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Berberine protects against neuronal damage via suppression of glia-mediated inflammation in traumatic brain injury.
PLoS One. 2014; 9(12):e115694.Plos

Abstract

Traumatic brain injury (TBI) triggers a series of neuroinflammatory processes that contribute to evolution of neuronal injury. The present study investigated the neuroprotective effects and anti-inflammatory actions of berberine, an isoquinoline alkaloid, in both in vitro and in vivo TBI models. Mice subjected to controlled cortical impact injury were injected with berberine (10 mg·kg(-1)) or vehicle 10 min after injury. In addition to behavioral studies and histology analysis, blood-brain barrier (BBB) permeability and brain water content were determined. Expression of PI3K/Akt and Erk signaling and inflammatory mediators were also analyzed. The protective effect of berberine was also investigated in cultured neurons either subjected to stretch injury or exposed to conditioned media with activated microglia. Berberine significantly attenuated functional deficits and brain damage associated with TBI up to day 28 post-injury. Berberine also reduced neuronal death, apoptosis, BBB permeability, and brain edema at day 1 post-injury. These changes coincided with a marked reduction in leukocyte infiltration, microglial activation, matrix metalloproteinase-9 activity, and expression of inflammatory mediators. Berberine had no effect on Akt or Erk 1/2 phosphorylation. In mixed glial cultures, berberine reduced TLR4/MyD88/NF-κB signaling. Berberine also attenuated neuronal death induced by microglial conditioned media; however, it did not directly protect cultured neurons subjected to stretch injury. Moreover, administration of berberine at 3 h post-injury also reduced TBI-induced neuronal damage, apoptosis and inflammation in vivo. Berberine reduces TBI-induced brain damage by limiting the production of inflammatory mediators by glial cells, rather than by a direct neuroprotective effect.

Authors+Show Affiliations

Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan, Republic of China.Department of Obstetrics and Gynecology, Chang Gung Memorial Hospital at Taipei and College of Medicine, Chang Gung University, Taipei, Taiwan, Republic of China.Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan, Republic of China.Departments of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, Republic of China; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.Departments of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, Republic of China; Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan, Republic of China; Departments of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, Republic of China.Department of Physical Medicine and Rehabilitation, Cheng Hsin General Hospital, Taipei, Taiwan, Republic of China; Departments of Physiology and Biophysics, National Defense Medical Center, Taipei, Taiwan, Republic of China.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

25546475

Citation

Chen, Chien-Cheng, et al. "Berberine Protects Against Neuronal Damage Via Suppression of Glia-mediated Inflammation in Traumatic Brain Injury." PloS One, vol. 9, no. 12, 2014, pp. e115694.
Chen CC, Hung TH, Lee CY, et al. Berberine protects against neuronal damage via suppression of glia-mediated inflammation in traumatic brain injury. PLoS ONE. 2014;9(12):e115694.
Chen, C. C., Hung, T. H., Lee, C. Y., Wang, L. F., Wu, C. H., Ke, C. H., & Chen, S. F. (2014). Berberine protects against neuronal damage via suppression of glia-mediated inflammation in traumatic brain injury. PloS One, 9(12), e115694. https://doi.org/10.1371/journal.pone.0115694
Chen CC, et al. Berberine Protects Against Neuronal Damage Via Suppression of Glia-mediated Inflammation in Traumatic Brain Injury. PLoS ONE. 2014;9(12):e115694. PubMed PMID: 25546475.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Berberine protects against neuronal damage via suppression of glia-mediated inflammation in traumatic brain injury. AU - Chen,Chien-Cheng, AU - Hung,Tai-Ho, AU - Lee,Chao Yu, AU - Wang,Liang-Fei, AU - Wu,Chun-Hu, AU - Ke,Chia-Hua, AU - Chen,Szu-Fu, Y1 - 2014/12/29/ PY - 2014/08/23/received PY - 2014/11/26/accepted PY - 2014/12/30/entrez PY - 2014/12/30/pubmed PY - 2015/9/5/medline SP - e115694 EP - e115694 JF - PloS one JO - PLoS ONE VL - 9 IS - 12 N2 - Traumatic brain injury (TBI) triggers a series of neuroinflammatory processes that contribute to evolution of neuronal injury. The present study investigated the neuroprotective effects and anti-inflammatory actions of berberine, an isoquinoline alkaloid, in both in vitro and in vivo TBI models. Mice subjected to controlled cortical impact injury were injected with berberine (10 mg·kg(-1)) or vehicle 10 min after injury. In addition to behavioral studies and histology analysis, blood-brain barrier (BBB) permeability and brain water content were determined. Expression of PI3K/Akt and Erk signaling and inflammatory mediators were also analyzed. The protective effect of berberine was also investigated in cultured neurons either subjected to stretch injury or exposed to conditioned media with activated microglia. Berberine significantly attenuated functional deficits and brain damage associated with TBI up to day 28 post-injury. Berberine also reduced neuronal death, apoptosis, BBB permeability, and brain edema at day 1 post-injury. These changes coincided with a marked reduction in leukocyte infiltration, microglial activation, matrix metalloproteinase-9 activity, and expression of inflammatory mediators. Berberine had no effect on Akt or Erk 1/2 phosphorylation. In mixed glial cultures, berberine reduced TLR4/MyD88/NF-κB signaling. Berberine also attenuated neuronal death induced by microglial conditioned media; however, it did not directly protect cultured neurons subjected to stretch injury. Moreover, administration of berberine at 3 h post-injury also reduced TBI-induced neuronal damage, apoptosis and inflammation in vivo. Berberine reduces TBI-induced brain damage by limiting the production of inflammatory mediators by glial cells, rather than by a direct neuroprotective effect. SN - 1932-6203 UR - https://www.unboundmedicine.com/medline/citation/25546475/Berberine_protects_against_neuronal_damage_via_suppression_of_glia_mediated_inflammation_in_traumatic_brain_injury_ L2 - http://dx.plos.org/10.1371/journal.pone.0115694 DB - PRIME DP - Unbound Medicine ER -