Melior Discovery in vivo models of Neurophysiology
in vivo Efficacy: Animal Models
Melior is a leading contract research provider of preclinical in vivo pharmacology services using rat and mouse models of Neurophysiology.
One of Melior’s greatest strengths consists of highly sophisticated electrophysiological evaluation of CNS function in rodents. This capability spans the range from routine peripheral nerve recording and chronic EEG evaluationof sleep wake architecture to single unit recording in the sub thalamic nucleus. The electrophysiology models and techniques listed below are applicable to many neurological diseases such as neurodegeneration (including neuropathy, axonopathy, myopathy, and motor paralysis), insomnia and sleep disorders, seizures, cognition, and stress.
EEG Frequency and Analyses
- Cortical EEG Frequency
- Pro-and Anti-Convulsant Evaluation
- Sleep/Wake and Motor Activity
- Status Epilepticus Epilepsy Model
Single Unit Recording
EEG Pro- and Anti-Convulsant Evaluation
Pro- or anti-convulsant activity can be evaluated using EEG power analysis and can be more sensitive than models utilizing chemical or electrical stimuluation and behavioral outcome measures. For example, quantitative anti-convulsant activity can be evaluated using sub-convulsant doses of PTZ that produce characteristic EEG frequency changes that can be quantitatively analyzed for several hours.
EEG Frequency Time Course After PTZ; Drug Treatment vs Vehicle:
Suppression of PTZ Bursting in Mice by Drug Treatment:
Model of Status Epilepticus
Status epilepticus (SE) is a form of epileptic seizure that is resistant to treatment with standard anti-epileptic drugs, in particular when they are administered more than 1 h post onset. Abrogation of the seizures in that case is very difficult, requiring days or weeks of treatment, and may ultimately fail. At Melior we can quantitatively evaluate treatment effects using EEG recording across a wide frequency range (0.3-96 Hz).
The figure below shows a typical example of an animal before and after initiating SE. The EEG activity is increased across all frequencies by over 10 fold. Treatment with vehicle (A) at the onset of SE has no effect, and seizure activity can continue for several hours. Treatment with 10 mg/kg s.c. “Compound” at the onset of SE (B) rapidly blocks seizure activity, returning EEG amplitudes to normal values.
Cortical EEG Frequency
Cortical EEG activity can be recorded from chronically implanted rats and mice and evaluated as a function of frequency to characterize or compare effects of psychoactive drugs. EEG activity (0.03 – 100 Hz) is recorded for 24 hours or more, and evaluated over discrete frequency ranges and time periods depending on the observed drug effects.
EEG power after treatment with compound (”Treatment”):
Cortical Sensory Evoked Potentials
Somatosensory (tibial n., auditory, etc.) evoked or event-related potentials can be recorded at various locations in the brains of rats and mice using surface or depth electrodes. These potentials can be used to monitor the effects of drugs on attentional and cognitive functions. Auditory evoked potentials have been recorded from the hippocampus, for example, to evaluate the effects of drugs on attention. A topographic map of EEG responses to auditory clicks shows functional localization of responses across the cortex.
Auditory Evoked Potentials: Topographic Mapping:
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