THE PROTECTIVE EFFECT OF NEUREGULIN-1 TO THE OLIGODENDRO-CYTE PROGENITOR CELLS AFTER ACUTE INJURY OF THE SPINAL CORD

Ruixi Li, Huiting Liu, Yan Sun, Ruihe Lin, Ying Liu and Yuwen PengDepartment of Anatomy, Histology and Embryology, Shanghai Medical College, Fudan University, Shanghai 200032, China

Neuregulin-1 (NRG-1) is a growth factor secreted mainly by neurons and glial cells. It plays an important role not only in regulating the survival, proliferation and differentiation of the oligodendrocyte lineage but also in neuroprotection after ischemic brain damage. In order to understand the protective effect of Neuregulin-1 (NRG-1) to the oligodendrocyte progenitor cells (OPCs), which generate the oligodendrocytes, after acute injury of the spinal cord, the expressions of the NRG-1 in the normal and injured spinal cord and the cultured OPCs of the rat were comparatively examined by the immunohistochemical and western blot methods. The results showed that 1) the NRG-1 inmmunoreactivity was extensively distributed throughout the white and gray matters in the normal spinal cord, 2) the expression of the NRG-1 was increased from the first day after an acute spinal cord injury, got to a peak which was double higher than that in the control in the second day, then decreased gradually from the third day after the injury, 3) the NRG-1 and its receptor ErbB4 were expressed basically in normal cultured OPCs, 4) the expression of NRG-1 in cultured OPCs decreased immediately after hypoxia within 2 h, and dramatically increased to reach the highest level at 4 h after reoxygenation, then downregulated again continuously till to the level that is hardly detected at 24h after reoxygenation, 5) the rate of apoptosis of OPCs and the expression of TNF-α were effectively reduced after the administration of NRG-1in the cultured OPCs. These results suggest that the abundant NRG-1 in the spinal cord may play important role in neuroprotection by protecting the OPCs from apoptosis and inflammatory reaction after exposure to hypoxia in the injury of the spinal cord.

Fig. 1 Expression of the NRG-1 in gray matter of the spinal cord

Fig. 2 Expression of the NRG-1 in white matter of the spinal cord

Fig. 3 Expression of the NRG-1 in the spinal cord after an acute injury

Fig. 4 Expression of the NRG-1 in cultured OPCs

Fig. 5 Expression of the receptors of the NRG-1 in the cultured OPCs

Fig. 6 Expression of NRG-1 in cultured OPCs after hypoxia

Fig. 7

Rate of apoptosis of OP

Cs after the administrati

on of NRG-1Neurosphere for OPC