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Investigations on Alterations of Hippocampal Circuit Function Following Mild Traumatic Brain Injury
Published on: November 19, 2012
Transient cerebral ischemia increases CA1 pyramidal neuron excitability.
Yuan Fan1, Ping Deng, Yu-Chi Wang
1Department of Neurology, Baylor College of Medicine, 6501 Fannin Street, NB204, Houston, TX 77030, USA. yf139876@gmail.com
Experimental Neurology
|June 19, 2008
Summary
Transient cerebral ischemia selectively kills hippocampal CA1 pyramidal neurons. Reduced intrinsic excitability, linked to decreased I(h) current, exacerbates this cell death, suggesting a potential therapeutic target.
Area of Science:
- Neuroscience
- Cell Biology
- Pathology
Background:
- The hippocampal CA1 region is highly vulnerable to ischemia.
- Selective and delayed neuronal death in CA1 pyramidal neurons after ischemia remains poorly understood.
Purpose of the Study:
- To investigate if increased intrinsic excitability of CA1 pyramidal neurons contributes to excitotoxicity after ischemia.
- To explore the role of the hyperpolarization-activated non-selective cationic current (I(h)) in ischemia-induced neuronal death.
Main Methods:
- Whole-cell patch-clamp recordings in brain slices 24 hours after transient cerebral ischemia.
- Assessment of neuronal excitability, input resistance, and membrane time constant.
- Pharmacological manipulation of I(h) using ZD7288 and lamotrigine.
Main Results:
- Ischemia significantly increased input resistance and membrane time constant in CA1 pyramidal neurons, indicating enhanced excitability.
- A decrease in voltage sag suggested a reduction in the I(h) current after ischemia.
- Blocking I(h) mimicked the increased excitability seen post-ischemia.
- Lamotrigine, an I(h) enhancer, significantly reduced CA1 cell loss when applied post-ischemia.
Conclusions:
- Increased intrinsic excitability of CA1 pyramidal neurons following ischemia may worsen cell loss.
- A reduction in dendritic I(h) current (channelopathy) likely contributes to this increased excitability.
- Targeting dendritic I(h) presents a potential therapeutic strategy to mitigate ischemia-induced neuronal death.
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