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Berberine Protects Secondary Injury in Mice with Traumatic Brain Injury Through Anti-oxidative and Anti-inflammatory Modulation

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Abstract

Traumatic brain injury (TBI) is one of the major causes of death and disability worldwide. Novel and effective therapy is needed to prevent the secondary spread of damage beyond the initial injury. The aim of this study was to investigate whether berberine has a neuroprotective effect on secondary injury post-TBI, and to explore its potential mechanism in this protection. The mice were randomly divided into Sham-saline, TBI-saline and TBI-Berberine (50 mg/kg). TBI was induced by Feeney’s weight-drop technique. Saline or berberine was administered via oral gavage starting 1 h post-TBI and continuously for 21 days. Motor coordination, spatial learning and memory were assessed using beam-walking test and Morris water maze test, respectively. Brain sections were processed for lesion volume assessment, and expression of neuronal nuclei (NeuN), cyclooxygenase 2 (COX-2), inducible nitric oxide synthase (iNOS), 8-hydroxy-2-deoxyguanosine (8-OHdG), ionized calcium-binding adapter molecule 1 (Iba1) and glial fibrillary acidic protein (GFAP) were detected via immunohistochemistry and immunofluorescence. There were statistically significant improvement in motor coordination, spatial learning and memory in the TBI-Berberine group, compared to the TBI-saline group. Treatment with berberine significantly reduced cortical lesion volume, neuronal loss, COX-2, iNOS and 8-OHdG expression in both the cortical lesion border zone (LBZ) and ipsilateral hippocampal CA1 region (CA1), compared to TBI-saline. Berberine treatment also significantly decreased Iba1- and GFAP-positive cell number in both the cortical LBZ and ipsilateral CA1, relative to saline controls. These results indicated that berberine exerted neuroprotective effects on secondary injury in mice with TBI probably through anti-oxidative and anti-inflammatory properties.

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Funding

This work was supported by the Natural Science Foundation of Guangdong Province China (S2013010015786), (2015A030310294) and the Natural Science Foundation of Shaoguan City, Guangdong Province, China (2010-01).

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Author notes

  1. Shu-Xuan Huang and Guozhen Qiu have contributed equally to this work.

Authors and Affiliations

  1. Cognitive Impairment Ward of Neurology Department, The Third Affiliated Hospital of Shenzhen University, 47 Youyi Rd., Shenzhen, 518001, Guangdong Province, China

    Guozhen Qiu, Chun-Chun Chen & Fei-Qi Zhu

  2. Department of Neurology, The Affiliated Yuebei People’s Hospital of Shantou University, Shaoguan, 512026, Guangdong Province, China

    Shu-Xuan Huang, Zhi Yang, Xu-Hui Deng, **-Hua Zhu, Wei-Feng Lin & Fei-Qi Zhu

  3. Department of Neurology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, Guangdong Province, China

    Shu-Xuan Huang

  4. Luohu District Health and Family Planning Bureau, Shenzhen, 518001, Guangdong Province, China

    Fu-Rong Cheng

  5. Department of Neurology, Sun Yat-sen University First Affiliated Hospital, Guangzhou, 510080, Guangdong Province, China

    Zhong Pei

  6. Department of Neurology, The Affiliated Shunde First People’s Hospital of Southern Medical University, Foshan, 528300, Guangdong Province, China

    Lue Chen

  7. Department of Neurology, Third Hospital of Hangzhou, Hangzhou, 310009, Zhejiang Province, China

    Yuan Liu

  8. Department of Neurology and Center for Translational Neuromedicine, University of Rochester Medical Center, Rochester, NY, 14642, USA

    Zhengshan Liu

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  1. Shu-Xuan Huang
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Correspondence to Fei-Qi Zhu.

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Huang, SX., Qiu, G., Cheng, FR. et al. Berberine Protects Secondary Injury in Mice with Traumatic Brain Injury Through Anti-oxidative and Anti-inflammatory Modulation. Neurochem Res 43, 1814–1825 (2018). https://doi.org/10.1007/s11064-018-2597-5

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