title: Dextromethorphan provides neuroprotection via anti-inflammatory and anti-excitotoxicity effects in the cortex following traumatic brain injury.
abstract: Traumatic brain injury (TBI) is caused by primary and secondary injury mechanisms. TBI induces a certain amount of inflammatory responses and glutamate excitotoxicity that are believed to participate in the pathogenesis of secondary injury. The non‑narcotic anti‑tussive drug dextromethorphan (DM) has been reported to have a high safety profile in humans and its neuroprotective against a variety of disorders, including cerebral ischemia, epilepsy and acute brain injury. However, few studies have explored the underlying mechanisms of the neuroprotective effects of DM in animals in the setting of TBI. The aim of the present study was to investigate the neuroprotective effects of DM on TBI and to determine the underlying mechanisms. Rats were subjected to a controlled cortical impact (CCI) injury and randomly divided into three groups: Sham‑operated, TBI and DM treatment groups. The DM treatment group was administered DM (30 mg/kg of body weight, intraperitoneally) immediately after injury. It was identified that DM treatment following TBI significantly reduced brain edema and neurological deficits, as well as increased neuronal survival. These effects correlated with a decrease of tumor necrosis factor α, interleukin‑1β (IL‑1β) and IL‑6 protein expression and an increase of glutamate/aspartate transporter and glutamate transporter‑1 in the cortex of the brain. These results provided in vivo evidence that DM exerts neuroprotective effects via reducing inflammation and excitotoxicity induced following TBI. The present study has shed light on the potential use of DM as a neuroprotective agent in the treatment of cerebral injuries.
authors.affiliation: Department of Neurosurgery, Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200333, P.R. China.
authors.forename: Benfang
authors.initials: B
authors.lastname: Pu
authors.affiliation: Department of Neurosurgery, Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200333, P.R. China.
authors.forename: Yonghua
authors.initials: Y
authors.lastname: Xue
authors.affiliation: Department of Neurosurgery, Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200333, P.R. China.
authors.forename: Qingming
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200333, P.R. China.
authors.forename: Chunhui
authors.initials: C
authors.lastname: Hua
authors.affiliation: Department of Neurosurgery, Tongren Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200333, P.R. China.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Li
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D001929:Brain Edema / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001930:Brain Injuries / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D003915:Dextromethorphan / Q000627:therapeutic use*; D007249:Inflammation / Q000150:complications / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D053583:Interleukin-1beta / Q000032:analysis / Q000276:immunology; D015850:Interleukin-6 / Q000032:analysis / Q000276:immunology; D008297:Male; D000066829:Neuroprotection / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D053583:Interleukin-1beta; D015850:Interleukin-6; D018696:Neuroprotective Agents; D014409:Tumor Necrosis Factor-alpha; D003915:Dextromethorphan