Cognitive effects of NSAIDs in cerebral ischemia: a hypothesis exploring mechanical action mediated pharmacotherapy.

Cerebral ischemia is associated with altered neuronal mechanics leading to dynamic reshaping of neuronal structures, giving rise to a cascade of biological pathways leading to many deleterious consequences and cognitive deficits. Memory and learning specifically are mediated by neurotransmitter release from vesicles clustered at the synapse. Mechanical tension is an important factor governing the amount of vesicular neurotransmitter release in response to an action potential. Neuroinflammation in cerebral ischemia leads to altered mechanical/physical forces on neurons which gives rise to abnormal mechanical tension along the neuron resulting in neurotransmitter imbalance leading to cognitive dysfunction. We consider the possibility that modulation of mechanical forces on neurons may be a therapeutic strategy to help prevent cognitive deficit in cerebral ischemia. Here we show how NSAIDs may act as candidate pharmacological molecules which have the ability to inhibit neuroinflammation and which can alter neuronal mechanics by their COX-2 inhibiting property.