Berberine Protects Secondary Injury in Mice with Traumatic Brain Injury Through Anti-oxidative and Anti-inflammatory Modulation
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.
KeywordsTraumatic brain injury Berberine Oxidative stress Inflammatory Secondary injury
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).
Compliance with ethical standards
Conflict of interest
The authors declare no conflict of interest.
- 3.Liu YR, Cardamone L, Hogan RE, Gregoire MC, Williams JP, Hicks RJ, Binns D, Koe A, Jones NC, Myers DE, O’Brien TJ, Bouilleret V (2010) Progressive metabolic and structural cerebral perturbations after traumatic brain injury: an in vivo imaging study in the rat. J Nucl Med 51(11):1788–1795CrossRefPubMedGoogle Scholar
- 24.Zilles K (2012) The cortex of the rat: a stereotaxic atlas. Springer, BerlinGoogle Scholar
- 41.Zhao Y, Patzer A, Herdegen T, Gohlke P, Culman J (2006) Activation of cerebral peroxisome proliferator-activated receptors gamma promotes neuroprotection by attenuation of neuronal cyclooxygenase-2 overexpression after focal cerebral ischemia in rats. FASEB J 20(8):1162–1175CrossRefPubMedGoogle Scholar