Читать книгу Canine and Feline Epilepsy - Luisa De Risio - Страница 30

Idiopathic epilepsy (see Chapter 6) is the most common cause of seizures in dogs (Podell and Hadjiconstantinou, 1997). Low levels of GABA and high levels of glutamate have been detected in the cerebrospinal fluid of epileptic dogs independent of time relation to recent seizure activity (Podell and Hadjiconstantinou, 1997). The glutamate elevations are not related whether the seizures were focal or generalized in character (Podell and Hadjiconstantinou, 1997). These findings may indicate the brains of epileptic dogs are under a state of chronic over-excitation. Although a separate study found that lower CSF GABA concentration was associated with a reduced response to phenobarbital therapy in dogs, there was no association between CSF glutamate and response to this therapy (Podell and Hadjiconstantinou, 1999). However, a negative association was found between CSF glutamate:GABA ratio and response to phenobarbital therapy (Podell and Hadjiconstantinou, 1999). Therefore glutamate-mediated mechanisms may be useful targets for anticonvulsant therapy in dogs. Intracerebral microdialysis was used to demonstrate elevation of extracellular levels of glutamate in four Shetland sheep-dogs with IE, suggesting an important role in the occurrence of seizure activity (Morita et al., 2005).

Gabapentin (see Chapter 17), a relatively new human anticonvulsant, has been evaluated in dogs refractory to phenobarbitone and potassium bromide with an approximate 50% success rate.

Gabapentin has been shown to modestly decrease glutamate levels in the brain (Errante and Petroff, 2003). Another new anticonvulsant, topiramate (see Chapter 19), produces its antiepileptic effect by several mechanisms, one of which is inhibition of kainite-mediated glutamate receptors (Angehagen et al., 2003a). This drug has also been demonstrated to protect neurons from excitotoxic levels of glutamate, potentially preventing brain damage during seizure activity (Angehagen et al., 2003b).