Brain Research Reviews最新文献

The cerebellum is classically considered to be a brain region involved in motor processing, but it has also been implicated in non-motor, and even cognitive, functions. Though previous research suggests that the cerebellum responds to noxious stimuli, its specific role during pain is unclear. Pain is a multidimensional experience that encompasses sensory discriminative, affective motivational, and cognitive evaluative components. Cerebellar involvement during the processing of pain could thus potentially reflect a number of different functional processes. This review will summarize the animal and human research to date that indicates that (1) primary afferents conduct nociceptive (noxious) input to the cerebellum, (2) electrical and pharmacological stimulation of the cerebellum can modulate nociceptive processing, and (3) cerebellar activity occurs during the presence of acute and chronic pain. Possible functional roles for the cerebellum relating to pain will be considered, including perspectives relating to emotion, cognition, and motor control in response to pain.

Alpha-synuclein aggregation is a neuropathological hallmark of many neurodegenerative diseases including Parkinson's disease (PD), Parkinson's disease with dementia (PDD) and dementia with Lewy bodies (DLB), collectively termed the α-synucleinopathies. Substantial advances in clinical criteria and neuroimaging technology over the last 20 years have allowed great strides in the detection and differential diagnosis of these disorders. Nevertheless, it is clear that whilst the array of different imaging modalities in clinical use allow for a robust diagnosis of α-synucleinopathy in comparison to healthy subjects, there is no clear diagnostic imaging marker that affords a reliable differential diagnosis between the different forms of Lewy body disease (LBD) or that could facilitate tracking of disease progression. This has led to a call for a biomarker based on the pathological hallmarks of these diseases, namely α-synuclein-positive Lewy bodies (LBs). This potentially may be advantageous in terms of early disease detection, but may also be leveraged into a potential marker of disease progression. We here aim to firstly review the current status of neuroimaging biomarkers in PD and related synucleinopathies. Secondly, we outline the rationale behind α-synuclein imaging as a potential novel biomarker as well as the potential benefits and limitations of this approach. Thirdly, we attempt to illustrate the likely technical hurdles to be overcome to permit successful in vivo imaging of α-synuclein pathology in the diseased brain. Our overriding aim is to provide a framework for discussion of how to address this major unmet clinical need.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy).

This article has been retracted at the request of the Editor and one of the authors in recognition that the authors have plagiarized parts of papers that had already appeared in other publications, including: Trends Neurosci., 28 [2005] 209–216, doi:10.1016/j.tins.2005.02.005, Mov. Disord., 21/S14 [2006] S305–S327, doi:10.1002/mds.20963,Annu. Rev. Neurosci., 29 [2006] 229–257, doi:10.1146/annurev.neuro.29.051605.112824.

One of the conditions of submission of a paper for publication is that authors declare explicitly that their work is original and has not appeared in a publication elsewhere. Re-use of any data should be appropriately cited. As such this article represents a severe abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.

The mammalian blood–brain barrier (BBB) consists of endothelial cells, linked by tight junctions, and the adjoining pericytes and extracellular matrix. It helps maintain a highly stable extracellular environment necessary for accurate synaptic transmission and protects nervous tissue from injury. An increase in its normally low permeability for hydrophilic and charged molecules could potentially be detrimental. Methods to assess the permeability of the BBB include histological staining for marker molecules in brain sections and measurement of the concentration of marker molecules in blood and brain tissue. Their advantages and disadvantages are discussed. Exposure to levels of radiofrequency electromagnetic fields (EMF) that increase brain temperature by more than 1 °C can reversibly increase the permeability of the BBB for macromolecules. The balance of experimental evidence does not support an effect of ‘non-thermal’ radiofrequency fields with microwave and mobile phone frequencies on BBB permeability. Evidence for an effect of the EMF generated by magnetic resonance imaging on permeability is conflicting and conclusions are hampered by potential confounders and simultaneous exposure to different types and frequencies of EMF. The literature on effects of low frequency EMF, which do not cause tissue heating, is sparse and does not yet permit any conclusions on permeability changes. Studies on the potential effect of EMF exposure on permeability of the BBB in humans are virtually absent. Future permeability studies should focus on low frequency effects and effects in humans. Care should be taken to avoid the methodological limitations of earlier studies and to determine the pathophysiological relevance of any changes found.

Prenatal stress (PS) has been linked to abnormal cognitive, behavioral and psychosocial outcomes in both animals and humans. Animal studies have clearly demonstrated PS effects on the offspring's brain, however, while it has been speculated that PS most likely affects the brains of exposed human fetuses as well, no study has to date examined this possibility prospectively using an independent stressor (i.e., a stressful event that the pregnant woman has no control over, such as a natural disaster). The aim of this review is to summarize the existing animal literature by focusing on specific brain regions that have been shown to be affected by PS both macroscopically and microscopically. These regions include the hippocampus, amygdala, corpus callosum, anterior commissure, cerebral cortex, cerebellum and hypothalamus. We first discuss the mechanisms by which the effects of PS might occur. In particular, we show that maternal and fetal hypothalamic–pituitary–adrenal (HPA) axes, and the placenta, are the most likely candidates for these mechanisms. We see that, although animal studies have obvious advantages over human studies, the integration of findings in animals and the transfer of these findings to human populations remains a complex issue. Finally, we show how it is possible to circumvent these challenges by studying the effects of PS on brain development directly in humans, by taking advantage of natural or man-made disasters and assessing the impact and consequences of such stressful events on pregnant women and their offspring prospectively.

The neurotransmitter histamine has been suggested to be involved in cognitive functioning. Generally, studies in animals have shown a decrease in performance after decreasing histamine neurotransmission and improved performance after increasing histamine neurotransmission. It is unclear, however, what role histamine plays in cognition in humans. Up until now, most data are derived from studies and reviews that aimed to assess the sedative potential of H₁-antagonists and not the effects on cognition in particular. The objective of this paper is specifically to review which cognitive domains are affected by H₁-antagonists. Taken together, 90 experimental studies on the performance effects of sedative H₁-antagonists published between 1973 and 2009 were reviewed. Results showed that psychomotor skills and attention are most frequently impaired and memory the least. Tasks assessing memory that were affected usually required rapid responses. It was concluded that both the complexity of the task as well as the demand for information processing speed determines the sensitivity to the effects of central H₁-antagonism. The importance of the sensitive cognitive domains to histaminergic dysfunction, as well as the relation between histamine related decrease in arousal and task performance deserve further research.

The first scientific and experimental approaches to the study of cerebrospinal fluid (CSF) formation began almost a hundred years ago. Despite researchers being interested for so long, some aspects of CSF formation are still insufficiently understood. Today it is generally believed that CSF formation is an active energy consuming metabolic process which occurs mainly in brain ventricles, in choroid plexuses. CSF formation, together with CSF absorption and circulation, represents the so-called classic hypothesis of CSF hydrodynamics. In spite of the general acceptance of this hypothesis, there is a considerable series of experimental results that do not support the idea of the active nature of CSF formation and the idea that choroid plexuses inside the brain ventricles are the main places of formation. The main goal of this review is to summarize the present understanding of CSF formation and compare this understanding to contradictory experimental results that have been obtained so far. And finally, to try to offer a physiological explanation by which these contradictions could be avoided. We therefore analyzed the main methods that study CSF formation, which enabled such an understanding, and presented their shortcomings, which could also be a reason for the erroneous interpretation of the obtained results. A recent method of direct aqueductal determination of CSF formation is shown in more detail. On the one hand, it provides the possibility of direct insight into CSF formation, and on the other, it clearly indicates that there is no net CSF formation inside the brain ventricles. These results are contradictory to the classic hypothesis and, together with other mentioned contradictory results, strongly support a recently proposed new working hypothesis on the hydrodynamics of CSF. According to this new working hypothesis, CSF is permanently produced and absorbed in the whole CSF system as a consequence of filtration and reabsorption of water volume through the capillary walls into the surrounding brain tissue. The CSF exchange between the entire CSF system and the surrounding tissue depends on (patho)physiological conditions that predominate within those compartments.

Glial cells are established as essential for many functions of the central nervous system, and this seems to hold also for glial cells in the peripheral nervous system. The main type of glial cells in most types of peripheral ganglia – sensory, sympathetic, and parasympathetic – is satellite glial cells (SGCs). These cells usually form envelopes around single neurons, which create a distinct functional unit consisting of a neuron and its attending SGCs. This review presents the knowledge on the morphology of SGCs in sympathetic and parasympathetic ganglia, and the (limited) available information on their physiology and pharmacology. It appears that SGCs carry receptors for ATP and can thus respond to the release of this neurotransmitter by the neurons. There is evidence that SGCs have an uptake mechanism for GABA, and possibly other neurotransmitters, which enables them to control the neuronal microenvironment. Damage to post- or preganglionic nerve fibers influences both the ganglionic neurons and the SGCs. One major consequence of postganglionic nerve section is the detachment of preganglionic nerve terminals, resulting in decline of synaptic transmission. It appears that, at least in sympathetic ganglia, SGCs participate in the detachment process, and possibly in the subsequent recovery of the synaptic connections. Unlike sensory neurons, neurons in autonomic ganglia receive synaptic inputs, and SGCs are in very close contact with synaptic boutons. This places the SGCs in a position to influence synaptic transmission and information processing in autonomic ganglia, but this topic requires much further work.