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Curcumin Prevents Cerebral Ischemia Reperfusion Injury Via Increase of Mitochondrial Biogenesis

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Abstract

Curcumin is known to have neuroprotective properties in cerebral ischemia reperfusion (I/R) injury. However, the underlying molecular mechanisms remain largely unknown. Recently, emerging evidences suggested that increased mitochondrial biogenesis enabled preventing I/R injury. Here, we sought to determinate whether curcumin alleviates I/R damage through regulation of mitochondrial biogenesis. Sprague-Dawley rats were subjected to a 2-h period of right middle cerebral artery occlusion followed by 24 h of reperfusion. Prior to onset of occlusion, rats had been pretreated with either low (50 mg/kg, intraperitoneal injection) or high (100 mg/kg, intraperitoneal injection) dose of curcumin for 5 days. Consequently, we found that curcumin pretreatment enabled improving neurological deficit, diminishing infarct volume and increasing the number of NeuN-labeled neurons in the I/R rats. Accordingly, the index of mitochondrial biogenesis including nuclear respiratory factor-1, mitochondrial transcription factor A and mitochondrial number significantly down-regulated in I/R rats were reversed by curcumin pretreatment in a dose-dependent manner, and the mitochondrial uncoupling protein 2 presented the similar change. Taken together, our findings provided novel evidence that curcumin may exert neuroprotective effects by increasing mitochondrial biogenesis.

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Abbreviations

I/R:

Ischemia reperfusion

IHC:

Immunohistochemistry

MCAO:

Middle cerebral artery occlusion

NRF-1:

Nuclear respiratory factors 1

OGD:

Oxygen glucose deprivation

PGC-1α:

Peroxisome proliferators-activated receptor γ coactivator-1α

ROS:

Reactive oxygen species

RT:

Reverse transcription

TFAM:

Mitochondrial transcription factor A

TTC:

Triphenyltetrazolium chloride

UCP2:

Uncoupling protein 2

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Acknowledgments

Our sincere gratitude is extended to Professor Yu Li for technical assistance. This work was supported by the National Science Foundation of China (30500170).

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Authors and Affiliations

  1. Department of Neurology, The First Affiliated Hospital of Chongqing Medical University, 1 Youyi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China

    Li Liu, Wenchao Zhang, Xi Lu, Yushuang Deng, Yuping Zhang, Xiuming Guo, Jun Mu & Gang Yu

  2. Department of Brain, The Chongqing Hospital of Traditional Chinese Medicine, Chongqing, 400021, People’s Republic of China

    Li Liu

  3. Chongqing Cancer Institute, Chongqing, 400010, People’s Republic of China

    Li Wang

  4. Department of Pathology, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Yu Li

  5. Institute of Neuroscience, Chongqing Medical University, Chongqing, 400016, People’s Republic of China

    Yu Li

  6. Department of Rehabilitation, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China

    Botao Tan

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  1. Li Liu
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  2. Wenchao Zhang
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  11. Gang Yu
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Correspondence to Gang Yu.

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Liu, L., Zhang, W., Wang, L. et al. Curcumin Prevents Cerebral Ischemia Reperfusion Injury Via Increase of Mitochondrial Biogenesis. Neurochem Res 39, 1322–1331 (2014). https://doi.org/10.1007/s11064-014-1315-1

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  • DOI: https://doi.org/10.1007/s11064-014-1315-1

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