Table 3.

Variables that should be controlled to introduce reproducibility and rigor and minimize experimental bias in rodent studies of seizures and epilepsy (see also Fig. 4).

VARIABLE	COMMENT
Environmental	These are factors in the environment that are recognized as having a significant influence on the outcome of seizure tests in rodents
Housing	Rodents should be group-housed to the extent possible. Group sizes should be similar between experimental and control animals. Experimental and control animals should be housed in identical caging and maintained in the same room.
Enrichment	Cage enrichments should be the same between experimental and control animals.
Food/water	The composition and source of food should be identical between experimental and control rodents, as should the source of water. Access to food and water should be identical as well.
Litter size	Animals selected to populate experimental and control groups should come from litters that have been culled to the same number of pups.
Experimental	These are parameters of seizures that can be quantified as endpoints to compare experimental and control animals and need to be carefully defined for each study.
Seizure frequency	This endpoint parameter may be defined as the number of discrete seizure events per unit of time. Seizure events may be defined behaviorally or electrographically.
Seizure duration	This endpoint parameter may be defined as the length of a single discrete seizure. Average seizure duration may be calculated for individual animals or groups.
Seizure threshold	This endpoint parameter may be calculated based upon stimulus intensity. Intensity is defined as a function of stimulus such as chemoconvulsant dose or electrical current level.
Biologic	These parameters include factors that are intrinsic to each organism.
Age	Susceptibility to seizures and epilepsy varies over the life cycle for rodents and it is imperative that experimental and control animals be closely matched for age.
Sex	Susceptibility to seizures and epilepsy differs between males and females. Ideally, sexes should be tested separately. Alternatively, experimental and control groups should contain the same number of each sex although this latter design may mask sex differences. All female rodents should be tested at the same time in their estrous cycle.
Genetic	Naturally-occurring genetic polymorphisms between rodents may impact responses in tests of seizures and epilepsy.
Genetic background	DNA polymorphisms, both characterized and uncharacterized, exist between different rodent lines and strains. Study designs should include a breeding strategy to insure that experimental and control groups share the same genetic background.
Genetic drift	New mutations may be introduced naturally into a rodent line or strain at any generation. Colony management should include a breeding strategy to maintain the integrity of the genetic background of all rodent lines and strains.