Objective To explore effects of decompressive craniectomy on cerebral blood flow volume and brain metabolism in different aged patients with severe traumatic brain injury. Methods 71 cases were divided into three grou...Objective To explore effects of decompressive craniectomy on cerebral blood flow volume and brain metabolism in different aged patients with severe traumatic brain injury. Methods 71 cases were divided into three groups according age: group A( 【 30 years) ,group B ( 30 ~ 50 years) 。展开更多
Background Hypoxic-ischemic brain injury (HIBI) after cardiopulmonary resuscitation is one of the most devastating neurological conditions that causing the impaired consciousness. However, there were few studies inv...Background Hypoxic-ischemic brain injury (HIBI) after cardiopulmonary resuscitation is one of the most devastating neurological conditions that causing the impaired consciousness. However, there were few studies investigated the changes of brain metabolism in patients with vegetative state (VS) after post-resuscitated HIBI. This study aimed to analyze the change of overall brain metabolism and elucidated the brain area correlated with the level of consciousness (LOC) in patients with VS after post-resuscitated HIBI. Methods We consecutively enrolled 17 patients with VS after HIBI, who experienced cardiopulmonary resuscitation. Overall brain metabolism was measured by F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) and we compared regional brain metabolic patterns from 17 patients with those from 15 normal controls using voxel-by-voxel based statistical parametric mapping analysis. Additionally, we correlated the LOC measured by the JFK-coma recovery scale-revised of each patient with brain metabolism by covariance analysis. Results Compared with normal controls, the patients with VS after post-resuscitated HIBI revealed significantly decreased brain metabolism in bilateral precuneus, bilateral posterior cingulate gyrus, bilateral middle frontal gyri, bilateral superior parietal gyri, bilateral middle occipital gyri, bilateral precentral gyri (PFEw correctecd 〈0.0001 ), and increased brain metabolism in bilateral insula, bilateral cerebella, and the brainstem (PFEWcorrectecd 〈0.0001 ). In covariance analysis, the LOC was significantly correlated with brain metabolism in bilateral fusiform and superior temporal gyri (P uncorrected 〈0.005). Conclusions Our study demonstrated that the precuneus, the posterior cingulate area and the frontoparietal cortex, which is a component of neural correlate for consciousness, may be relevant structure for impaired consciousness in patient with VS after post-resuscitated HIBI. In post-resuscitated HIBI, measurement of brain metabolism using PET images may be helpful for investigating the brain function that cannot be obtained by morphological imaging and can be used to assess the brain area responsible for consciousness.展开更多
BACKGROUND:The signal of choline containing compounds(Cho)in proton magnetic resonance spectroscopy(1H-MRS)is elevated in brain tumors.[<sup>11</sup>C]choline uptake as assessed using positron emission...BACKGROUND:The signal of choline containing compounds(Cho)in proton magnetic resonance spectroscopy(1H-MRS)is elevated in brain tumors.[<sup>11</sup>C]choline uptake as assessed using positron emission tomography(PET)has also been suggested to be higher in brain tumors than in the normal brain.We examined whetherquantitative analysis of choline accumulation and content using these 1wo novel techniques would be helpful innon-invasive,preoperative evaluation of suspected brain tumors and tumor malignancy grade.METHODS:12patients with suspected brain tumor were studied using[<sup>11</sup>C]choline PET,gadolinium enhanced 3-D magneticresonance imaging and<sup>1</sup>H-MRS prior to diagnostic biopsy or resection.Eleven normal subjects served as展开更多
To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (sTBI).Methods All 33 patients with sTBI(GCS≤8) were randomly divided into hyp...To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (sTBI).Methods All 33 patients with sTBI(GCS≤8) were randomly divided into hypothermic group and control group.Microdialysis catheters were inserted into the cerebral cortex of perilesion,relative normal brain tissue and subcutaneous tissue of abdomen in order to analyze the concentrations of lactate/pyruvate (L/P),lactate/glucose (L/G) and the glycerol(Gly) in extracellular fluid (ECF).Results In comparison with the control group,the concentration of L/G,L/P and Gly in periphery and that of L/P in ECF of the “normal brain tissue” were significantly decreased in the hypothermic group.In control group,concentration of L/G,L/P and Gly in periphery were higher than those in relative normal brain.In the hypothermic group,L/P concentration in periphery was higher than that in relative normal brain.Conclusion Mild hypothermia protects brain by decreasing concentrations of L/G,L/P and Gly in periphery and L/P concentration in “normal brain tissue”.The energy crisis and membrane phospholipid breakage in periphery are easier to happen after TBI,where mild hypothermia exerts significant protgective role.12 refs,3 tabs.展开更多
OBJECTIVE The receptor-tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile.In the present study,we investigate the potential role of endothelial ErbB4 receptor signaling...OBJECTIVE The receptor-tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile.In the present study,we investigate the potential role of endothelial ErbB4 receptor signaling in the brain. METHODS ErbB4 conditional KO mice were generated by a lox P/Cre strategy. The experimenter conducting the experimentsand scoring the behavior was blinded to the genotype of the mice. Open field test,Y-maze and novel-object exploration test,novel object recognition task,step-through passive avoidance task,Morris water maze and memory reconsolidation task were carried out in WT and Cdh5-Cre; ErbB4^(loxP/loxP)mice. A high-resolution micro PET/CT scanner was used for brain metabolism imaging. RESULTS Here,we show that Cdh5Cre; ErbB4^(f/f) mice have lower levels ofexploration activity as measured by these particular behavior tests. However,our data indicate that conditional knockout of ErbB4 in endothelial cells did not impair working memory,memory acquisition,retrieval,and reconsolidation in mice. Furthermore,^(18)F-FDG-uptake was reduced in the Cdh5Cre; ErbB4^(f/f) mice as revealed by the significantly decreased SUVs in compared with the WT mice. Consistently,the immunoblot data demonstrate the downregulation of brain Glut1,phosphoULK1(Ser555) and TIGAR in the endothelial ErbB4 conditional knockout mice. Collectively,the endothelial ErbB4 deletion induced impairment in exploratory activity in adult mice,which may be due to the decreased brain energy metabolism. CONCLUSION Our study provides insight into the potential pathophysiological mechanisms of endothelial ErbB 4 and therapeutic strategies for neurological disorders.展开更多
Background: The association between cellular phones and brain tumors is a question that is frequently asked of the medical and scientific community. The prevalence of cell phone use and the significant morbidity and m...Background: The association between cellular phones and brain tumors is a question that is frequently asked of the medical and scientific community. The prevalence of cell phone use and the significant morbidity and mortality of brain tumors contribute to this pairing. Cell phones are known to emit radio frequency energy in the form of both ionizing and non-ionizing radiation. Ionizing radiation is known to be within X-rays, which do have an association with cancer. Objective: To assess if the use of the cell phone has an association with brain tumors. Methods: The searches performed through PubMed were conducted to find studies that sought to provide evidence as to whether or not increased cell phone exposure contributed to the development of brain tumors. Also searched for was increased regional metabolism of the brain with the use of the cell phone switched in the on position. Studies were restricted to being published during or after the year 2000 and presented in the English language. Results: The studies largely support the conclusion that cell phone usage does not lead to the development of brain cancer. Studies employed different strategies, such as the prospective cohort and case-control studies to reach this conclusion. Both studies failed to show statistically significant evidence that cell phones were associated with brain tumors of the central nervous system. Conclusions: Questions raised by crossover studies demonstrating increased regional brain glucose metabolism continue to remain largely unanswered by current research and remain a starting point for future research. The prevalence of the issue strengthens its position among others as a matter that the medical community must continue to address to meet the needs of an increasingly exposed patient population. The overall hypothesis that cell phone usage does not lead to the development of brain tumors was supported.展开更多
Information on brain metabolism is very important, especially concerning the sequence of hypoxic ischemic episodes. Ultrasound, magnetic resonance image (MRI) and computer aided topography (CAT) allow visualization ...Information on brain metabolism is very important, especially concerning the sequence of hypoxic ischemic episodes. Ultrasound, magnetic resonance image (MRI) and computer aided topography (CAT) allow visualization of changes due to hemorrhages. However, these methods do not detect the biochemical effects due to hypoxia and ischemia. This paper presents in vivo observations of brain metabolism attested by hypoxide and ischemia made using magnetic resonance spectroscopy(MRS), a noninvasive and nondestructive method which can identify the chemical compounds and monitor their changes during the biochemical reaction process for in vivo dynamic observation.展开更多
Background: Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung ...Background: Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. Methods: One hundred and twenty patients with primary untreated lung cancer, who visited People's Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases), squamous cell carcinoma (43 cases), and small-cell carcinoma (25 cases). The whole body ^18F-fiuorodeoxyglucose (^18F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software, with 50 age-matched and gender-matched healthy controls for comparison. Results: The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292). Conclusions: The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.展开更多
Obesity is a worldwide health,economic and social concern,despite efforts made to counteract the spreading wave of eating and nourishment-associated disorders.The review aims to show how the glial cells,astrocytes,con...Obesity is a worldwide health,economic and social concern,despite efforts made to counteract the spreading wave of eating and nourishment-associated disorders.The review aims to show how the glial cells,astrocytes,contribute to the central regulation of appetite and energy metabolism.The hypothalamus is the brain center responsible for nutrients and nutritional hormone sensing,signal processing,and execution of metabolic and behavioral responses,directed at sustaining energy homeostasis.The astrocytes are endowed with receptors,transporters and enzymatic machinery responsible for glucose,lactate,fatty acids,ketone bodies,as well as leptin or ghrelin transport and metabolism,and that render them supporters and partners for neurons in governing the brain and body energy intake and expenditure.However,the role of astrocytes associated with brain energy metabolism reaches far beyond simple fuel contingent-they contribute to cognitive performance.The cognitive decline which often accompanies high fat-and/or high-calorie diets and correlates with neuroinflammation and astrogliosis,is a major concern.The last two decades of research enabled us to acknowledge the astroglia in obesity-associated dysfunctions and to investigate astrocytes as contributors to the pathology,as well as targets for therapy.展开更多
The fluorescence lifetime of nicotinamide adenine dinucleotide(NADH),a key endogenous coenzyme and metabolic biomarker,can reflect the metabolic state of cells.To implement metabolic imaging of brain tissue at high re...The fluorescence lifetime of nicotinamide adenine dinucleotide(NADH),a key endogenous coenzyme and metabolic biomarker,can reflect the metabolic state of cells.To implement metabolic imaging of brain tissue at high resolution,we assembled a two-photon fluorescence lifetime imaging microscopy(FLIM)platform and verified the feasibility and stability of NADH-based two-photon FLIM in paraformaldehydefixed mouse cerebral slices.Furthermore,NADH based metabolic state oscillation was observed in cerebral nuclei suprachiasmatic nucleus(SCN).The free NADH fraction displayed a relatively lower level in the daytime than at the onset of night,and an ultradian oscillation at night was observed.Through the combination of high-resolution imaging and immunostaining data,the metabolic tendency of different cell types was detected after the first two hours of the day and at night.Thus,two-photon FLIM analysis of NADH in paraformaldehyde-fixed cerebral slices provides a high-resolution and label-free method to explore the metabolic state of deep brain regions.展开更多
Cerebrovascular diseases are caused by interruption or significant impairment of the blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and m...Cerebrovascular diseases are caused by interruption or significant impairment of the blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphological damage. These pathophysiological changes can be assessed by positron emission tomography (PET), which permits the regional measurement of physiological parameters and imaging of the distribution of molecular markers. PET has broadened our understanding of the flow and metabolic thresholds critical for the maintenance of brain function and morphology: in this application, PET has been essential in the transfer of the concept of the penumbra (tissue with perfusion below the functional threshold but above the threshold for the preservation of morphology) to clinical stroke and thereby has had great impact on developing treatment strategies. Radioligands for receptors can be used as early markers of irreversible neuronal damage and thereby can predict the size of the final infarcts; this is also important for decisions concerning invasive therapy in large ("malignant") infarctions. With PET investigations, the reserve capacity of blood supply to the brain can be tested in obstructive arteriosclerosis of the supplying arteries, and this again is essential for planning interventions. The effect of a stroke on the surrounding and contralateral primarily unaffected tissue can be investigated, and these results help to understand the symptoms caused by disturbances in functional networks. Chronic cerebrovascular disease causes vascular cognitive disorders, including vascular dementia. PET permits the detection of the metabolic disturbances responsible for cognitive impairment and dementia, and can differentiate vascular dementia from degenerative diseases. It may also help to understand the importance of neuroinflammation after stroke and its interaction with amyloid deposition in the development of dementia. Although the clinical application of PET investigations is limited, this technology had and still has a great impact on research into cerebrovascular diseases.展开更多
In animal experiments,ischemic stroke is usually induced through middle cerebral artery occlusion(MCAO),and quality assessment of this procedure is crucial.However,an accurate assessment method based on 18F-fluorodeox...In animal experiments,ischemic stroke is usually induced through middle cerebral artery occlusion(MCAO),and quality assessment of this procedure is crucial.However,an accurate assessment method based on 18F-fluorodeoxyglucose(FDG)positron emission tomography(PET)is still lacking.The difficulty lies in the inconsistent preprocessing pipeline,biased intensity normalization,or unclear spatiotemporal uptake of FDG.Here,we propose an image feature-based protocol to assess the quality of the procedure using a 3D scale-invariant feature transform and support vector machine.This feature-based protocol provides a convenient,accurate,and reliable tool to assess the quality of the MCAO procedure in FDG PET studies.Compared with existing approaches,the proposed protocol is fully quantitative,objective,automatic,and bypasses the intensity normalization step.An online interface was constructed to check images and obtain assessment results.展开更多
文摘Objective To explore effects of decompressive craniectomy on cerebral blood flow volume and brain metabolism in different aged patients with severe traumatic brain injury. Methods 71 cases were divided into three groups according age: group A( 【 30 years) ,group B ( 30 ~ 50 years) 。
文摘Background Hypoxic-ischemic brain injury (HIBI) after cardiopulmonary resuscitation is one of the most devastating neurological conditions that causing the impaired consciousness. However, there were few studies investigated the changes of brain metabolism in patients with vegetative state (VS) after post-resuscitated HIBI. This study aimed to analyze the change of overall brain metabolism and elucidated the brain area correlated with the level of consciousness (LOC) in patients with VS after post-resuscitated HIBI. Methods We consecutively enrolled 17 patients with VS after HIBI, who experienced cardiopulmonary resuscitation. Overall brain metabolism was measured by F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) and we compared regional brain metabolic patterns from 17 patients with those from 15 normal controls using voxel-by-voxel based statistical parametric mapping analysis. Additionally, we correlated the LOC measured by the JFK-coma recovery scale-revised of each patient with brain metabolism by covariance analysis. Results Compared with normal controls, the patients with VS after post-resuscitated HIBI revealed significantly decreased brain metabolism in bilateral precuneus, bilateral posterior cingulate gyrus, bilateral middle frontal gyri, bilateral superior parietal gyri, bilateral middle occipital gyri, bilateral precentral gyri (PFEw correctecd 〈0.0001 ), and increased brain metabolism in bilateral insula, bilateral cerebella, and the brainstem (PFEWcorrectecd 〈0.0001 ). In covariance analysis, the LOC was significantly correlated with brain metabolism in bilateral fusiform and superior temporal gyri (P uncorrected 〈0.005). Conclusions Our study demonstrated that the precuneus, the posterior cingulate area and the frontoparietal cortex, which is a component of neural correlate for consciousness, may be relevant structure for impaired consciousness in patient with VS after post-resuscitated HIBI. In post-resuscitated HIBI, measurement of brain metabolism using PET images may be helpful for investigating the brain function that cannot be obtained by morphological imaging and can be used to assess the brain area responsible for consciousness.
文摘BACKGROUND:The signal of choline containing compounds(Cho)in proton magnetic resonance spectroscopy(1H-MRS)is elevated in brain tumors.[<sup>11</sup>C]choline uptake as assessed using positron emission tomography(PET)has also been suggested to be higher in brain tumors than in the normal brain.We examined whetherquantitative analysis of choline accumulation and content using these 1wo novel techniques would be helpful innon-invasive,preoperative evaluation of suspected brain tumors and tumor malignancy grade.METHODS:12patients with suspected brain tumor were studied using[<sup>11</sup>C]choline PET,gadolinium enhanced 3-D magneticresonance imaging and<sup>1</sup>H-MRS prior to diagnostic biopsy or resection.Eleven normal subjects served as
文摘To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (sTBI).Methods All 33 patients with sTBI(GCS≤8) were randomly divided into hypothermic group and control group.Microdialysis catheters were inserted into the cerebral cortex of perilesion,relative normal brain tissue and subcutaneous tissue of abdomen in order to analyze the concentrations of lactate/pyruvate (L/P),lactate/glucose (L/G) and the glycerol(Gly) in extracellular fluid (ECF).Results In comparison with the control group,the concentration of L/G,L/P and Gly in periphery and that of L/P in ECF of the “normal brain tissue” were significantly decreased in the hypothermic group.In control group,concentration of L/G,L/P and Gly in periphery were higher than those in relative normal brain.In the hypothermic group,L/P concentration in periphery was higher than that in relative normal brain.Conclusion Mild hypothermia protects brain by decreasing concentrations of L/G,L/P and Gly in periphery and L/P concentration in “normal brain tissue”.The energy crisis and membrane phospholipid breakage in periphery are easier to happen after TBI,where mild hypothermia exerts significant protgective role.12 refs,3 tabs.
文摘OBJECTIVE The receptor-tyrosine kinase ErbB4 is present throughout the primate brain and has a distinct functional profile.In the present study,we investigate the potential role of endothelial ErbB4 receptor signaling in the brain. METHODS ErbB4 conditional KO mice were generated by a lox P/Cre strategy. The experimenter conducting the experimentsand scoring the behavior was blinded to the genotype of the mice. Open field test,Y-maze and novel-object exploration test,novel object recognition task,step-through passive avoidance task,Morris water maze and memory reconsolidation task were carried out in WT and Cdh5-Cre; ErbB4^(loxP/loxP)mice. A high-resolution micro PET/CT scanner was used for brain metabolism imaging. RESULTS Here,we show that Cdh5Cre; ErbB4^(f/f) mice have lower levels ofexploration activity as measured by these particular behavior tests. However,our data indicate that conditional knockout of ErbB4 in endothelial cells did not impair working memory,memory acquisition,retrieval,and reconsolidation in mice. Furthermore,^(18)F-FDG-uptake was reduced in the Cdh5Cre; ErbB4^(f/f) mice as revealed by the significantly decreased SUVs in compared with the WT mice. Consistently,the immunoblot data demonstrate the downregulation of brain Glut1,phosphoULK1(Ser555) and TIGAR in the endothelial ErbB4 conditional knockout mice. Collectively,the endothelial ErbB4 deletion induced impairment in exploratory activity in adult mice,which may be due to the decreased brain energy metabolism. CONCLUSION Our study provides insight into the potential pathophysiological mechanisms of endothelial ErbB 4 and therapeutic strategies for neurological disorders.
文摘Background: The association between cellular phones and brain tumors is a question that is frequently asked of the medical and scientific community. The prevalence of cell phone use and the significant morbidity and mortality of brain tumors contribute to this pairing. Cell phones are known to emit radio frequency energy in the form of both ionizing and non-ionizing radiation. Ionizing radiation is known to be within X-rays, which do have an association with cancer. Objective: To assess if the use of the cell phone has an association with brain tumors. Methods: The searches performed through PubMed were conducted to find studies that sought to provide evidence as to whether or not increased cell phone exposure contributed to the development of brain tumors. Also searched for was increased regional metabolism of the brain with the use of the cell phone switched in the on position. Studies were restricted to being published during or after the year 2000 and presented in the English language. Results: The studies largely support the conclusion that cell phone usage does not lead to the development of brain cancer. Studies employed different strategies, such as the prospective cohort and case-control studies to reach this conclusion. Both studies failed to show statistically significant evidence that cell phones were associated with brain tumors of the central nervous system. Conclusions: Questions raised by crossover studies demonstrating increased regional brain glucose metabolism continue to remain largely unanswered by current research and remain a starting point for future research. The prevalence of the issue strengthens its position among others as a matter that the medical community must continue to address to meet the needs of an increasingly exposed patient population. The overall hypothesis that cell phone usage does not lead to the development of brain tumors was supported.
文摘Information on brain metabolism is very important, especially concerning the sequence of hypoxic ischemic episodes. Ultrasound, magnetic resonance image (MRI) and computer aided topography (CAT) allow visualization of changes due to hemorrhages. However, these methods do not detect the biochemical effects due to hypoxia and ischemia. This paper presents in vivo observations of brain metabolism attested by hypoxide and ischemia made using magnetic resonance spectroscopy(MRS), a noninvasive and nondestructive method which can identify the chemical compounds and monitor their changes during the biochemical reaction process for in vivo dynamic observation.
文摘Background: Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors. This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types. Methods: One hundred and twenty patients with primary untreated lung cancer, who visited People's Hospital of Zhengzhou University from February 2012 to July 2013, were divided into three groups based on histological types confirmed by biopsy or surgical pathology, which included adenocarcinoma (52 cases), squamous cell carcinoma (43 cases), and small-cell carcinoma (25 cases). The whole body ^18F-fiuorodeoxyglucose (^18F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied. The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software, with 50 age-matched and gender-matched healthy controls for comparison. Results: The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction. The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal, bilateral superior and middle temporal and inferior and middle temporal gyrus. Besides, the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group. The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292). Conclusions: The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.
文摘Obesity is a worldwide health,economic and social concern,despite efforts made to counteract the spreading wave of eating and nourishment-associated disorders.The review aims to show how the glial cells,astrocytes,contribute to the central regulation of appetite and energy metabolism.The hypothalamus is the brain center responsible for nutrients and nutritional hormone sensing,signal processing,and execution of metabolic and behavioral responses,directed at sustaining energy homeostasis.The astrocytes are endowed with receptors,transporters and enzymatic machinery responsible for glucose,lactate,fatty acids,ketone bodies,as well as leptin or ghrelin transport and metabolism,and that render them supporters and partners for neurons in governing the brain and body energy intake and expenditure.However,the role of astrocytes associated with brain energy metabolism reaches far beyond simple fuel contingent-they contribute to cognitive performance.The cognitive decline which often accompanies high fat-and/or high-calorie diets and correlates with neuroinflammation and astrogliosis,is a major concern.The last two decades of research enabled us to acknowledge the astroglia in obesity-associated dysfunctions and to investigate astrocytes as contributors to the pathology,as well as targets for therapy.
基金supported by the National Key R&D Program of China(Nos.2016YFA0400900 and 2017YFA0505301)National Natural Science Foundation of China(No.U1832181)。
文摘The fluorescence lifetime of nicotinamide adenine dinucleotide(NADH),a key endogenous coenzyme and metabolic biomarker,can reflect the metabolic state of cells.To implement metabolic imaging of brain tissue at high resolution,we assembled a two-photon fluorescence lifetime imaging microscopy(FLIM)platform and verified the feasibility and stability of NADH-based two-photon FLIM in paraformaldehydefixed mouse cerebral slices.Furthermore,NADH based metabolic state oscillation was observed in cerebral nuclei suprachiasmatic nucleus(SCN).The free NADH fraction displayed a relatively lower level in the daytime than at the onset of night,and an ultradian oscillation at night was observed.Through the combination of high-resolution imaging and immunostaining data,the metabolic tendency of different cell types was detected after the first two hours of the day and at night.Thus,two-photon FLIM analysis of NADH in paraformaldehyde-fixed cerebral slices provides a high-resolution and label-free method to explore the metabolic state of deep brain regions.
文摘Cerebrovascular diseases are caused by interruption or significant impairment of the blood supply to the brain, which leads to a cascade of metabolic and molecular alterations resulting in functional disturbance and morphological damage. These pathophysiological changes can be assessed by positron emission tomography (PET), which permits the regional measurement of physiological parameters and imaging of the distribution of molecular markers. PET has broadened our understanding of the flow and metabolic thresholds critical for the maintenance of brain function and morphology: in this application, PET has been essential in the transfer of the concept of the penumbra (tissue with perfusion below the functional threshold but above the threshold for the preservation of morphology) to clinical stroke and thereby has had great impact on developing treatment strategies. Radioligands for receptors can be used as early markers of irreversible neuronal damage and thereby can predict the size of the final infarcts; this is also important for decisions concerning invasive therapy in large ("malignant") infarctions. With PET investigations, the reserve capacity of blood supply to the brain can be tested in obstructive arteriosclerosis of the supplying arteries, and this again is essential for planning interventions. The effect of a stroke on the surrounding and contralateral primarily unaffected tissue can be investigated, and these results help to understand the symptoms caused by disturbances in functional networks. Chronic cerebrovascular disease causes vascular cognitive disorders, including vascular dementia. PET permits the detection of the metabolic disturbances responsible for cognitive impairment and dementia, and can differentiate vascular dementia from degenerative diseases. It may also help to understand the importance of neuroinflammation after stroke and its interaction with amyloid deposition in the development of dementia. Although the clinical application of PET investigations is limited, this technology had and still has a great impact on research into cerebrovascular diseases.
基金supported by R4012-18,C6021-19EF and GRF 16306919 from the Research Grant Council(RGC)ITS/480/18FP and MHP/033/20+2 种基金from the Innovation and Technology Commission(ITC)of the Hong Kong S.A.R.,Hetao Shenzhen-Hong Kong Science and Technology Innovation Cooperation Zone Projec(HZQB-KCZYB-2020083)the National Natural Science Foundation of China(U1809204)the Talent Program of Zhejiang Province(2021R51004)。
文摘In animal experiments,ischemic stroke is usually induced through middle cerebral artery occlusion(MCAO),and quality assessment of this procedure is crucial.However,an accurate assessment method based on 18F-fluorodeoxyglucose(FDG)positron emission tomography(PET)is still lacking.The difficulty lies in the inconsistent preprocessing pipeline,biased intensity normalization,or unclear spatiotemporal uptake of FDG.Here,we propose an image feature-based protocol to assess the quality of the procedure using a 3D scale-invariant feature transform and support vector machine.This feature-based protocol provides a convenient,accurate,and reliable tool to assess the quality of the MCAO procedure in FDG PET studies.Compared with existing approaches,the proposed protocol is fully quantitative,objective,automatic,and bypasses the intensity normalization step.An online interface was constructed to check images and obtain assessment results.