ABSTRACT
Based on the neurovascular unit(NVU), neurovascular coupling functions as a barrier to maintain the homeostasis of the microenvironment by regulating the signaling and metabolic activity of nerve cells and capillaries. Widely dispersed across the retina, the NVU is essential to preserving its normal physiological function. A disturbance in retinal neurovascular homeostasis produced by a range of factors can result in a variety of retinal disorders, such as diabetic retinopathy(DR), glaucoma, retinitis pigmentosa(RP)and age-related macular degeneration(ARMD). The retina also has a widespread distribution of brain-derived neurotrophic factor(BDNF), which functions to promote neuron growth and repair damage by binding to its receptor TrkB. In recent years, BDNF was found to play a protective role against damage in the early stage of retinal neurovascular homeostasis imbalance, often known as the neurodegenerative stage. It also helps to reduce the production of pro-angiogenic substances of neurological origin and offers a fresh approach for the early detection and treatment of associated eye disorders.
ABSTRACT
Objectives To investigate the incidence of brain injuri in premature infants in ten hospitals of seven large cities in China sponsored by the Subspecialty Group of Neonatology of Pediatric Society, China Medical Association. Methods All premature infants with gestational age less than 37 weeks in ten hospitals were given routine cranial ultrasound within three days of birth, and then repeated every 3-7 days till the discharge from the hospital during January 2005 to August 2006. Results Incidence of intraventricular hemorrhage (IVH) and severe IVH were 10.8% (406/3 768) and 2.4% (92/3 768) with 22.6% (92/406) for grade 1, 54.7% (222/406) for grade 2, 17.2% (70/406) for grade 3 and 5.4% (22/406) for grade 4 in nine hospitals; incidence of periventricular leukomalacia (PVL) and cystic PVL were 2.3% (112/4 933) and 0.3% (16/4 933) with 85.7% (96/112) for grade 1, 12.5% (14/112) for grade 2, and 1.8% (2/112) for grade 3 including all ten hospitals, respectively. Risk factors associated with increased severity of IVH were vaginal delivery (OR = 1.874, 95% CI = 1.172 - 2.997, P < 0.01), perinatal asphyxia (OR = 1.598, 95% CI = 1.077 - 2.372, P < 0.05), mechanical ventilation (OR = 3.988, 95% CI= 2.448 -6.948, P< 0.01), and amniotic fluid contamination (OR = 2.192, 95% CI = 1.054 - 4.544, P< 0.05). Risk factors that might result in the development of cystic PVL were vaginal delivery (OR = 1.400, 95% CI = 1.186 - 1.652, P < 0.001) and mechanical ventilation (OR = 3.000, 95% CI = 1.015 - 8.864, P < 0.05). Conclusions These data reflect basically the prevalence of brain injuriy in premature infants in major cities of China. However, more than 60% of population lives in the rural area, further multicenter investigation including the rural area is expected to be undertaken in future.
ABSTRACT
BACKGROUND: The researches on the onset mechanism and intervention of periventricular leukomalacia (PVL) are affected due to few cases of generally-acknowledged animal model, so it is necessary to establish a reliable animal model for the study of PVL.0BJECTIVE: To establish PVL animal model of the 2-day-old SD rats.DESIGN: Randomized control animal trial.SETTING: Department of Pediatrics, West China Second University Hospital, Sichuan University.MATERIALS: A total of 36 2-day-old SD rats of cleaning grade and either gender, weighing 6-8 g, were provided by the West China Experimental Animal Center of Sichuan University; Mice anti-O4 was purchased by Chemicon Company,rabbit anti-glial fibrillary acidic protein (GFAP), rabbit anti-β-amyloid precursor protein (β-APP), rabbit anti-myeline basic protein (MBP), SABC immunohistochemical kit and DAB color reagent were all offered by Wuhan Boster Biological Technology Co., Ltd. Rabbit anti-mice IgG-FITC was obtained from Zhongshan Golden Bridge BioTechnology Co., Ltd.METHODS: The experiment was accomplished in the Laboratory of Women and Children, West China Second Hospital of Sichuan University between May and December in 2005. Totally 36 rats Were randomly divided into experimental PVL group and control group, 18 in each. The experimental PVL group was subjected to unilateral carotid ligation (UCL), and then they were put into a box filled with 6% oxygen and 94% nitrogen for 4 hours. Six rats were executed at ischemic 72hours, 14 days and 28 days respectively. Meanwhile sham surgeries were performed on the control group without ligation or exposure to hypoxia. And the time segment was identical with that of experimental group. ①Histopathological examination: Rat hearts were fixed by perfusion and stained with hematoxylin-eosin (HE). Light and electronic microscopy were used to observe the brain pathological and ultrastructure changes, ②Immunohistochemistry method was used to detect the distribution and expression of GFAP, β-APP, MBP and O4 in the white matter of both experimental and the control groups 72 hours post-operation. ③Neuroethology examination: Hanging test (rats were forced to hold the horizontal glass rod with forelegs, and the time of dropping was recorded in the distance of 45 cm.Scoring: 1 point: ＜ 10 s; 2 points: 10-30 s; 3 points: 30 s-2 minutes; 4 points: 2-5 minutes; 5 points: ＞ 5 minutes),inclined plane test (rats were laid on the inclined plate at the angle of 45° while rat heads turning upwards at the angle of more than 135°), open field test (square box without summit was divided into 9 equal grills at the bottom, rats were placed in the central grill to observe the activity within 30 seconds. Scoring: 1 point as rats entered the neighbor cage above half the body; 1 point as standing by hind limbs; total scores were the addition of the two), and cylinder test (rats were put in the cylinder of 20 cm×30 cm×5 cm to record the time of initial forepaw of each weight-bearing contact with the wall during a full rear, right (ipsilateral) or left (contralateral) percentage of total forepaw contacts at initiation was calculated.) were tested on the SD rats at 28 days post-operation. Then statistical management was conducted.MATN OUTCOME MEASURES: ①HE stain and electronic microscope were used to detect the histopathology changes after ischemia and hypoxia.②lmmunohistochemistry method was used to detect the expressions of GFAP, β-APP, MBP and O4 in the corresponding cell and tissue after ischemia and hypoxia. ③Neuroethology examination was used to evaluate the rats after ischemia and hypoxia by scores of each test.RESULTS: All 36 rats were involved in the result analysis. ①White matter damage was observed in the periventricular white matter in the PVL group by light and electronic microscopy at the early stage of post-operation; Ventricular dilatation and the loss of medullary sheath were detected in the white matter at the latter stage. ②The integrated optical density (IOD) of GFAP in PVL group was stronger than that of the control group (6 566.93±455.56, 1 069.32±791.71,P ＜ 0.05), and the mean diameter of GFAP-immunoreactive cells was increased in the brain tissue of PVL group compared with those of the control group [(11.69±0.97), (8.24±0.22), P ＜ 0.05]; β-APP immunohistochemistry demonstrated the IOD of PVL group was stronger than that of the control group [(59 304.07±6 864.03), (15 132.29±2 455.52),P＜ 0.05]; MBP IOD of the PVL group was decreased compared with the control group [(21 764.29±1 981.63), (69 174.72±3 199.90), P ＜ 0.05]; The density of O4-immunoreactive pyknotic cells was dramatically increased in the PVL group compared with the control group [(54.08±11.99), (1.25±0.51), P＜ 0.05].③In PVL group, the hanging time was shorter in the hanging test than that of the control group [(1.27±0.14), (4.24±0.59) minutes, P ＜ 0.05]; The turning-around time was longer in the inclined plane test than that of the control group [(7.17±2.32), (3.27±0.82) s, P ＜ 0.05]; The score in the open field test was decreased than that of the control group [(3.68±0.82), (12.67±1.00) s, P ＜ 0.05]; In the cylinder test the activity of the left limb was less than that of the right limb [(19.25±2.77), (64.55±0.36)%, P ＜ 0.05].CONCLUSION: PVL animal model can be successfully established by the method of UCL-hypoxia using the 2-day-old SD rat, and appears the obvious white atter damage, abnormal neurobehavior, reasonable pathological and behavior change.
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Objective To observe the change of neuron-specific enolase (NSE) an d glial fibrillary acidic protein (GFAP) in neonatal rats' cerebral cortex with hypoxic-ischemic brain damage (HIBD). Methods The 7 day- old SD rats were subjected to the ligation of right carotid artery, then were pu t into a hypoxic box to establish a HIBD model. The immunohistochemical method w as used to detect the expression of NSE and GFAP in rats' cerebral cortex. Results ① The NSE decreased in damaged cerebral cortex in HIBD 24 h group, after 7 days it gradually increased but was still lower than that of the controls. ② The expression of GFAP was limited and scarce in control and it did not change in HIBD 24 h group, while in HIBD 7 d group GFAP expression was increased and spread widely in the damaged cerebral cortex. Conclu sion ① The NSE decreases in damaged cerebral cortex in early stage of neonatal rat HIBD, suggesting that NSE is a specific marker for neuron damage . ② The GFAP increases in damaged cerebral cortex in the recovery stage of neon atal rat HIBD, suggesting that GFAP participates the repair of lesion region.
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Objective To investigate relationship of serum insulin like growth factors(IGFs) and catch up growth. Methods The model of rats intrauterine growth retardation (IUGR) was built by clamping bilateral uterine arteries and veins of pregnant rats. The growth parameters (body weight and length), organs weights (brain, lungs and liver) and serum concentrations of IGF Ⅰ, Ⅱ of all neonatal rats was measured at birth and postnatal day 3 and day 5, respectively. Results (1)At birth, the serum levels of IGF Ⅰ, Ⅱ and the average growth parameters, organs weights in IUGR rats were significantly lower than those in control group( P 0.05). The serum of IGF Ⅱ in high catch up group was significantly higher than that at birth( P 0.05). Conclusion Both IGF Ⅰ, Ⅱmay play an important role in the regulation of catch up growth and the decrease of IGF Ⅰ, Ⅱlevels may be the internal factors contributing to the absence of postnatal catch up growth in IUGR rats.