[Neuroregeneration of newborn rats with hypoxic-ischemic brain damage following antibody-mediated neutralization of paired-immunoglobulin-like receptor B].
OBJECTIVE
To study changes in paired-immunoglobulin-like receptor B (PirB) expression after hypoxic-ischemic brain damage (HIBD) as well as the role for targeted inhibition of PirB activity in nerve regeneration in rats.


METHODS
Newborn Sprague-Dawleyrats rats were divided into: a sham operation group (n=30), a HIBD group (n=30), and an anti PirB antibody treatment group (n=6). In the HIBD group, HIBD was induced by right carotid artery ligature and subsequent exposure to hypoxia (8% O2) for 3 hours. In the sham operation group, right carotid artery was dissected as in the HIBD group but no ligature and hypoxic exposure was not applied. In the two groups, 6 animals were sacrificed at 0, 6, 12, 24 and 72 hours after the operation and hypoxic exposure. In the antibody treatment group, after carotid artery ligation and hypoxia exposure as in the HIBD group, an anti PirB antibody was injected intracerebrally and animals were sacrificed 72 hours after the injection. Immediately after sacrifice of the animals at designated time points, brain tissue specimens were collected. The presence and content of PirB protein were assessed by immunohistochemistry and Western blot analysis respectively, the abundance of PirB mRNA was determined by RT-PCR, and the Rho kinase (Rock) activity was determined by immunoprecipitation.


RESULTS
At 72 hours after operation, PirB mRNA abundance and protein content in the brain were significantly increased as compared with the measurements at 0 hour after operation in the HIBD group (P<0.05); ROCK activity was significantly increased in the HIBD group as compared with the sham operation and anti PirB antibody groups (P<0.05).


CONCLUSIONS
PirB might be involved in HIBD through a Rho-ROCK-dependent mechanism and antibody-mediated neutralization of PirB in the brain may offer a novel therapeutic strategy for HIBD.
Department of Neonatology, West China Second Hospital Sichuan University, Chengdu 610041, China. dezhimu@yahoo.com.
Hua
H
Wang
De-Zhi
DZ
Mu
D000818:Animals; D000831:Animals, Newborn; D020925:Hypoxia-Ischemia, Brain / Q000503:physiopathology* / Q000628:therapy; D009416:Nerve Regeneration; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D011971:Receptors, Immunologic / Q000037:antagonists & inhibitors / Q000235:genetics / Q000502:physiology*; D015398:Signal Transduction; D054460:rho-Associated Kinases / Q000378:metabolism
C491380:Pirb protein, rat; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D054460:rho-Associated Kinases