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Neuroprotective effects of nitidine against traumatic CNS injury via inhibiting microglia activation
Yimin Yuan1, Feng Zhu1, Yingyan Pu1
1Institute of Neuroscience and Key Laboratory of Molecular Neurobiology of Ministry of Education, Second Military Medical University, Shanghai, China.
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.
Insights
Nitidine, a natural compound, reduces harmful microglial activation after traumatic brain and spinal cord injuries. This neuroprotective effect promotes tissue repair and improves functional recovery in animal models.
Area of Science:
- Neuroscience
- Cell Biology
- Pharmacology
Background:
- Glial cell activation, particularly microglia, is a key factor in secondary damage following central nervous system (CNS) injuries like traumatic brain injury (TBI) and spinal cord injury (SCI).
- While microglia clear debris, their excessive activation releases inflammatory mediators that worsen neural tissue damage and hinder repair.
- Inhibiting this detrimental microglial response (microgliosis) is a promising therapeutic strategy for CNS trauma.
Purpose of the Study:
- To investigate the therapeutic potential of nitidine, a benzophenanthridine alkaloid, in mitigating reactive microgliosis and promoting CNS repair.
- To elucidate the molecular mechanisms underlying nitidine's effects on microglial activation.
Main Methods:
- In vitro studies using cultured microglia exposed to lipopolysaccharide (LPS) to assess nitidine's effect on activation pathways (ERK, NF-κB).
- In vivo studies involving TBI and SCI models in mice to evaluate nitidine's impact on microgliosis, neuronal survival, and tissue damage.
- Behavioral assessments (Basso Mouse Scale, swimming test) to measure functional recovery after SCI in nitidine-treated mice.
Main Results:
- Nitidine inhibited LPS-induced reactive activation of cultured microglia by regulating ERK and NF-κB signaling pathways.
- In vivo, nitidine treatment reduced microgliosis in injured brain and spinal cord tissues.
- Nitidine administration led to increased neuronal survival, decreased neural tissue damage, and improved functional recovery in SCI mice.
Conclusions:
- Nitidine effectively attenuates reactive microgliosis in the CNS following traumatic injury.
- Nitidine demonstrates neuroprotective effects, enhancing tissue sparing and functional recovery.
- Nitidine represents a potential therapeutic agent for treating CNS injuries by modulating glial cell responses.
