The lithium-pilocarpine model reproduces most clinical and neuropathological features of human temporal lobe epilepsy (TLE). After status epilepticus (SE), rats exhibit a latent seizure-free phase characterized by the development of extensive damage in limbic areas and occurrence of spontaneous recurrent seizures. Creative Biolabs conducts contract studies in this lithium-pilocarpine model of TLE to evaluate the neuroprotective and anti-epileptogenic effects of putative agents.

Introduction of Lithium-Pilocarpine Model

Variations of the pilocarpine model have been established by combining this convulsant with other drugs, such as lithium. Lithium is extensively used as a mood stabilizer in manic-depressive illness, and it has been more recently introduced in the treatment of acute brain injuries and chronic neurodegenerative disease. Here, lithium is combined with pilocarpine to induce SE.

Generally, lithium chloride (3 mEq/kg) is administered 24 h before the injection of pilocarpine for the induction of SE. The sequence of behavioral changes observed in animals undergoing an SE is very similar for lithium-pilocarpine compared to pilocarpine administered alone. Firstly, it is characterized by staring, head bobbing, blinking, and wet-dog shakes. Subsequently, seizures appear about 30 min later. Moreover, similarly, in the lithium-pilocarpine model, neuronal damage occurs in the hippocampus, piriform cortex, entorhinal cortex, amygdala, thalamus, and septum.

Rodent Lithium-Pilocarpine Model of Temporal Lobe Epilepsy (TLE) Fig.1 Electroencephalographic patterns from a representative rat during the first several days after lithium-pilocarpine injection. (Wang et al. 2015)

Features of Pilocarpine-Induced TLE Model

  • The rate of success in developing tonic-clonic seizures and SE after lithium pretreatment is higher.
  • In this model, lithium is given to increase the sensitivity of animals to pilocarpine.
  • The use of lithium also reduces the dose of pilocarpine (30 mg/kg) required to produce SE and induces more stable convulsions in rats.

Assessments

A number of behavior assessments can be incorporated into a specific study plan, including seizure behavior, cognitive behavior, and global motor activity. Moreover, magnetic resonance imaging (MRI) scan of the brain and EGG monitoring can be employed. 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

Rodent Lithium-Pilocarpine Model of Temporal Lobe Epilepsy (TLE)Fig.2 Immunohistochemical analysis of Iba1-immunopositive cells in the hippocampal CA1 (A-D) and the adjacent cortex (E-H) at 3, 7, and 14 days after SE. Con: control; SE: status epilepticus; Iba1: ionized calcium-binding adaptor molecule 1. (Wang et al. 2015)

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

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:

Our highly experienced technical team is based on PhD-level scientists, ensuring that we provide expert scientific support to our clients. To meet the needs of your specific epilepsy drug discovery project we also have the flexibility and expertise to develop custom in vivo models. For more information please contact us or send us an inquiry.

Reference

  1. Wang, N.; et al. Minocycline inhibits brain inflammation and attenuates spontaneous recurrent seizures following pilocarpine-induced status epilepticus[J]. Neuroscience. 2015, 287:144-156.

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