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EXCITOTOXICITY on CORTICAL NEURONS
Model of EXCITOTOXICITY on CORTICAL NEURONS
INTRODUCTION
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease characterised by upper and lower motor neuron death with ascending paralysis leading to death. The role of excitotoxicity in the ALS physiopathology is now recognised and that glutamate receptors activation contributes greatly in mediating injury to motor neurons. In vitro, a brief exposure to glutamate causes neuronal death mainly by excessive stimulation of NMDA receptors (Choi et al., 1988).
COMPOUND TESTING
Cortical neuron cultures are injured by an acute intoxication with glutamate or NMDA. The neuroprotective effect of compounds is evaluated based on their ability to inhibit on this damage. In the pre-treatment protocol, test compound is added 24h before intoxication and in the post-treatment one, test compound is added immediately after intoxication. Neuronal death is assessed by measuring LDH activity (Lactate deshydrogenase) in the media at 24h after glutamate / NMDA exposure.
Culture of cortical neuron
under control condition.
Culture of cortical neuron
injured by glutamate (10min, 75µM).
Release of LDH by neuronal culture in response to increasing doses of acute glutamate.
Effect of Riluzole, the only therapy available for the treatment of ALS patients, on neuronal death induced by glutamate
(75 µM, 10 min)
REFERENCES
CHOI D.W., KOH J. and PETERS S. (1988). Pharmacology of glutamate neurotoxicity in cortical cell cultures: attenuation by NMDA antagonists.
J. Neurosci., 8, 185-196.
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