Animal Models

Question 1

Classical models of Parkinson’s

Answer 1

Toxic models:

• MPTP (mice, primates)
• 6-hydroxydopamine (rats, mice)
• paraquat (rats, mice)
• rotenone (rats)

Question 2

PD sporadic vs familial

Answer 2

90% - sporadic
- environment
- possibly genetic factors
10% - familial
- mutations

Question 3

Symptoms of PD

Answer 3

Akinesia 
Postural imbalance
Rigidity 
Olfactory loss
Tremor 
Cognitive disorders (implicit memory)
Affective disorders (depression / anxiety / apathy)
Sleep disturbances
Autonomic disorders (hypotension)
Digestive symptoms (constipation)

Other Symptoms:

- Constipation (Lewy bodies found in the neurons of the intestinal wall)
- Various neurons with long axons show Lewy bodies before the dopaminergic ones
- Sleep disorders
- Depression
- psychosis
- Anosmia

- Mask face
- Micrographia
- Hypersalivation

Question 4

Allocation concealment

Answer 4

Concealing the allocation sequence from those assigning animals to intervention groups, until the moment of assignment.

Question 5

Bias

Answer 5

Systematic distortion of the estimated intervention effect away from the “truth,” caused by inadequacies in the design, conduct, or analysis of an experiment.

Question 6

Blinding (masking)

Answer 6

Keeping the persons who perform the experiment, collect data, and assess outcome unaware of the treatment allocation

Question 7

External validity

Answer 7

The extent to which the results of an animal experiment provide a correct basis for generalisations to the human condition.

Question 8

Intention-to-treat analysis

Answer 8

Analysis of data of all animals included in the group to which they were assigned, regardless of whether they completed the intervention.

Question 9

Internal validity

Answer 9

The extent to which the design and conduct of the trial eliminate the possibility of bias.

Question 10

Biases threatening internal validity:

Answer 10

• selection bias (biased allocation to treatment groups) [sol.: randomization, allocation concealment]
• performance bias (systematic differences in care between groups apart from the intervention) [sol.: blinding]
• detection (ascertainment, assessment, or observer bias: systematic distortion of the results of a study that occurs when the person assessing the outcome has knowledge of treatment assignment) [sol.; blinding]
• attrition bias (unequal occurrence and handling of deviations from protocols and loss to follow-up between treatment groups) [sol:blinding, intention-to-treat, reporting drop outs]
• false positive report bias (bias due to poor statistical power) [sol: adequate sample size]

Question 11

Common problems with external validity:

Answer 11

• Induction of one disease in animals that are young and healthy, whereas in patients the disease mainly occurs in elderly people with co-morbidities.
• Assessment of the effect of a treatment in a homogeneous group of animals versus a heterogeneous group of patients.
• The use of either male or female animals, whereas the disease occurs in male and female patients.
• use of models for inducing a disease or injury with insufficient similarity to the human condition.
• Unrealistic timing and dosage of treatment in animals vs human.
• Differences in outcome measures and the timing of outcome assessment between animal studies and clinical trials.

Question 12

Aspects of a study to be reported:

Answer 12

• sample size calculation
• eligibility criteria
• treatment allocation (If this allocation was by randomisation, the method of randomisation)
• allocation concealment
• blinding
• flow of animals (Flow of animals through each stage of the study, with a specific attention to animals excluded from the analyses. Reasons for exclusion from the analyses.)
• control of physiological variables
• control of study conduct (Whether a third party controlled which parts of the conduct of the study.)
• statistical

Question 13

Stages for describing seizure behavior:

Answer 13

Racine 1972
- I freeze / mild facial clonus
- II severe facial clonus
- III forelimb clonus
- IV rearing
- V falling
Fully Kindled = 5 * stage V

Question 14

EEG readout info in epilepsy

Answer 14

• latency - time between hit and
• epileptic spikes
• seizure duration
• spike frequency

Question 15

Side effects of VNS:

Answer 15

• bradycardia and decreased respiration rate (at stronger current)
• SO2 96% to 86%
• coughing
• immobility
• Horner’s syndrome
• vocalizing
• grooming
• polyuria
• trears
• headturn
• > defecation frequency
• drooling swallow

Question 16

Features of VNS that define its efficiency

Answer 16

• electrode design, ?
• electrode is (not) around the carotid artery, ?
• stimulation parameters
• anesthesia no/yes, how?
• responder definition