The Glymphatic System: A Review

The brain represents 2% of the adult body mass; conversely, it is responsible for 20% to 25% of the glucose and 20% of the oxygen consumption, receiving 15% of the cardiac output. This substantial metabolic rate is associated with a significant production of biological debris, which is potentially toxic. Therefore, a complex and efficient clearance system is required to prevent the accumulation of byproducts and ensure optimal function. However, until today, there is little knowledge about this topic. The glymphatic system, also known as perivascular pathway, is a recently described glialdependent network that is responsible for the clearance of metabolites from the central nervous system (CNS), playing a role equivalent to the one played by the lymphatic vessels present in other organs. Studies have demonstrated that the glymphatic pathway has a paramount role in protein homeostasis, and that the malfunction of this system may be related to the development of neurodegenerative disorders such as Alzheimer disease and normal pressure hydrocephalus. They also showed that body posture, exercise and the state of consciousness influence the glymphatic transport. In this context, the understanding of this clearance system could not only clarify the pathophysiology of several diseases, but also contribute to future therapeutic interventions. In the present article, we will evaluate the glymphatic pathway, focusing on the factors that regulate its flow, as well as on its role in CNS physiology and in disease initiation and progression, including dementia, hydrocephalus, glaucoma and traumatic brain injury. Ultimately, this review also aims to encourage further research on novel therapeutic targets.

Current progress in neuroimaging research on treatment resistant depression / 生物医学工程学杂志

Depression is a common psychiatric disorder, and approximately 30% patients with depression do not respond effectively to standard antidepressant medication; this condition is termed treatment resistant depression (TRD) and its neurobiological mechanism remains unclear. Neuroimaging techniques can non-invasively explore changes in brain structure, function and metabolism. These techniques have been applied in neurobiological research of TRD and revealed critical abnormalities in brain structure, function and metabolism in fronto-limbic system. In this paper, we reviewed the latest progress in neuroimaging researches on TRD, providing new insight and imaging evidence for further neurobiological studies of TRD.

1H-MRS research of cerebral metabolic changes in patients with type 2 diabetes mellitus / 实用放射学杂志

Objective To determine the efficacy of glucose-loweringtreatment by proton magnetic resonance spectroscopy (1H-MRS).Methods Bilateral frontal lobes of 45 male patients with type 2 diabetes mellitus (T2DM) underwent 1 H-MRS separately bythe time it was first diagnosed.Among them,30 were treated with insulin,15 were rejected.The bilateral frontal lobes of all patients were re-examined with 1 H-MRS after 6 months.The ratios of metabolites in the frontal lobe were recorded and compared,and observing whether the lactate(Lac) peak appeared or not.Results Significantly higher values of the N-acetylaspartate (NAA)/creatine (Cr)ratio and NAA/choline (Cho) ratio after 6 months (2.414 2± 0.206 6 and 2.244 2±0.341 5) were found in bilateral frontal lobes compared with pre-therapy (1.905 3±0.135 7 and 1.906 0±0.322 1)(P＜0.05).Significantly lower values of the NAA/Cr ratio and NAA/Cho ratio in the refuse treatment group(1.504 2 ± 0.262 4 and 1.510 0± 0.220 8) were found in bilateral frontal lobes compared with pre therapy (1.960 0±0.175 0 and 1.880 8±0.297 0)(P＜0.05).Lac peak was not detected in the all experiments.Conclusion 1 H-MRS provides valuable information in the assessment and evaluation of clinical efficacy and prognosis of T2DM by detecting the changes of brain metabolism.

A PET study on brain of chronic unpredictable mild stimulations (CUMS)-induced depressive rats / 军事医学

Objective To observe the metabolic changes in the whole brain of chronic unpredictable mild stimulations ( CUMS)-induced depressive rats using PET imaging technology.Methods After 4 weeks’ of CUMS, rats of experimental group were divided into two groups:Group D( depression) and Group ND( no depression) , according to the degree of sugar addiction, distance of spontaneous activity and relative body mass.Then metabolic changes in the whole brain of these rats and those in control group ( CON) were observed using PET technology, and the differences were companred between the threegroups.Results (1)ComparedwithGroupCON,metabolismofGroupDwaselevatedinbilateralS1,thalamus, globus pallidus, insula, M2 and left claustrum, but descended in right inferior colliculus, splenium of corpus callosum and cerebellum.(2) Metabolism of Group D increased in the bilateral CA3 region of hippocampus, M1, M2, striatum, S1 and olfactory bulb, but decreased in the left cuneate nucleus and hippocampus compared to Group ND.( 3 ) Compared with Group CON, there was no region of the brain in Group ND where metabolism was enhanced, but metabolism in the lateral septal nucleus, bilateral striatum, hypothalamic paraventricular nucleus, bilateral S1 and right globus pallidus of Group ND was reduced.Conclusion The metabolic characteristic in the brain of depressive rats is that heightened regions are all in front of the coronal plane 4 mm post bregma, while lowered regions are behind.Moreover, both cerebral hemispheres are roughly symmetrical.It can be concluded that abnormal interactions between different regions of the brain contributes to the occurrence of depression.

The "selfish brain" hypothesis for metabolic abnormalities in bipolar disorder and schizophrenia / A hipótese do "cérebro egoísta" para alterações metabólicas no transtorno bipolar e na esquizofrenia

Metabolic abnormalities are frequent in patients with schizophrenia and bipolar disorder (BD), leading to a high prevalence of diabetes and metabolic syndrome in this population. Moreover, mortality rates among patients are higher than in the general population, especially due to cardiovascular diseases. Several neurobiological systems involved in energy metabolism have been shown to be altered in both illnesses; however, the cause of metabolic abnormalities and how they relate to schizophrenia and BD pathophysiology are still largely unknown. The "selfish brain" theory is a recent paradigm postulating that, in order to maintain its own energy supply stable, the brain modulates energy metabolism in the periphery by regulation of both allocation and intake of nutrients. We hypothesize that the metabolic alterations observed in these disorders are a result of an inefficient regulation of the brain energy supply and its compensatory mechanisms. The selfish brain theory can also expand our understanding of stress adaptation and neuroprogression in schizophrenia and BD, and, overall, can have important clinical implications for both illnesses (AU)

Alterações metabólicas são frequentes em pacientes com esquizofrenia e transtorno bipolar (TB), levando a uma alta prevalência de diabetes e síndrome metabólica nessa população. Além disso, as taxas de mortalidade entre pacientes são mais altas do que na população geral, especialmente em decorrência de doenças cardiovasculares. Vários sistemas neurobiológicos envolvidos no metabolismo energético têm demonstrado alterações nas duas doenças; no entanto, a causa das alterações metabólicas e a forma como elas se relacionam com a fisiopatologia da esquizofrenia e do TB ainda são arenas em grande parte desconhecidas. A teoria do "cérebro egoísta" é um paradigma recente que postula que, para manter estável seu próprio fornecimento de energia, o cérebro modula o metabolismo da energia na periferia regulando tanto a alocação quanto a ingestão de nutrientes. Apresentamos neste artigo a hipótese de que as alterações metabólicas observadas nesses transtornos são resultado de uma regulação ineficiente do fornecimento de energia do cérebro e seus mecanismos compensatórios. A teoria do cérebro egoísta também pode expandir nosso entendimento sobre a adaptação ao estresse e a neuroprogressão na esquizofrenia e no TB, e, acima de tudo, pode ter implicações clínicas importantes para as duas doenças (AU)

Statistical Mapping Analysis of Brain Metabolism in Patients with Subcortical Aphasia after Intracerebral Hemorrhage: A Pilot Study of F-18 FDG PET Images

PURPOSE: This study was aimed to evaluate the brain metabolism in patients with subcortical aphasia after intracerebral hemorrhage (ICH) and the relationship between the severity of aphasia and regional brain metabolism, by using statistical mapping analysis of F-18 fluorodeoxyglucose positron emission tomography (F-18 FDG PET) images. MATERIALS AND METHODS: Sixteen right-handed Korean speaking patients with subcortical aphasia following ICH were enrolled. All patients underwent Korean version of the Western Aphasia Battery and the brain F-18 FDG PET study. Using statistical parametric mapping analysis, we compared the brain metabolisms shown on F-18 FDG PET from 16 patients with subcortical aphasia and 16 normal controls. In addition, we investigated the relationship between regional brain metabolism and the severity of aphasia using covariance model. RESULTS: Compared to the normal controls, subcortical aphasia after ICH showed diffuse hypometabolism in the ipsilateral cerebrum (frontal, parietal, temporal, occipital, putamen, thalamus) and in the contralateral cerebellum (P corrected <0.001), and showed diffuse hypermetabolism in the contralateral cerebrum (frontal, parietal, temporal) and in the ipsilateral cerebellum (P FDR corrected <0.001). In the covariance analysis, increase of aphasia quotient was significantly correlated with increased brain metabolism in the both orbitofrontal cortices, the right hippocampal and the right parahippocampal cortices (P uncorrected <0.01). CONCLUSION: Our findings suggest that frontal, parietal, and temporal cortices, which are parts of neural network for cognition, may have a supportive role for language performance in patients with subcortical aphasia after ICH.

Traumatismo encefalocraneano en pediatría / Traumatic brain injury in pediatrics

Traumatic Brain Injury (TBI) is an important Public Health issue in Chile and the world. It represents a frequent cause of consultation, constituting a significant cause of morbidity and mortality in the population under 45 years of age. Accidents are the main reason for TBI among the pediatric population, but child abuse is an important cause in children below 2 y.o. A proper evaluation is essential to develop timely and efficient treatment that avoids or decreases brain damage and eventual complications. For this purpose, it is essential that brain physiology and physiopathological changes triggered by TBI are clear and well known. Current concepts are presented in this paper, emphasizing brain hemodynamics, metabolism, and brain self-regulation.

El traumatismo encefalocraneano (TEC) es un importante problema de salud pública tanto en Chile como en el mundo. Representa un motivo de consulta frecuente constituyendo una de las mayores causas de morbi-mortalidad en la población menor de 45 años. Los accidentes son la principal causa de TEC en la población pediátrica, pero el maltrato infantil es una causa etiológica importante a considerar en los menores de 2 años. Realizar una correcta evaluación al paciente con TEC es fundamental para instaurar un tratamiento oportuno y eficiente con el fin de evitar y/o disminuir el daño cerebral y así prevenir eventuales complicaciones. Para ello es imprescindible el conocimiento de la fisiología cerebral y los cambios fisiopatológicos que se desencadenan posterior al TEC, conceptos que son revisados en este artículo con énfasis en la hemodinamia cerebral, metabolismo y autorregulación cerebral.

Preventive effects of physical exercise on the inhibition of creatine kinase in the cerebral cortex of mice exposed to cigarette smoke / Efeitos preventivos do exercício físico sobre a inibição da creatina quinase em córtex cerebral de camundongos expostos à fumaça de cigarro

Recent studies have shown the health benefits of physical exercise, increasing the oxidative response of muscle. However, the effects of exercise on the brain are poorly understood and contradictory. The inhibition of creatine kinase (CK) activity has been associated with the pathogenesis of a large number of diseases, especially in the brain. Theobjective of this study was to determine the preventive effects of physical exercise in the hippocampus and cerebral cortex of mice after chronic cigarette smoke exposure. Eight to 10-week-old male mice (C57BL-6) were divided into four groups and submitted to an exercise program (swimming), 5 times a week, for 8 weeks. After this period, the animalswere passively exposed to cigarette smoke for 60 consecutive days, 3 times a day (4 Marlboro red cigarettes per session), for a total of 12 cigarettes. CK activity was measured in cerebral cortex and hippocampal homogenates. Enzyme activity was inhibited in the cerebral cortex of animals submitted to the inhalation of cigarette smoke.However, exercise prevented this inhibition. In contrast, CK activity remained unchanged in the hippocampus. This inhibition of CK by inhalation of cigarette smoke might be related to the process of cell death. Physical exercise played a preventive role in the inhibition of CK activity caused by exposure to cigarette smoke.

O exercício físico aeróbico tem demonstrado benefícios em pesquisas recentes, uma vez que aumenta a resposta oxidativa muscular, porém os efeitos do exercício sobre o cérebro são pouco conhecidos e bastante contraditórios. A inibição da atividade da enzima creatina quinase(CK) está relacionada à patogênese de um grande número de doenças, especialmente no cérebro, e que a disfunção mitocondrial leva ao dano na síntese de ATP. Este trabalho tem como objetivo verificar os efeitos preventivos do exercício físico no hipocampo e córtex cerebral de camundongos submetidos à exposição crônica da fumaça de cigarro. Foram utilizados 24 camundongos C57BL-6machos, com idade de entre 8-10 semanas, divididos em 4 grupo, foram submetidos a um programa de exercício (natação), cinco vezes por semana, durante 8 semanas, após esse período os animais foram expostos passivamente à fumaça de cigarro por 60 dias consecutivos, 3 vezes ao dia totalizando em 12 cigarros, 4 cigarros por vez, da marca Marlboro vermelho. A atividade enzimática da CK foi determinada em hipocampo e córtex cerebral. Os resultados mostraramque a atividade da enzima CK foi inibida no córtex cerebral dos animais submetidos à inalação da fumaça do cigarro, porém o exercício conseguiu prevenir esta alteração. A atividade da CK não foi alterada no hipocampo dos animais. Essa inibição da CK pela inalação da fumaça do cigarro pode estar relacionada com processos de morte celular. O exercício preventivo mostrou um papel protetor sobre a inibição dessa enzima.

Isquemia encefálica, cascatas vasodilatadoras e alterações bioquímicas / Biochemical and hemodynamic alterations in brain ischemia

Procede-se a uma revisão das alterações bioquímicas e hemodinâmicas causadas pela isquemia do tecido nervoso. Trata-se de uma visão introdutória que aborda a fisiopatologia e as repercussões da terapêutica sobre a hemodinâmica encefálica.

This is a review on the biochemical and hemodynamic alterations caused by the isquemia in the neural tissue. This text introduce the pathophysiology and the therapeutic effects of this ischemic alterations.

Changes of the Cerebral Metabolite Patterns in Patients Undergoing Hemodialysis due to Chronic Renal Failure: Evaluation with Proton Magnetic Resonance Spectroscopy

PURPOSE: We wanted to evaluate the cerebral metabolites in patients with chronic renal failure (CRF) and who were undergoing hemodialysis by performing proton MR spectroscopy and we wanted to evaluate the correlation between the changes in the cerebral metabolite ratios and the duration after starting the initial hemodialysis. MATERIALS AND METHODS: Proton MR spectroscopy was performed in 15 patients with CRF and who were undergoing hemodialysis and in ten healthy volunteers. The changes in N-acetylaspartate (NAA), choline-containing compounds (Cho), myo-inositol (Myo), glutamine/glutamate complex (Glx), and creatine (Cr) were analyzed. MR spectroscopy was performed before and after hemodialysis. RESULTS: For the patients with CRF before hemodialysis, the Cho/Cr ratio in the gray matter (p<0.001) and the Myo/Cr ratio in both the gray and white matter (p<0.01) were significantly elevated compared with those in the control subjects. For the patients with CRF after hemodialysis, their Cho/Cr ratios were significantly reduced in both the gray and white matter compared with that before hemodialysis (p<0.05). There was a significant positive correlation between the Cho/Cr ratio and serum Cr in the gray matter of CRF patients after hemodialysis (r=0.54, p<0.05). The cerebral metabolite ratios were not significantly correlated with the duration after starting the initial hemodialysis. CONCLUSION: The cerebral metabolite patterns are significantly different between the patients with CRF and who are undergoing hemodialysis and the normal controls. The cerebral metabolite ratios are not significantly correlated with the duration after starting the initial hemodialysis.

Marchiafava-Bignami Disease with Abnormal PET Findings: Case Report

We report the FDG PET findings in a patient with Marchiafava-Bignami disease (MBD) in whom there was diffusely reduced metabolism in the whole brain cortex and strongly decreased metabolism in the thalami. The use of FDG PET helps provide an understanding of the neurologic manifestations and prognosis of MBD.

Fire-Related Post-Traumatic Stress Disorder: Brain 1H-MR Spetroscopic Findings

OBJECTIVE: To investigate the MR imaging and 1H-MR spectroscopic findings of acute fire-related post-traumatic stress disorder (PTSD). MATERIALS AND METHODS: Sixteen patients (M: F=10: 6; mean age, 16 years) with fire-related PTSD underwent MR imaging and 1H-MR spectroscopy, and for control purposes, the procedures were repeated in eight age-matched normal volunteers. In all patients and controls, the regions of interest where data were acquired at MRS were the basal ganglia (BG), frontal periventricular white matter (FWM), and parietal periventricular white matter (PWM). RESULTS: In all patients with PTSD, MR images appeared normal. In contrast, MRS showed that in the BG, NAA/Cr ratios were significantly lower in patients than in volunteers. This decrease did not, however, show close correlation with the severity of the neuropsychiatric symptoms. In patients, neither NAA/Cr ratios in FWM nor PWM, nor Cho/Cr ratios in all three regions, were significantly different from those in the control group. CONCLUSION: Decreased NAA/Cr ratios in the BG, as seen at 1H-MRS, might be an early sign of acute fire-related PTSD.

MRI Finding of Ethylmalonic Encephalopathy: Case Report

Ethylmalonic encephalopathy is a rare syndrom characterized by developmental delay, acrocyanosis, petechiae, chronic diarrhea, and ethylmalonic, lactic, and methylsuccinic aciduria. We report the MRI finding of ethylmalonic encephalopathy including previously unreported intracranial hematoma.

Localized Proton MR Spectroscopic Detection of Nonketotic Hyperglycinemia in an Infant

Nonketotic hyperglycinemia (NKH) is a rare metabolic brain disease caused by deficient activity of the glycine cleveage system. Localized proton MR spectroscopy (echo-time 166 msec), performed in an infant with the typical clinical and biochemical features of neonatal NKH, showed a markedly increased peak intensity at 3.55 ppm, which was assigned to glycine. Serial proton MR spectrosocpic studies indicated that glycine/choline and glycine/total creatine ratios correlated closely with the patient's clinical course. Proton MR spectroscopy was useful for the non-invasive detection and monitoring of cerebral glycine levels in this infant with NKH.

Diffusion-weighted image and MR spectroscopic analysis of a case of MELAS with repeated attacks

We report the clinical and MR manifestations of an 18 year-old girl with mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS) syndrome. Recurrent status epilepticus caused reversible cytotoxic edema on diffusion-weighted images (DWI). Initial and one month follow-up MR spectroscopy, after seizure control, showed some discrepancies in the ratio of metabolites. N-acetylaspartate (NAA) partially recovered (NAA/creatine (Cr) ratio: 1.27-->1.84). This was because of a normalization of decreased NAA due to cellular dysfunction as a result of status epilepticus. A low ratio of NAA/Cr due to abnormal mitochondria remained in the decreased state. Reversible NAA/Cr ratios in the acute lesion suggested that NAA reflects the neuronal function as well as the level of neuronal structural damage. The altered NAA/Cr ratio better correlated with the abnormal signal intensity area of T2-weighted images (T2WI) and DWI than the lactate (Lac)/Cr ratio. With conservative treatment with anti-epileptics not accompanied by coenzyme Q or sodium dichloroacetate, lactate persistently increased (Lac/Cr ratio: 1.01-->1.21) because of the continued production of lactate in cells with respiratory deficiency, which is the main pathology of MELAS.

MR Imaging of Kernicterus: A Case Report

Kernicterus is a neurologic syndrome, resulting from the preferential deposition of unconjugated bilirubin in the globus pallidus, subthalamus, hippocampus, and brain stem. The characteristic finding of kernicterus revealed by T2-weighted MR imaging is irreversible, bilaterally symmetrical high signal intensities in the globus pallidus. We report an atypical case of kernicterus, in which follow-up MR imaging of the globus pallidus demonstrated reversible signal intensity.

Wilson's Disease: Brain MR Findings

PURPOSE: To analyze the abnormal findings of brain MR imaging seen in Wilson's disease. MATERIALS AND METHODS: The authors retrospectively reviewed the MR imaging findings (location, signal intensity and contrastenhancement of lesions, and brain atrophy) of nine patients with Wilson's disease confirmed by neurologicalsymptoms, laboratory findings and physical examination. RESULTS: The putamen, midbrain, pons and middlecerebellar peduncle were involved bilaterally and symmetrically in all nine patients, and the thalamus(6/9),corpus callosum(5/9), globus pallidus(3/9), posterior limb of the internal capsule(3/9), superior cerebellarpeduncle(3/9), caudate nucleus head(2/9), subcortical white matter(2/9) and medulla oblongata(1/9) were involvedin decreasing sequence. In all patients, the signal intensity of lesions was low on T1-weighted image and high onproton density- and T2-weighted images. Three patients with contrast enhancement showed no definite enhancement oflesions. Diffuse brain atrophy involving the cerebrum, cerebellum and brain stem was found in three patients.CONCLUSION: Knowledge of the characteristic MR findings of Wilson's disease is helpful in differentiating otherdiseases involving similar locations

Quantitative1 H MR Spectroscopy of the Brain in Patients with Congestive Heart Failure before and after Cardiac Transplantation

PURPOSE: To evaluate the effects of cardiac transplantation on the brain in patients with congestive heart failure (CHF), using quantitative 1H MR spectroscopy (1H-MRS). MATERIALS AND METHODS: Ten patients with CHF underwent MRI and quantitative1H -MRS before and 1 -2 and 4 -9 months after cardiac transplantation. MR spectra were obtained from parietal white matter (PWM) and occipital gray matter (OGM) using PROBE (PROton Brain Exam). Changes in MR signal intensity were evaluated, and the cerebral metabolic concentrations in PWM and OGM were compared. For comparative purposes, 20 normal Volunteers were included. RESULTS: No abnormal MR signal intensity was seen in the brain before or after cardiac transplantation. Changes in cerebral metabolic concentrations were observed on 1H-MRS; concentrations of creatine (Cr) in PWM, and of N-acetylacepartate (NAA), Cr and myo - Inositol(mI) in OGM were significantly lower before transplantation. After successful trans-plantation, Cr levels returned to their normal range in PWM and OGM, while a slightly increase choline (Cho) level was observed in PWM. CONCLUSION: Cerebral hypoperfusion in CHF can be evaluated using 1H-MRS. MRS may play a substantial role in monitoring the effect of cardiac transplantation.

Leigh Syndrome: Serial MRI Findings

PURPOSE: The purpose of this study was to evaluate the effect of the temporal changes in brain lesions onserial MR images during the course of Leigh syndrome. MATERIALS AND METHODS: We retrospectively reviewed 11 MRimages in four patients diagnosed as suffering from Leigh syndrome on the basis of clinical features, MRIfindings, and biochemical data. Follow-up and earlier, MR images were compared and temporal changes in lesionswere analyzed, with particular attention to location, size, signal intensity, and contrast enhancement. RESULTS: Initial MRI showed that in order of frequency, the following were involved : bilateral putamina (4/4), caudatenuclei (2/4), the brain stem (2/4), medial thalamic nuclei (1/4), and the cerebral cortex (1/4). In two patients,the size of acute putaminal lesions, as seen on follow-up MRI, decreased in the short term (within two weeks); inone patient, strong contrast enhancement of the lesions was observed twelve days after initial MRI. Long termfollow-up MRI, over 7 - 19 months, showed newly developed lesions (2/4) and atrophy (2/4) or obliteration ofprevious lesions (3/4) in the basal ganglia, thalami, and brain stem. CONCLUSION: Serial MRI demonstratedtemporal changes in brain lesions during the course of Leigh syndrome. On follow-up MRI, the appearance ofbilateral lesions in basal ganglia and the brain stem, not present on initial MRI, may be helpful corroborativeevidence to support a diagnosis of this syndrome.