Tissue plasminogen activator does not alter development of acquired epilepsy

Area of Science:

• Neuroscience
• Epileptology
• Stroke Research

Background:

• Tissue plasminogen activator (t-PA) is crucial for neuronal activity and synaptic plasticity.
• Elevated t-PA expression after seizures suggests a role in seizure propagation.
• This raises concerns about the potential for t-PA treatment in stroke to increase poststroke epilepsy risk.

Purpose of the Study:

• To investigate the role of t-PA in epilepsy development using experimental and clinical models.
• To determine if t-PA influences seizure susceptibility and the development of epileptogenesis.

Main Methods:

• Mice lacking t-PA (t-PA(-/-)) and mice overexpressing neuronal t-PA (T4) were subjected to amygdala kindling to assess seizure threshold and kindling rates.
• A clinical study compared early and late seizure/epilepsy incidence in acute ischemic stroke patients treated with intravenous t-PA versus those who were not.

Main Results:

• T4 mice exhibited lower seizure thresholds compared to wild-type controls, indicating increased seizure proneness.
• Neither T4 nor t-PA(-/-) mice showed significant differences in the rate of kindling development.
• No significant difference in the incidence of early or late seizures, or epilepsy development, was observed between stroke patients who received t-PA and those who did not.

Conclusions:

• While overexpression of endogenous t-PA can lower seizure threshold, it does not appear to influence the process of kindling epileptogenesis.
• Therapeutic administration of t-PA in human stroke patients does not affect the development of acquired poststroke epilepsy.