PMID- 36834841 OWN - NLM STAT- MEDLINE DCOM- 20230228 LR - 20230301 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 24 IP - 4 DP - 2023 Feb 8 TI - Neurovascular Unit Compensation from Adjacent Level May Contribute to Spontaneous Functional Recovery in Experimental Cervical Spondylotic Myelopathy. LID - 10.3390/ijms24043408 [doi] LID - 3408 AB - The progression and remission of cervical spondylotic myelopathy (CSM) are quite unpredictable due to the ambiguous pathomechanisms. Spontaneous functional recovery (SFR) has been commonly implicated in the natural course of incomplete acute spinal cord injury (SCI), while the evidence and underlying pathomechanisms of neurovascular unit (NVU) compensation involved in SFR remains poorly understood in CSM. In this study, we investigate whether compensatory change of NVU, in particular in the adjacent level of the compressive epicenter, is involved in the natural course of SFR, using an established experimental CSM model. Chronic compression was created by an expandable water-absorbing polyurethane polymer at C5 level. Neurological function was dynamically assessed by BBB scoring and somatosensory evoked potential (SEP) up to 2 months. (Ultra)pathological features of NVUs were presented by histopathological and TEM examination. Quantitative analysis of regional vascular profile area/number (RVPA/RVPN) and neuroglial cells numbers were based on the specific EBA immunoreactivity and neuroglial biomarkers, respectively. Functional integrity of blood spinal cord barrier (BSCB) was detected by Evan blue extravasation test. Although destruction of the NVU, including disruption of the BSCB, neuronal degeneration and axon demyelination, as well as dramatic neuroglia reaction, were found in the compressive epicenter and spontaneous locomotor and sensory function recovery were verified in the modeling rats. In particular, restoration of BSCB permeability and an evident increase in RVPA with wrapping proliferated astrocytic endfeet in gray matter and neuron survival and synaptic plasticity were confirmed in the adjacent level. TEM findings also proved ultrastructural restoration of the NVU. Thus, NVU compensation changes in the adjacent level may be one of the essential pathomechanisms of SFR in CSM, which could be a promising endogenous target for neurorestoration. FAU - Li, Guang-Sheng AU - Li GS AD - Spinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, China. AD - Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China. FAU - Chen, Guang-Hua AU - Chen GH AUID- ORCID: 0000-0002-8877-1322 AD - Spinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, China. FAU - Wang, Kang-Heng AU - Wang KH AD - Spinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, China. FAU - Wang, Xu-Xiang AU - Wang XX AD - Spinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, China. FAU - Hu, Xiao-Song AU - Hu XS AD - Spinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, China. FAU - Wei, Bo AU - Wei B AD - Spinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, China. FAU - Hu, Yong AU - Hu Y AUID- ORCID: 0000-0003-0305-5616 AD - Spinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, China. AD - Department of Orthopaedics and Traumatology, The University of Hong Kong, Hong Kong, China. LA - eng GR - 2021YFF0501604/National Key Research and Development Program of China/ GR - 82072507/National Natural Science Foundation of China/ GR - NO.2018A0303130105, NO.2016A030313679/Natural Science Foundation of Guangdong Province, China/ PT - Journal Article DEP - 20230208 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 SB - IM MH - Rats MH - Animals MH - *Spinal Cord Compression/pathology MH - Recovery of Function MH - *Spondylosis/pathology MH - *Spinal Cord Diseases MH - Evoked Potentials, Somatosensory MH - *Spinal Cord Injuries PMC - PMC9962900 OTO - NOTNLM OT - cervical spondylotic myelopathy OT - chronic compressive spinal cord injury OT - neurovascular unit compensation COIS- The authors declare no conflict of interest. EDAT- 2023/02/26 06:00 MHDA- 2023/03/03 06:00 PMCR- 2023/02/08 CRDT- 2023/02/25 02:41 PHST- 2022/11/18 00:00 [received] PHST- 2022/12/23 00:00 [revised] PHST- 2023/02/06 00:00 [accepted] PHST- 2023/02/25 02:41 [entrez] PHST- 2023/02/26 06:00 [pubmed] PHST- 2023/03/03 06:00 [medline] PHST- 2023/02/08 00:00 [pmc-release] AID - ijms24043408 [pii] AID - ijms-24-03408 [pii] AID - 10.3390/ijms24043408 [doi] PST - epublish SO - Int J Mol Sci. 2023 Feb 8;24(4):3408. doi: 10.3390/ijms24043408.