Dataset Information

Blockade of Kv1.3 channels ameliorates radiation-induced brain injury.

ABSTRACT:

Background

Tumors affecting the head, neck, and brain account for significant morbidity and mortality. The curative efficacy of radiotherapy for these tumors is well established, but radiation carries a significant risk of neurologic injury. So far, neuroprotective therapies for radiation-induced brain injury are still limited. In this study we demonstrate that Stichodactyla helianthus (ShK)-170, a specific inhibitor of the voltage-gated potassium (Kv)1.3 channel, protected mice from radiation-induced brain injury.

Methods

Mice were treated with ShK-170 for 3 days immediately after brain irradiation. Radiation-induced brain injury was assessed by MRI scans and a Morris water maze. Pathophysiological change of the brain was measured by immunofluorescence. Gene and protein expressions of Kv1.3 and inflammatory factors were measured by quantitative real-time PCR, reverse transcription PCR, ELISA assay, and western blot analyses. Kv currents were recorded in the whole-cell configuration of the patch-clamp technique.

Results

Radiation increased Kv1.3 mRNA and protein expression in microglia. Genetic silencing of Kv1.3 by specific short interference RNAs or pharmacological blockade with ShK-170 suppressed radiation-induced production of the proinflammatory factors interleukin-6, cyclooxygenase-2, and tumor necrosis factor-? by microglia. ShK-170 also inhibited neurotoxicity mediated by radiation-activated microglia and promoted neurogenesis by increasing the proliferation of neural progenitor cells.

Conclusions

The therapeutic effect of ShK-170 is mediated by suppression of microglial activation and microglia-mediated neurotoxicity and enhanced neurorestoration by promoting proliferation of neural progenitor cells.

SUBMITTER: Peng Y

PROVIDER: S-EPMC3956348 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Publications

Blockade of Kv1.3 channels ameliorates radiation-induced brain injury.

Peng Ying Y Lu Kui K Li Zichen Z Zhao Yaodong Y Wang Yiping Y Hu Bin B Xu Pengfei P Shi Xiaolei X Zhou Bin B Pennington Michael M Chandy K George KG Tang Yamei Y

Neuro-oncology 20131204 4

<h4>Background</h4>Tumors affecting the head, neck, and brain account for significant morbidity and mortality. The curative efficacy of radiotherapy for these tumors is well established, but radiation carries a significant risk of neurologic injury. So far, neuroprotective therapies for radiation-induced brain injury are still limited. In this study we demonstrate that Stichodactyla helianthus (ShK)-170, a specific inhibitor of the voltage-gated potassium (Kv)1.3 channel, protected mice from rad ...[more]

PMID: 24305723

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Dataset Information

Blockade of Kv1.3 channels ameliorates radiation-induced brain injury.

Background

Methods

Results

Conclusions

Publications

Blockade of Kv1.3 channels ameliorates radiation-induced brain injury.

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