Effects of pro-inflammatory cytokines in experimental spinal cord injury

Secondary mechanisms, including inflammation and microglia activation, serve as targets for the development and application of pharmacological strategies in the management of spinal cord injury (SCI). Tetramethylpyrazine (TMP), an active ingredient of Ligusticum wallichii (chuanxiong), has shown anti-inflammatory and neuroprotective effects against SCI. However, it remains uncertain whether the inflammation-suppressive effects of TMP play a modulatory role over microglia activation in SCI. The present study investigated the effects of TMP on microglia activation and pro-inflammatory cytokines in spinal cord compression injury in mice. For a real-time PCR measurement of pro-inflammatory cytokines, SCI was induced in mice by the clip compression method (30 g force, 1 min) and TMP (15 or 30 mg/kg, i.p.) was administered once, 30 minutes before the SCI induction. For immunohistochemistry, TMP (30 mg/kg, i.p.) treatment was given three times during the first 48 hours after the SCI. 30 mg/kg of TMP treatment reduced the up-regulation of TNF-α, IL-1β and COX-2 mRNA in the spinal tissue at four hours after the SCI induction. TMP also significantly attenuated microglia activation and neutrophil infiltration at 48 hours after the SCI induction. In addition, iNOS expression in the spinal tissue was attenuated with TMP treatment. These results suggest that TMP plays a modulatory role in microglia activation and may protect the spinal cord from or potentially delay secondary spinal cord injury.

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Faculty Opinions recommendation of Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1116570.572609 ◽

2008 ◽

Author(s):

Michael Fehlings ◽

James Austin

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neuropathic Pain ◽

Inflammatory Cytokines ◽

Cord Injury ◽

Pro Inflammatory Cytokines

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Faculty Opinions recommendation of Remote activation of microglia and pro-inflammatory cytokines predict the onset and severity of below-level neuropathic pain after spinal cord injury in rats.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.1116570.575787 ◽

2008 ◽

Author(s):

Mellar Davis

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Neuropathic Pain ◽

Inflammatory Cytokines ◽

Cord Injury ◽

Pro Inflammatory Cytokines

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Leucine rich repeats and calponin homology domain containing 1 inhibits microglia-mediated neuroinflammation in a rat traumatic spinal cord injury model

10.21203/rs.2.18899/v2 ◽

2020 ◽

Author(s):

Wen-Kai Chen ◽

Lin-Juan Feng ◽

Qiao-Dan Liu ◽

Qing-Feng Ke ◽

Pei-Ya Cai ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Inflammatory Cytokines ◽

Negative Regulator ◽

Mitogen Activated Protein Kinase ◽

Neuron Death ◽

Microglial Polarization ◽

Cord Injury ◽

Pro Inflammatory Cytokines

Abstract Background Spinal cord injury (SCI) triggers the primary mechanical injury and secondary inflammation-mediated injury. Neuroinflammation-mediated insult causes secondary and extensive neurological damage after SCI. Microglia play a pivotal role in the initiation and progression of post-SCI neuroinflammation. Methods To elucidate the significance of LRCH1 to microglial functions, we applied lentivirus-induced LRCH1 knockdown in primary microglia culture, and tested the role of LRCH1 in microglia-mediated inflammatory reaction both in vitro and in a rat SCI model. Results We found that LRCH1 was down-regulated in microglia after traumatic SCI. LRCH1 knockdown increased the production of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 after in vitro priming with lipopolysaccharide and adenosine triphosphate. Furthermore, LRCH1 knockdown promoted the priming-induced microglial polarization towards the pro-inflammatory inducible nitric oxide synthase (iNOS)-expressing microglia. LRCH1 knockdown also enhanced microglia-mediated N27 neuron death after priming. Further analysis revealed that LRCH1 knockdown increased priming-induced activation of p38 mitogen-activated protein kinase (MAPK) and Erk1/2 signaling, which are crucial to the inflammatory response of microglia. When LRCH1-knockdown microglia were adoptively injected into rat spinal cords, they enhanced post-SCI production of pro-inflammatory cytokines, increased SCI-induced recruitment of leukocytes, aggravated SCI-induced tissue damage and neuronal death, and worsened the locomotor function. Conclusion Our study reveals for the first time that LRCH1 serves as a negative regulator of microglia-mediated neuroinflammation after SCI, and provides clues for developing novel therapeutic approaches against SCI.

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Therapeutic Effects of Risperidone against Spinal Cord Injury in a Rat Model of Asphyxial Cardiac Arrest: A Focus on Body Temperature, Paraplegia, Motor Neuron Damage, and Neuroinflammation

Veterinary Sciences ◽

10.3390/vetsci8100230 ◽

2021 ◽

Vol 8 (10) ◽

pp. 230

Author(s):

Tae-Kyeong Lee ◽

Jae-Chul Lee ◽

Hyun-Jin Tae ◽

Hyung-Il Kim ◽

Myoung Cheol Shin ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Cardiac Arrest ◽

Inflammatory Cytokines ◽

Motor Neurons ◽

Anterior Horn ◽

Motor Deficits ◽

Cord Injury ◽

Anti Inflammatory ◽

Pro Inflammatory Cytokines

Cardiac arrest (CA) causes severe spinal cord injury and evokes spinal cord disorders including paraplegia. It has been reported that risperidone, an antipsychotic drug, effectively protects neuronal cell death from transient ischemia injury in gerbil brains. However, until now, studies on the effects of risperidone on spinal cord injury after asphyxial CA (ACA) and cardiopulmonary resuscitation (CPR) are not sufficient. Therefore, this study investigated the effect of risperidone on hind limb motor deficits and neuronal damage/death in the lumbar part of the spinal cord following ACA in rats. Mortality, severe motor deficits in the hind limbs, and the damage/death (loss) of motor neurons located in the anterior horn were observed two days after ACA/CPR. These symptoms were significantly alleviated by risperidone (an atypical antipsychotic) treatment after ACA. In vehicle-treated rats, the immunoreactivities of tumor necrosis factor-alpha (TNF-α) and interleukin 1-beta (IL-1β), as pro-inflammatory cytokines, were increased, and the immunoreactivities of IL-4 and IL-13, as anti-inflammatory cytokines, were reduced with time after ACA/CPR. In contrast, in risperidone-treated rats, the immunoreactivity of the pro-inflammatory cytokines was significantly decreased, and the anti-inflammatory cytokines were enhanced compared to vehicle-treated rats. In brief, risperidone treatment after ACA/CPR in rats significantly improved the survival rate and attenuated paralysis, the damage/death (loss) of motor neurons, and inflammation in the lumbar anterior horn. Thus, risperidone might be a therapeutic agent for paraplegia by attenuation of the damage/death (loss) of spinal motor neurons and neuroinflammation after ACA/CPR.

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Leucine rich repeats and calponin homology domain containing 1 inhibits microglia-mediated neuroinflammation in a rat traumatic spinal cord injury model

10.21203/rs.2.18899/v1 ◽

2019 ◽

Author(s):

Wen-Kai Chen ◽

Lin-Juan Feng ◽

Qiao-Dan Liu ◽

Qing-Feng Ke ◽

Pei-Ya Cai ◽

...

Keyword(s):

Spinal Cord ◽

Spinal Cord Injury ◽

Inflammatory Cytokines ◽

Negative Regulator ◽

Mitogen Activated Protein Kinase ◽

Neuron Death ◽

Microglial Polarization ◽

Cord Injury ◽

Pro Inflammatory Cytokines

Abstract Background Spinal cord injury (SCI) triggers the primary mechanical injury and secondary inflammation-mediated injury. Neuroinflammation-mediated insult causes secondary and extensive neurological damage after SCI. Microglia play a pivotal role in the initiation and progression of post-SCI neuroinflammation.Methods To elucidate the significance of LRCH1 to microglial functions, we applied lentivirus-induced LRCH1 knockdown in primary microglia culture, and tested the role of LRCH1 in microglia-mediated inflammatory reaction both in vitro and in a rat SCI model.ResultsWe found that LRCH1 was down-regulated in microglia after traumatic SCI. LRCH1 knockdown increased the production of pro-inflammatory cytokines such as IL-1β, TNF-α, and IL-6 after in vitro priming with lipopolysaccharide and adenosine triphosphate. Furthermore, LRCH1 knockdown promoted the priming-induced microglial polarization towards the pro-inflammatory M1 type, as demonstrated by increased differentiation into inducible nitric oxide synthase (iNOS)+ microglia. LRCH1 knockdown also enhanced microglia-mediated N27 neuron death after priming. Further analysis revealed that LRCH1 knockdown increased priming-induced activation of p38 mitogen-activated protein kinase (MAPK) and Erk1/2 signaling, which are crucial for M1 polarization of microglia. When LRCH1-knockdown microglia were adoptively injected into rat spinal cords, they enhanced post-SCI production of pro-inflammatory cytokines, increased SCI-induced recruitment of leukocytes, aggravated SCI-induced tissue damage and neuronal death, and worsened the locomotor function.Conclusion Our study reveals for the first time that LRCH1 serves as a negative regulator of microglia-mediated neuroinflammation after SCI, and provides clues for developing novel therapeutic approaches against SCI.

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