title: Neuroprotective effects of nitidine against traumatic CNS injury via inhibiting microglia activation.
abstract: Glial cell response to injury has been well documented in the pathogenesis after traumatic brain injury (TBI) and spinal cord injury (SCI). Although microglia, the resident macrophages in the central nervous system (CNS), are responsible for clearing debris and toxic substances, excessive activation of these cells will lead to exacerbated secondary damage by releasing a variety of inflammatory and cytotoxic mediators and ultimately influence the subsequent repair after CNS injury. In fact, inhibition of microgliosis represents a therapeutic strategy for CNS trauma. We here showed that nitidine, a benzophenanthridine alkaloid, restricted reactive microgliosis and promoted CNS repair after traumatic injury. Nitidine was shown to prevent cultured microglia from LPS-induced reactive activation by regulation of ERK and NF-κB signaling pathway. Furthermore, the nitidine-mediated inhibition of microgliosis was also shown in injured brain and spinal cord, which significantly increased neuronal survival and decreased neural tissue damage after injury. Importantly, behavioral analysis revealed that nitidine-treated mice with SCI had improved functional recovery as assessed by Basso Mouse Scale and swimming test. Together, these findings indicated that nitidine increased CNS tissue sparing and improved functional recovery by attenuating reactive microgliosis, suggestive of the potential therapeutic benefit for CNS injury.
authors.affiliation: Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Yuan
authors.affiliation: Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai, China.
authors.forename: Yingyan
authors.initials: Y
authors.lastname: Pu
authors.affiliation: Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Wang
authors.affiliation: Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai, China.
authors.forename: Aijun
authors.initials: A
authors.lastname: Huang
authors.affiliation: Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Hu
authors.affiliation: Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai, China.
authors.forename: Shangyao
authors.initials: S
authors.lastname: Qin
authors.affiliation: Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai, China.
authors.forename: Xiu
authors.initials: X
authors.lastname: Sun
authors.affiliation: Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai, China. Electronic address: suzhida@smmu.edu.cn.
authors.forename: Zhida
authors.initials: Z
authors.lastname: Su
authors.affiliation: Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai, China. Electronic address: chenghe@smmu.edu.cn.
authors.forename: Cheng
authors.initials: C
authors.lastname: He
mesh_terms: D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology*; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008262:Macrophage Activation / Q000187:drug effects*; D051379:Mice; D017628:Microglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020127:Recovery of Function; D015398:Signal Transduction / Q000187:drug effects* / Q000502:physiology; D013119:Spinal Cord Injuries / Q000378:metabolism* / Q000473:pathology
chemical_list: D053119:Benzophenanthridines; D008070:Lipopolysaccharides; D016328:NF-kappa B; D018696:Neuroprotective Agents; C013615:nitidine
keywords: Microglia; Neuroprotection; Nitidine; Spinal cord injury; Traumatic brain injury