Background: After spinal cord injury (SCI), destructive immune cell subsets are dominant in the local microenvironment, which are the important mechanism of injury. Studies have shown that inflammasomes play an important role in the inflammation following SCI, and apoptosis associated speck like protein containing a card (ASC) is the adaptor protein shared by inflammasomes. Therefore, we speculated that inhibiting ASC may improve the local microenvironment of injured spinal cord. In this study, CRID3, a blocker of ASC oligomerization, was used to study its effect on the local microenvironment and the possible role in neuroprotection following SCI.
Methods: Murine SCI model was created using an Infinite Horizon impactor at T9 vertebral level with a force of 50 Kdynes and CRID3 (50 mg/kg) was intraperitoneally injected following injury. ASC and its downstream molecules in inflammasome signaling pathway were measured by western blot. The immune cell subsets were detected by immunohistofluorescence (IHF) and flow cytometry (FCM). The spinal cord fibrosis area, neuron survival, myelin preservation and functional recovery were assessed.
Results: Following SCI, CRID3 administration inhibited inflammasome-related ASC and caspase-1, IL-1β and IL-18 activation, which consequently suppressed M1 microglia, Th1 and Th1Th17 differentiation, and increased M2 microglia and Th2 differentiation. Accordingly, the improved histology and behavior also been found.
Conclusions: CRID3 may ameliorates murine SCI by inhibiting inflammasome activation, reducing proinflammatory factor production, restoring immune cell subset balance and improving local immune microenvironment, and early administration may be a promising therapeutic strategy for SCI.
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Posted 13 Apr, 2020
On 29 Aug, 2020
Received 06 Jul, 2020
On 06 Jul, 2020
Received 22 Jun, 2020
On 07 Jun, 2020
On 12 May, 2020
Invitations sent on 20 Apr, 2020
On 09 Apr, 2020
On 08 Apr, 2020
On 07 Apr, 2020
On 07 Apr, 2020
Posted 13 Apr, 2020
On 29 Aug, 2020
Received 06 Jul, 2020
On 06 Jul, 2020
Received 22 Jun, 2020
On 07 Jun, 2020
On 12 May, 2020
Invitations sent on 20 Apr, 2020
On 09 Apr, 2020
On 08 Apr, 2020
On 07 Apr, 2020
On 07 Apr, 2020
Background: After spinal cord injury (SCI), destructive immune cell subsets are dominant in the local microenvironment, which are the important mechanism of injury. Studies have shown that inflammasomes play an important role in the inflammation following SCI, and apoptosis associated speck like protein containing a card (ASC) is the adaptor protein shared by inflammasomes. Therefore, we speculated that inhibiting ASC may improve the local microenvironment of injured spinal cord. In this study, CRID3, a blocker of ASC oligomerization, was used to study its effect on the local microenvironment and the possible role in neuroprotection following SCI.
Methods: Murine SCI model was created using an Infinite Horizon impactor at T9 vertebral level with a force of 50 Kdynes and CRID3 (50 mg/kg) was intraperitoneally injected following injury. ASC and its downstream molecules in inflammasome signaling pathway were measured by western blot. The immune cell subsets were detected by immunohistofluorescence (IHF) and flow cytometry (FCM). The spinal cord fibrosis area, neuron survival, myelin preservation and functional recovery were assessed.
Results: Following SCI, CRID3 administration inhibited inflammasome-related ASC and caspase-1, IL-1β and IL-18 activation, which consequently suppressed M1 microglia, Th1 and Th1Th17 differentiation, and increased M2 microglia and Th2 differentiation. Accordingly, the improved histology and behavior also been found.
Conclusions: CRID3 may ameliorates murine SCI by inhibiting inflammasome activation, reducing proinflammatory factor production, restoring immune cell subset balance and improving local immune microenvironment, and early administration may be a promising therapeutic strategy for SCI.
Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6
Figure 7
Figure 8
Figure 9
Figure 10
Figure 11
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