The Involvement of CRMP-2 on Axonal and Dendrictic Injury after Hypoxic-Ischemic Brain Injury in Neonatal Rat

XIONG Tao, CHEN Hong-ju, QU Yi. et al

Abstract

To investigate the activity of collapsin response mediator protein 2 (CRMP 2) and its possible regulation for axonal and dendrictic injury under hypoxia ischemia (HI). Methods Postnatal day 10 SO rats were suffered the right common carotid artery ligation and 8/"o mixture of oxygen and nitrogen hypoxia 2. 5 h to produce HI model. The expression of total and phosphorylated CRMP-2 and amyloid precursor protein (APP) were detected by Western blot after HI. After pretreatment of protein kinase Ii (Akt) inhibitor, wortmannin or LY294002. western blot and immunohistochemistry were applied to detect the expression of total and phosphorylated of CRMP-2 at 4 h and 24 h after HI. At 72 h after HI. APP was detected by Western blot and immunohistochemistry. axonal and dendrictic injury was determined by electron microscope. Results Total CRMP 2 was not obviously changed after HI. compared with that of sham controls. However, the phosphorylated CRMP 2 (p-CRMP 2) protein transiently increased at 0. 5 h. started to decrease at 2 h. remained at a low level at the rest of the time points, compared with that of sham controls. APP protein started to increase at 2 h, remained at a high level at 4. 8. 24 h. and then progressively increased at 48 and 72 h. In wortmannin and LY294002 group. CRMP 2 protein was not obviously changed at 4 h and 24 h after HI. However. p-CRMP 2 increased at 4 h and 24 h. At 72 h. wortmannin pretreatment increased APP expression, leading to more severe ultrastructure failure of axon and dendrite. Conclusion As a downstream effector of Akt pathway. CRMP 2 is involved in axonal and dendritic injury regulation after HI in neonatal rat.


Keywords: Collapsin response mediator protein 2, Amyloid precursor protein, Signaling, Hypoxia-ischemia, Axon Dendrite


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