HIF-1伪/VEGF signaling pathway may play a dual role in secondary pathogenesis of cervical myelopathy

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• 作者：Hou-Qing Long^a ; ¹ ; ^{houqinglong@163.com} ; Guang-Sheng Li^a ; ¹ ; Yong Hu^b ; Chun-Yi Wen^b ; Wen-Han Xie^a
• 刊名：Medical Hypotheses
• 出版年：2012
• 期刊代码：4_03069877
• 类别：pha
• 出版时间：July, 2012
• 卷：79
• 期：1
• 页码：82-84
• 文件大小：138 K

摘要

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-1伪 (HIF-1伪) in acute periods. HIF-1伪/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-1伪/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.