PMID- 36466180 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20221206 IS - 1662-4548 (Print) IS - 1662-453X (Electronic) IS - 1662-453X (Linking) VI - 16 DP - 2022 TI - Ultrastructural destruction of neurovascular unit in experimental cervical spondylotic myelopathy. PG - 1031180 LID - 10.3389/fnins.2022.1031180 [doi] LID - 1031180 AB - BACKGROUND AND PURPOSE: The pathogenesis of cervical spondylotic myelopathy (CSM) remains unclear. This study aimed to explore the ultrastructural pathology of neurovascular unit (NVU) during natural development of CSM. METHODS: A total of 24 rats were randomly allocated to the control group and the CSM group. Basso-Beattie-Bresnahan (BBB) scoring and somatosensory evoked potentials (SEP) were used as functional assessments. Hematoxylin-eosin (HE), toluidine blue (TB), and Luxol fast blue (LFB) stains were used for general structure observation. Transmission electron microscopy (TEM) was applied for investigating ultrastructural characteristics. RESULTS: The evident compression caused significant neurological dysfunction, which was confirmed by the decrease in BBB score and SEP amplitude, as well as the prolongation of SEP latency (P < 0.05). The histopathological findings verified a significant decrease in the amount of Nissl body and myelin area and an increase in vacuolation compared with the control group (P < 0.05). The TEM results revealed ultrastructural destruction of NVU in several forms, including: neuronal degeneration and apoptosis; disruption of axonal cytoskeleton (neurofilaments) and myelin sheath and dystrophy of axonal terminal with dysfunction mitochondria; degenerative oligodendrocyte, astrocyte, and microglial cell inclusions with degenerating axon and dystrophic dendrite; swollen microvascular endothelium and loss of tight junction integrity; corroded basement membrane and collapsed microvascular wall; and proliferated pericyte and perivascular astrocytic endfeet. In the CSM group, reduction was observed in the amount of mitochondria with normal appearance and the number of cristae per mitochondria (P < 0.05), while no substantial drop of synaptic vesicle number was seen (P > 0.05). Significant narrowing of microvascular lumen size was also observed, accompanied by growth in the vascular wall area, endothelial area, basement membrane thickness, astrocytic endfeet area, and pericyte coverage area (rate) (P < 0.05). CONCLUSION: Altogether, the findings of this study demonstrated ultrastructural destruction of NVU in an experimental CSM model with dorsal-lateral compression, revealing one of the crucial pathophysiological mechanisms of CSM. CI - Copyright (c) 2022 Li, Wang, Tan, Wang, Hu and Hu. FAU - Li, Guang-Sheng AU - Li GS AD - Spinal Division of Orthopaedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Wang, Xu-Xiang AU - Wang XX AD - Spinal Division of Orthopaedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Tan, Ron-Bang AU - Tan RB AD - Spinal Division of Orthopaedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. FAU - Wang, Kang-Heng AU - Wang KH AD - Spinal Division of Orthopaedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. AD - Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. FAU - Hu, Xiao-Song AU - Hu XS AD - Spinal Division of Orthopaedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. AD - Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. FAU - Hu, Yong AU - Hu Y AD - Spinal Division of Orthopaedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang, China. AD - Department of Orthopaedics and Traumatology, The University of Hong Kong-Shenzhen Hospital, Shenzhen, China. AD - Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, Hong Kong SAR, China. LA - eng PT - Journal Article DEP - 20221116 PL - Switzerland TA - Front Neurosci JT - Frontiers in neuroscience JID - 101478481 PMC - PMC9709118 OTO - NOTNLM OT - cervical spondylotic myelopathy OT - chronic OT - compressive OT - neurovascular unit OT - spinal cord injury OT - ultrastructural evidence OT - ultrastructural pathology COIS- The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. EDAT- 2022/12/06 06:00 MHDA- 2022/12/06 06:01 PMCR- 2022/01/01 CRDT- 2022/12/05 03:57 PHST- 2022/08/29 00:00 [received] PHST- 2022/10/25 00:00 [accepted] PHST- 2022/12/05 03:57 [entrez] PHST- 2022/12/06 06:00 [pubmed] PHST- 2022/12/06 06:01 [medline] PHST- 2022/01/01 00:00 [pmc-release] AID - 10.3389/fnins.2022.1031180 [doi] PST - epublish SO - Front Neurosci. 2022 Nov 16;16:1031180. doi: 10.3389/fnins.2022.1031180. eCollection 2022.