CSF from amyotrophic lateral sclerosis patients produces glutamate independent death of rat motor brain cortical neurons: Protection by resveratrol but not riluzole

The neurotoxic effects of cerebrospinal fluid (CSF) from patients suffering amyotrophic lateral sclerosis (ALS), have been reported by various authors. However, variable results have been communicated and the mechanism of such neurotoxicity has been attributed to excess glutamate concentrations in ALS/CSF. We have studied here the properties of 14 CSFs from control patients and 29 CSFs from patients of ALS. We found that while ALS/CSF impairs the viability of rat brain cortical motoneurons maintained in primary cultures, this effect seemed to be exerted through a glutamate-independent mechanism. Resveratrol protected against such neurotoxic effects and antagonized the [Ca+ 2]c elevation produced by ALS/CSF. However, riluzole did not afford protection and antagonized the resveratrol-elicited neuroprotective effects. We conclude that ALS/CSF elicited neurotoxicity on in vitro cultures of rat brain cortical motor neurons may become a sound microassay to test available novel multitargeted neuroprotective compounds with potential therapeutic application in ALS patients.

► The neurotoxic effects of CSF/ALS are independent of glutamate.
► The antioxidant polyphenol resveratrol protects against the neurotoxic effects of ALS/CSF.
► Resveratrol mitigates the elevation of the basal [Ca2+] elicited by ALS/CSF exposure.
► Riluzole did not protect against ALS/CSF neurotoxicity and antagonized the neuroprotective effects of resveratrol.