Abstract

Intracerebral microinjection is a commonly used technique for local delivery of biologically active agents. However, it is known that mechanical injury of the cortex can induce spreading depression (SD), a wave of transient cellular depolarization. We examined the effects of intracortical microinjections of a new selective Ih channel antagonist ORG 34167 and of different control treatments (saline and sham microinjections) on spontaneously occurring spike-wave discharges (SWDs) in WAG/Rij rats, a valid genetic model of absence epilepsy. Electroencephalographic (EEG) recording in awake rats has shown that both the drug and control microinjections are followed by long-term (for more than an hour) suppression of SWDs. dc-EEG recording in WAG/Rij rats has revealed that sham microinjections induce SD in 65% (31/48) cases. Number of SWDs decreased substantially for at least 90min after the sham injections which induced cortical SD but remained unchanged if SD was not triggered by microinjection. These findings suggest that SD induced by intracortical microinjection may contribute to long-term suppression of non-convulsive epileptic activity after this experimental procedure.

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