Biomedical Engineering Reference
In-Depth Information
application of different pharmacological substances that act specifically on
glutamatergic synapses. Moreover, determination of the glutamate released by
cortical neuronal networks in combination with the recording of integrated
activity allowed correlation between the drug effects on the activity patterns
and on functioning of glutamatergic excitatory synapses to be established. In
fact, activation of high anity NMDA receptors (by low micromolar NMDA
concentrations) evoked changes of firing and bursting rate highly correlated to
the effects on glutamatergic transmission, as assessed by glutamate release.
Cultured neural networks respond to neurotransmitters, blockers and many
pharmacological substances such that in vivo behavior of neurons can be
mimicked in vitro. For example, bicuculline blocks the main inhibitory
neurotransmitter GABA, causing an increased spiking frequency, as does the
chloride channel antagonist strychnine. Such cultures are cultured for long-
term monitoring of neuronal electrophysiological activity including devel-
opment, neuronal plasticity and axonal regeneration, all of which may be
affected by the introduction of pharmaceutical compounds.
The peripheral nervous system has also been the focus of several studies.
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Repetitive patterns of neural activity in spinal cord are responsible for behavior
such as locomotion; they were investigated using neuronal networks of cells
from the vertebrate spinal cord, and coupling properties were elucidated by
using pharmacological methods. Bursting network activity and intrinsic
activity in these cultures were modulated by 5-hydroxytryptamine (5-HT,
serotonin) and the cholinergic agonist muscarine. Rhythmic activity in spinal
cord slices has been monitored over long durations using MEAs.
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Current neurotoxicity assessment studies for new compounds are performed
through in vivo neurobehavioral and neurotoxicity testing. Such testing
procedures do not always accurately predict responses in humans, are costly,
and require the use of numerous laboratory animals, the number of which
could be limited by the introduction of in vitro methods.
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3.10.4 Microelectrode Arrays in Toxicology
MEA technology is perfectly suited for the high throughput screening of toxic
compounds. The recordings from multiple, separate cell networks can be made
simultaneously from neuron cells situated in multi-well chips or plates.
Compound toxicity can also be assessed in such electrophysiological
approaches that allow .the transition from animal-intensive, descriptive toxicity
testing to in vitro, predictive screening. The requirement for a better under-
standing of the potential hazards of the tens of thousands of chemicals
currently used, as well as the necessity to increase the number of chemicals
characterized for potential toxicity, are primary driving forces behind this
change. The need to reduce the time, cost and numbers of animals used in
contemporary toxicity tests also contributes to the shifts in approaches to
hazard assessment. Ethical issues will also disappear. The need to extrapolate
from animal to human models will be avoided, especially if human stem cells
from renewable sources could be used. The future relies heavily on the use of
