Expression of Nogo-A and NgR in the developing rat brain after hypoxia-ischemia.
Nogo-A and its receptor, NgR, have been shown to inhibit neurite growth in the adult rat. Therefore, we hypothesized that Nogo-A and NgR will be upregulated and thus play a similar role in the damage in developing rat brain following hypoxia-ischemia (HI). To test this hypothesis, we subjected postnatal day 7 (P7) rats to HI by permanently ligating the right common carotid artery, followed by exposure to 8%O2/92% N2 for 3 h. Rat brains at 0 h, 6 h, 12 h, 24 h and 72 h after HI, as well as from sham controls, were collected to determine histopathological damage and expression levels of Nogo-A and NgR using hematoxylin and eosin (H&E) staining, immunohistochemistry, fluorescence immunolabeling, Western blot analysis and reverse transcriptase-polymerase chain reaction (RT-PCR). We found neuronal degeneration and edema in the ischemic cortex, becoming most prominent at 24 h following HI in this model. Accordingly, the expression of Nogo-A and NgR protein was significantly upregulated at 24 h compared with the sham controls (p<0.01). The upregulated Nogo-A and NgR immunoreactive cells were mainly located in the core of the ischemic cortex and colocalized to neurons. Meanwhile, we found the expression of both Nogo-A and NgR mRNA was increased at 6 h and peaked at 12 h in the ischemic cortex after HI, compared with sham controls. Our findings of upregulation of neurite growth inhibitor Nogo-A and its receptor NgR in ischemic cortex suggest that Nogo-A and NgR may participate in the pathology seen after HI in neonatal rats.
Wang
Hua
H
Department of Pediatrics, West China Second University Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
Yao
Yujia
Y
Jiang
Xiangning
X
Chen
Dapeng
D
Xiong
Ying
Y
Mu
Dezhi
D
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern / Q000379:methods; D001921:Brain / Q000254:growth & development* / Q000378:metabolism*; D058851:GPI-Linked Proteins; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism / Q000473:pathology*; D007150:Immunohistochemistry / Q000379:methods; D009185:Myelin Proteins / Q000235:genetics / Q000378:metabolism*; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013997:Time Factors
D058851:GPI-Linked Proteins; D009185:Myelin Proteins; D000070798:Nogo Proteins; D000070816:Nogo Receptor 1; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C000603197:Rtn4 protein, rat; C486581:Rtn4r protein, rat; D010751:Phosphopyruvate Hydratase