Thrombin facilitates seizures through activation of persistent sodium current
Elena Isaeva1, Amanda Hernan, Dmytro Isaev
1Department of Neurology, Neuroscience Center at Dartmouth, Dartmouth Medical School, Lebanon, NH, USA. olena.isaeva@gmail.com
Annals of Neurology
|August 29, 2012
Summary
Thrombin in intracerebral hemorrhage (ICH) increases neuronal excitability in immature rat brains by altering sodium channels, potentially explaining seizures in newborns and offering therapeutic targets.
Area of Science:
- Neuroscience
- Cellular Biology
- Neurology
Background:
- Epileptic seizures are common in intracerebral hemorrhage (ICH) but cellular mechanisms remain unclear.
- Blood constituents entering brain tissue during ICH affect neuronal function.
- Thrombin is a key blood component that can evoke seizures upon entering brain tissue.
Purpose of the Study:
- To investigate if thrombin increases neuronal excitability in immature brains by altering voltage-gated sodium channels.
- To elucidate the cellular mechanisms underlying thrombin-induced seizures in the context of ICH.
Main Methods:
- Electrophysiological recordings (extracellular and intracellular) in hippocampal slices from immature rats.
- Assessment of thrombin's effect on neuronal excitability and voltage-gated sodium channels.
- Investigation using N-methyl-D-aspartate (NMDA) and tetrodotoxin (TTX) to probe channel activity.
Main Results:
- Thrombin significantly increased neuronal excitability in the immature hippocampus independently of NMDA receptors.
- Thrombin depolarized the membrane potential and shifted the activation of persistent, TTX-sensitive sodium channels.
- Thrombin did not affect transient sodium channels or action potential threshold.
Conclusions:
- Thrombin amplifies persistent voltage-gated sodium current, impacting resting membrane potential and seizure threshold.
- This mechanism provides a novel explanation for seizures following ICH in newborns.
- Findings suggest potential therapeutic strategies for preventing post-ICH seizures.
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