Advances in cellular and molecular biology underpin most current therapeutic advances in medicine. Such advances for neurological and neurodegenerative diseases are hindered by the lack of similar specimens. It is becoming increasingly evident that greater access to human brain tissue is necessary to understand both the cellular biology of these diseases and their variation. Research in these areas is vital to the development of viable therapeutic options for these currently untreatable diseases. The development and coordination of human brain specimen collection through brain banks is evolving. This perspective article from the Sydney Brain Bank reviews data concerning the best ways to collect and store material for different research purposes.
Aging ; pathology ; physiology ; Biomedical Research ; methods ; Brain ; pathology ; physiopathology ; Humans ; Neurodegenerative Diseases ; pathology ; physiopathology ; therapy ; Tissue Banks ; Tissue Preservation

Investigating the pathophysiological mechanisms underlying brain disorders is a priority if novel therapeutic strategies are to be developed. In vivo studies of animal models and in vitro studies of cell lines/primary cell cultures may provide useful tools to study certain aspects of brain disorders. However, discrepancies among these studies or unsuccessful translation from animal/cell studies to human/clinical studies often occur, because these models generally represent only some symptoms of a neuropsychiatric disorder rather than the complete disorder. Human brain slice cultures from postmortem tissue or resected tissue from operations have shown that, in vitro, neurons and glia can stay alive for long periods of time, while their morphological and physiological characteristics, and their ability to respond to experimental manipulations are maintained. Human brain slices can thus provide a close representation of neuronal networks in vivo, be a valuable tool for investigation of the basis of neuropsychiatric disorders, and provide a platform for the evaluation of novel pharmacological treatments of human brain diseases. A brain bank needs to provide the necessary infrastructure to bring together donors, hospitals, and researchers who want to investigate human brain slices in cultures of clinically and neuropathologically well-documented material.
Brain ; drug effects ; physiopathology ; Brain Diseases ; drug therapy ; physiopathology ; Humans ; Tissue Culture Techniques

Cerebral pericytes are perivascular cells that stabilize blood vessels. Little is known about the plasticity of pericytes in the adult brain in vivo. Recently, using state-of-the-art technologies, including two-photon microscopy in combination with sophisticated Cre/loxP in vivo tracing techniques, a novel role of pericytes was revealed in vascular remodeling in the adult brain. Strikingly, after pericyte ablation, neighboring pericytes expand their processes and prevent vascular dilatation. This new knowledge provides insights into pericyte plasticity in the adult brain.
Animals ; Brain ; blood supply ; physiology ; physiopathology ; Brain Diseases ; physiopathology ; Capillaries ; physiology ; Cellular Microenvironment ; Diabetic Retinopathy ; physiopathology ; Endothelial Cells ; physiology ; Humans ; Pericytes ; physiology ; Vascular Remodeling

A 68-year-old man presented with a three-week history of rapidly progressive dementia, gait ataxia and myoclonus. Subsequent electroencephalography showed periodic sharp wave complexes, and cerebrospinal fluid assay revealed the presence of a 14-3-3 protein. A probable diagnosis of sporadic Creutzfeldt-Jakob disease was made, which was further supported by magnetic resonance (MR) imaging of the brain showing asymmetric signal abnormality in the cerebral cortices and basal ganglia. The aetiology, clinical features, diagnostic criteria, various MR imaging patterns and radiologic differential diagnosis of sporadic Creutzfeldt-Jakob disease are discussed in this article.
Aged ; Brain ; pathology ; Cerebral Cortex ; Cerebrospinal Fluid ; metabolism ; Creutzfeldt-Jakob Syndrome ; diagnostic imaging ; Dementia ; physiopathology ; Diagnosis, Differential ; Diffusion Magnetic Resonance Imaging ; Electroencephalography ; Humans ; Hypoxia-Ischemia, Brain ; diagnostic imaging ; Male ; Prion Diseases ; physiopathology

Growth differentiation factor-15 (GDF-15) is a member of the transforming growth factor beta superfamily. GDF-15 expression is dramatically upregulated during acute brain injury, cancer, cardiovascular disease, and inflammation, suggesting its potential value as a disease biomarker. It has been suggested that GDF-15 has neurotropic effects in the nervous system. Our studies showed that GDF-15 modulated the expression of neuronal Kand Caion channels and increased the release of excitatory transmitter in the medial prefrontal cortex of mice. GDF-15 is also involved in the complex modulation of cancer and cardiovascular disease. Here, we reviewed studies involving the modulation of GDF-15 expression and its mechanisms, the primary pathological and physiological functions of GDF-15 in neurological and cardiovascular systems, and its role in cancer progression. The biological effects and the values of GDF-15 in basic research and clinical applications were also addressed.
Animals ; Brain Injuries ; physiopathology ; Calcium Channels ; metabolism ; Cardiovascular Diseases ; physiopathology ; Disease Progression ; Growth Differentiation Factor 15 ; metabolism ; Humans ; Inflammation ; Mice ; Neoplasms ; physiopathology ; Nervous System ; metabolism ; Potassium Channels ; metabolism ; Prefrontal Cortex ; metabolism ; Transforming Growth Factor beta ; Up-Regulation

INTRODUCTIONWe assessed the local prevalence, characteristics and 10-year outcomes in a heart failure (HF) cohort from the emergency room (ER).

MATERIALS AND METHODSPatients presenting with acute dyspnoea to ER were prospectively enrolled from December 2003 to December 2004. HF was diagnosed by physicians' adjudication based on clinical assessment and echocardiogram within 12 hours, blinded to N-terminal-pro brain natriuretic peptide (NT-proBNP) results. They were stratified into heart failure with preserved (HFPEF) and reduced ejection fraction (HFREF) by left ventricular ejection fraction (LVEF).

RESULTSAt different cutoffs of LVEF of ≥50%, ≥45%, ≥40%, and >50% plus excluding LVEF 40% to 50%, HFPEF prevalence ranged from 38% to 51%. Using LVEF ≥50% as the final cutoff point, at baseline, HFPEF (n = 35), compared to HFREF (n = 55), had lower admission NT- proBNP (1502 vs 5953 pg/mL, P <0.001), heart rate (86 ± 22 vs 98 ± 22 bpm, P = 0.014), and diastolic blood pressure (DBP) (75 ± 14 vs 84 ± 20 mmHg, P = 0.024). On echocardiogram, compared to HFREF, HFPEF had more LV concentric remodelling (20% vs 2%, P = 0.003), less eccentric hypertrophy (11% vs 53%, P <0.001) and less mitral regurgitation from functional mitral regurgitation (60% vs 95%, P = 0.027). At 10 years, compared to HFREF, HFPEF had similar primary endpoints of a composite of cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, and rehospitalisation for congestive heart failure (CHF) (HR 0.886; 95% CI, 0.561 to 1.399; P = 0.605), all-cause mortality (HR 0.663; 95% CI, 0.400 to 1.100; P = 0.112), but lower cardiovascular mortality (HR 0.307; 95% CI, 0.111 to 0.850; P = 0.023).

CONCLUSIONIn the long term, HFPEF had higher non-cardiovascular mortality, but lower cardiovascular mortality compared to HFREF.

Aged ; Aged, 80 and over ; Cardiovascular Diseases ; mortality ; Dyspnea ; diagnosis ; physiopathology ; Echocardiography ; Emergency Service, Hospital ; Female ; Heart Failure ; blood ; diagnostic imaging ; epidemiology ; physiopathology ; Humans ; Hypertrophy, Left Ventricular ; Male ; Middle Aged ; Mitral Valve Insufficiency ; epidemiology ; Myocardial Infarction ; epidemiology ; Natriuretic Peptide, Brain ; blood ; Peptide Fragments ; blood ; Prevalence ; Prospective Studies ; Singapore ; epidemiology ; Stroke ; epidemiology ; Stroke Volume ; Tertiary Care Centers ; Ventricular Remodeling

OBJECTIVETo observe the effect of intrapartum and postpartum factors on abnormal neurological findings in the extremely preterm infants.

METHODClinical data of 62 premature infants (33 of male, 29 of female) were retrospectively analyzed. None of the premature infants had birth defect; their gestational ages were all less than 28 weeks (23(+ 6)-27(+ 6) weeks). They were hospitalized within 12 hours after birth in the neonatal intensive care unit (NICU) of BAYI Children's Hospital from November 2010 to June 2013. The blood gas, birth condition, complications, the mechanical ventilation and the ultrasonic encephalography were recorded. The 62 cases were divided into 2 groups, alive group and died group. Meanwhile, all cases of survial were divided into brain injuries group and normal brain group. Data were analyzed with t-test, Chi square test and Spearman correlation analysis.

RESULTFifty-six cases were alive, and 6 cases died (3 were during the treatment and 3 were after parents gave up). The average birth weight of brain injuries group was (954 ± 182) g; and that of the normal brain group was (1 071 ± 136) g. There were significant differences between the two groups in gender (χ(2) = 4.314, P = 0.038), gestational age (χ(2) = 11.622, P = 0.001), birth weight (t = 2.728, P = 0.009), which had significant correlation with neurological outcomes. The Spearman correlative coefficients were -0.278, 0.456 and 0.364 respectively. And P values were 0.038, 0.000 and 0.006. The rates of multiple pregnancy, lung hemorrhage and surgical operation in brain injuries group were 45%(9/20), 55%(11/20), 40%(8/20), which were significantly higher than those in normal brain group, 3%(1/36), 17%(6/36), 11%(4/36)(χ(2) = 12.800, 8.936, 4.773, P all < 0.05). These three factors were the high risk factors for adverse neurological outcomes, the odds ratios were 28.64, 6.11 and 5.33 respectively. There was no significant difference in delivery mode, amniotic fluid, maternal infection, asphyxia, necrotizing enterocolitis, patent ductus arteriosus, sepsis, mechanical ventilation, inhaled nitric oxide therapy, blood glucose, blood gas analysis, doses of dopamine between brain injuries group and normal brain group. The birth weight in alive group was (1 029 ± 163) g, which was significantly higher than those in died group (870 ± 144)g (r=0.29, P=0.022). There was no significant difference in other factors between alive group and died group(P all>0.05).

CONCLUSIONGender, gestational age and birth weight may have relation with the neurological outcomes of extremely preterm infants. Multiple pregnancy, pulmonary hemorrhage and surgical operation are the risk factors of brain injuries. Birth weight is related to the survival of extremely preterm infants.

Birth Weight ; Brain Injuries ; physiopathology ; Female ; Gestational Age ; Humans ; Infant, Extremely Premature ; Infant, Newborn ; Infant, Premature, Diseases ; Lung ; pathology ; Male ; Pregnancy ; Pregnancy, Multiple ; Retrospective Studies ; Risk Factors

Neurodegenerative disease is characterized by progressive loss of neurons in specific brain regions that results in neuronal dysfunction of the central nervous system. Although the pathological mechanism is not fully established, the activation of glial cells mediated neuroinflammation appears to be involved. Heat shock protein 70 (HSP70) is originally described as intracellular chaperone, which plays an important role in protein quality control in cells. However, recent study showed that up-regulation of HSP70 had anti-inflammatory effects in the brain. HSP70 protected neurons from damage and improved neurological function by decreasing inflammatory response as indicated by inactivation of glial cells and inhibition of pro-inflammatory cytokine release. So it is of great significance to find new compounds targeting at HSP70 as neuroprotective agents to delay the progress of neurodegenerative disease. This review will focus on the role of HSP70 in neuroinflammation and the recent advances in using HSP70 as a target for the treatment of neurodegenerative disease.
Brain ; physiopathology ; Cytokines ; HSP70 Heat-Shock Proteins ; physiology ; Humans ; Inflammation ; pathology ; Neurodegenerative Diseases ; physiopathology ; Neurons ; pathology ; Neuroprotection ; Up-Regulation

OBJECTIVETo compare the difference of clinical efficacy on sleeping disorder in the children with encephalopathy between the combined therapy of acupuncture at head points and seed-pressure at ear points and the simple acupuncture at head points.

METHODSThirty cases of sleeping disorder induced by encephalopathy werei randomized into an observation group and a control group, 15 cases in each one. In the observation group, the combined therapy of acupuncture at head points and seed-pressure at ear points was adopted. The head points in cluded Sishencong (EX-HN 1), Shenting (GV 24) and Benshen (GB 13). The ear points were the positive reactive sites in the cymba and cavum conchae. In the control group, acupuncture was applied simply to the acupoints on the head. The treatment was given once on every Tuesday and Friday a week separately, 30 min each time. Totally, 16 treatments were required. Children's sleeping habit questionnaire (CSHQ) was used to observe the sleep improvements and the efficacy in the patients of the two groups.

RESULTSIn the observation group, the results of sleep resistance, sleep anxiety, night sleep wake, parasomnias, sleep dyspnea, daytime somnolence and the total score after treatment were all improved apparently as compared with those before treatment (all P<0. 05). In the control group, the results of night sleep wake, parasomnias, daytime somnolence and the total score after treatment were improved apparently than those before treatment (all P<0. 05). In the observation group, the results of sleep resistance, sleep dyspnea and the total score after treatment were better than those in the control group (all P<0. 05) and the scores of sleep anxiety and daytime somnolence in the control group were better than those in the observation group after treatment (both P<0. 05).

CONCLUSIONThe combined therapy of acupuncture at head points and seed-pressure at the positive reactive sites in the cymba and cavum conchae achieves the superior efficacy on sleep resistance and sleep dyspnea as compared with the simple acupuncture. The efficacy of simple acupuncture is more satisfactory on sleep anxiety and daytime somnolence.

Acupuncture Points ; Acupuncture Therapy ; Acupuncture, Ear ; Brain Diseases ; complications ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Male ; Sleep ; Sleep Wake Disorders ; etiology ; physiopathology ; therapy

The cAMP-responsive element binding protein (CREB)-regulated transcription coactivator, CRTC (also known as transducer of regulated CREB, TORC), is identified as a potent modulator of cAMP response element (CRE)-driven gene transcription. The CRTC family consists of three members (CRTC1-3), among which the CRTC1 shows the highest expression in the brain. Several studies have demonstrated that the CRTC1 plays critical roles in neuronal dendritic growth, long-term synaptic plasticity, memory consolidation and reconsolidation etc., whereas dysfunction of CRTC1 is mainly involved in neurodegenerative disorders. In light of these findings, we aim to review recent research reports that indicate the CRTC1 dysfunction and its underlying mechanisms in the neurodegenerative disorders.
Brain ; physiology ; Dendrites ; physiology ; Humans ; Neurodegenerative Diseases ; physiopathology ; Neuronal Plasticity ; Transcription Factors ; physiology