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Updated: Oct 8, 2025
In Vivo SiRNA Transfection and Gene Knockdown in Spinal Cord via Rapid Noninvasive Lumbar Intrathecal Injections in Mice
Published on: March 22, 2014
Lidocaine relieves spinal cord ischemia-reperfusion injury via long non-coding RNA MIAT-mediated Notch1
Junkai Hou, Huixin Li1, Changjiang Xue1
1Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, 1 Jianshe East Rd., Zhengzhou 450052, People's Republic of China.
Abstract:
Microglial activation and inflammatory response play a critical role in spinal cord ischemia reperfusion injury (SCIRI). This study aimed to investigate whether lidocaine relieves SCIRI via modulating myocardial infarction-associated transcript (MIAT)-mediated Notch1 downregulation. Mouse SCIRI was induced by the obstruction of the aortic arch. Lidocaine was injected after reperfusion. Microglial activation and inflammatory response were assessed by Iba1, interleukin 1 beta (IL-1β) and tumour necrosis factor alpha (TNF-α) levels. The interaction between MIAT and Notch1 was assessed by RNA pull-down and RNA immunoprecipitation assays. Lidocaine treatment relieved SCIRI by reducing Iba1 and serum TNF-α and IL-1β levels. After lidocaine treatment, MIAT expression was elevated in lipopolysaccharide-induced BV2 cells. The interference of MIAT and the overexpression of MIAT and Notch1 restored TNF-α and IL-1β levels in supernatants. Notch1 protein was existent in MIAT-pull-down compounds, and the expression of MIAT was markedly elevated in Notch1-immunoprecipitants. The overexpression of MIAT markedly promoted the degradation of Notch1 and increased the level of ubiquitin-bound Notch1 complex. The therapeutic effect of lidocaine on SCIRI mice could be reversed by adeno-associated virus-mediated MIAT knockdown. In conclusion, lidocaine treatment relieved SCIRI via inhibiting microglial activation and reducing the inflammatory response. The molecular mechanism was partly through MIAT-mediated Notch1 downregulation.
Insights
Lidocaine alleviates spinal cord ischemia reperfusion injury (SCIRI) by reducing inflammation. It achieves this by modulating the myocardial infarction-associated transcript (MIAT)-Notch1 pathway, inhibiting microglial activation.
Area of Science:
- Neuroscience
- Cardiovascular Research
- Molecular Biology
Background:
- Microglial activation and inflammation are key drivers of spinal cord ischemia reperfusion injury (SCIRI).
- Understanding the molecular mechanisms underlying SCIRI is crucial for developing effective treatments.
Purpose of the Study:
- To investigate if lidocaine ameliorates SCIRI by modulating the MIAT-Notch1 pathway.
- To elucidate the role of MIAT in lidocaine's therapeutic effects on SCIRI.
Main Methods:
- Mouse model of SCIRI induced by aortic arch obstruction.
- Assessment of microglial activation (Iba1) and inflammatory markers (IL-1β, TNF-α).
- RNA pull-down and immunoprecipitation assays to determine MIAT-Notch1 interaction; in vitro studies using BV2 cells.
Main Results:
- Lidocaine treatment reduced SCIRI severity, Iba1, TNF-α, and IL-1β levels.
- Lidocaine increased MIAT expression and modulated Notch1 levels, suggesting a regulatory interaction.
- MIAT was found to interact with Notch1, promoting its degradation and influencing inflammatory responses.
Conclusions:
- Lidocaine exerts therapeutic effects on SCIRI by inhibiting microglial activation and inflammation.
- The mechanism involves lidocaine-induced modulation of the MIAT-Notch1 axis, leading to Notch1 downregulation.
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