[show abstract][hide abstract] ABSTRACT: To investigate the effect of intraventricular injection of human dental pulp stem cells (DPSCs) on hypoxic-ischemic brain damage (HIBD) in neonatal rats.
Thirty-six neonatal rats (postnatal day 7) were assigned to control, HIBD, or HIBD+DPSC groups (n = 12 each group). For induction of HIBD, rats underwent left carotid artery ligation and were exposed to 8% to 10% oxygen for 2 h. Hoechst 33324-labeled human DPSCs were injected into the left lateral ventricle 3 days after HIBD. Behavioral assays were performed to assess hypoxic-ischemic encephalopathy (HIE), and on postnatal day 45, DPSC survival was assessed and expression of neural and glial markers was evaluated by immunohistochemistry and Western blot.
The HIBD group showed significant deficiencies compared to control on T-maze, radial water maze, and postural reflex tests, and the HIBD+DPSC group showed significant improvement on all behavioral tests. On postnatal day 45, Hoechst 33324-labeled DPSC nuclei were visible in the injected region and left cortex. Subsets of DPSCs showed immunostaining for neuronal (neuron-specific enolase [NSE], Nestin) and glial markers (glial fibrillary acidic protein [GFAP], O4). Significantly decreased staining/expression for NSE, GFAP, and O4 was found in the HBID group compared to control, and this was significantly increased in the HBID+DPSC group.
Intraventricular injection of human DPSCs improves HIBD in neonatal rats.
PLoS ONE 01/2013; 8(6):e66748. · 3.73 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: There is a large number (1.5 million per year) of premature births in China. It is necessary to obtain the authentic incidences of intraventricular hemorrhage (IVH) and periventricular leukomalacia (PVL), the common brain injuries, in Chinese premature infants. The present multicenter study aimed to investigate the incidence of brain injuries in premature infants in ten urban hospitals in China. METHODS: The research proposal was designed by the Subspecialty Group of Neonatology of Pediatric Society of the Chinese Medical Association. Ten large-scale urban hospitals voluntarily joined the multicenter investigation. All premature infants with a gestational age ≤34 weeks in the ten hospitals were subjected to routine cranial ultrasound within three days after birth, and then to repeated ultrasound every 3-7 days till their discharge from the hospital from January 2005 to August 2006. A uniform data collection sheet was designed to record cases of brain injuries. RESULTS: The incidences of overall IVH and severe IVH were 19.7% (305/1551) and 4.6% (72/1551), respectively with 18.4% (56/305) for grade 1, 58.0% (177/305) for grade 2, 17.7% (54/305) for grade 3 and 5.9% (18/305) for grade 4 in nine hospitals. The incidences of overall PVL and cystic PVL were 5.0% (89/1792) and 0.8% (14/1792) respectively, with 84.3% (75/89) for grade 1, 13.5% (12/89) for grade 2, and 2.2% (2/89) for grade 3 in the ten hospitals. The statistically significant risk factors that might aggravate the severity of IVH were vaginal delivery (OR=1.883, 95% CI: 1.099-3.228, P=0.020) and mechanical ventilation (OR=4.150, 95% CI: 2.384-7.223, P=0.000). The risk factors that might result in the development of cystic PVL was vaginal delivery (OR=21.094, 95% CI: 2.650-167.895, P=0.000). CONCLUSIONS: The investigative report can basically reflect the incidence of brain injuries in premature infants in major big cities of China. Since more than 60% of the Chinese population live in the rural areas of China, it is expected to undertake a further multicenter investigation covering the rural areas in the future.
World Journal of Pediatrics 12/2012; · 1.08 Impact Factor
[show abstract][hide abstract] ABSTRACT: To study the pathological changes in the non-myelin sheath by observing histological damages to the neurofilament protein and apoptosis of neurons in rats with experimental autoimmune encephalomyelitis (EAE).
Forty-eight Wistar rats were randomly divided into two groups: control and EAE (24 rats in each group). Behavioral changes were observed. Inflammation reactions and demyelination were observed by hematoxylin eosin staining and LOYEZ staining.The level of neurofilament was detected by immunohistochemistry. Apoptosis of the neuron in the spinal cord was detected by TUNEL.
Behavioral and histological results confirmed that the model of EAE rats was prepared successfully. In the EAE group, typical morphological features of axonal damage (sparsed axonal density, axonal distortion, axonal transection and even axonal disappearance) were found from the seventh day after immunization and the morphological changes were the most obvious on the fourteenth day. Neurofilament density in the EAE group was significantly lower than in the control group (P<0.01) at 7, 14 and 21 days after immunization. The neuronal apoptosis index in the EAE group at 7, 14 and 21 days after immunization was significantly higher than in the control group (P<0.01).
In addition to inflammatory demyelination, axonal damage and neuronal apoptosis can be observed in the early stage of EAE. Pathological changes may be associated with neurological dysfunction.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 04/2012; 14(4):306-9.
[show abstract][hide abstract] ABSTRACT: Cerebral palsy (CP) is a very common neural system development disorder that can cause physical disability in human. Here, we studied the neuroprotective effect of vascular endothelial growth factor (VEGF)-transfected neural stem cells (NSCs) in newborn rats with cerebral palsy (CP). Seven-day-old Sprague-Dawley rats were randomly divided into four groups: sham operation (control group), PBS transplantation (PBS group), VEGF+NSCs transplantation (transgene NSCs group) and NSCs transplantation groups (NSCs group). PBS, Transgene NSCs and NSCs groups respectively received stereotactic injections of PBS, lentiviral vector (pGC-FU-VEGF) infected NSCs or a NSCs suspension in the left sensory-motor cortex 3 days after CP model was established. The NSCs activity, their impacts on neural cell growth and apoptosis, brain development and animal behaviors were examined on the animals up to age 35-days. As expected, unilateral carotid artery occlusion plus hypoxia (cerebral palsy model) resulted in severe neural developmental disorders, including slowed growth, increased in cortical neuron apoptosis, decreased cerebral cortex micro-vessel density and retarded behavior developments. Transplantation of NSCs not only resulted in increases in VEGF protein expression in rat brains, but also largely prevented the behavioral defects and brain tissue pathology that resulted from cerebral palsy procedure, with animals received VEGF transfected NSCs always being marginally better than these received un-transfected cells. In conclusion, NSCs transplantation can partially prevent/slow down the brain damages that are associated with CP in the newborn rats, suggesting a new possible strategy for CP treatment.
Behavioural brain research 02/2012; 230(1):108-15. · 3.22 Impact Factor
[show abstract][hide abstract] ABSTRACT: To study the epidemiology of births in urban China.
A retrospective study was conducted on neonates born in 2005 in the maternity departments of 72 urban hospitals from 22 provinces in China.
A total of 45722 infants born between January 1, 2005 and December 31, 2005 were enrolled. The male to female sex ratio was 1.13:1. Preterm births accounted for 8.1%. The incidence of very low birth weight infants was 0.7%. A total of 99.7% of mothers delivering at term had conceived naturally and 0.3% had experienced assisted reproduction. A total of 98.4% of mothers who delivered preterm had conceived naturally and 1.6% had experienced assisted reproduction. The proportion of vaginal deliveries was 50.8% compared to 49.2% delivered by cesarean sections. Many cesarean sections (38.1%) were due to social factors. Infants with an Apgar score≤7 at 1 minute accounted for 4.8%, and 1.6% of infants had an Apgar score≤7 at 5 minutes. Of all the infants included in the study, 7.14% were admitted to neonatal units for treatment. The death rate of all included infants was 0.74%.
The proportion of preterm births was higher in 2005 than in 2002-2003. The proportion of cesarean section deliveries was much higher in urban China than in most other Asian countries and America.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 01/2012; 14(1):7-10.
[show abstract][hide abstract] ABSTRACT: To study the therapeutic efficacy of baicalin and its effect on apoptosis of inflammatory cells in spinal cords in Wistar rats with autoimmune encephalomyelitis (EAE).
Forty-four rats were randomly divided into four groups: normal control group (control, n=10), EAE group (n=12), and two intervention groups with dexamethasone (DXM) or baicalin. Seven days after immunization, the two intervention groups were injected intraperitoneally with DXM (1 mg/kg) and baicalin (200 mg/kg) for 1 week, respectively. The spinal cords were removed 14 days after immunization, and stained with hematoxylin and eosin. MBP expression in spinal cords was detected by immunohistochemistry. The apoptosis of inflammatory cells in spinal cords was detected by TUNEL.
The weight gain rate in the untreated EAE and the DXM or baicalin intervention groups were significantly lower than that in the control group (P<0.05). The weight gain rate in the baicalin intervention group was significantly higher than that in the untreated EAE and the DXM intervention groups (P<0.05). The scores of neurological function in the two intervention groups were significantly higher than that in the untreated EAE group (P<0.05). DXM or baicalin treatment significantly increased the MBP expression compared with the untreated EAE group (P<0.05). The apoptosis of inflammatory cells increased more in the DXM and the baicalin intervention groups compared with the untreated EAE groups (P<0.05).
Baicalin has protective effects against EAE in rats. It can promote the apoptosis of inflammatory cells in spinal cords.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 08/2011; 13(8):665-8.
[show abstract][hide abstract] ABSTRACT: To investigate the birth information of newborn infants from obstetric departments in the Central South Region of China.
A retrospective investigation was carried out in 15582 newborns from obstetric departments of 23 hospitals in the Central South Region of China between January 1 and December 31 of 2005.
The sex ratio (male/female) of neonates was 1.16∶1. The proportion of preterm infants was 8.11%. The very low birth weight infants accounted for 0.73%. The neonates born by spontaneous labor accounted for 57.52%. Cesarean sections accounted for 40.82% (social factor of cesarean section: 29.91%). The incidence of neonatal asphyxia was 3.78%, in which 0.75% of the cases were severe asphyxia. The mortality of newborn infants was 0.55%, in which the mortality of preterm infants was 5.56%.
The proportion of preterm infants and the incidence of neonatal asphyxia is high in the Central South Region of China. The proportion of births delivered by cesarean section is high, and social factors are probably responsible for the high rate.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 06/2011; 13(6):458-61.
[show abstract][hide abstract] ABSTRACT: β-catenin, a protein that functions in both cell adhesion and Wnt signaling, plays a key role in mammalian neural development. To investigate the role of β-catenin in hyperbaric oxygen therapy (HBO)-induced neurogenesis after hypoxic ischemic brain damage (HIBD), we transfected β-catenin siRNA and negative control siRNA into neural stem cells (NSCs) after HIBD. We found that HBO promoted NSCs differentiate into neurons or oligodendrocytes, and inhibited NSCs differentiate into astrocytes; HIBD brain tissue extract conditioned cultures promoted NSCs differentiate into neurons; β-Catenin siRNA decreased the NSE-positive neurons and increased GFAP-positive astrocytes in the NSCs in vitro. Furthermore, the expression of Ngn1 protein and mRNA in NSCs was increased when HBO promoted NSCs differentiate into neurons after HIBD, and the expression of BMP-4 protein and mRNA was decreased when HBO depressed NSCs differentiate into astrocytes after HIBD. These results showed that β-catenin-mediated transcriptional activation functions in the decision of NSCs to proliferate neurogenesis during HBO-induced after HIBD, and suggested that HBO therapy promotes the proliferation of neural stem cells in vitro, an effect that may be correlated with β-catenin protein and HBO therapy could promote neurogenesis by β-catenin-induced activated Ngn1 gene and repress astrocytogenesis by β-catenin-induced down-regulated BMP-4 gene.
Cellular and Molecular Neurobiology 10/2010; 31(1):101-9. · 2.29 Impact Factor
[show abstract][hide abstract] ABSTRACT: To study the effect of hyperbaric oxygen (HBO) administered at different pressures and different exposure time on the differentiation of neural stem cells (NSCs) in vitro.
The cerebral cortices from newborn rats (0-3 days old) were sterilely collected, digested, and centrifuged. After removal of the supernatant, the cells were re-suspended with DMEM/F12 medium containing B27, bFGF and EGF. The NSCs of 2-3 passages were randomly divided into seven groups: a control (untreated) and 6 HBO treatment groups that NSCs were subjected to HBO treatment of different pressures (1, 2 or 3 ATA) and different exposure time (30 or 60 minutes). The differentiated NSCs were examined by neuron-specific enolase (NSE) immunocytochemistry 24 hrs later. Percentage of NSE positive cells differentiated from NSCs was assessed by fluorescent microscopy.
The percentage of NSE positive cells differentiated from NSCs was the highest in the HBO 2ATA-60 min group (9.17+/-0.50%) (P<0.01), followed by the HBO 3ATA-60 min (7.89+/-0.62%), HBO 2ATA-30 min (6.72+/-0.76%), HBO 3ATA-30 min (6.08+/-0.57%), HBO 1ATA-60 min (5.45+/-0.52%), HBO 1ATA 30 min (3.85+/-0.44%) and control groups (3.72+/-0.88%). In addition to the HBO 1ATA-30 min group, the other HBO treatment groups had increased significantly percentage of NSE positive cells compared with the control group (P<0.01). Under the same pressure, the 60 min treatment groups had increased significantly percentage of NSE positive cells compared with the 30 min treatment groups (P<0.01).
HBO treatment (2 ATA, 60 minutes) produces a best effect in the differentiation of NSCs into neurons.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 05/2010; 12(5):368-72.
[show abstract][hide abstract] ABSTRACT: Previous studies have showed that vascular endothelial growth factor (VEGF) displayed neurotrophic and neuroprotective activities. To examine whether target delivery of VEGF gene directly into brain may prevent ischemic brain damage, the VEGF expression adenoviral vectors, AVHP.VEGF-with 476bp of the human preproendothelin-1 (ppET-1) promoter and 35bp of the hypoxia-reponse element (HRE) driving VEGF expression and CMV.VEGF were transferred into hypoxic-induced ischemic (HI) rat brains. Seven-day-old rats that were underwent left carotid ligation followed by 2h of hypoxic stress (8% O(2) at 37 degrees C) were received VEGF adenoviral vectors or buffer (PBS) injection 3 days after HI. The body weight, VEGF expression, neuronal apoptosis, cerebral morphology and brain functional assays were performed between 7 and 28 days after HI. There were remarkable increases in the body weight and VEGF protein expression, and decrease in the number of TUNEL-positive cells in the VEGF vector groups as compared with PBS group. The VEGF vector groups also had better brain functional performs than PBS group. The better performs by the animals that received VEGF vectors may be directly linked to the inhibitory effect of VEGF on neuronal apoptosis because the animals had less neural loss in the cortex and hippocampal CA1 region as compared with PBS group. Overall, these results indicated that over-expression of VEGF in the brain exerted a neuroprotective effect and promoted neural functional recovery in neonatal rats after hypoxic-ischemic brain damage, suggesting that in vivo target VEGF gene transfer to brain may be a promising approch for the treatment of such implications.
Brain research bulletin 11/2009; 81(4-5):372-7. · 2.18 Impact Factor
[show abstract][hide abstract] ABSTRACT: To explore the effects of hyperbaric oxygen (HBO) treatment on the migration and differentiation of endogenous neural stem cells (NSCs) in neonatal rats with hypoxic-ischemic brain damage (HIBD).
Seven-day-old Sprague-Dawley rats were randomly divided into the normal control (CON), the HIBD model and the HBO groups (HBO treatment was administered at 2 ATA, once daily for 7 days within 3 hrs after HIBD). HIBD model was prepared according to the classic Rice-Vannucci method. BrdU/DCX, BrdU/beta-tubulin, BrdU/GFAP and BrdU/O4 immunofluorescence were examined by confocal microscopy in the subventricular zone (SVZ) and the cortex 7, 14 and 28 days after HBO treatment.
The BrdU(+)DCX(+) cells in the SVZ (84 +/- 21 cells/mm2) in the HBO group were significantly higher than those in the CON group (39 +/- 14 cells/mm2) (p<0.05) and the HIBD model group (68 +/- 17 cells/mm2) (p<0.05) 7 days after HBO treatment. Fourteen days after HBO treatment, the BrdU(+) DCX(+) cells decreased in the SVZ and more cells were observed in the cortex in the HBO group as compared with the CON group (p<0.01). The BrdU(+) beta-tubulin(+), BrdU(+)GFAP(+) and BrdU(+) O4(+) cells were observed in the cortex, and more BrdU(+)beta-tubulin(+) and BrdU(+) O4(+) cells were observed in the HBO group as compared with the CON and the HIBD model groups (p<0.05) 28 days after HBO treatment.
HBO treatment may promote endogenous NSCs to migrate to the cortex and differentiate into mature neurocytes in neonatal rats with HIBD.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 09/2009; 11(9):749-52.
[show abstract][hide abstract] ABSTRACT: To study the protective effects of multiple course hyperbaric oxygen (HBO) treatment against hypoxic-ischemic brain damage (HIBD) in neonatal rats when HBO treatment is delayed (96 hrs after the HIBD event).
Eighty-eight 7-day-old Sprague-Dawley rat pups were randomly assigned to control, HIBD and HBO groups. The HBO group was subdivided into cohorts receiving treatment 2 h, 48 h and 96 h, respectively, after HIBD was induced. The three subgroups comprising different therapeutic windows were further randomly assigned to receive 1, 2 or 3 courses of HBO treatment ("HBO-1, -2 and -3 sub-groups"). HBO was administered once daily (2 ATA), a course lasting for seven days. There was an interval of three days between the courses. All pups were sacrificed at the end of HBO treatment (31 days after HIBD). TUNEL staining was used for testing neuronal apoptosis in the cortex and the CA1 of the hippocampus, and NSE staining was used to ascertain cortical neuronal population.
1.There were significantly more TUNEL positive cells in the HIBD group than in the control group; NSE positive cells were significantly lower than in controls (P<0.01). 2. With the more delayed therapeutic window, the effects of apoptosis inhibition and neuronal protection of a single course of HBO were gradually reduced. 3. With increasing courses of HBO treatment, the effects of apoptosis inhibition and neuronal protection of HBO increased gradually in rats receiving treatment 48 and 96 hrs after HIBD. In the HBO group receiving treatment 2 hrs after HIBD, the number of apoptotic cells and NSE positive cells were close to that of the control group after one course of HBO treatment.
One course of HBO administered within 2 hrs after HIBD can effectively inhibit neuron apoptosis and protect neurons. The effects of apoptosis inhibition and neuron protection of HBO can be increased through increasing the number of HBO treatment courses in neonatal rats with HIBD even if initiation of treatment is delayed after HIBD.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 06/2009; 11(6):464-70.
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: To understand the disease spectrum and treatment outcome on hospitalized neonates in China, a nationwide epidemiologic survey was performed. This paper reports the investigation results. METHODS: A retrospective study of 43 289 hospitalized neonates from 86 hospitals in 47 Chinese cities (22 provinces) between January 1, 2005 and December 31, 2005 was performed. RESULTS: (1) The sex ratio of male to female was 1.73:1. (2) Premature infants accounted for 26.2% of the hospitalized neonates, which was higher than that reported in 2002 (19.7%). (3) The top three diseases that the neonates were susceptible to in turn were jaundice, pneumonia, and hypoxic-ischemic encephalopathy. (4) The percentage of pneumonia, meconium aspiration syndrome, and bilirubin encephalopathy in term infants was higher than that in premature infants, but the percentage of asphyxia, respiratory distress syndrome, and pulmonary hemorrhage in term infants was lower than that in premature infants. (5) The percentage of asphyxia, small for gestational age infant, and wet lung were higher in neonates whose mother had pregnancy induced hypertension. (6) The infants who recovered accounted for 63.9%, improved for 27.3%, requested own discharge for 7.6%, and died for 1.2%. Neonatal death of 46.4% occurred within 24 hrs after admission. CONCLUSIONS: The incidence of premature birth is increasing in hospitalized neonates. The neonatal deaths occur mostly within 24 hrs after admission.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 02/2009; 11(1):15-20.
[show abstract][hide abstract] ABSTRACT: To investigate the therapeutical effect of adenovirus-mediated vascular endothelial growth factor (VEGF)165 gene transplantation in treatment of hypoxic-ischemic brain damage.
Recombinant vector of adenovirus-mediated VEGF165 gene (Ad-VEGF) was constructed by bacterial homologous recombination technology. Sixty 7-day-old Sprague-Dawley rats were randomly divided into 3 equal groups: hypoxic-ischemic brain damage (HIBD) group undergoing ligation of the left common carotid artery and inhalation of 8% oxygen for 2 hours, Ad-VEGF group undergoing injection of Ad-VEGF into the left sensorimotor cortex with the help of stereo-positioner 3 days after hypoxia-ischemia (HI), and sham operation group. Seven days after transplantation, 5 rats from each group were killed with their left brains taken out. The VEGF protein expression was detected by immunohistochemistry, and the neuron apoptosis was detected by terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nickel end labeling (TUNEL). Since the age of 28 days T-maze foraging test was conducted. At the age of 34 days, sensorimotor tests were performed. After the behavioral tests all the rats were killed. The number of neurons in the CA1 region of the hippocampus and cerebral cortex was detected by Nissl's staining.
Immunohistochemistry showed that the density levels of VEGF positive cells in cerebral cortex and hippocampus of the Ad-VEGF group were (68.09 +/- 3.37) and (68.37 +/- 3.17) respectively, both significantly higher than those of the HIBD group [(24.65 +/- 3.14) and (25.14 +/- 1.86) respectively, both P < 0.05]. TUNEL showed that the number of apoptotic neurons of the Ad-VEGF group was (151.4 +/- 21.7), significantly lower than that of the HIBD group [(264.4 +/- 16.3), P < 0.05]. Behavioral tests showed the percentages of accuracy on day 4 of the Ad-VEGF and sham operation groups were both significantly higher than that of the HIBD group (both P < 0.01). Nissl's staining showed that the numbers of neurons per unit area in the hippocampal CA1 area and cortex of the Ad-VEGF group were (70.6 +/- 2.3) and (95.1 +/- 2.8) respectively, both significantly higher than those of the HI group [(55.3 +/- 2.1) and (70.1 +/- 2.7) respectively, both P < 0.05].
Adenovirus vector-mediated VEGF gene therapy increases the VEGF protein expression, decreases neuron apoptosis, improves the long-term behavioral function after brain damage, and reduces hypoxic ischemic brain injury, thus possessing neuroprotective effects.
[show abstract][hide abstract] ABSTRACT: To investigate the protective effects of adenovirus-mediated vascular endothelial growth factor (Ad-VEGF)165 gene transfer against hypoxic-ischemic brain damage (HIBD) in neonatal rats.
Ad-VEGF recombinant adenovirus was constructed by bacterial homologous recombination technology. Seven-day-old Sprague-Dawley rats were randomly assigned to 4 groups: sham-operated (n=20), HIBD (n=25), buffer-treated (n=20), and Ad-VEGF-treated (n=25). The HIBD model was prepared by permanent occlusion of left common carotid artery, followed by exposure to 8% oxygen for 2 hrs. In the Ad-VEGF-treated and the Buffer-treated groups, 2 microL recombinant adenovirus suspension or buffer was injected into the left sensorimotor cortex of the rat brain 3 days after HIBD. Seven days after transplantation, VEGF165 mRNA expression was detected using RT-PCR. Neuronal apoptosis was detected by the terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nickel end labeling (TUNEL). CD34 and VEGF protein were detected using immunohistochemistry. Microvascular density in the cerebral cortex was measured based on CD34 positive cells. A radial arm maze test was performed from 30 postnatal days to evaluate long-term learning and memory functions. At 35 postnatal days, the rats were sacrificed for cerebral histological examinations by hematoxylin and eosin.
The expression of VEGF165 mRNA increased in the Ad-VEGF-treated group more than in the untreated HIBD and the buffer-treated groups (p<0.05). The number of apoptotic neurons was less in the Ad-VEGF-treated group compared with that in the untreated HIBD and the buffer-treated groups (p<0.05). Microvascular density and VEGF positive cells increased in the Ad-VEGF-treated group compared with that in the untreated HIBD and the buffer-treated groups (p<0.05). In the radial arm maze test, the Ad-VEGF-treated group had more improved achievements than the HIBD and the buffer groups (p<0.05). Neuronal degeneration and necrosis were lessened in the Ad-VEGF-treated group compared with the HIBD and the buffer groups.
Ad-VEGF gene transfer can increase the expression of VEGF mRNA and VEGF protein, decrease neuronal apoptosis, and increase angiopoiesis in the brain. This attenuates brain damage and improves long-term learning and memory functions in neonatal rats after HIBD.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 12/2008; 10(6):737-42.
[show abstract][hide abstract] ABSTRACT: Previous studies showed that hyperbaric oxygen (HBO) promoted cell proliferation in hypoxic-ischemic (HI) neonate rats. Neural stem cells (NSC) existed in the brain lifelong and can be activated. This study was undertaken to assess whether HBO treatment promoted the proliferation of NSC and repaired the brain damage regardless of when it is started, thus to explore the therapeutic window of HBO treatment. Seven-day-old Sprague-Dawley rats underwent left carotid ligation followed by 2 h of hypoxic stress (8% O(2) at 37 degrees C). Hyperbaric oxygen therapy was administered 3, 6, 12, 24, and 72 h after HI. 5-bromo-2'-deoxyurindine and 5-bromo-2'-deoxyuridine/nestin were detected by immunofluorescence and nestin was examined by western blot analysis 10 days after HI. T-maze forced alternation, the foot-fault test, and the radial arm maze were conducted at P 22 days (14 days after HI), P 30 days, and P 34 days. Thereafter, cerebral morphology was examined by Nissl-staining 28 days after HI. There were remarkable increases in the proliferation of neural stem cells in the HBO-treated group, 3, 6, 12, and 24 h after HI, as compared with the HIBD group. The HBO-treated group, 3, 6, and 12 h after HI, performed better in the behavioral test and had less neural loss in the hippocampal CA1 region as compared with the HIBD group. The therapeutic window for effective HBO treatment could be delayed up to 12 h after HIBD, while the effect decreased 24 h after HI.
Brain Research 08/2008; 1222:87-94. · 2.88 Impact Factor
[show abstract][hide abstract] ABSTRACT: To study the effect of intracerebral transplantation of bone marrow stromal cells (BMSCs) on brain white matter of neonatal rats with hypoxic-ischemic brain damage (HIBD).
Thirty-four 7-day-old neonatal rats were randomly assigned to three groups: normal control (n=10), HIBD (n=12) and HIBD+BMSCs transplantation (n=12). The HIBD and the HIBD+BMSCs transplantation group rats were subjected to left carotid artery ligation, followed by hypoxia exposure for 2 hrs, in order to induce HIBD. The rats in the HIBD+BMSCs transplantation group received transplantation of BMSCs labeled nucleus with Hochest 33324 into the left hippocampus 24 hrs after HIBD induction. Myelin basic protein (MBP) expression in the left corpus callosum and the subcortical white matter and the number of oligodendrocyte precursors positively stained O4 in the left periventricular area and the subcortical white matter were detected by immunohistochemistry at ages of 45 days.
The labeled BMSCs survived and were found mainly in the left hemisphere 37 days after transplantation. The positive rate of O4 expressed by the transplanted BMSCs was 3.70+/-1.09%. More hypomyelination in the left corpus callosum and the subcortical white matter, and less number of O4 positive oligodendrocytes in the left periventricular area and the subcortical white matter were found in the HIBD group compared with the normal control group (P<0.01). The HIBD rats receiving BMSCs transplantation had increased O4 positive oligodendrocytes in the left periventricular area and the subcortical white matter and improved MBP immunoreactivity in the left corpus callosum and the subcortical white matter compared with the HIBD group (P<0.01).
Intracerebral transplantation of BMSCs can improve brain white matter damage in neonatal rats with HIBD.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 04/2008; 10(2):183-7.
[show abstract][hide abstract] ABSTRACT: To study the effects of heat shock preconditioning on the expression of heat shock protein-70 (HSP70) and apoptosis of the neuron in experimental autoimmune encephalomyelitis (EAE) rats.
Thirty-six Wistar rats were randomly divided into control, EAE and heat shock preconditioning groups (n=12 each). The EAE animal model was induced with guinea pig myelin basic protein. Heat shock preconditioning was performed 24 hrs prior to the EAE model inducement. No treatment was done in the control group. The neurological signs were observed after immunization. The spinal cords were removed and stained with hematoxylin and eosin. HSP70 was detected by immunohistochemistry. Apoptosis of the neuron was measured by TUNEL.
Heat shock preconditioning significantly alleviated clinical signs and neuronal injury. HSP70 expression in the heat shock preconditioning group was significantly higher than in the untreated EAE group (21.08 +/- 0.87 vs 10.17 +/- 0.51; P < 0.01). Heat shock preconditioning suppressed apoptosis of the neuron compared with the EAE group (apoptosis rate: 21.92 +/- 1.00% vs 58.92 +/- 1.67%; P < 0.01).
Heat shock preconditioning might improve the neurological outcome in EAE rats, possibly through the induction of HSP70 synthesis and the reduction of apoptosis of the neuron in spinal cords.
Zhongguo dang dai er ke za zhi = Chinese journal of contemporary pediatrics 12/2007; 9(6):563-6.
[show abstract][hide abstract] ABSTRACT: To explore the effect of hepatocyte growth factor (HGF) on the proliferation, apoptosis and function of hyperoxia exposed Type II alveolar epithelial cells (AEC II) isolated from premature rat lungs, and to explore the mechanism of the protective effect of HGF on hyperoxia-induced lung injury.
Type II alveolar epithelial cells from fetal rat lungs were cultured. After being purified, AEC II was randomly dividid to 4 groups: air group (Air), hyperoxia group (HO), air plus hepatocyte growth factor group (Air+HGF), hyperoxia plus hepatocyte growth factor group (HO+HGF) . The mRNA levels of surfactant associated protein, SPs (including SPA, SPB, SPC) were measured by RT-PCR. The proliferation and apoptosis of AEC II were analyzed with flow cytometric assay and Western blot.
(1) Compared with Air group, the apoptosis rate increased significantly in the HO group, while G(2)/M phase percentage and the protein expression levels of proliferating cell nuclear antigen (PCNA) decreased significantly (P<0.01); the S phase percentage and the protein expression levels of PCNA increased significantly in the Air+HGF group. (2) In the HO +HGF group, the apoptosis rate was not significantly different, G0/G1 phase percentage decreased significantly, S phase, G(2)/M phase percentage and the protein expression levels of PCNA increased significantly compared with the HO group. (3) SPs mRNA levels significantly decreased in the HO group compared with those in the Air group. After HGF was added, SPs mRNA levels increased in the HO +HGF group and the Air+HGF group compared with the HO group.
Hyperoxia can inhibit the proliferation, increase the apoptosis rate and decrease SPs mRNAs levels of AEC II in vitro in premature rats, while HGF can partly inhibit the changes of SPs mRNAs levels and cell proliferation of AEC II resulted from hyperoxia, and HGF may play a protective role in hyperoxia-induced lung injury.
Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences 12/2007; 32(6):1051-7.