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The purpose of this study was to evaluate the roles of different housing environments in neurological function,cerebral metabolism,cerebral infarction and neuron apoptosis after focal cerebral ischemia.Twenty-eight Sprague-Dawley rats were divided into control group (CG) and cerebral ischemia group,and the latter was further divided into subgroups of different housing conditions:standard environment (SE) subgroup,individual living environment (IE) subgroup,and enriched environment (EE) subgroup.Focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO).Beam walking test was used to quantify the changes of overall motor function.Cerebral infarction and cerebral metabolism were studied by in vivo magnetic resonance imaging and 1H-magnetic resonance spectra,respectively.Neuron necrosis and apoptosis were detected by hematoxylin-eosin and TUNEL staining methods,respectively.The results showed that performance on the beam-walk test was improved in EE subgroup when compared to SE subgroup and IE subgroup.Cerebral infarct volume in IE subgroup was significantly larger than that in SE subgroup (P＜0.05) and EE subgroup (P＜0.05) on day 14 after MCAO.NAA/Cr and Cho/Cr ratios were lower in MCAO groups under different housing conditions as compared to those in CG (P＜0.05).NAA/Cr ratio was lower in IE subgroup (P＜0.05) and higher in EE subgroup (P＜0.05) than that in SE subgroup.NAA/Cr ratio in EE was significantly higher than that in IE subgroup (P＜0.05).Cho/Cr ratio was decreased in MCAO groups as compared to that in CG (P＜0.05).A significant decrease in normal neurons in cerebral cortex was observed in MCAO groups as compared to CG (P＜0.05).The amount of normal neurons was less in IE subgroup (P＜0.05),and more in EE subgroup (P＜0.05) than that in SE subgroup after MCAO.The amount of normal neurons in EE subgroup was significantly more than that in IE subgroup after MCAO (P＜0.05).The ratio of TUNEL-positive neurons in EE was significantly lower than that in SE subgroup (P＜0.05) and IE subgroup (P＜0.05).Correlation analysis showed that the beam walking test was negatively correlated with NAA/Cr ratio (P＜0.05).Cerebral infarct volume was negatively correlated with both NAA/Cr ratio (P＜0.01) and Cho/Cr ratio (P＜0.01).The amount of normal cortical neurons was positively correlated with both NAA/Cr ratio (P＜0.01) and Cho/Cr ratio (P＜0.05).The TUNEL-positive neurons showed a negative correlation with both NAA/Cr ratio (P＜0.01) and Cho/Cr ratio (P＜0.01).This study goes further to show that EE may improve neurological functional deficit and cerebral metabolism,decrease cerebral infarct volume,neuron necrosis and apoptosis,while IE may aggravate brain damage after MCAO.
ABSTRACT
The purpose of this study was to evaluate the roles of different housing environments in neurological function,cerebral metabolism,cerebral infarction and neuron apoptosis after focal cerebral ischemia.Twenty-eight Sprague-Dawley rats were divided into control group (CG) and cerebral ischemia group,and the latter was further divided into subgroups of different housing conditions:standard environment (SE) subgroup,individual living environment (IE) subgroup,and enriched environment (EE) subgroup.Focal cerebral ischemia was induced by the middle cerebral artery occlusion (MCAO).Beam walking test was used to quantify the changes of overall motor function.Cerebral infarction and cerebral metabolism were studied by in vivo magnetic resonance imaging and 1H-magnetic resonance spectra,respectively.Neuron necrosis and apoptosis were detected by hematoxylin-eosin and TUNEL staining methods,respectively.The results showed that performance on the beam-walk test was improved in EE subgroup when compared to SE subgroup and IE subgroup.Cerebral infarct volume in IE subgroup was significantly larger than that in SE subgroup (P＜0.05) and EE subgroup (P＜0.05) on day 14 after MCAO.NAA/Cr and Cho/Cr ratios were lower in MCAO groups under different housing conditions as compared to those in CG (P＜0.05).NAA/Cr ratio was lower in IE subgroup (P＜0.05) and higher in EE subgroup (P＜0.05) than that in SE subgroup.NAA/Cr ratio in EE was significantly higher than that in IE subgroup (P＜0.05).Cho/Cr ratio was decreased in MCAO groups as compared to that in CG (P＜0.05).A significant decrease in normal neurons in cerebral cortex was observed in MCAO groups as compared to CG (P＜0.05).The amount of normal neurons was less in IE subgroup (P＜0.05),and more in EE subgroup (P＜0.05) than that in SE subgroup after MCAO.The amount of normal neurons in EE subgroup was significantly more than that in IE subgroup after MCAO (P＜0.05).The ratio of TUNEL-positive neurons in EE was significantly lower than that in SE subgroup (P＜0.05) and IE subgroup (P＜0.05).Correlation analysis showed that the beam walking test was negatively correlated with NAA/Cr ratio (P＜0.05).Cerebral infarct volume was negatively correlated with both NAA/Cr ratio (P＜0.01) and Cho/Cr ratio (P＜0.01).The amount of normal cortical neurons was positively correlated with both NAA/Cr ratio (P＜0.01) and Cho/Cr ratio (P＜0.05).The TUNEL-positive neurons showed a negative correlation with both NAA/Cr ratio (P＜0.01) and Cho/Cr ratio (P＜0.01).This study goes further to show that EE may improve neurological functional deficit and cerebral metabolism,decrease cerebral infarct volume,neuron necrosis and apoptosis,while IE may aggravate brain damage after MCAO.
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Objective To investigate the anti-ulcer effects of Albizia chinensis(Osbeck)Merr. extract on rats with acetic acid-induced chronic gastric ulcer and explore the anti-inflammatory mechanism. Methods Wistar male rats(n=50)were randomized in-to five groups:control,model,famotidine,Albizia chinensis extract 100 and 200 mg/kg groups. In the experiment,30%acetic acid was used to induce chronic gastric ulcer in rats. The anti-ulcer effects of A. chinensis extract were evaluated by measuring the changes in general behavior of rats,gastric tissue morphology and the ulcer area after 12 d treatments. Wistar male rats(n=48)were random-ized into three groups:control,model and A. chinensis extract(200 mg/kg)groups. At 3 d after operation,the animals were sacrificed and stomachs were rapidly removed and processed for subsequent assays. The contents of TNF-αand IL-6 were evaluated by ELISA. The activity of myeloperoxidase(MPO)was tested by o-dianisidine method. Furthermore Western blot was used to examine the phos-phorylation of P38 and JNK. Results Compared with the model group,the gastric ulcer areas of rats were reduced by 38.4%(P<0.05)and the activity of MPO declined by 37.3%(P<0.01)in A. chinensis extract(200 mg/kg)group. Meanwhile the contents of TNF-αand IL-6 in A. chinensis extract(200 mg/kg)group respectively decreased by 43.8%(P<0.01)and 32.7%(P<0.01)com-pared with the model group. A. chinensis extract(200 mg/kg)obviously suppresed the phosphorylation of P38(P<0.01),but phos-phorylation of JNK and expression of P38 and JNK remained nearly unaltered. Conclusion A. chinensis extract(200 mg/kg)exhibits a protective effect on acetic acid-induced chronic gastric ulcer,which might be relevant to anti-inflammation by inhibiting the p38 sig-naling pathway but not JNK signaling pathway. A. chinensis extract(200 mg/kg)has no effect on JNK signaling pathway.
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Objective To investigate the effect of transcription factor FOXO3a on mitophagy in hepatic ischemia-reperfusion injury in mice. Methods A total of 30 male C57BL/6 mice were randomly divided into Sham operation group (Sham) and ischemia reperfusion (IR) 2 h, 6 h, 12 h and 24 h groups, 6 mice in each group. The mouse model of liver ischemia -reperfusion injury was established. Blood biochemical methods were used to detect changes of alanine aminotransferase (ALT) and aspartate aminotransferase (AST). HE staining and TUNEL were used to observe the damages of liver tissue and apoptosis. Western blot assay and qRT-PCR were used to detect the expressions of transcription factor FOXO3a, mitochondrial autophagy-related protein Nix protein and its mRNA expression in each group. Mouse liver AML12 cells were treated with FOXO3a and Nix interfering RNA, and the model was established for 6 h after hypoxia for 1.5 h.These cells were divided into siRNA-NC group, FOXO3a siRNA group and Nix siRNA group. MTT assay was used to detect the viability of cells in each group. The number and distribution of autophagy in each group were observed by confocal microscopy. The expressions of FOXO3a, Nix, microtubule-associated protein LC3, apoptotic protein P62 and Caspase-3 were detected by Western blot assay. Results The levels of ALT and AST in all groups of IR were reduced, and reached the peak value at 6 h (P<0.05). HE and TUNEL results showed that liver injury and apoptosis were the most serious at 6 h after reperfusion. The expression of FOXO3a and Nix was higher in IR group than that in the Sham group, and the expression level of FOXO3a mRNA was the highest at 12 h after reperfusion, the expression of Nix mRNA was the highest at 6 h after reperfusion (P<0.05). Western blot assay showed the highest expression of FOXO3a in the reperfusion of 12 h, and the highest expression levels of Nix, Caspase-3 and LC3Ⅱin reperfusion 6 h. After interfering with the expression of FOXO3a, MTT showed a marked reduction in cell survival (P<0.05), Western blot assay showed that the expression level of FOXO3a was significantly higher in siRNA-NC group than that in FOXO3a siRNA group, and the expression levels of Nix, Caspase-3 and LC3Ⅱwere significantly lower than those of FOXO3a siRNA group. Confocal microscopy showed that the number and distribution of autophagosomes were significantly lower in siRNA-NC group than those in FOXO3a siRNA group. After interfering with the expression of Nix, MTT showed a marked increase in cell survival (P<0.05), Western blot assay showed that the expression levels of Nix, P62 and LC3Ⅱ were significantly higher in siRNA-NC group than those in Nix siRNA group. Conclusion FOXO3a can reduce the hepatic ischemia-reperfusion injury in mice, which may be related to the FOXO3a inhibition for liver cell mitophagy and apoptosis.
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Objective To investigate the gastric protective effect of Albizia chinensis extract on acute gastric ulcer model in rats and its mechanism related to H+,K+-ATPase in gastric parietal cells. Methods Rats were injected intraperitoneally with indo?metacin or kept under water immersion-restraint stress(WRS)to establish acute gastric ulcer model. Test samples were orally given 30 min before induction of gastric ulcer,and the gastric ulcer index and inhibitory rate were used to evaluate the effect of A. chinensis extract. Gastric mucosa pathological tissues in rats were observed by HE staining,the enzymatic activity of proton pump on isolated gastric parietal cells was measured,and the translocation of gastric proton pump was observed by immunofluorescence cell staining. Results The A. chinensis extract inhibited the gastric ulcer with the inhibition rate of 70.0%and 75.4%at 300 mg/kg in the WRS and indomethacin-induced rat model,respectively. The extract could also inhibit the enzymatic activity of gastric proton pump with the in?hibition rate of 21.5%,29.4%,44.1%,51.9%,57.7%and 62.9%(P<0.01)at 15,30,60,120 and 480 mg/L,respectively. The half-effective dosage(ID50)of the extract was determined to be 130 mg/L. The extract showed no significant effect on the translocation of gastric proton pump. Conclusion The A. chinensis extract(300 mg/kg,ig)could significantly prevent the formation of gastric ul?cer in rats via inhibiting the enzymatic activity of gastric proton pump.
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Based on the recently proposed Chinese ischemic stroke subclassification (CISS) system, intracranial branch atheromatous disease (BAD) is divided into large artery atherosclerosis (LAA) and penetrating artery disease (PAD). In the current retrospective analysis, we compared the general characteristics of BAD-LAA with BAD-PAD, BAD-LAA with non-BAD-LAA and BAD-PAD with non-BAD-PAD. The study included a total of 80 cases, including 45 cases of BAD and 35 cases of non-BAD. Subjects were classified using CISS system: BAD-LAA, BAD-PAD, non-BAD-LAA and non-BAD-PAD. In addition to analysis of general characteristics, the correlation between the factors and the two subtypes of BAD was evaluated. The number of cases included in the analysis was: 32 cases of BAD-LAA, 13 cases of BAD-PAD, 21 cases of non-BAD-LAA, and 14 cases of non-BAD-PAD. Diabetes mellitus affected more non-BAD-LAA patients than BAD-LAA patients (P=0.035). In comparison with non-BAD-PAD, patients with BAD-PAD were younger (P=0.040), had higher initial NIHSS score (P<0.001) and morbidity of ischemic heart disease (P=0.033). Within patients with BAD, the PAD subtype was associated with smoking (OR=0.043; P=0.011), higher low-density lipoprotein (OR=5.339; P=0.029), ischemic heart disease (OR=9.383; P=0.047) and diabetes mellitus (OR=12.59; P=0.020). It was concluded that large artery atherosclerosis was the primary mechanism of BAD. The general characteristics showed no significant differences between the CISS subtypes of LAA and PAD within BAD, as well as between the BAD and non-BAD within LAA subtype. Several differences between PAD subtypes of BAD and non-BAD were revealed.
Subject(s)
Aged , Female , Humans , Male , Middle Aged , Brain Ischemia , Pathology , China , Stroke , PathologyABSTRACT
Under global cerebral ischemia, the effect of different brain temperature on cerebral ischemic injury was studied. Male Sprague-Dawley rats were divided into normothermic (37-38°C) ischemia, mild hypothermic (31-32°C) ischemia, hyperthermic (41-42°C) ischemia and sham-operated groups. Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model and brain temperature was maintained at defined level for 60 min after 20-min ischemia. The expression of c-fos protein and the levels of malondialdehyde (MDA) and lactate in brain regions were detected by immunochemistry and spectrophotometrical methods, respectively. C-fos positive neurons were found in the hippocampus and cerebral cortex after cerebral ischemia reperfusion. Mild hypothermia increased the expression of c-fos protein in both areas, whereas hyperthermia decreased the expression of c-fos protein in the hippocampus at 24 h reperfusion, and the cerebral cortex at 48 h reperfusion when compared to normothermic conditions. In normothermic, mild hypothermic and hyperthermic ischemia groups, the levels of MDA and lactate in brain tissue were increased at 24, 48 and 72 h reperfusion following 20-min ischemia as compared with the sham-operated group (P<0.01). The levels of MDA and lactate in mild hypothermic group were significantly lower than those in normothermic group (P<0.01). It is suggested that brain temperature influences the translation of the immunoreactive protein product of c-fos after global cerebral ischemia, and MDA and lactate are also affected by hypothermia and hyperthermia.
Subject(s)
Animals , Male , Rats , Body Temperature , Brain , Metabolism , Brain Ischemia , Metabolism , Cerebral Cortex , Metabolism , Hippocampus , Metabolism , Immunochemistry , Lactic Acid , Metabolism , Malondialdehyde , Metabolism , Proto-Oncogene Proteins c-bcl-2 , Metabolism , Proto-Oncogene Proteins c-fos , Metabolism , Rats, Sprague-Dawley , Reperfusion Injury , Metabolism , Spectrophotometry , Temperature , Time Factors , Tumor Suppressor Protein p53 , MetabolismABSTRACT
Under global cerebral ischemia, the effect of different brain temperature on cerebral ischemic injury was studied. Male Sprague-Dawley rats were divided into normothermic (37-38°C) ischemia, mild hypothermic (31-32°C) ischemia, hyperthermic (41-42°C) ischemia and sham-operated groups. Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model and brain temperature was maintained at defined level for 60 min after 20-min ischemia. The expression of c-fos protein and the levels of malondialdehyde (MDA) and lactate in brain regions were detected by immunochemistry and spectrophotometrical methods, respectively. C-fos positive neurons were found in the hippocampus and cerebral cortex after cerebral ischemia reperfusion. Mild hypothermia increased the expression of c-fos protein in both areas, whereas hyperthermia decreased the expression of c-fos protein in the hippocampus at 24 h reperfusion, and the cerebral cortex at 48 h reperfusion when compared to normothermic conditions. In normothermic, mild hypothermic and hyperthermic ischemia groups, the levels of MDA and lactate in brain tissue were increased at 24, 48 and 72 h reperfusion following 20-min ischemia as compared with the sham-operated group (P<0.01). The levels of MDA and lactate in mild hypothermic group were significantly lower than those in normothermic group (P<0.01). It is suggested that brain temperature influences the translation of the immunoreactive protein product of c-fos after global cerebral ischemia, and MDA and lactate are also affected by hypothermia and hyperthermia.
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<p><b>BACKGROUND</b>Dementia is a chronic progressive disease seriously affecting the patient's daily life and working skills and may cause the patient disability and dependence. Thus, caring for dementia patients inevitably falls on families in the mainland of China. Unfortunately, there are rarely enough reports available about mental health and social support in family caregivers for domestic dementia patients. This study aimed to investigate the changes in psychological status and social support in domestic dementia family caregivers and hope the government and relevant departments pay more attention to the family caregiver's psychological change, which may be better for dementia patients.</p><p><b>METHODS</b>Fifty-eight immediate family caregivers (family group) for dementia patients, including 21 Alzheimer's disease (AD) and 37 vascular dementia inpatients, were recruited for interview. Fifty-eight age- and sex-matched normal volunteers (control group) were also interviewed in the same period. The psychiatric distress was assessed by the Symptom Checklist 90 (SCL-90), family functioning was assessed by the Family Assessment Device (FAD), and the social support was assessed by the Multidimensional Scale of Perceived Social Support (MSPSS). Group differences were analyzed using unpaired t test for comparison of SCL-90, FAD, and MSPSS mean scores. Pearson's correlation coefficient was used to find the association between the various dimensions of FAD and the social support from dementia family caregivers.</p><p><b>RESULTS</b>Except phobic anxiety dimension, the other dimensions of SCL-90 mean scores were significantly higher in the family group than those in the control group (P < 0.05). In the family group, except affective involvement dimension, the other dimensions of FAD mean scores were within the scope of unhealthy family functioning. Significant differences in problem solving, communication, roles, affective responsiveness, behavioral control, general functioning, and the total MSPSS mean scores were seen between the family group and the control group (P < 0.01). Except affective involvement dimension, the other dimensions of the family functioning correlated with the perceived social support in the family group (P < 0.05 or 0.01).</p><p><b>CONCLUSIONS</b>Dementia patients have a negative effect on families' mental health in the mainland of China. Dementia family caregivers experience defected family functioning and low levels of social support.</p>
Subject(s)
Adult , Aged , Female , Humans , Male , Middle Aged , Caregivers , China , Dementia , Psychology , Family , Psychology , Social Support , Stress, Psychological , Psychology , Surveys and QuestionnairesABSTRACT
This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment (VCI) with the goal of providing a target for the treatment and prevention of VCI. Inpatients with proven cerebral infarction on cranial computed tomography (CT) were recruited as the ischemic cerebrovascular diseases (ICVD) group, and the patients with mixed stroke were excluded. In ICVD group, 12 patients were diagnosed as having VCI and served as VCI group. Inpatients undergoing surgical operation in our hospital were enrolled as control group. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was employed to detect the levels of hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid of patients with ICVD. Associations between the levels of these factors and the Mini-Mental State Examination (MMSE) score were evaluated. In ICVD and VCI groups, the levels of HIF-1α and NGF in the cerebrospinal fluid were markedly lower than those in control group (P=0.037 and P=0.000; P=0.023 and P=0.005). In ICVD and VCI groups, the MMSE score was negatively related to VEGF level in the cerebrospinal fluid (r=-0.327, P=0.021; r=-0.585, P=0.046). In VCI group, HIF-1α level was correlated with NGF level (r=0.589, P=0.044). HIF-1α and NGF are involved in ischemic and hypoxic cerebral injury. The HIF signaling pathway plays an important role in intrinsic neuroprotection. Upregulation and maintenance of HIF-1α and NGF expression may attenuate VCI. Changes in VEGF levels are related to the occurrence and development of cognitive impairment.
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It is very common that increased carotid intima media thickness (CIMT) and carotid plaque coexist in a single subject in elderly patients with white matter lesions (WMLs). In this study we investigated whether the coexistence of increased CIMT and carotid plaque is more strongly associated with the presence and extent of WMLs than either alone. All patients were classified into 1 of the following 4 groups: without either increased CIMT (I) or carotid plaque (P): I(-)P(-); with only increased CIMT: I(+)P(-); with only carotid plaque: I(-)P(+); and with both increased CIMT and carotid plaque: I(+)P(+). The presence and severity of periventricular WMLs (PWMLs) and deep WMLs (DWMLs) were assessed and the prevalence of MRI findings by the Cochran-Armitage trend test was calculated. The characteristics of subjects showed that the percentages of patients with increased CIMT and carotid plaque in the DWMLs group and the PWMLs group were significantly higher than those without WMLs group. Both DWMLs and PWMLs were strongly associated with age, carotid plaque and CIMT. Furthermore, the Cochran-Armitage trend test indicated that the prevalence of MRI findings of PWMLs and DWMLs increased in the order of I(-)P(-)< I(+)P(-)< I(-)P(+)< I(+)P(+) (P<0.0001). For the patients with DWMLs, the grades of both I(+)P(-) and I(+)P(+) were increased significantly compared to I(-)P(-) (P<0.0025, P<0.05, respectively) without such a difference found in patients with PWMLs. Our results suggested that the coexistence of increased CIMT and carotid plaque is most closely associated with WMLs, and that increased CIMT is associated with the severity of DWMLs, whereas carotid plaque is related to the presence of WMLs.
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It is very common that increased carotid intima media thickness (CIMT) and carotid plaque coexist in a single subject in elderly patients with white matter lesions (WMLs). In this study we investigated whether the coexistence of increased CIMT and carotid plaque is more strongly associated with the presence and extent of WMLs than either alone. All patients were classified into 1 of the following 4 groups: without either increased CIMT (I) or carotid plaque (P): I(-)P(-); with only increased CIMT: I(+)P(-); with only carotid plaque: I(-)P(+); and with both increased CIMT and carotid plaque: I(+)P(+). The presence and severity of periventricular WMLs (PWMLs) and deep WMLs (DWMLs) were assessed and the prevalence of MRI findings by the Cochran-Armitage trend test was calculated. The characteristics of subjects showed that the percentages of patients with increased CIMT and carotid plaque in the DWMLs group and the PWMLs group were significantly higher than those without WMLs group. Both DWMLs and PWMLs were strongly associated with age, carotid plaque and CIMT. Furthermore, the Cochran-Armitage trend test indicated that the prevalence of MRI findings of PWMLs and DWMLs increased in the order of I(-)P(-)< I(+)P(-)< I(-)P(+)< I(+)P(+) (P<0.0001). For the patients with DWMLs, the grades of both I(+)P(-) and I(+)P(+) were increased significantly compared to I(-)P(-) (P<0.0025, P<0.05, respectively) without such a difference found in patients with PWMLs. Our results suggested that the coexistence of increased CIMT and carotid plaque is most closely associated with WMLs, and that increased CIMT is associated with the severity of DWMLs, whereas carotid plaque is related to the presence of WMLs.
Subject(s)
Aged , Aged, 80 and over , Female , Humans , Male , Brain , Pathology , Carotid Intima-Media Thickness , Carotid Stenosis , Diagnostic Imaging , Pathology , Nerve Fibers, Myelinated , Pathology , Reproducibility of Results , Sensitivity and Specificity , Statistics as TopicABSTRACT
This study was carried out to investigate the role of intrinsic neuroprotective mechanisms in the occurrence and development of vascular cognitive impairment (VCI) with the goal of providing a target for the treatment and prevention of VCI. Inpatients with proven cerebral infarction on cranial computed tomography (CT) were recruited as the ischemic cerebrovascular diseases (ICVD) group, and the patients with mixed stroke were excluded. In ICVD group, 12 patients were diagnosed as having VCI and served as VCI group. Inpatients undergoing surgical operation in our hospital were enrolled as control group. Double-antibody sandwich enzyme-linked immunosorbent assay (ELISA) was employed to detect the levels of hypoxia-inducible factor 1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF) in the cerebrospinal fluid of patients with ICVD. Associations between the levels of these factors and the Mini-Mental State Examination (MMSE) score were evaluated. In ICVD and VCI groups, the levels of HIF-1α and NGF in the cerebrospinal fluid were markedly lower than those in control group (P=0.037 and P=0.000; P=0.023 and P=0.005). In ICVD and VCI groups, the MMSE score was negatively related to VEGF level in the cerebrospinal fluid (r=-0.327, P=0.021; r=-0.585, P=0.046). In VCI group, HIF-1α level was correlated with NGF level (r=0.589, P=0.044). HIF-1α and NGF are involved in ischemic and hypoxic cerebral injury. The HIF signaling pathway plays an important role in intrinsic neuroprotection. Upregulation and maintenance of HIF-1α and NGF expression may attenuate VCI. Changes in VEGF levels are related to the occurrence and development of cognitive impairment.
Subject(s)
Female , Humans , Male , Middle Aged , Biomarkers , Cerebrospinal Fluid , Brain-Derived Neurotrophic Factor , Cerebrospinal Fluid , Cerebral Infarction , Cerebrospinal Fluid , Diagnosis , Cognition Disorders , Cerebrospinal Fluid , Diagnosis , Hypoxia-Inducible Factor 1, alpha Subunit , Cerebrospinal Fluid , Nerve Growth Factor , Cerebrospinal Fluid , Reproducibility of Results , Sensitivity and Specificity , Vascular Endothelial Growth Factor A , Cerebrospinal FluidABSTRACT
<p><b>BACKGROUND</b>The optimal time window for the administration of hypothermia following cerebral ischemia has been studied for decades, with disparity outcomes. In this study, the efficacy of mild brain hypothermia beginning at different time intervals on brain endogenous antioxidant enzyme and energy metabolites was investigated in a model of global cerebral ischemia.</p><p><b>METHODS</b>Forty-eight male Sprague-Dawley rats were divided into a sham-operated group, a normothermia (37°C - 38°C) ischemic group and a mild hypothermic (31°C - 32°C) ischemia groups. Rats in the last group were subdivided into four groups: 240 minutes of hypothermia, 30 minutes of normothermia plus 210 minutes of hypothermia, 60 minutes of normothermia plus 180 minutes of hypothermia and 90 minutes of normothermia plus 150 minutes of hypothermia (n = 8). Global cerebral ischemia was established using the Pulsinelli four-vessel occlusion model for 20 minutes and mild hypothermia was applied after 20 minutes of ischemia. Brain tissue was collected following 20 minutes of cerebral ischemia and 240 minutes of reperfusion, and used to measure the levels of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), reduced glutathione (GSH) and adenosine triphosphate (ATP).</p><p><b>RESULTS</b>Mild hypothermia that was started within 0 to 60 minutes delayed the consumption of SOD, GSH-Px, GSH, and ATP (P < 0.05 or P < 0.01) in ischemic tissue, as compared to a normothermic ischemia group. In contrast, mild hypothermia beginning at 90 minutes had little effect on the levels of SOD, GSH-Px, GSH, and ATP (P > 0.05).</p><p><b>CONCLUSIONS</b>Postischemic mild brain hypothermia can significantly delay the consumption of endogenous antioxidant enzymes and energy metabolites, which are critical to the process of cerebral protection by mild hypothermia. These results show that mild hypothermia limits ischemic injury if started within 60 minutes, but loses its protective effects when delayed until 90 minutes following cerebral ischemia.</p>
Subject(s)
Animals , Male , Rats , Adenosine Triphosphate , Metabolism , Antioxidants , Metabolism , Brain Ischemia , Metabolism , Glutathione , Metabolism , Glutathione Peroxidase , Metabolism , Hypothermia, Induced , Rats, Sprague-Dawley , Superoxide Dismutase , Metabolism , TemperatureABSTRACT
<p><b>OBJECTIVE</b>To observe the therapeutic effect of Yangxue Qingnao Granule (, YXQNG) on cognitive impairment induced by chronic cerebral hypoperfusion and to investigate its impact on oxidative stress, apoptosis, and the cholinergic system.</p><p><b>METHODS</b>Adult male Wistar rats were subjected to chronic cerebral hypoperfusion by permanent occlusion of bilateral common carotid arteries (2-VO). Thirty rats were randomly assigned to one of the five treatment groups in a 1:1:1:1:1 ratio: sham operation plus normal saline treatment, 2-VO plus normal saline treatment, 2-VO plus YXQNG at a dose of 2 g·kg(-1)·d(-1) or 4 g·kg(-1)·d(-1), or 2-VO plus rivastigmine 2 mg·kg(-1)·d(-1). The Morris water maze test was used to assess the spatial memory retrieval. Apoptosis, total antioxide capacity (T-AOC), acetylcholine esterase (AchE) and choline acetyl transferase (ChAT) activities in the hippocampus and the cortex were investigated.</p><p><b>RESULTS</b>In the chronic cerebral hypoperfusion model, the 2-VO plus saline treatment resulted in impaired special learning as shown by the significantly prolonged escape latency and shorter swim time in the first quadrant as compared to the sham operation. The impairment was associated with apoptosis and significant decreases in T-AOC, AchE and ChAT activities in the hippocampus and the cortex. Treatment with YXQNG at either 2 g·kg(-1)·d(-1) or 4 g·kg(-1)·d(-1) dose, or rivastigmine resulted in significantly shorter escape latencies and longer swim time in the first quadrant. YXQNG at both doses, but not rivastigmine, had significant reduction in apoptosis, and significant increases in T-AOC and ChAT activity in both the hippocampus and the cortex. Unlike rivastigmine, neither dose of YXQNG showed significant reduction in AchE activity.</p><p><b>CONCLUSIONS</b>YXQNG ameliorated cognitive impairment induced by chronic cerebral hypoperfusion. The protective effect may be mediated through its regulation of apoptosis and activities of T-AOC and ChAT in the hippocampus and cortex of the rats in the chronic cerebral hypoperfusion model, a mechanism that is different from rivastigmine.</p>
Subject(s)
Animals , Male , Rats , Apoptosis , Brain , Pathology , Chemistry, Pharmaceutical , Chronic Disease , Cognition Disorders , Drug Therapy , Pathology , Disease Models, Animal , Drug Evaluation, Preclinical , Drugs, Chinese Herbal , Therapeutic Uses , Hypoxia-Ischemia, Brain , Drug Therapy , Pathology , Maze Learning , Rats, Wistar , Spatial Behavior , Task Performance and AnalysisABSTRACT
<p><b>OBJECTIVE</b>To study the therapeutic effect of Angelica Injection (AI) in treating acute cerebral infarction (ACI).</p><p><b>METHODS</b>One thousand four hundred and four patients, who were treated with AI (692 patients in Group A), compound salvia (390 patients in Group B) and low molecular dextran injection (322 patients in Group C) respectively. Indexes such as CT scanning on infarcted volume, scoring of clinical neuro-function deficit taking on the 1st, 3rd, 7th, 15th and 25th day, clinical therapeutic effectiveness evaluated by the end of the 2nd week and the improvement of Barthel index scores were observed.</p><p><b>RESULTS</b>The total effective rate in Group A, B and C was 78.7%, 63.6% and 59.3% respectively, that in Group A was significantly higher than in the other two groups (P < 0.05). The improvement of neuro-function deficit scores and Barthel scores in Group A were better than those in Group B and C (on the 25th day, P < 0.01), and the decrement of infarcted volume in Group A was larger than that in Group C (P < 0.01).</p><p><b>CONCLUSION</b>AI has evident therapeutic effect in treating ACI.</p>