Zebrafish: A Predictive Model for Assessing Seizure Liability - Zebrafish: Methods for Assessing Drug Safety and Toxicity - page 160

13.1.1 Seizures Are Complex Disorders
Seizures are complex brain disorders caused by abnormal neuronal excitability
accompanied by either a variety of mild neurological symptoms or severe life-
threatening convulsions. Seizures, which can be global (generalized) or focal
(partial), are classified by anatomical origin. Because a large region of the brain is
affected, generalized seizures are characterized by severe, life-threatening symptoms.
Types of generalized seizures include (1) absence (petit mal)—a staring spell,
(2) myoclonic—single or repetitive brief jerking muscle movement without loss of
consciousness, (3) clonic—rhythmic jerking movement of arms and legs, sometimes
on both sides of the body, (4) tonic—muscle stiffening with loss of consciousness and
body rigidity, and (5) tonic-clonic (grandmal)—generalized convulsions inwhich the
tonic phase is followed by the clonic phase. Depending on the area of brain affected
and severity, partial seizures can include motor, sensory, autonomic, emotional, or
cognitive abnormalities; symptoms of partial seizures include a blank stare, loss of
consciousness, distortion of sensory perception (scents, music, or flashes of light), or
uncontrolled muscle contractions (Luders et al., 1998; Tuxhorn and Kotagal, 2008).
There are many underlying causes for seizures including epilepsy, genetics,
congenital and developmental conditions, tumors, head trauma, and infectious dis-
eases, including HIV/AIDS. Numerous compound classes including antimicrobials,
psychotropic agents, antidepressants, antipsychotics, anesthetics and antiarrhythmic
agents, sedative-hypnotic agents, and, unfortunately, antiepileptic compounds them-
selves can induce seizures (Alldredge and Simon, 1991). Due to complexity, seizure
diagnosis is typically done by (1) taking a detailed medical history describing seizure-
related neurological symptoms and chronicling episodes, and (2) imaging and
electrical assessment, by magnetic resonance imaging (MRI), single-photon emission
computed tomography (SPECT), positron emission tomography (PET), magnetoen-
cephalography (MEG), or electroencephalography (EEG). Imaging and electrical
assessment are necessary for physiological and anatomical characterization.
13.1.2 Conventional Models for Assessing Seizures
Since seizures are systemic disorders involving several biological processes and
organs, studies are best performed in physiologically intact animals. Diverse animal
models ranging from fruit flies to nonhuman primates have been invaluable for
understanding disease etiology and developing antiepileptic treatment strategies
(Sarkisian, 2001a, 2001b; Cole et al., 2002; Martin and Pozo, 2006). Criteria necessary
for validating seizure animal models include (1) EEG activity, that is, interictal
and ictal spike-wave discharges, (2) etiology—genetic predisposition and injury,
(3) developmental age, (4) brain-specific pathologies, focal lesions, and cortical
dysplasia, (5) response to anticonvulsants, and (6) behavioral characteristics. Not
surprisingly, since there are more than 100 different types of human seizures and
epileptic disorders, no single animal model recapitulates the complete range of
phenotypes observed in humans.