GPR17 plays a role in ischemia-induced endogenous repair of immature neonatal cerebral White matter.

Whether GPR17 has the same distribution and repair mechanism in immature white matter with periventricular leukomalacia (PVL) as in the adult brain remains to be determined. This study tried to explore the expression phase and site of GPR17, and to investigate the effect of silencing GPR17 on endogenous repair mechanism of immature white matter with PVL. Ischemic PVL in vivo results showed that GPR17 gene and protein expression increased more in the PVL than in the sham group at 12 h-24 h and 72h to 7 days after PVL.

CaSR is required for ischemia-induced proliferation and differentiation of white matter progenitor cells from neonatal rats.

This study was designed to investigate whether calcium-sensing receptor (CaSR) could induce immture white matter progenitor cells proliferation and differentiation into oligodendrocyte(OL) precursor cells after oxygen-glucose deprivation (OGD) in vitro. Progenitor cells of immature white matter originating from five-day-old newborn rats were divided into control, OGD, control + CaSR silencing, OGD + CaSR silencing, control + adenosine triphosphate magnesium chloride (ATP-MgCl2) and OGD + ATP-MgCl2 groups. Immunofluorescence, real-time RT-PCR, gene silencing, Hoechst 33342/propidium iodide (PI) and Flow cytometry tests were used to examine the proliferation, differentiation and survival of the white matter progenitor cells in the different treatment groups.

White matter and SVZ serve as endogenous sources of glial progenitor cells for self-repair in neonatal rats with ischemic PVL.

Mounting evidence suggests that endogenous progenitor cells may initiate cerebral WM repair. This study was designed to determine whether endogenous glial progenitor cells derived from either the subventricular zone (SVZ) or the white matter (WM) contribute to WM repair in a neonatal rat model of ischemic periventricular leukomalacia (PVL). Additionally, the role of G protein-coupled receptor 17 (GPR17), recently shown to act as a sensor for WM damage, was explored to assess its potential recruitment and activation of endogenous glial progenitor cells for such WM self-repair.

[Effect of single or combined application of UDP-glucose, GDNF and memantine on improvement of white matter injury in neonatal rats assessed with light and electron microscopy pathologically].

Objective: To evaluate pathologically the effect of the single or combined application of UDP-glucose, GDNF and memantine on the improvement of white matter injury in neonatal rats with periventricular leukomalacia (PVL) under light and electron microscopy.

Methods: A five-day-old neonatal rat model for PVL was established by ligation of the lateral common carotid artery following 120-minute hypoxia. Rats were randomly divided into six groups (30 rats in each group): sham-operated, PVL, UDP-glucose (UDP-glucose 2000 mg/kg intraperitoneally after PVL), GDNF (GDNF 100 μg/kg intracerebrally after PVL), tmemantine (memantine 20 mg/kg intraperitoneally after PVL), and a combination administration of three drugs (UDP-glucose, GDNF and memantine).

Periventricular leukomalacia long-term prognosis may be improved by treatment with UDP-glucose, GDNF, and memantine in neonatal rats.

The therapeutic effects of UDP-glucose (UDPG), an endogenous agonist of GPR17 that may promote the self-repair of white matter, glial cell line-derived neurotrophic factor (GDNF), a neurotrophic factor correlated with the growth and survival of nerve cells, and memantine, an antagonist of NMDA receptors, were evaluated for functional improvement of neonatal rats with experimental periventricular leukomalacia (PVL). Five day-old neonatal rat pups were subjected to an ischemia-induced model of PVL. The pups were then randomly divided into sham, PVL, PVL plus UDPG, PVL plus GDNF, and PVL plus memantine groups.

[Endogenous self-repair in immature white matter induced by ischemia in neonatal rats].

Objective: To study in vivo the endogenous self-repair mechanism in immature white matter induced by ischemia in neonatal rats with periventricular leukomalacia (PVL).

Methods: Five-day-old neonatal Sprague-Dawley (SD) rats were randomly divided into sham and PVL groups. Rat model of PVL was prepared by ligation of the right common carotid artery following 2 hours of exposure to 8% oxygen.