Rodent Kindling Model of Temporal Lobe Epilepsy (TLE)

Kindling has been used as a chronic model of temporal lobe epilepsy (TLE) for more than 3 decades, not only for the investigation of epilepsy mechanisms but also for the preclinical evaluation of antiepileptic drugs. Drug testing in this chronic model of epilepsy yields data which are more predictive of clinical efficacy and adverse effects, compared to the use of acute seizure animals. Creative Biolabs conducts contract studies on drug candidates by which epilepsy can be prevented or modified using this kindling model of TLE.

Introduction of the Kindling Model

This model is based on the kindling phenomenon, which involves the progressive development of EEG and behavioral seizures evoked by repeated electrical stimulation of certain brain structures. Repetitive electrical brain stimulation produces an increase in convulsive behavior and eventually generalized motor seizures. The progression of motor seizures proceeds through several stages as defined by Racine for the amygdala kindling protocol. The seizure assessment can be scored as follows according to the Racine scale:

• Score 0-No seizure response
• Score 1-Immobility, eye closure, ear twitching, snuffing, and facial clonus
• Score 2-Head nodding
• Score 3-Forelimb clonus
• Score 3.5-Bilateral forelimb clonus without rearing
• Score 4-Bilateral forelimb clonus with rearing
• Score 4.5-Falling on a side, loss of righting reflex accompanied by generalized clonic seizure
• Score 5-Rearing and falling

Thus, the more advanced the animal in this process, the more intense the seizures and the more widespread and prolonged the electrical seizures or afterdischarges (i.e., the most sensitive parameter of focal seizure activity in kindled rats). Kindling occurs best in neuroplastic areas of the brain; the amygdala is the brain region most susceptible to kindling.

Fig.1 Z944 delays the progression to kindling. ETX, ethosuximide; Z944, a high-affinity pan-T-type Ca²⁺ channel antagonist. (Casillasespinosa et al. 2015)

Features of The Kindling Model

• Precise focal activation of the target brain sites is possible.
• Development of chronic epileptogenesis is reliably observed.
• The pattern of seizure propagation and generalization is readily monitored, and interictal, ictal, and postictal periods are easily manipulated.
• Kindling experiments can be relatively labor intensive, given that electrodes are typically implanted into the brain and multiple, spaced stimulations are required.
• Also, spontaneous seizures do not develop unless a very large number of kindling stimulations are applied.

Assessments

Animals are assessed for seizure-like behavior 24 h post-surgery and the progression of seizure behavior to record the spontaneous seizures and are scored according to Racine's classification. Histological and immunocytochemical analyses are conducted to evaluate the neuroprotective effect of the test articles. Briefly, Creative Biolabs offers assessments including but not limited to:

• Seizure behavior assessment and scoring
• Histological and immunocytochemical analysis
• Cognitive status tests and global motor activity tests (e.g., Elevated plus-maze test, Morris water maze)
• Electrophysiological analysis (e.g., EEG recording)
• Magnetic resonance imaging (MRI) analysis

Creative Biolabs also offers additional models of epilepsy that you may be interested in:

• Pilocarpine Model of Temporal Lobe Epilepsy
• Lithium-Pilocarpine Model of Temporal Lobe Epilepsy
• Maximal Electroshock (MES)-Induced Convulsions
• Pentylenetetrazol (PTZ)-Induced Convulsions

Creative Biolabs has conducted in vivo efficacy testing for different neurological disorders for years. The extensive range of rodent neurological disease models available at Creative Biolabs covers:

To better meet individual requirements, Creative Biolabs provides expert scientific support to our clients, including consultation with our clients to identify an appropriate model to meet their scientific objectives, to design customized study plans and protocols, and to discuss feasible methods and timelines. Contact us for more information or a formal quote.

Reference

1. Casillasespinosa, P M.; et al. Z944, a novel selective T-type calcium channel antagonist delays the progression of seizures in the amygdala kindling model[J]. 2015. 10(8):90-98.

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