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Objective To investigate the role of poly(ADP-ribose) polymerase (PARP) inhibitor PJ34 in regulating blood-brain barrier (BBB) permeability and matrix metalloproteinases-9 (MMP-9) expression in a mouse model of traumatic brain injury (TBI).Methods A total of 136 adult male BALB/c mice were randomly divided into sham-operated group,injured group and PJ34-treated group according to the random number table.Controlled cortical impact in mice was established.At 6 and 24hours postinjury,neurological deficit was evaluated,including motor,sensory,reflex and beam balance tests ; BBB permeability and brain water content were detected using Evans blue test and gravimetric technique; brain contusion volume was measured using HE staining; levels of MMP-9 in cytosolic fractions were detected using Western blotting.Results At 6 and 24 hours postinjury,neurological severity score in PJ34-treated group (8.00 ± 0.26,7.50 ±0.25) were lower than those in injured group (12.50 ±0.39,11.80 ± 0.32) ; brain contusion volume in PJ34-treated group [(11.25 ± 0.91) mm3,(13.55 ±1.06) mm3] was lower than those in injured group [(25.37 ± 1.75) mm3,(28.24 ± 1.51) mm3] ; BBB permeability in PJ34-treated group [(440.08 ± 3.10) μg/mg,(860.46 ± 3.86) μg/mg] was lower than those in injured group [(936.96 ± 4.71) μg/mg,(1 302.23 ± 5.89) μg/mg] (all P ＜ 0.01).Brain water content lowered significantly in PJ34-treated group than in injured group at 6 hours postinjury [(80.77 ± 0.76) ％ vs (82.55 ± 0.73) ％,P ＜ 0.0l],but between-group difference was not significant at 24 hours postinjury.Lower levels in MMP-9 were also observed in PJ34-treated group compared with injured group at 6 and 24 hours postinjury(P ＜ 0.05 or 0.01).Conclusion PARP inhibitor PJ34 can attenuate MMP-9 up-regulation,inhibit BBB injury and hence protect the brain against TBI in mice.
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@#ObjectiveTo explore the expression of N-cadherin and β-catenin mRNA in human brainstem and supratentorial gliomas. MethodsN-cadherin and β-catenin mRNA expression in 18 cases of brainstem gliomas and 18 cases of supratentorial gliomas tissues were detected with PT-PCR. Resultsβ-catenin mRNA expression was more in human brainstem gliomas than in supratentorial gliomas （t=2.255,P<0.05）, but was not significantly different of N-cadherin mRNA (P＞0.05). The expression of N-cadherin mRNA in human brainstem gliomas of grades Ⅰ～Ⅱ were less than those in human gliomas of grades Ⅲ～Ⅳ (t=2.711，P<0.05), but was not of β-catenin mRNA (P＞0.05). N-cadherin mRNA expression was positively correlated with the β-catenin mRNA expression in either brainstem gliomas or supratentorial gliomas （r=0.480，r=0.809 respectively, P<0.05）. ConclusionThe over expressions of N-cadherin and β-catenin may play an important role in the invasion and malignant progress of human brainstem gliomas.
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@#Nervous system develops from multipotential stem cells of the embryonic neural tube.The discovery of cells of stem-like properties in the adult central nervous system(CNS)has provoked an intense search for ways to utilize their potential for treatments of multiple neurological disorders.Expansion and recruitment of endogenous progenitors may be limited in treating widespread cell loss in the adult CNS.Transplantation of neural stem cells(NSCs)or more restricted progenitors to replace cells lost to injury or disease may facilitate functional recovery in a spectrum of neurological disorders.A major challenge to the development of effective NSCs therapies is to direct the fate of the newly generated cells to specifically replace those lost to disease.The key to the effective treatment of NSCs is molecular regulation of the differentiation of NSCs and their progeny in areas of injury to the adult CNS,the fate of transplanted stem cells is also important.
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@#Objective To investigate the migration and survival of neural stem cells(NSCs)in vivo.Methods NSCs cultured in vitro were transfected by lentiviral vectors expressing green fluorescent protein(GFP)to construct GFP-NSCs,then trans-seeded into lactide-co-glycolide(PLGA)scaffold and implanted into the injured site of T9 spinal cord in rat.One month after transplantation,the migration of NSCs in spinal cord was examined by fluorescence microscope,and the survival rate of NSCs was counted out.Results NSCs labeled GFP had strong expression of green fluorescence.One month after transplanting,part of NSCs expressing GFP could be seen in PLGA scaffolds and rostral,caudal spinal core.The survival rate counted out was 1.4911±0.0313%.Conclusion NSCs marked by GFP and transplanted to rat injured spinal cord could migrate into the spinal cord tissues and the minority of them could survive.