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

Guoli Zheng; Anna-Kathrin Harms; Mohamed Tail; Hao Zhang; Alan Nimmo; Thomas Skutella; Karl Kiening; Andreas Unterberg; Klaus Zweckberger; Alexander Younsi

doi:10.3389/fnmol.2023.1128545

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

Front Mol Neurosci. 2023 May 12:16:1128545. doi: 10.3389/fnmol.2023.1128545. eCollection 2023.

Authors

Affiliations

¹ Department of Neurosurgery, Heidelberg University Hospital, Heidelberg, Germany.
² College of Medicine and Dentistry, James Cook University, Cairns, QLD, Australia.
³ Department of Neuroanatomy, Institute for Anatomy and Cell Biology, University of Heidelberg, Heidelberg, Germany.

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.

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