Abstract:

The most important risk factor for stroke and neurodegeneration is aging. In fact, survival after stroke diminishes largely with aging. Thus, recovery after brain artery occlusion is dramatically worsened with aging and even normal aging is also associated with neuron damage and cognitive decline. Mechanisms by which aging promotes cognitive decline and susceptibility to neuron damage in stroke and neurodegeneration are largely unknown. One of the most important mechanisms contributing to neural dysfunction and death is excitotoxicity. This process, initially proposed by Olney in 1969, is based in that the excessive stimulation of glutamate receptors leads to hyperactivation and neuronal damage. This overstimulation may be due to increased concentration of glutamate, or prolonged activation of the receptors by a mild increase in the concentration of the excitatory amino acid.
Protecting the aging brain against damage remains a big challenge for neurologists and neuroscientists. Interestingly, a large number of basic and clinical studies have provided strong evidence indicating that the prolonged use of non-steroidal anti-inflammatory drugs (NSAIDs) may reduce the incidence of Alzheimer's Disease, the most common form of dementia. NSAIDs also decrease glutamate excitotoxicity both in vitro, in rat primary neuronal cultures and hippocampal slices, and in vivo, protecting rats against rotenone-induced parkinsonism. Recent evidence suggests that NSAIDs may even protect against the cognitive decline associated to healthy aging in humans.