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Objective To investigate changes of striatal DAT following hypoxic ischemic (HI)brain injury in newborn piglets using 11C-N-2-carbomethoxy-3-(4-fluorophenyl)-tropane (CFT) PET/CT,and to evaluate the value of 11C-CFT PET/CT in brain injury.Methods Newborn piglets with HI brain injury (n =20) were taken as a model group,and five piglets were used as a control group.Radioligand 11CCFT (55.5-74.0 MBq) was injected through the jugular vein,and PET/CT imaging was performed to observe the changes of striatal DAT in newborn piglets.The ST/occipital lobe (OC) ratio was calculated.Model group was divided into 0-6 h,20-24 h,44-48 h and 68-72 h sub-groups after HI in accordance with the imaging time.The piglets were sacrificed immediately after 11C-CFT PET/CT scanning,and then the brains were removed for pathological analysis.Data analysis was performed with one-way analysis of variance and Pearson linear correlation analysis.Results After intravenous injection of 11C-CFT,the radioactivity accumulation in cortical,striatum,and cerebellum was shown clearly in the control and model groups.The radioactivity accumulation was lower in the white matter.The radioactivity in cortical and cerebellum exhibited decreased with time,while the striatum was still clear.After HI,the ST/OC activity ratio in the striatum was initially increased,and the ratio of 0-6 h group (1.34 ± 0.04) was statistically significant compared with that of thecontrol group (1.18 ± 0.06 ; F =4.658,P ＜ 0.05),followed by a gradual decrease.ST/OC ratios of other HI subgroups were 1.27 ±0.01,1.27 ±0.10 and 1.18 ±0.05,respectively.There was a positive correlation between the number of DAT positive neurons ((13 ± 3),(13 ± 4),(8 ±3) and (4 ±4)/high power field) and 11C-CFT ST/OC activity ratios (r =0.844,P ＜0.05).Conclusion 11C-CFT PET/CT study can accurately reflect the changes of DAT in the striatum,and the amount of DAT is related to the severity of the ischemic insult in a newborn piglet model of HI.
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Objective The aim of this study was designed to investigate the changes of macrophages and activated microglias in white matter damage (WMD) in premature infants and effects of allopurinol. Methods An animal model for WMD was established by bilateral carotid artery occulation (BCAO). Forty-two newborn SD rats (1 day old) were divided randomly into 3 groups: sham surgery group (Sham), BCAO group (BCAO) and allopurinol treated group (ALLO). Pathological changes were studied 7 days and 14 days after BCAO, respectively. Macrophages and activated microglias were detected by immunohistochemistry 7 days and 14 days after BCAO, respectively. Results In BCAO group, Ten cases had mild or severe rarefaction in the corpus callosum area, especially at the cingulum. Pathological changes of white matter were found in 4 cases in internal capsule. Eight cases had subcortex white matter rarefaction. The extent of white matter rarefaction in ALLO group was reduced significantly. Enlargement of bilateral ventricles was found in 6 of 8 cases in BCAO group. Compared to BCAD group [(3.27±0.73)%] the average ventricle size was reduced significantly in ALLO group [(2.44±0.71)%] (P<0.05). ED1 positive cells were found in corpus callosum,hippocampus, and internal capsule in all groups. BCAO group had more ED1 positive cells than the other two groups, and the staining extent in BCAO group was stronger than that in the other two groups. Conclusions BCAO could be used in newborn rats (1 day old) to establish a premature WMD animal model. Macrophages and microglias may play an important role in premature WMD. ALLO may have a potential protective effect on premature SD rat with ischemic WMD.
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AIM: To study the protective effects of nimodipine liposomes for injection (NDLI) on injuries of total cerebral ischemia/reperfusion(I/R) in rats and anoxia in mice. METHODS: Acute anoxia in mice was produced by hypoxia under normal pressure and decapitation. In these two models the survival time and persistent time of gasping were observed. Ameliorated pulsinelli four-vessel occlusion method was used to make global brain ischemia model. The EEG, the time of righting reflex recovery and Evans blue content in the homogenate of the brain tissues were recorded. RESULTS: NDLI obviously prolonged the survival time and persistent time of gasping in mice subjected to acute anoxia, remarkably shortened the time of EEG recovery and righting reflex recovery, and reduced Evens blue content in the homogenate. CONCLUSION: NDLI has significantly protective effects on injuries of total cerebral I/R and anoxia.
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Objective To observe the changes of water, potassium and sodium in the hypoxic cerebral tissues in mice and the effects of progesterone on the tissues and investigate the neuroprotective role of progesterone (PROG)in the cerebral anoxia. Methods Thirty - two male mice were divided into control group, simple hypoxia group, lower dosage group and higher dosage group. Progesterone was injected intraperitoneally in the dosage of 4 mg/kg or 8 mg/kg respectively 30 min before hypoxia in the last two groups. The contents of water, potassium and sodium in brain tissues in mice were evaluated at 24 hours after cerebral anoxia. Results The water, potassium and sodium contents in simple hypoxia group were significantly higher than those in control group(P0.05)in higher dosage group(8 mg/kg PROG)compared with those of simple hypoxia group. Conclusions At 24 hours after cerebral anoxia, there are significant increases of water, potassium and sodium in brain tissues. Progesterone may pro-duce neuroprotective role by inbibiting the rise of them.
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Objective To explore the effect of N-acetylcysteine (NAC) on intercellular adhesion molecule-1(ICAM-1) expression and apoptosis in neonatal rats brain after hypoxic and ischemic brain damage (HIBD). Methods Ninety 7-day old SD rats were divided into sham operative group, HIBD group and NAC treatment group, each group containing 30 animals. ICAM-1 expression and the apoptotic rate of brain cells were measureed at 6h, 12h, 24h, 48h and 7days after model establishment by immunohistochemistry and TUNEL, respectively. Results Compared with sham operative group and NAC treatment group, the number of ICAM-1 expression cells and apoptotic cells in the brain tissue significantly increased in HIBD group. Conclusion NAC could inhibit ICAM-1 expression and cell apoptosis in the brain with HIBD, and had the preventive effect on hypoxic and ischemic brain damage in neonatal rats.
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Objective To study the effect of hypoxia ischemia on cysteinyl aspartate specific proteinases (caspase 3) activity in cerebral tissue of neonatal rat and probe into its significance Methods To induce hypoxic ischemic brain damage (HIBD), the left carotid artery of rats at day 7 was ligated and animals were exposed to 8% oxygen for 2 hours 0 5,12,24,and 48 hours after HIBD, both ipsilateral and contralateral cerebral tissue were ditected and homogenized caspase 3 activity was measured by cleavage of the colorimetric substrate DEVD pNA Results Caspase 3 activity in ipsilateral cerebral tissue increased gradually after HIBD and peaked at 24 hours, and then decreased significantly at 48 hours( P 0 05) Conclusions Significant activation of caspase 3 after cerebral hypoxia ischemia strongly suggests that apoptosis is involved in HIBD Application of caspase inhibitors or other anti apoptotic agents may become a new therapeutics of HIBD
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Objective To investigate the mechanism of intracellular calcium and other ions disturbance by measuring the activity of Ca 2+ adenosine triphosphatase (Ca 2+ ATPase) and Na + K + adenosine triphosphatase (Na + K + ATPase) Methods Model of fetal rats ischemia and reperfusion was established The duration of ischemia was 15,30,45 and 60mins respectively;after ischemia for 15 mins, reperfusion for 1,4,8,15 and 24 hours There were 7 11 fetal rats sacrificed at different time points respectively, 12 rats in sham for control The mitochondria and endoplasmic reticulium (microsomia) were estracted and the activity of the enzyme was measured Results In the ischemia group: with the development of ischemia, the activity of Ca 2+ ATPase in mitochondria decreased gradually ( P
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Objective To study the expression of ICAM 1 at gene transcription level in neonatal rats after hypoxic ischemic brain damage(HIBD). Method Intercellular adhesion molecule 1(ICAM 1) mRNA was detected in cortex of neonatal rats at different times after HIBD and control by reverse transcription polymerase chain reaction(RT-PCR) technique. Result In the ischemic cortex, levels of ICAM 1 mRNA increased markedly at 6 h(2.5 fold, t=2.33, P
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0.05 ) and Hb were elevated significantly( P
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Objective To explore the relationship between the expression of c fos gene and delayed neuron death in perinatal hypoxia ischamia encephalopathy (HIE). Methods Terminal deo xynuleotidyl transferase mediated dUTP nick end labeling (TUNEL), immuno histochemistry andreverse transcription PCR(RT PCR) were used to detect the apoptosis and transcription and translation of c fos gene in the hippocampus following HIE. Results Positive signal of apoptosis from CA1 to CA4 sections were observed in experimental hippocampi. Marked signal appeared earlier and longer in CA1 section than in the other sections[CA1: 1 h: (14.6?2.3),24 h: (51?6),72 h: (17.4?0.3);CA4:1 h :1.3?1.6),24 h: (47?8),72 h: (21.6?0.6) apoptosis cell number/ mm 2 ],compared with the sham group of CA1 section P
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Objective To early diagnose fetal and neonatal brain damage and intracranial hemorrhage resulted from perinatal hypoxia ischemia. Method From April 1987 to April 1999, the brain of 880 high risk neonates delivered were examined by high resolution ultrasound equipment. The fetal brain were observed carefully at prenatal ultrasonography for high risk fetus. Results There were 365 cases of abnormal ultrasound findings (41.5%). Among which 110 cases were found to have hypoxic-ischemic encephalopathy (HIE), (including brain edema or periventricular echodensities), 233 cases of intracranial hemorrhages (among them six cases were detected in uterus and confirmed after birth.), 7 cases of hydrocephalus (two cases detected in uterus), 2 cases of congenital callosal agenesis (one case detected in uterus), one case of cerebral tumor and others 12 cases. The morbidity of intracranial hemorrhage was obviously higher in the neonates of small for gestational age or with pregnant complications. Conclusions Because it is useful for early diagnosis, proper management, and prediction for prognosis, cranial ultrasonography should be done routinely for high risk fetus and neonate.
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Objective To study the clinical characteristics and long term prognosis of the neonates with hypoxic ischemic encephalopathy (HIE) and explore therapy to improve the prognosis. Methods Data of 1150 newborns with HIE were analyzed. retrospectively. Results There were 942 full term babies(81.9%) and 208 prematures(18.1%). Most of them were caused by anoxia occurring in intrauterine period or at birth, 75.0% of them with superimposed intracranial hemorrhage. The mortality rate was 7.0%(32.8% severe HIE, 4.2% moderate HIE). Among 852 surviors with follow up, the sequenlae rate is 10%(60.7% in severe HIE,4.5% in moderate HIE). The prognosis were bad. The therapy to improve the prognoses are as follow:(1)Early diagnosis and clinical intervention.(2)To maintein the hemostasis is the major principle of treatment.(3)To prevent organ function damage.(4)Long term(4 to 6 months) of Hyperbaric oxygen therapy should be applied to newborns with severe HIE.(5)Early follow up from newborn period and preventive intervention. Conclusion Prognoses of both newborn with sever HIE and prematures are bad. Long term treatment after newborn period is necessary to improve the prognosis.
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Objective To investigate the optimal mild hypothermia course and cerebral temperature of the neonatal rats after hypoxic-ischemic brain injury. Methods The posthypoxic-ischemic rats of experimental group (n=60) were placed in the glass jars immeresd in water bath held constaut at either 29 C or 3l C for 24h, 48h or 72h. While the rats of room temperature group (n=22) were stayed in room air. Blood glucose, blood gases and neuropathology findings were studied to determine the therapeutic effects. Results The brain temperature droped 3C or 5C when enviro ment temperature was 31C or 29C respectively. The blood glucose remained normal. Neuropathology findings reveled that the brain damage of experimental rats reduced 46%～86% compared to the room temperature group. Conclusion Reducing the cerebral temperature by 4～5 C for 72 hours after hypoxic-ischemic brain injury can lead to superior protective effect.
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Objective To investigate the cerebral protection of Memantine in neonatal rats with hypoxic ischemia. Methods Memantine was intraperitoneally injected at a dose of 20 mg/kg in neonatal rats of cerebral hypoxic ischemia (HI). Employing a quantized score system of cerebral pathology for hypoxic ischemia developed, the neuroprotective effect of Memantine was evaluated pathologically. Results There were significantly decreased scores in either PRE group (Memantine was given one hour before HI) or POST group (Memantine was given after HI immediately) comparing to HI group with higher score. Conclusion Memantine can improve cerebral hypoxic ischemic damage significantly, and be potentially valuable for the treatment of neonatal hypoxic ischemic brain damage.
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Objective To evaluate prognostic value of electroencephalogram (EEG) in neonatal with hypoxic ischemic encephalopathy (HIE). Methods Sixty two infants with HIE was studied by doing physical examination, intelligence test, CT and EEG. Their clinical outcome was compared to their EEG in the first month after birth. Results Incidence of sequelae in normal or mild abnormal EEG and severe abnormal EEG were 3%, 29%, respectively. Among three infants of EEG cases, two dead and one developed cerebral palsy infant. Among four of burst suppression found in the EEGs, two cases dead, one developed cerebral palsy, one was normal. In five of hypoactive EEG, one dead, one developed cerebral palsy, and the other was with low IQ. Conlusion The prognosis is related to the background activity of EEG. The presence of a burst suppression EEG pattern and a hypoactive/flat EEG are negative prognostic criteria.
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Objective To investigate the neuroprotection of different brain regions after transplantation of genetically modified myoblasts producing brain derived neurotrophic factor (BDNF) into cortices of neonatal rats subjected to hypoxic ischemic encephalopathy (HIE). Methods Seven day old pups were randomized into sham operated group (C), HIE+BDNF group (B) and HIE+mock transplantation group (A). A rat myoblast cell line expressing and secreting BDNF (BDNF(+)/L 6TG) was constructed. A stereotaxical intracerebroparenchymal transplantation of either BDNF(+)/L 6TG (B) or BDNF(-)/L 6TG (absence of BDNF, A) at 0.8 ?l of cell suspension (4?10 4/?l) into the left cortex of the brain was carried out shortly after HIE undergone by ligation of left common carotid artery followed by a 2.5 h inhalation of humidified 8% O 2+92% N 2 at 37℃. Changes of areas of different brain regions of cortex, hippocampus and striatum at different sections were observed 21 d after the procedure. Injury severity scores of brain tissues were also performed. Results Twenty one days after the manipulation, various degrees of atrophy were observed in the three regions of left hemispheres in group A or B versus contralateral corresponding regions or group C whereas this atrophy in group B was significantly reduced when compared to group A. Not only was the atrophy of cortex near the grafting point alleviated but some other regions of left hemispheres. A similar change pattern was seen in injury severity scores of the tissue. Conclusion Present data suggest that intracerebral transplantation of genetically modified myoblasts producing BDNF has a beneficial effect on the protection from damage of both circumscriptus brain tissues and some other areas distanced from the grafted place.
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Objective To study the changes of the blood Platelet activating factor (PAF)levels in neonatal hypoxic ischemic encephalopathy(HIE),and explore the relationship between PAF levels and severity of brain damage. Method The levels of blood PAF and SOD were measured in neonates with HIE by radio immunoassay and compared with that of normal term neonates. Results Blood PAF levels were much higher in acute stage of HIE,and PAF levels increased with the severity of HIE.Blood SOD and platelets were much lower compared with PAF. PAF is negatively correlated to SOD and PLT.( r=-0.467 and r=-0.359,P
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Objective To study the variation of endothelin 1(ET 1) and calcitonin generelated peptide(cGRP) and its clinical implication, and to analyze the influence of ET 1 and cGRP on cerebral arteries hemodynamics in neonates with hypoxic ischemic encephalopathy(HIE). Methods The variation of ET 1,cGRP in cord blood and peripheral blood were prospectively observed at the time of 1 day,3 days and 7 days after birth in HIE and healthy control infants by radioimmuneassay. The cerebral arteries hemodynamics were determined immediately using color Doppler ultrasonography at 1 day after blood samples were obtained. Results (1) The following factors in cord blood and vein one day after birth in neonatal HIE and healthy controls was: ET 1(70?25)ng/L vs (38?19) ng/L ( P
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Objective To explore the immunologic changes and its immunologic mechanism in neonatal hypoxic ischemic encephalopathy(HIE).Methods T lymphocyte subpopulation, serum interleukin 2 receptor (SIL 2R), interleukin 6(IL 6), interleukin 8 (IL 8), tumor necrosis factor alpha (TNF ?), nitric oxide (NO), immunioglobin(Ig), complement (C 3), the percentage of RBC C 3b receptor rosette(E C 3b RR), RBC immune complex rosette ( E ICR) and cerebral artery hemodynamics was tested in newborns with HIE and normal controls. The umbilical blood samples and peripheral blood samples were obtained at the time of 1 day, 3 days, 7 days, 12～14 days and 26～28 days after birth. Results Birth asphyxia and HIE were associated with under regulated immune function, which include:(1) T Cell population disorder. In HIE and control group, CD 3 +were(62?8)%vs(65?10)%,CD 4 +(39?7)% vs (46?8)%,CD 8 +(33?6)% vs (19?5)%,CD 4 +/CD 8 + ratio (1.8?0.7) vs (2.5?0.7) on 1 to 3 days after birth. There were no signficant difference in both group on 26 to 28 days after bith ). (2)The IgM and C 3 were decreased.(3)The cytokins were abnormal. (4) RI was negetively correlated with IL 6 ( r=-0.61,P
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Objective Hypoxic-ischemic brain damage (HIBD) is a life-threatening neonatal disease during perinatal stage. Since excitatory amino acids (EAAs) and their receptors are involved in the pathogenesis. Sodium hydroxybutyrate ( r-OH ), an intermediate metabolite of GABA, may have beneficial effects on HIBD. Methods One-hundred seven-day (7d) SD rat pups were randomly assigned to one of three groups:(Ⅰ) control group (n= 20);(Ⅱ) sham operation group (n=20)and (Ⅲ) r-OH group which was further divided into 3 subgroups according to the dose of r-OH 50 mg?kg-1 (r-OH1) (n=20),100 mg?kg-1 (r-OH2) (n=20),200mg?kg-1 (r-OH3) ( n=20).Animals in control group and r-OH group were subjected to left carotid artery ligation followed by 2 h of hypoxia (O2 :N2=8%:92%).Normal saline ( NS) was administered ip immediately after sham operation or hypoxia,then 3 times a day for 7 days in group Ⅰ and Ⅱ.In r-OH group r-OH was administered ip instead of NS. Brain damage was evaluated by survival rate, pathology, the ratio of weight of left to right hemisphere on the 28 th day after ischemia-hypoxia and the capacity of learning and memory using Y-Maze test. Results (1) The survival rate on the 28 th day after hypoxia or sham operation was significant lower in control group (60%) than that in the other groups (85%-95% ) (P