Neurovascular Unit Compensation from Adjacent Level May Contribute to Spontaneous Functional Recovery in Experimental Cervical Spondylotic Myelopathy
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 underlyin...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/4/3408 |
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| author | Guang-Sheng Li Guang-Hua Chen Kang-Heng Wang Xu-Xiang Wang Xiao-Song Hu Bo Wei Yong Hu |
| author_facet | Guang-Sheng Li Guang-Hua Chen Kang-Heng Wang Xu-Xiang Wang Xiao-Song Hu Bo Wei Yong Hu |
| author_sort | Guang-Sheng Li |
| collection | DOAJ |
| description | 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. |
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| spelling | doaj.art-374196f581b84f1a8191e9e4225c9b862023-11-16T20:59:53ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244340810.3390/ijms24043408Neurovascular Unit Compensation from Adjacent Level May Contribute to Spontaneous Functional Recovery in Experimental Cervical Spondylotic MyelopathyGuang-Sheng Li0Guang-Hua Chen1Kang-Heng Wang2Xu-Xiang Wang3Xiao-Song Hu4Bo Wei5Yong Hu6Spinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, ChinaSpinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, ChinaSpinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, ChinaSpinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, ChinaSpinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, ChinaSpinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, ChinaSpinal Division of Orthopedic and Traumatology Center, The Affiliated Hospital of Guangdong Medical University, Zhanjiang 524002, ChinaThe 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.https://www.mdpi.com/1422-0067/24/4/3408neurovascular unit compensationchronic compressive spinal cord injurycervical spondylotic myelopathy |
| spellingShingle | Guang-Sheng Li Guang-Hua Chen Kang-Heng Wang Xu-Xiang Wang Xiao-Song Hu Bo Wei Yong Hu Neurovascular Unit Compensation from Adjacent Level May Contribute to Spontaneous Functional Recovery in Experimental Cervical Spondylotic Myelopathy International Journal of Molecular Sciences neurovascular unit compensation chronic compressive spinal cord injury cervical spondylotic myelopathy |
| title | Neurovascular Unit Compensation from Adjacent Level May Contribute to Spontaneous Functional Recovery in Experimental Cervical Spondylotic Myelopathy |
| title_full | Neurovascular Unit Compensation from Adjacent Level May Contribute to Spontaneous Functional Recovery in Experimental Cervical Spondylotic Myelopathy |
| title_fullStr | Neurovascular Unit Compensation from Adjacent Level May Contribute to Spontaneous Functional Recovery in Experimental Cervical Spondylotic Myelopathy |
| title_full_unstemmed | Neurovascular Unit Compensation from Adjacent Level May Contribute to Spontaneous Functional Recovery in Experimental Cervical Spondylotic Myelopathy |
| title_short | Neurovascular Unit Compensation from Adjacent Level May Contribute to Spontaneous Functional Recovery in Experimental Cervical Spondylotic Myelopathy |
| title_sort | neurovascular unit compensation from adjacent level may contribute to spontaneous functional recovery in experimental cervical spondylotic myelopathy |
| topic | neurovascular unit compensation chronic compressive spinal cord injury cervical spondylotic myelopathy |
| url | https://www.mdpi.com/1422-0067/24/4/3408 |
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