Effects of a neurokinin-1 receptor antagonist in the acute phase after thoracic spinal cord injury in a rat model

Frontiers in Molecular Neuroscience

Molecular Neuroscience

Alan Nimmo¹  Thomas Skutella²  Andreas Unterberg³  Anna-Kathrin Harms³  Klaus Zweckberger³  Mohamed Tail³  Alexander Younsi³  Karl Kiening³  Hao Zhang³  Guoli Zheng³ 

[1] College of Medicine and Dentistry, James Cook University, Cairns, QLD, Australia;Department of Neuroanatomy, Institute for Anatomy and Cell Biology, University of Heidelberg, Heidelberg, Germany;Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany;

关键词: spinal cord injury;    animal model;    neurokinin-1 (NK1) antagonist;    blood spinal cord barrier;    inflammation;    behavioral assessment;   

DOI  :  10.3389/fnmol.2023.1128545

 received in 2022-12-20, accepted in 2023-04-17,  发布年份 2023

来源: Frontiers

【 摘 要 】

ObjectiveDisruption 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.MethodsFemale 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.ResultsSubstance-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.ConclusionIntrathecal 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.

【 授权许可】

Unknown   
Copyright © 2023 Zheng, Harms, Tail, Zhang, Nimmo, Skutella, Kiening, Unterberg, Zweckberger and Younsi.