Epilepsy pilocarpine model

Voutsinos-Porche B., Koning E., Clement Y., Kaplan H., Ferrandon A., Motte J., and Nehlig A. (2006). EAAC1 glutamate transporter expression in the rat lithium-pilocarpine model of temporal lobe epilepsy. J. Cereb. Blood Flow Metab 26 1419-1430. 

A confusing picture emerges when cannabinoids are evaluated in animal models of epilepsy (Karler and Turkanis 1981 Consroe and Snider 1986). CBD has anticonvulsant properties with a spectrum distinct from standard anticonvulsants, apparently not hampered by the development of tolerance but with a varying profile according to the species tested. THC can produce seizures in some circumstances but is anticonvulsant in others. In a recent study, THC (10 mg/kg) completely abolished spontaneous seizures in the rat pilocarpine model of epilepsy (Wallace et al. 2003). The results also indicated that endogenous cannabinoid tone may modulate seizure termination and duration via the CBi receptor. 

Jones DM, Esmaeil N, Maren S et al. (2002). Characterization of pharmacoresistance to benzodiazepines in the rat Li-pilocarpine model of status epilepticus. Epilepsy Res, 50, 301-312. 

Andre, V, Ferrandon, A, Marescaux, C, Nehlig, A (2001) Vigabatrin protects against hippocampal damage but is not antiepileptogenic in the hthium-pilocarpine model of temporal lobe epilepsy. Epilepsy Res, 47 99-117. 

CapeUa, HM, Lemos, T (2002) Effect on epUeptogenesis of carbamazepine treatment during the silent period of the pilocarpine model of epilepsy. Epilepsia, 43 (Suppl 5) 110-111. 

Houser, CR, Esclapez, M (1996) Vulnerability and plasticity of the GABA system in the pilocarpine model of spontaneous recurrent seizures. Epilepsy Res, 26 207-218. 

Rigoulot, MA, Koning, E, Ferrandon, A, Nehlig, A (2004) Neuroprotective properties of topiram-ate in the Uthium-pilocarpine model of epilepsy. J Pharmacol Exp Ther, 308 787-795. 

Williams, PA, Wuarin, JP, Dou, P, Ferraro, DJ, Dudek, FE (2002) Reassessment of the effects of cycloheximide on mossy fiber sprouting and epileptogenesis in the pilocarpine model of temporal lobe epilepsy. J Neurophysiol, 88 2075-2087. 

Prolonged or repetitive early life seizures increase the subsequent risk of developing epilepsy by affecting hippocampal excitability. Animal studies confirm this in the lithium-pilocarpine model (Zhang et al., 2004). 

Isokawa, M. 1998. Remodeling dendritic spines in the rat pilocarpine model of temporal lobe epilepsy. Neurosci Lett 258(2) 73-76... 

Vianna EP, Ferreira AT, Dona F, Cavalheiro EA, Silva Fernandes MJ (2005) Modulation of seizures and synaptic plasticity by adenosinergic receptors in an experimental model of temporal lobe epilepsy induced by pilocarpine in rats. Epilepsia 46(Suppl 5) 166-173 Volpini R, Costanzi S, Lambertucci C, Taffi S, Vittori S, Klotz KN, Cristalli G (2002) N(6)-alkyl-2-alkynyl derivatives of adenosine as potent and selective agonists at the human adenosine A(3) receptor and a starting point for searching A(2B) ligands. J Med Chem 45(15) 3271-3279... 

Additional studies carried out in animal models of temporal lobe epilepsy (TLE) further support the use of selective ABCBl inhibitors to reverse drug resistance in RE. Thus, tariquidar potentiates the effect of phenytoin and countervails resistance to phenobarbital in a rat model of TLE. Furthermore, cyclosporin A helps reverse resistance to phenytoin in a rat model of AED-resistant status epilepticus. Finally, verapamil counteracts resistance to oxacarbazepine in rats with pilocarpine-induced seizures [42]. 

Turski, L, Ikonomidou, C, Turski, WA, Bortolotto, ZA, Cavalheiro, EA (1989) Review cholinergic mechanisms and epileptogenesis. The seizures induced by pilocarpine a novel experimental model of intractable epilepsy. Synapse, 3 154—171. 

Both peri-ictal and post-ictal changes in DU occur in animal models and in human epilepsy after SE and brief seizures. In the peri-ictal phase, reduced diffusivity is seen in animal models and in up to 50% of patients after seizures in one series (Diehl et al., 2005). This may be secondary to cellular swelling and reduced extracellular space due to the failure of ATPase which results in the accumulation of intracellular sodium and water (Wang et al., 1996). Transient decreases in diffusivity are seen post-ictally in kainic acid-induced SE in rodents. Increase in diffusivity is seen with chronic pilocarpine-induced seizures thought to be due to the loss of cellular and structural integrity. 

Systemic or intracerebral administration of pilocarpine hydrochloride in high doses induces seizures in rodents. These seizures are characterized by a sequential development of behavioral patterns and electrographic activity [69]. The pilocarpine seizure induces status epilepticus like in humans mimicking the pathogenesis and progression of mesial temporal lobe epilepsy [70]. It can be useful to exploit these model properties to design new therapeutic approaches for treating refractory epilepsies. 

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