothelial interface restricts uptake of neurotherapeutics. A renewable cell source for human BBB modeling could prove enabling for brain research and pharmaceutical development. We recently demonstrated that endothelial cells generated from human pluripotent stem cells (hPSCs) can be specified to possess many BBB attributes, including well-organized tight junctions, polarized efflux transport, and nutrient transporter expression. Importantly, hPSC-derived BBB endothelial cells respond to cues provided by other cells of the neurovascular unit such as human pericytes, astrocytes and neurons to generate very tight barrier properties as measured by transendothelial electrical resistance (~5000 ohmxcm2), while exhibiting molecular permeability that correlates well with in vivo brain uptake. In this talk, we will demonstrate that the process of hPSC differentiation to BBB cells is also compatible with disease modeling using patient-derived induced pluripotent stem cell lines, can be used in the isogenic modeling of the neurovascular unit, and the can be employed for the evaluation of experimental drug permeability attributes.