Neurochip results compare well with in vivo values
Neurochip-generated dose-response curves for agents acting on receptors or ion-channels such as magnesium, glutamate, NMDA, APV, GABA, and bicuculline reveal respective network IC50 values as described in the literature.
Concentration dependent inhibition of action potentials by application of tetrodo toxin (TTX), a voltage gated Na+-channel blocker, yields a network IC50 of 1.1 nM comparable to literature values determined in vivo.
Functional network-driven effects occur in absence of neurotoxicity
Pinacolyl methylphosphonate (PMP), the primary hydrolysis product of the chemical agent soman, immediately induces total burst cessation on Neurochips, but shows no cytotoxic effect when applied for 14 days.
Neurochip-screening of 7 novel prospective AChE inhibitors showed acute functional network inhibition – even irreversible in 2 compounds – in the absence of any cytotoxicity.
Long-term (pre-) synaptic effects are revealed by Neurochip screening
Application of tetanus toxin at a concentration of 1 nM blocks presynaptic mechanisms of vesicle release for the inhibitory and excitatory neurotransmitters glycine and glutamate on different time scales of 90 to 180 minutes.
Presynaptic effects are undetectable in single-cell patch-clamp experiments
Anti-depressant drugs like fluoxetine (“Prozac”: selective inhibitor of serotonin reuptake in the synaptic cleft) or clozapine (“Clozaril”: binding to dopamine and serotonin receptors) show characteristic concentration-dependent effects on the time scale of hours.
Clinical relevance of human metabolites in hyperhomocysteinemia
Patients with elevated plasma concentrations of homocysteine often present with acute neuronal dysfunction including seizures and psychosis. However, Neurochip tests detected that this dysfunction probably is not due to homocysteine but rather to oxidized metabolites acting via a NMDA receptor mediated pathway, which may affect therapeutic strategies.
Literature:
Pancrazio et al. (2001) NeuroToxicology 22:393-400.
Keefer et al. (2001) NeuroToxicology 22 (1): 3-12
Xia et al. (2003) Brain Research 973: 151-160
Otto et al. (2003) J. Neuroscience Methods 128/1-2: 173-181
Görtz et al. (2003) J. Neurol. Sciences ; submitted
Last modified 02/07/06 06:32 Upward