Upregulation of Vascular Endothelial Growth Factor Receptors Flt-1 and Flk-1 Following Acute Spinal Cord Contusion in Rats

Jeong-Sun Choi ¹, Ha-Young Kim ¹, Jung-Ho Cha ¹, Jae-Youn Choi ¹, Sang In Park ¹, Chang Hyun Jeong ¹, Sin-Soo Jeun ¹ and Mun-Yong Lee ^1*

¹ Department of Anatomy (J-SC,H-YK,J-HC,J-YC,M-YL) and Department of Neurosurgery (SIP,CHJ,S-SJ), College of Medicine, The Catholic University of Korea, Seoul, Korea

^* To whom correspondence should be addressed. E-mail: munylee{at}catholic.ac.kr.

Submitted on November 1, 2006
Accepted on 20 March 2007

	Abstract

To investigate the possible role of vascular endothelial growth factor (VEGF) in the injured spinal cord, we analyzed the distribution and time course of the two tyrosine kinase receptors for VEGF, Flt-1 and Flk-1, in the rat spinal cord following contusion injury using a weight-drop impactor. The semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) analysis of Flt-1 and Flk-1 in the spinal cord showed slight upregulation of these receptors following spinal cord injury. Although messenger RNAs for Flt-1 and Flk-1 were constitutively expressed in neurons, vascular endothelial cells, and some astrocytes in laminectomy control rats, their upregulation was induced in association with microglia/macrophages and reactive astrocytes in the vicinity of the lesion within one day in rats with a contusion injury and persisted for at least 14 days. The spatiotemporal expression of Flt-1 in the contused spinal cord mirrored that of Flk-1 expression. In the early phase of spinal cord injury, upregulation of Flt-1 and Flk-1 mRNA occurred in microglia/macrophages that infiltrated the lesion. In addition, the expression of both receptors increased progressively in reactive astrocytes within the vicinity of the lesion, predominately in the white matter, and almost all reactive astrocytes coexpressed Flt-1 or Flk-1 and nestin. These results suggest that VEGF may be involved in the inflammatory response and the astroglial reaction to contusion injuries of the spinal cord via specific VEGF receptors .

Key Words: Flt-1, Flk-1, VEGF, reactive astrocyte, microglia/macrophage, spinal cord injury

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