Effects of a neurokinin-1 receptor antagonist in the acute phase after thoracic spinal cord injury in a rat model
Zheng, Guoli, Harms, Anna Kathrin, Tail, Mohamed, Zhang, Hao, Nimmo, Alan, Skutella, Thomas, Kiening, Karl, Unterberg, Andreas, Zweckberger, Klaus, and Younsi, Alexander (2023) Effects of a neurokinin-1 receptor antagonist in the acute phase after thoracic spinal cord injury in a rat model. Frontiers in Molecular Neuroscience, 16. 1128545.
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Abstract
Objective: Disruption of the blood-spinal cord barrier (BSCB) with subsequent edema formation and further neuroinflammation contributes to aggravation of spinal cord injury (SCI). We aimed to observe the effect of antagonizing the binding of the neuropeptide Substance-P (SP) to its neurokinin-1 (NK1) receptor in a rodent SCI model.
Methods: Female Wistar rats were subjected to a T9 laminectomy with or without (Sham) a T9 clip-contusion/compression SCI, followed by the implantation of an osmotic pump for the continuous, seven-day-long infusion of a NK1 receptor antagonist (NRA) or saline (vehicle) into the intrathecal space. The animals were assessed via MRI, and behavioral tests were performed during the experiment. 7 days after SCI, wet & dry weight and immunohistological analyses were conducted.
Results: Substance-P inhibition via NRA showed limited effects on reducing edema. However, the invasion of T-lymphocytes and the number of apoptotic cells were significantly reduced with the NRA treatment. Moreover, a trend of reduced fibrinogen leakage, endothelial and microglial activation, CS-GAG deposition, and astrogliosis was found. Nevertheless, only insignificant general locomotion recovery could be observed in the BBB open field score and the Gridwalk test. In contrast, the CatWalk gait analysis showed an early onset of recovery in several parameters.
Conclusion: Intrathecal administration of NRA might reinforce the integrity of the BSCB in the acute phase after SCI, potentially attenuating aspects of neurogenic inflammation, reducing edema formation, and improving functional recovery.
| Item ID: | 78989 |
|---|---|
| Item Type: | Article (Research - C1) |
| ISSN: | 1662-5099 |
| Keywords: | animal model, behavioral assessment, blood spinal cord barrier, inflammation, neurokinin-1 (NK1) antagonist, spinal cord injury |
| Copyright Information: | © 2023 Zheng, Harms, Tail, Zhang, Nimmo, Skutella, Kiening, Unterberg, Zweckberger and Younsi. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). |
| Date Deposited: | 07 Nov 2023 01:46 |
| FoR Codes: | 32 BIOMEDICAL AND CLINICAL SCIENCES > 3209 Neurosciences > 320999 Neurosciences not elsewhere classified @ 100% |
| SEO Codes: | 28 EXPANDING KNOWLEDGE > 2801 Expanding knowledge > 280112 Expanding knowledge in the health sciences @ 100% |
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