title: HIF-1α/VEGF signaling pathway may play a dual role in secondary pathogenesis of cervical myelopathy.
abstract: Cervical spondylotic myelopathy (CSM) is one of the most common spinal cord disorders affecting the elderly. Yet the exact pathophysiology of CSM remains unclear. Vascular response to initial mechanical compression and associated ischemia may involve in secondary pathophysiology. Chronic compressive lesions to cervical cord resulting in lack of perfusion have established considerable evidences to support ischemia as an important pathogenesis both in patients and animal models, a similarity as that of acute spinal cord injury (SCI). In hypoxic condition following SCI, the up-regulation of vascular endothelial growth factor (VEGF), is consistent with increasing hypoxia induced factor-1α (HIF-1α) in acute periods. HIF-1α/VEGF signaling pathway is thought to play a dual role following SCI. In one hand, VEGF was demonstrated to be correlated with angiogenesis (protecting vascular endothelial cells, increasing blood vessel density and improving regional blood flow), neurogenesis (antiapoptotic, neurotrophic, attenuate axonal degradation), and locomotor ability improvement. In other hand, some studies revealed that VEGF have limited therapeutic effect, even exacerbate the secondary damage following SCI. VEGF administrations in acute or subacute periods result in elevation of blood-spinal cord barrier (BSCB) permeability even last for chronic course. BSCB permeability elevation initiates a secondary cascade of events involving excitotoxicity, infiltration of leukocytes and tissue edema. With comprehensive understanding of temporal and spatial of HIF-1α/VEGF signaling pathway, development of therapeutic strategies to promote new vessel growth while minimize the deleterious effects of VEGF-induced microvascular permeability, and thereby improve neurologic function, seems to be feasible and promising.
authors.affiliation: Department of Spinal Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China. houqinglong@163.com
authors.forename: Hou-Qing
authors.initials: HQ
authors.lastname: Long
authors.forename: Guang-Sheng
authors.initials: GS
authors.lastname: Li
authors.forename: Yong
authors.initials: Y
authors.lastname: Hu
authors.forename: Chun-Yi
authors.initials: CY
authors.lastname: Wen
authors.forename: Wen-Han
authors.initials: WH
authors.lastname: Xie
mesh_terms: D002574:Cervical Vertebrae; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008962:Models, Theoretical; D015398:Signal Transduction; D013118:Spinal Cord Diseases / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*
chemical_list: C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D042461:Vascular Endothelial Growth Factor A