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

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.

Dexmedetomidine Attenuates Neuroinflammatory–Induced Apoptosis after Traumatic Brain Injury via Nrf2 signaling pathway

“…NF‐ κ B is a proinflammatory regulatory cytokine that can intensify inflammatory responses . Upregulation of Nrf2 activity could improve clinical outcomes through reduction of oxidative stress and post‐traumatic inflammatory responses . By contrast, repression of the NF‐ κ B inhibitor system in an experimental model of closed‐head injury promoted neuronal cell death, worsened the neurological outcome and increased post‐traumatic mortality rate.…”

Inhibition of Elevated Hippocampal CD24 Reduces Neurogenesis in Mice With Traumatic Brain Injury

“…After TBI, neuron loss in the ipsilateral hippocampus away from the primary injury site causes neurological and functional complications. 33 Medicationinduced increase in hippocampal neurogenesis could ameliorate impaired cognitive functions because of newly immature neurons possessing essential properties of functional neurons in uninjured adult mice. 34 We guess that CD24 may indirectly affect cognitive function by regulating neurogenesis.…”

SIRT1 Activation by Natural Phytochemicals: An Overview

“…Berberine (BBR) is an isoquinoline alkaloid reported to have analgesic, anticancer, anti-inflammatory, and myocardial protective properties (Cicero and Baggioni, 2016). It was found to exert protective antioxidative effects in different physiologic and pathologic conditions (Huang et al, 2018;Li et al, 2020b). However, the mechanisms underlying these effects remain unclear.…”