[Expression of Nogo receptor in brain and neuroprotective effect of NEP1-40 on hypoxic ischemic brain damage in newborn rats].
OBJECTIVE
The hypoxic-ischemic encephalopathy caused by asphyxia in peripartum is a serious disease in newborn infants, with a high disability and mortality rate. Lack of regenerative ability in central nervous system after injury is considered as the fundamental cause. However, in recent years many studies have revealed that there are myelin-associated neurite growth inhibitory factors that exert inhibiting effect through the Nogo receptor (NgR). This study aimed to investigate the expression level of NgR and the possible neuroprotective effect of NEP1-40 in newborn rats with hypoxic ischemic brain damage (HIBD).


METHODS
Eighty healthy Wistar rats aged 7 days were randomly divided into 4 groups; 8 in control group, 24 in HIBD model group, 24 in GM-1 group and 24 in NEP1-40 group. The rats of the control group and HIBD group were injected with normal saline (0.25 ml/kg) intraperitoneally, while those in NEP1-40 group and GM-1 group with NEP1-40 12.5 microg/d, GM-1 10 mg/(kg.d) for continuous 3 days of 72-hour group or 7 days of 168-hour group, respectively. In situ hybridization was adopted for detecting the expression of NgR in the brain of the rats at the time point of 24 hours, 72 hours and 7 days. Meanwhile histopathological changes of neurons and axon were detected by transmission electron microscopy (TEM). The SPSS statistical software package for Windows, version 10.0, was used to run Chi-square tests and least significance difference (LSD-t) on the data presented, and P value of less than 0.05 was regarded as statistically significant.


RESULTS
The expression level of Nogo-A receptor in the control group was higher than that of the other groups at different time point (t value was 5.48, 6.11, 6.96, 8.24, 5.99 and 5.34, respectively, and all P values were less than 0.05). There were no significant differences in Nogo-A receptor level among the HIBD group, the GM-1 group and the NEP1-40 at 24 hours (t was 1.48, 2.76 and 1.29, respectively, and all P > 0.05), while the expression of Nogo-A receptor of NEP1-40 at 72 hours and 7 days was lower than that of the HIBD group and the GM-1 group at the same time point, respectively (all P < 0.05). Repair of neurons in damaged brain to some extent was found after GM-1 treatment and satisfactory repair of neurons and axon regeneration was obtained with NEP1-40 administration as shown by TEM.


CONCLUSIONS
Hypoxic ischemic brain damage can down-regulate the expression of Nogo-A receptor in the central nervous system. NEP1-40 contributes to the regeneration of axon and repair of brain damage, thus exerts neuroprotective effect.
Zhu
Wei-wei
WW
Department of Pediatrics, Jinan Central Hospital Affiliated to Shandong University, Jinan 250013, China.
Zhao
Hong-yang
HY
Wen
Tian-lian
TL
Guo
Ai-li
AL
Bi
Mei-rong
MR
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D058851:GPI-Linked Proteins; D020925:Hypoxia-Ischemia, Brain / Q000378:metabolism* / Q000473:pathology; D009185:Myelin Proteins / Q000494:pharmacology*; D000070816:Nogo Receptor 1; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide / Q000378:metabolism*
D058851:GPI-Linked Proteins; D009185:Myelin Proteins; C509624:NEP1-40 protein, human; D000070816:Nogo Receptor 1; D010446:Peptide Fragments; D011956:Receptors, Cell Surface; D018000:Receptors, Peptide; C486581:Rtn4r protein, rat