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OBJECTIVES@#To study the correlation of the expression of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue with hepatic fat content in rats with intrauterine growth retardation (IUGR).@*METHODS@#Pregnant rats were given a low-protein (10% protein) diet during pregnancy to establish a model of IUGR in neonatal rats. The pregnant rats in the control group were given a normal-protein (21% protein) diet during pregnancy. The neonatal rats were weighed and liver tissue was collected on day 1 and at weeks 3, 8, and 12 after birth, and visceral adipose tissue was collected at weeks 3, 8, and 12 after birth. The 3.0T 1H-magnetic resonance spectroscopy was used to measure hepatic fat content at weeks 3, 8, and 12 after birth. Real-time PCR was used to measure mRNA expression levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. Western blot was used to measure protein levels of Lipin2 in liver tissue and Lipin1 in visceral adipose tissue. A Pearson correlation analysis was performed to investigate the correlation of mRNA and protein expression of Lipin with hepatic fat content.@*RESULTS@#The IUGR group had significantly higher mRNA and protein expression levels of Lipin1 in visceral adipose tissue than the control group at weeks 3, 8, and 12 after birth (P<0.05). Compared with the control group, the IUGR group had significantly lower mRNA and protein expression levels of Lipin2 in liver tissue on day 1 after birth and significantly higher mRNA and protein expression levels of Lipin2 at weeks 1, 3, 8, and 12 after birth (P<0.05). At week 3 after birth, there was no significant difference in hepatic fat content between the IUGR and control groups (P>0.05), while at weeks 8 and 12 after birth, the IUGR group had a significantly higher hepatic fat content than the control group (P<0.05). The protein and mRNA expression levels of Lipin1 were positively correlated with hepatic fat content (r=0.628 and 0.521 respectively; P<0.05), and the protein and mRNA expression levels of Lipin2 were also positively correlated with hepatic fat content (r=0.601 and 0.524 respectively; P<0.05).@*CONCLUSIONS@#Upregulation of the mRNA and protein expression levels of Lipin1 in visceral adipose tissue and Lipin2 in liver tissue can increase hepatic fat content in rats with IUGR and may be associated with obesity in adulthood.
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Adult , Animals , Female , Humans , Pregnancy , Rats , Fetal Growth Retardation , Gene Expression , Liver/metabolism , Organic Chemicals , RNA, Messenger/metabolismABSTRACT
Objective:To investigate the diagnostic value of diffusion weighted imaging and 1H magnetic resonance spectroscopy for the neonatal hypoxic ischemic encephalopathy (HIE).Methods:37 cases of patients with neonatal hypoxic ischemic encephalopathy admitted in our hospital were selected as the study group,another 40 healthy neonates were selected as the control group,both groups of neonates underwent diffusion-weighted imaging and 1H magnetic resonance spectroscopy,ordinary MR1 and diffusion weighted imaging findings of neonates in the study group were observed,the neonatal cerebral metabolic compounds relative concentration were observed and compared between two groups.Results:The detection rate of diffusion-weighted imaging was significantly higher compared with the ordinary MRI (P＜0.05).The relative ratio of brain metabolic compounds NAA/Cr of study group were obviously lower than those of the control group,while the Cho/Cr,MI/Cr,Glu-Glr/Cr,Lac/Cr were significantly higher (P＜0.05).Conclusion:Diffusion weighted imaging combined with 1H magnetic resonance spectroscopy could improve the diagnostic accuracy of neonatal hypoxic ischemic encephalopathy,the analysis of the concentrations of brain metabolic compounds could contribute to evaluate the severity of HIE.
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Objective To study the thalamic metabolic alterations and its correlation with cognitive impairment in patients with cerebral small vessel disease(CSVD).Methods The cognitive function of 34 patients with CSVD and 26 matched volunteers were evaluated by Montreal cognitive assessment(MoCA), and received single voxel 1H-MRS examination to detect the content of NAA,Cho and Cr,and record the ratio of NAA/Cr and Cho/Cr on bilateral thalami.The differences of NAA/Cr, Cho/Cr on bilateral thalami between the two groups were compared, and the correlation between NAA/Cr,Cho/Cr and MoCA total score and its sub-items score in CSVD group were analyzed.Results ①The MoCA of total score as well as its sub-items such as visual space and executive ability,memory,attention and language for CSVD group were significantly lower than that for the control group(P0.05);③In CSVD group, the ratio of NAA/Cr on both bilateral thalami were significantly positively correlated with MoCA score (left r=0.83,right r=0.79,P0.05).Conclusion The thalamic neuron has been damaged and dysfunctioned in patients with CSVD,and this metabolic abnormality may be related to a wide range of cognitive impairment in CSVD patients.
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Objective To investigate the characteristic changes of the metabolism products in the auditory cortex (transverse temporal gyrus)in patients with metabolic syndrome combined with sensorineural deafness using 1 H magnetic resonance spectroscopy (1 H-MRS),and to find out the early warning indicators of sensorineural deafness in patients with metabolic syndrome.Methods The pure tone audiometry (PTA)was performed in 142 pa-tients with metabolic syndrome (diagnosed by endocrinology department),and 15 healthy subjects as the control group.The patients were divided into four groups:the metabolic syndrome group;the metabolic syndrome group with unilateral,the bilateral deafness group,and the control group.Cerebral metabolism was studied by assessing the ratios of nitro-acetyl aspartate contrast to choline (NAA/Cho)as well as to creatine (NAA/Cr),myo-inosi-tol to creatine (mI/Cr)and choline to creatine (Cho/Cr)ratios in the auditory cortical separately in these groups. ROC curves were made for those metabolism markers to find the best diagnostic threshold.Results Significantly lower values of NAA/Cho ratio and higher values of Cho/Cr were observed in metabolic syndrome in the control group (P<0.05),Cho/Cr higher than those (P<0.05).NAA/Cho ratios in the injured and uninjured auditory cortex of MS with unilateral deafness were significantly lower than those in the control group (P<0.05).A self-comparison was made between the inj ured and uninj ured auditory cortex,the result showed that NAA/Cho ratio had significant differences.All of the metabolisms were tested by the curve of ROC.The area of NAA/Cho under the ROC curve was 81%,which had a higher accuracy.NAA/Cho equating to 1 .82 could be used as the boundary indi-cators between metabolic syndrome without deafness and with deafness groups.The areas of the other indicators un-der the ROC curve were <50%.Conclusion NAA/Cho may be the early warning marker of sensorineural deafness in patients with metabolic syndrome.
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Objective To identify the features of 1H-magnetic resonance spectroscopy(1H-MRS) in patients with chronic obstructive pulmonary disease(COPD) of the hippocampus.Methods 32 patients with COPD randomly selected and 30 normal controls were selected.1H-MRS of the hippocampus was performed given to on all the subjects on hippocampus.The ratios of NAA/Cr and Cho/Cr were determined.Results In the bilateral hippocampus, the NAA/Cr ratio in patients with COPD demonstrated lower than that in normal controls(t=4.963,P=0.007 and t=4.856,P=0.023).The Cho/Cr ratio in patients with COPD showed higher than that in normal controls, the differences was were statistically significant(t=3.469,P=0.013 and t=3.019,P=0.047) Conclusion Abnormal metabolism of neurons on the hippocampus in patients with COPD is showed.
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Medulloblastoma was a common malignant, invasive neoplasm of the central nervous system occurring in children. This disease had the characteristics of easy recurrence and the prognosis remained relatively poor, which heavily influenced healthy and quality of life of children. In recent years, advanced magnetic resonance imaging (MRI) techniques such as diffusion weighted imaging (DWI), diffusion tensor imaging (DTI)and 1H- magnetic resonance spectroscopy (1H- MRS) were the new noninvasive technique of diagnostic imaging to be used in the diagnosis and prognosis of medulloblastoma, which showed very significant clinical value and made some new progress. In this study, we talked about the DWI, DTI and 1H-MRS used in medulloblastoma.
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Objective To investigate the variation of multivoxel 1 H magnetic resonance spectroscopy(1 H-MRS)before and after continuous positive airway pressure(CPAP)treatment in obstructive sleep apnea hypopnea syndrome(OSAHS).Methods Brain multivoxel 1 H-MRS examinations were performed in 25 cases of moderate or severe OSAHS patients before and after CPAP treat-ment,and 25 cases of healthy.The ratios of brain metabolites of the frontal lobe were recorded and analyzed respectively.To observe whether the lactate(Lac)peak appeared or not.Results In the frontal lobe,the NAA/Cr,NAA/Cho of the patients before treatment (2.021 2±0.231 2 and 1.608 8±0.257 1,respectively)was decreased compared with the healthy (2.726 8±0.607 1 and 2.445 6± 0.437 5).The NAA/Cr,NAA/Cho of the patients after treatment (2.314 0±0.312 8 and 2.01 6 4±0.424 0,respectively)was in-creased compared with the patients before treatment (2.021 2±0.231 2 and 1.608 8±0.257 1).The NAA/Cr,NAA/Cho of the pa-tients after treatment (2.314 0±0.312 8 and 2.01 6 4±0.424 0,respectively)was decreased compared with the healthy (2.726 8± 0.607 1 and 2.445 6±0.437 5),and the difierences were statistically significant (P <0.01).The Cho/Cr of the patients before treatment (1.293 2±0.261 5)was increased compared with the healthy (1.129 2±0.157 7),the difference was statistically significant(P <0.05).Lac peak was not detected in all.Conclusion Multivoxel 1 H-MRS can demonstrate sensitively the changes of brain metabolism in pa-tients with OSAHS before and after CPAP treatment,and may provide imaging evidence for clinical therapeutic effect and prognostic evaluation.
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Objective To investigate the characteristic changes of the metabolism products in the auditory cortex (transverse temporal gyrus) in diabetes combined with nerve deafness using 1 H magnetic resonance spectros‐copy (1 H -MRS) ,and to discover the early warning indicator of nerve deafness in type 2 diabetes .Methods PTA was performed in 98 patients with type 2 diabetes (diagnosed by Endocrinology Department) ,and in 15 healthy sub‐jects in the control group .The patients were classified into four groups :the group of type 2 diabetes;type 2 diabe‐tes with unilateral and bilateral deafness ,and the normal control group .Cerebral metabolism was studied by assess‐ing the ratios of nitro -acetyl aspartate contrast to choline (NAA/Cho) as well as to creatine (NAA/Cr) ,myo-in‐ositol to creatine (mI/Cr) and choline to creatine (Cho/Cr) ratios in the auditory cortical separately in these groups . The Pearson correlation analysis was applied to determine blood glucose value with the nerve metabolites while the ROC curves were made for those metabolism markers to find the best diagnostic threshold .Results NAA/Cr and NAA/Cho were negatively correlated with AHI index and Cho/Cr ,mI/Cr was positively correlated with blood glu‐cose value .Significantly lower values of NAA/Cho ratio were found in patients'(diabetes without deafness) auditory cortex compared with 15 age-matched control subjects (P<0 .05) .NAA/Cr and NAA/Cho ratio in diabetes with deafness were significantly lower than those in control group (P< 0 .05) ,Cho/Cr higher than those of in other groups (P<0 .05) .NAA/Cr and NAA/Cho ratio in injured and uninjured auditory cortex of diabetes with unilateral deafness were significantly lower than those of in control group (P<0 .05) ,then we made a self -comparison be‐tween the injured and uninjured auditory cortex ,finding that NAA/Cho ratio had a significant difference .All of the metabolisms were tested by the curve of ROC .The area of NAA/Cho under the ROC curve was 81% ,which had a higher accuracy .NAA/Cho equal to 1 .65 can be used as boundary indicators between diabetes without deafness and diabetes with deafness groups ,the areas of the remaining indicators under the ROC curve was<50% .Conclusion NAA/Cho may be the early warning marker of nerve deafness in type 2 diabetes .
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Objective To investigate the characteristic changes of the metabolism products in auditory cortex (transverse temporal gyrus) in patients with OSAHS combined with nerve deafness using 1 H magnetic resonance spectroscopy (1 H - MRS) ,and to discovery the early warning indicator of nerve deafness in OSAHS .Methods PTA was performed in 95 patients with OSAHS (diagnosed by PSG) ,and 15 healthy control subjects ,the patients were classified into four groups :the group of OSAHS ;OSAHS with unilateral and bilateral deafness ,the normal control group .Cerebral metabolism was studied by assessing the ratios of nitro -acetyl aspartate contrast to choline (NAA/Cho) as well as to creatine (NAA/Cr) ,myo -inositol to creatine (mI/Cr) and choline to creatine (Cho/Cr) ratios in the auditory cortical separately in these groups .ROC curves were made for those metabolism markers to find the best diagnositic threshold .Results Significantly lower values of NAA/Cho ratio were found in patients'(OSAHS with deafness) auditory cortex compared with 15 age-matched control subjects (P<0 .05) and OSAHS without deafness (P<0 .05) .Auditory cortical NAA and NAA/Cho ratio in OSAHS with unilateral nerve sensorineual hearing were significantly lower than those of in normal control (P<0 .05) ,but there was no significant difference be-tween the abnormal and ontralateral normal auditory cortex by a self comparison .All of the metabolisms were tested by the curve of ROC .Conclusion Combined with the changes of metabolism ,and the curve of ROC ,NAA/Cho may be the early warning markers of sensorineual hearing was in OSAHS patients .
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Objective To study the feature of brain functional in front gyrus,anterior cingulate cortex and hippocampus of patients with generalized anxiety disorder (GAD).Methods 19 patients with GAD and 20 healthy volunteers were scanned on brain using proton magnetic resonance spectroscopic imaging (1H-MRS).The levels of Choline (Cho),Creatine (Cr),N-acetyl-aspartate (NAA) were measured in the frontal gyrus,anterior cingulate cortex and hippocampus of all subjects.The 1H-MRS data were compared between two groups.Results Compared with the healthy matched control,the levels of Cho (7.22 ± 1.99),Cr (5.44 ± 1.68),NAA (12.09 ±2.30)in right frontal gyrus white matter,the levels of Cho(9.89 ±2.40),Cr(8.59 ± 1.71) in right anterior cingulate cortex and the levels of NAA in left anterior cingulate cortex were significantly high (P ＜ 0.05).The ratio of NAA/Cr and Cho/Cr were not difference in two groups.In the hippocampus of the patients,the Cho,Cr,NAA,NAA/Cr and Cho/Cr ratio were not significantly higher or lower than those in control (P ＞ 0.05).Conclusion The brain substance metabolisms of the patients with GAD are abnormal and asymmetrical between left and right brain,especially occurred in right brain.
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Objective To approach potential abnormalities of neuro-chemical compounds in cerebrum of obsessive-compulsive disorder and to analyze the relationship among the abnormalities with duration of illness and symptom severity. Methods 19 patients with obsessive-compulsive disorder and 22 comparison subjects were scanned by 1H magnetic resonance spectroscopy to exam bilateral prefrontal lobe, temporal lobe, parietal lobe, occipital lobe, anterior cingutate and caudate nucleus, hippocampus as well as splenium and genu of corpus callosum,thalamus. The ratios of N-acetylaspartate (NAA) and choline (Cho) to creatine (Cr) were respectively recorded.The severities of obsessive-compulsive symptoms were assessed by Yale-Brown Obsessive-Compulsive Scale. Results ( 1 ) The ratios of NAA/Cr in right caudate nucleus and left hippocampus were higher than those in normal controls (1.23 ±0.37 vs 1.0 ±0.33, t=2.14, P=0.039;1.34 ±0.25 vs 1. 10 ±0.45, t=2.41, P=0.021 ), but NAA/Cr ratios in genu of corpus callosum were lower(0. 97 ±0.30 vs 1.19 ± 0. 26, t = -2.47, P= 0.018 ).(2) The Cho/Cr ratios in right caudate nucleus and left temporal lobe were higher than those in control groups (1.09±0.51 vs0. 67±0.21,t=3.32, P=0.003;2.58±0.62vs0.84±0.17, t=2.21,P=0.03). (3) The duration of illness was negatively correlated with the Cho/Cr ratios of right prefrontal lobe ( r = - 0. 507, P =0. 027 ). (4) The NAA/Cr ratios of genu of corpus callosum as well as the Cho/Cr ratios of left temporal lobe were negatively correlated with YBOCS score ( r 1 = - 0.457, P = 0.049; r 2 = - 0. 585, P = 0.009 ). Conclusion Neuronal functions increase in right caudate nucleus and left hippocampus which are opposite in genu of corpus callosum. These abnormalities may play an important role in pathogenesis of OCD.
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OBJECTIVE: To test the hypothesis that a transient non-lethal ischemia (ie. ischemic preconditioning(IPC)) would protect against subsequent traumatic brain injury (TBI) using 1H-magnetic resonance spectroscopy (MRS). METHOD: Sprague-Dawley rats were randomized to sham ischemia procedures followed by TBI, IPC followed by TBI, and IPC followed by sham TBI. IPC was induced by 20 min of right common carotid artery occlusion 24 hour prior to TBI, and experimental injury was induced using lateral fluid percussion model of moderate severity. We measured metabolic changes with 1H-MRS and conducted motor function and 4 arm maze tests to identify neurobehavioral deficits and cognitive deficits, respectively, at 1 day to 4 weeks post-injury. RESULTS: The NAA/Cr ratios in the affected hemisphere were significantly lower in TBI than in IPC-TBI group at 2 (p=0.006) and 4 (p=0.012) weeks and in the unaffected hemisphere at 4 weeks (p=0.030). TBI group also showed a trend towards reduction in NAA/Cho ratio in the affected hemisphere at 4 weeks (p=0.054). CONCLUSION: Brief IPC 24 hours before moderate lateral fluid percussion brain injury increases the resistance to brain damage and that is associated with changes in brain metabolites. These findings indicate that IPC induces neuroprotection against TBI in rat brains.
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Animals , Rats , Arm , Brain , Brain Injuries , Carotid Artery, Common , Ischemia , Ischemic Preconditioning , Neuroprotective Agents , Percussion , Rats, Sprague-Dawley , Salicylamides , Spectrum AnalysisABSTRACT
Pilocytic Astrocytomas (PA) treatment and prognosis is variable depending on location. ¹H Magnetic Resonance Spectroscopy (MRS) is used to characterize tumor metabolism providing additional information to the Magnetic Resonance Imaging (MRI) evaluation assessing the therapy response. This study was designed to evaluate brain metabolic changes that result from Temozolomide (TMZ) administration on pediatric PA using MRS. Twenty children with PA were studied. We performed MRI and MRS pretreatment and after 12 months of therapy on a 3.0 Tesla scanner in order to monitor the chemotherapy response to 5-day treatment with oral TMZ (200 mg/mt² x day) given every 28 days for 12 cycles. Multivoxel Proton Spectroscopic Imaging was performed using a Point Resolved Spectroscopy sequence (PRESS). Analysis of Variance (ANOVA) was applied to the results in order to evaluate the possible statistical differences. Pairwise comparisons with Bonferroni correction test were assessed in order to verify the differences among ratio means. It was observed a significant decrease in Cho/Cr ratio (p<0.05) and a significant increase in NAA/Cr ratio (p<0.05) while TMZ therapy was taking place. These results are linked with tumor size reduction (r = 0.95, p< 0.05) detected by MRI. Results show MRS can detect early tumor reaction to therapy prior to MRI. Therefore, MRS could provide a useful tool to monitor the answer of pediatric PA to TMZ. The link between metabolic markers changes due to TMZ treatment assessed by MRS and the tumor volume reduction may also provide a fertile ground to developa TMZ-based therapy for pediatric PA and to predict its efficacy to improve PAs response to treatment.
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Humans , Male , Adolescent , Female , Child , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/therapeutic use , Astrocytoma/diagnosis , Astrocytoma/drug therapy , Magnetic Resonance Imaging/methods , Medical OncologyABSTRACT
OBJECTIVE: To investigate the relationship between cognitive impairment and 1H magnetic resonance spectroscopy (1H MR spectroscopy) in patients with subarachnoid hemorrhage (SAH) caused by rupture of middle cerebral artery (MCA) aneurysm. METHOD: 1H MR spectroscopy was performed in 6 patients with SAH after rupture of MCA aneurysm and in 20 controls. Image-guided localized 1H MR spectra were obtained from left parietal white matter (PWM). The cognitive status was evaluated using the Mini Mental Status Examination (MMSE), and the scores were correlated with N-acetyl aspartate/creatine (NAA/Cr), choline/creatine (Cho/ Cr), and myoinositol/creatine (mI/Cr) metabolic ratios. RESULTS: NAA/Cr was significantly lower, and Cho/Cr was higher in SAH patients than in controls in the left PWM (p0.05). CONCLUSION: 1H MR spectroscopy could be helpful in the evaluation of cognitive impairment in SAH.
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Humans , Aneurysm , Intracranial Aneurysm , Magnetic Resonance Spectroscopy , Middle Cerebral Artery , Rabeprazole , Rupture , Subarachnoid HemorrhageABSTRACT
BACKGROUND: The heme oxygenase system catalyzes the conversion of heme to free iron, carbon monoxide and bilirubin. This study was purposed to evaluate the effect of the heme oxygenase inhibitor, Tin protoporphyrin IX (SnPPIX) on the hypoxic ischemic brain injury in a neonatal rat. METHODS: Seven-day old Sprague-Dawley rat pups were used. The rats were divided into two groups; control group (n = 9) and SnPPIX group (n = 6). SnPPIX 50 micromol/kg and the dissolvent were administered respectively intraperitoneally. For hypoxic ischemic brain injury, the right common carotid artery was ligated with 5-0 silk and the rats were put in the moisturized hypoxic gas chamber for 150 minutes. Lipid/N-acetyl aspartate and Lipid/Creatine ratio of 1H magnetic resonance spectroscopy were evaluated on the 1st day and the 7th day after hypoxic ischemic brain injury. All rats were sacrificed 2 weeks after hypoxic ischemic brain injury for morphological study. RESULTS: There were no statistically significant differences between two groups in the result of MRS and Lip/Cr and Lip/NAA ratio on 1th day and 7th day after hypoxic ischemic brain injury. In addition, there was no significant difference in the gross morphological evaluation on the 14th day. CONCLUSIONS: Our results suggest that the pretreatment of the Tin protoporphyrin IX does not affect the degree of brain damage which is caused by apoptosis in the model of hypoxic ischemic brain injury in a neonatal rat.
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Animals , Rats , Apoptosis , Aspartic Acid , Bilirubin , Brain Injuries , Brain , Carbon Monoxide , Carotid Artery, Common , Heme Oxygenase (Decyclizing) , Heme , Iron , Magnetic Resonance Spectroscopy , Rats, Sprague-Dawley , Silk , TinABSTRACT
0.05). The NAA/Cr and NAA/Cho in the Group A were significantly higher than those in the Group B (t=4.235, P=0.011; t=2.832, P=0.031), and the Cho/Cr in the Group A was significantly lower than that in the Group B (t=-2.323, P=0.042). Conclusions ~1H magnetic resonance spectroscopy can improve the diagnostic accuracy of glioma.
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OBJECTIVE: The frontal lobe white matter (FLWM) is suggested to play an important role in the pathophysiology of depression. In this study, metabolites in the normal appearing FLWM and their clinical meaning in female subjects were evaluated. METHODS: Using proton-magnetic resonance spectroscopy, the ratios of metabolite peaks in the FLWM were measured in vivo in 14 female patients with major depressive disorder and were compared with 12 age-matched normal controls. The ratios' clinical significance was analyzed with respect to severity of depression (Hamilton Depression rating Scale score and Beck Depression Inventory score) and trait of impulsivity (Barratt Impulsiveness Scale). RESULTS: There were no significant differences in the NAA/Cr, Cho/Cr, Cho/NAA ratio between depressed and control subjects. But right FLWM Cho/Cr ratios in control and depressed subjects were found to be positively correlated with total and motor impulsiveness score as measured by the Barratt Impulsiveness Scale. CONCLUSION: The biochemical changes in the FLWM may provide some of the neurobiological substrates to personality trait, impulsivity. Further researches on the underlying mechanisms of impulsivity traits are needed.
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Female , Humans , Depression , Depressive Disorder, Major , Frontal Lobe , Impulsive Behavior , Spectrum AnalysisABSTRACT
BACKGROUND: Inducible nitric oxide synthase (iNOS) is expressed during the late stage of ischemia and may play an important role in the delayed progression of ischemic brain injury. This study was conducted to investigate the effect of N-(3-[aminomethyl] benzyl] acetamidine (1,400 W), a selective inhibitor of iNOS on hypoxic ischemic injury in a neonatal rat model. METHODS: Seven-day old Sprague-Dawley rats were used. The right common carotid artery was ligated under halothane anesthesia. Three 3 hours after recovery, animals were exposed to 8% oxygen in 92% nitrogen. The treatment group (n = 14) received 7 intraperitoneal injection of 20 mg/kg of 1,400 W. The first dose was given 18 hours after the injury and interval between injections was 8 hours. The control group (n = 13) did not receive 1,400 W. The degree of ischemic damage and apoptosis were evaluated 3 days after injury by 1H magnetic resonance spectroscopy (MRS) and terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end-labeling (TUNEL) staining. The authors obtained Lipid/N-acetyl aspartate (Lip/NAA) and lipid/ creatine (Lip/Cr) ratios as apoptotic markers via 1H MRS, and counted the apoptotic cell number by TUNEL staining in the right hemisphere. Data were analyzed using the unpaired t-test. RESULTS: There were no significant differences in the Lip/NAA or Lip/Cr ratios of the 2 groups, and no significant differences were found in terms of the number of TUNEL positive cells between 2 groups, either. CONCLUSIONS: The iNOS inhibitor investigated did not show protective effects against delayed neuronal damage and apoptosis after the hypoxic-ischemic injury in newborn rats, at least during the 3 days following injury. Our results suggest that NO has different roles in cerebral hypoxia-ischemia according to the stage of neonatal cerebral development.
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Animals , Humans , Infant, Newborn , Rats , Anesthesia , Apoptosis , Aspartic Acid , Brain Injuries , Brain , Carotid Artery, Common , Cell Count , Creatine , Halothane , Hypoxia-Ischemia, Brain , In Situ Nick-End Labeling , Injections, Intraperitoneal , Ischemia , Magnetic Resonance Spectroscopy , Models, Animal , Neurons , Nitric Oxide Synthase Type II , Nitrogen , Oxygen , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Poly (ADP-ribose) polymerase (PARP) has been described as an important candidate for mediation of neurotoxicity after brain ischemia. This study was purposed to evaluate the effects of a PARP inhibitor on hypoxic-ischemic injury in the neonatal rat brain. In this study, a highly potent inhibitor of PARP, 3, 4-Dihydro-5-[4-(1-piperidinyl) butoxy]-1 (2H)-isoquinolinone (DPQ) was investigated. METHODS: Seven-day old Sprague-Dawley rat pups were used. The right common carotid artery was ligated under halothane anesthesia. After a recovery period of 3 hours, they were exposed to 8% oxygen at 37degreesC for about 120 minutes. The animals were divided into four groups: the pre-treatment group (n = 13) and post-treatment group (n = 21) were given DPQ 10 mg/kg and the pre-control group (n = 7) and post-control group (n = 14) were given a vehicle for controls. Pre-treatment and pre-control groups were injected 30 minutes prior to the hypoxic injury while post-treatment and post-control groups were injected 30 minutes after the hypoxic period intraperitoneally. The right cerebral hemisphere of the rats were examined with localized (1)H magnetic resonance spectroscopy on day 1 and 7 after the hypoxic insult. Lipid/N-acetyl aspartate (Lip/NAA) and lipid/creatine (Lip/Cr) ratios were used as apoptotic markers. On day 14, the degree of brain injury was scored by morphological changes. RESULTS: In the DPQ treated groups, the Lip/NAA and Lip/Cr ratios were lower than those of the control groups on day 1 after the hypoxic-ischemic injury (P < 0.05). However on day 7, only the ratios of the pre-treatment group were lower than those of the control group (P < 0.05). The degree of morphological changes of the brain injury on day 14 were lower in the DPQ treated groups (P < 0.05). CONCLUSIONS: These results suggest that DPQ exerts a neuroprotective effect in cerebral hypoxic-ischemic injury probably by inhibiting apoptosis especially in the early stage after an insult. Acute inhibition of PARP can have a therapeutic value in preventing ischemic brain injury.
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Animals , Rats , Anesthesia , Apoptosis , Aspartic Acid , Brain Injuries , Brain Ischemia , Brain , Carotid Artery, Common , Cerebrum , Halothane , Magnetic Resonance Spectroscopy , Negotiating , Neuroprotective Agents , Oxygen , Rats, Sprague-DawleyABSTRACT
PURPOSE: This study was designed to evaluated the relationship between the morphological changes of hypoxic-ischemic injured brain and the magnetic resonance spectroscopic (MRS) findings, and the efficacy of Egb 761, a free radical scavenger, as a neuroprotective agent for hypoxic-ischemic brain injury. METHODS: Seven-day old Sprague-Dawley rat pups were used. Right common carotid artery was ligated under halothene anesthesia. After a recovery period of 3 hours, they were divided into two groups : for group 1, EGb 761 100 mg/kg (treatment group) and for group 2, normal saline (control group) were given intraperitoneally. Both groups were exposed to 8% oxygen at 37degrees C for 90 minutes. Sixty-four rat pups (30 control, 34 treatment group) were examined with localized 1H MRS on days 1 and 7 after the hypoxic insult. One day 14, the degree of brain injury was scored by morphological changes. RESULTS: The 1H MRS obtained on day 1 after the hypoxic insult showed increased Lip/NAA and Lip/Cr ratios in the right cerebral hemisphere in comparison with those in the left hemisphere (P<0.01). The degree of morphological changes of the brain injury on day 14 correlated with both Lip/NAA and Lip/Cr ratios obtained on days! and 7 after the hypoxic insult [r=0.410, 0.457 on day 1, and r=0.749, 0.720 on day 7, respectively (P< 0.01)]. The therapeutic potential of EGb 761 for the hypoxic-ischemic brain seemed insignificant, as was evident from no differences between the control group and the EGb 761 treatment group in the Lip/NAA and Lip/Cr ratios as well as in morphological changes. CONCLUSION: Early changes of Lip/NAA and Lip/Cr ratios in the 1H MRS seems to be related to the degree of morphological changes in the rat brain of hypoxic-ischemic injury. Therefore, the increased lipid content of brain observed by 1H MRS can be used as a marker to predict the degree of the hypoxic-ischemic injury. The neuroprotectiveeffect of EGb 761 in hypoxic-ischemic brain injury is insignificant.