Berberine Protects against Neuronal Damage via Suppression of Glia-Mediated Inflammation in Traumatic Brain Injury

被引:64
作者
Chen, Chien-Cheng [1 ]
Hung, Tai-Ho [2 ,3 ]
Lee, Chao Yu [1 ]
Wang, Liang-Fei [4 ,5 ,6 ]
Wu, Chun-Hu [4 ,5 ,6 ]
Ke, Chia-Hua [1 ,4 ,5 ]
Chen, Szu-Fu [1 ,4 ,5 ]
机构
[1] Cheng Hsin Gen Hosp, Dept Phys Med & Rehabil, Taipei, Taiwan
[2] Chang Gung Mem Hosp, Dept Obstet & Gynecol, Taipei 10591, Taiwan
[3] Chang Gung Univ, Coll Med, Taipei, Taiwan
[4] Natl Def Med Ctr, Dept Physiol, Taipei, Taiwan
[5] Natl Def Med Ctr, Dept Biophys, Taipei, Taiwan
[6] Natl Def Med Ctr, Grad Inst Life Sci, Taipei, Taiwan
关键词
CONTROLLED CORTICAL IMPACT; COPTIDIS-RHIZOMA EXTRACT; CEREBRAL-ISCHEMIA; INTESTINAL INJURY; TYROSINE KINASE; NERVOUS-SYSTEM; NITRIC-OXIDE; IN-VITRO; MICROGLIA; MICE;
D O I
10.1371/journal.pone.0115694
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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-kappa B 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.
引用
收藏
页数:30
相关论文
共 55 条
[1]   Absence of TLR4 Reduces Neurovascular Unit and Secondary Inflammatory Process after Traumatic Brain Injury in Mice [J].
Ahmad, Akbar ;
Crupi, Rosalia ;
Campolo, Michela ;
Genovese, Tiziana ;
Esposito, Emanuela ;
Cuzzocrea, Salvatore .
PLOS ONE, 2013, 8 (03)
[2]   TNFα-induced and berberine-antagonized tight junction barrier impairment via tyrosine kinase, Akt and NFκB signaling [J].
Amasheh, Maren ;
Fromm, Anja ;
Krug, Susanne M. ;
Amasheh, Salah ;
Andres, Susanne ;
Zeitz, Martin ;
Fromm, Michael ;
Schulzke, Joerg-Dieter .
JOURNAL OF CELL SCIENCE, 2010, 123 (23) :4145-4155
[3]  
Barreto George, 2011, Central Nervous System Agents in Medicinal Chemistry, V11, P164
[4]  
Baskaya MK, 1997, NEUROSCI LETT, V226, P33
[5]  
Batchelor PE, 1999, J NEUROSCI, V19, P1708
[6]   Microglia and inflammation-mediated neurodegeneration: Multiple triggers with a common mechanism [J].
Block, ML ;
Hong, JS .
PROGRESS IN NEUROBIOLOGY, 2005, 76 (02) :77-98
[7]   Pathophysiology of cerebral ischemia and brain trauma: Similarities and differences [J].
Bramlett, HM ;
Dietrich, WD .
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2004, 24 (02) :133-150
[8]   Inflammatory Neurodegeneration and Mechanisms of Microglial Killing of Neurons [J].
Brown, Guy C. ;
Neher, Jonas J. .
MOLECULAR NEUROBIOLOGY, 2010, 41 (2-3) :242-247
[9]   Flow cytometric analysis of inflammatory cells in ischemic rat brain [J].
Campanella, M ;
Sciorati, C ;
Tarozzo, G ;
Beltramo, M .
STROKE, 2002, 33 (02) :586-592
[10]  
Carson MJ, 1998, GLIA, V22, P72, DOI 10.1002/(SICI)1098-1136(199801)22:1<72::AID-GLIA7>3.0.CO