• Ping Deng and Zao C Xu.
• Department of Anatomy and Cell Biology, Indiana University School of Medicine, 635 Barnhill Drive, Indianapolis, IN 46202, USA. pideng@iupui.edu
• J. Neurotrauma. 2011 Jul 1; 28 (7): 1173-83.

AbstractTraumatic brain injury (TBI) causes selective neuronal damage in the hippocampus; however, the underlying mechanisms are still unclear. Post-traumatic alterations of ion channel activity, which actively regulate neuronal excitability and thus impact on excitotoxicity, may be involved in TBI-induced neuronal injury. Here we report that hyperpolarization-activated cation current (I(h)) contributes to the distinct vulnerability of hippocampal neurons in TBI. In a rat model of controlled cortical injury, moderate TBI produced neuronal death of both hippocampal CA3 neurons and mossy cells in the hilus, but not CA1 pyramidal cells. Treatment with lamotrigine, which enhances dendritic I(h), ameliorated TBI-induced neuronal damage to CA3 neurons and mossy cells. In contrast, intraventricular administration of I(h) channel blocker caused cell death in the CA1 region after TBI. Whole-cell recordings revealed that, differently from CA3 neurons, CA1 pyramidal cells expressed larger I(h) and exhibited a post-traumatic increase of I(h) amplitude. Moreover, blocking I(h) led to an increase of neuronal excitability, with greater effects seen in post-traumatic CA1 pyramidal cells than in CA3 neurons. In addition, the I(h) in mossy cells was dramatically inhibited early after TBI. Our findings indicate that differential changes of I(h) in hippocampal neurons may be one of the mechanisms of selective cell death, and that an enhancement of functional I(h) may protect hippocampal neurons against TBI.

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