Neuronal chemokines:new insights into neuronal communication after injury

<正>Classically,chemokines were described as small proteins driving leukocyte migration.Nonetheless,more and more studies are showing the great variety of cell functions and tissues in which they participate,including neural cells.During the last years,research has highlighted the importance of chemokines in the nervous system,governing a wide range of processes (MesquidaVeny et al.,2021).This is evidenced for example by the crucial role played by CXCL12 during cortical development,or the h...     

Hippocampal neuronal regeneration after epilepsy

Changes in hippocampal ultrastructure and gene expression of various nerve factors are strongly associated with the pathogenesis of epilepsy during seizure. Recent studies have shown that     

Intrinsic neuronal determinants of regeneration.

Axon growth and axon regeneration are co-operative processes; the speed and extent of axon growth are influenced both by the properties of the environment surrounding the axon growth cone, and the properties of the neuron itself. In recent years, the environmental influences on axon growth have received most of the attention directed towards this area of research, but the properties of the neurons themselves are likely to be just as important. Within both adults and embryos there are differences in the growth potential of different neuronal types, and there is also evidence for an overall decrease in the vigour of axon growth with neuronal age.     

Restrictions in time and space--new insights into generation of specific neuronal subtypes in the adult mammalian brain

Key questions in regard to neuronal repair strategies are which cells are best suited to regenerate specific neuronal subtypes and how much of a neuronal circuit needs to persist in order to allow its functional repair. Here we discuss recent findings in the field of adult neurogenesis, which shed new light on these questions. Neural stem cells in the adult brain generate very distinct types of neurons depending on their regional and temporal specification. Moreover, distinct brain regions differ in the mode of neuron addition in adult neurogenesis, suggesting that different brain circuits may be able to cope differently with the incorporation of new neurons. These new insights are then considered in regard to the choice of cells with the appropriate region-specific identity for repair strategies.     

New insights into craniosynostosis

Craniosynostosis is a congenital developmental disorder involving premature fusion of cranial sutures, often associated with multiple neurological manifestations. The perspective of this group of disorders has changed dramatically in the new era of molecular genetics. In the last decade a large literature with new concepts in craniosynostosis has appeared. More than 100 syndromes associated with craniosynostosis have been described, and in about a dozen, the molecular defect has been identified. Pediatric neurologists are less aware than geneticists, neurosurgeons, and craniofacial surgeons of these changes. General concepts about craniosynostosis are here presented with updates of clinical and genetic aspects of well-defined syndromes such as Apert, Crouzon, Pfeiffer, Saethre-Chotzen. Evidence of their relationship with fibroblast growth factor receptors (FGFRs) 1, 2, and 3, and with causative genes such as TWIST has been documented. New and other less common syndromes also are discussed. The differences between positional and synostotic plagiocephaly are important, as well as the cause of nonsyndromic craniosynostosis. The prognosis and neurological outcome of patients, including "benign" forms of craniosynostosis, are other important aspects. Major advances have occurred in understanding pathogenesis, diagnosis, and treatment of craniosynostosis. The role of local dura mater and apoptosis; modalities of imaging such as prenatal ultrasound and three-dimensional and spiral CT have improved the accuracy in diagnosis, and the new approaches in surgical treatment involving efficient and less invasive methods, are evidence of these advances.     

Neurogenesis and neuronal regeneration in the adult reptilian brain

Evidence accumulated over the last few decades demonstrates that all reptiles examined thus far continue to add neurons at a high rate and in many regions of the adult brain. This so-called adult neurogenesis has been described in the olfactory bulbs, rostral forebrain, all cortical areas, anterior dorsal ventricular ridge, septum, striatum, nucleus sphericus, and cerebellum. The rate of neuronal production varies greatly among these brain areas. Moreover, striking differences in the rate and distribution of adult neurogenesis have been noted among species. In addition to producing new neurons in the adult brain, lizards, and possibly other reptiles as well, are capable of regenerating large portions of their telencephalon damaged as a result of experimentally-induced injuries, thus exhibiting an enormous potential for neuronal regeneration. Adult neurogenesis and neuronal regeneration take advantage of the same mechanisms that are present during embryonic neurogenesis. New neurons are born in the ependyma lining the ventricles and migrate radially through the brain parenchyma along processes of radial glial cells. Several lines of evidence suggest that radial glial cells also act as stem cells for adult neurogenesis. Once they reach their final destination, the young neurons extend axons that reach appropriate target areas. Tangential migration of neurons alongside the ventricular ependyma has also been reported. Most of these tangentially migrating neurons seem to be destined for the olfactory bulbs and are, thus, part of a system similar to the mammalian rostral migratory stream. The proliferation and recruitment of new neurons appear to result in continuous growth of most areas showing adult neurogenesis. The functional consequences of this continuous generation and integration of new neurons into existing circuits is largely conjectural, but involvement of these phenomena in learning and memory is one likely possibility.     

New insights into childhood ependymomas

Childhood ependymomas, which comprise approximately 10% to 15% of all brain tumors arising in patients less than 18 years of age, remain a highly problematic group of tumors to treat. Relapse-free survival rates vary significantly in contemporary series, and therapeutic approaches remain unsettled.     

New insights into migraine pathophysiology

PURPOSE OF REVIEW: This article will review new and exciting developments in migraine research, with particular emphasis on mutations associated with familial hemiplegic migraine and the role of cortical spreading depression in its pathophysiology and treatment. RECENT FINDINGS: The recent discovery of multiple point mutations in familial hemiplegic migraine has led to the suggestion that migraine and its variants may be due to a paroxysmal disturbance in ion-translocating mechanisms. Mutations associated with familial hemiplegic migraine render the brain more susceptible to prolonged cortical spreading depression caused by either excessive synaptic glutamate release or decreased removal of glutamate and potassium from the synaptic cleft, or persistent sodium influx. Suppression of cortical spreading depression has become an interesting target for preventive migraine treatment. Prolonged treatment with beta-blockers, valproate, topiramate, methysergide or amitriptyline reduced the number of potassium-evoked cortical spreading depressions and elevated the electrical stimulation threshold for the induction of cortical spreading depression in rats. Recent imaging studies in patients suffering from migraine without aura also point to the presence of silent cortical spreading depression as an underlying mechanism. Repeated waves of cortical spreading depression may have deleterious effects on brain function, and perhaps cause silent ischaemic lesions in vulnerable brain regions such as the cerebellum in susceptible individuals. SUMMARY: This review emphasizes several neurobiological aspects of migraine that reveal paroxysmal disturbances in neuronal and vascular function, that in turn reflect disturbances in the maintenance of ionic gradients.     

New insights into Parkinson's disease

Parkinson's disease (PD) is the most common neurodegenerative movement disorder. Recent advances in genetics and pathophysiology have led to new insights into the pathogenesis of PD. Ten loci have been linked to hereditary PD. Mutations in alpha-synuclein and ubiquitin carboxy hydrolase L1 (UchL1) cause autosomal dominant PD and mutations in parkin and DJ-1 cause autosomal recessive PD. alpha-Synuclein has emerged as an important protein in the pathogenesis of PD, as it appears to be the major structural component of Lewy bodies and its accumulation/aggregation seems to play a prominent role in sporadic PD. Mutations in parkin are the most common cause of hereditary PD, and mutations in parkin are thought to lead to a loss of parkin's ubiquitin E3 ligase activity. Derangements in parkin function as well as mutations in UCH-L1 fit with the notion that derangements in the ubiquitin proteasomal pathway (UPP) may play important roles in the demise of dopamine neurons in PD. DJ-1 is a protein of unknown function that is linked to autosomal recessive PD. Oxidative stress and impairment in mitochondrial complex I activity are important in sporadic PD, and there is emerging interest in the role of herbicides, fungicides and insecticides that inhibit mitochondrial complex I activity and their role in contributing to the development of PD. These important findings serve as the foundation for discovering new pathways that may lead to the development of new therapies for PD.     

Genetic insights into schizophrenia.

OBJECTIVE: To outline new insights into the genetic etiology of schizophrenia. METHODS: We discuss several commonly held beliefs about the genetic issues in schizophrenia. RESULTS: The complex genetic nature of the illness poses a challenge for investigators seeking causative genetic mutations. Multiple independent research findings are, however converging to identify a relatively small number of chromosomal locations that appear to contain schizophrenia susceptibility genes. Also, a clinically relevant genetic subtype of schizophrenia (22qDS) has been identified. We are developing a better understanding of how schizophrenia relates to other psychiatric disorders. While investigations into the possible roles of dopaminergic and serotonergic systems continue, other approaches that do not require theories of the mechanism of illness are also being used to identify candidate susceptibility genes. CONCLUSIONS: Research to date suggests that our understanding of the pathophysiology of schizophrenia will soon be fundamentally altered by genetic approaches to this complex disease.     

Recent insights into Rasmussen encephalitis

Rasmussen encephalitis (RE) is a severe and at the same time pathophysiologically fascinating condition. The chronic inflammation affects one of the two cerebral hemispheres and destroys it during the disease process that lasts from months to years. The patients -- mostly children -- suffer from frequent pharmacoresistant seizures, often in the form of epilepsia partialis continua. In parallel to the atrophy of the affected hemisphere, the neurological functions associated with it decline continuously. This results in a final stage with a usually high-grade sensorimotor hemisyndrome, hemianopia, cognitive impairment and -- if the language-dominant hemisphere is affected -- aphasia. Research results in the last 5 years have contributed to a deeper understanding of the pathogenesis of this condition. Formal diagnostic criteria have been proposed, and new therapeutic options have emerged by which the disease progression can be slowed or stopped. This article summarizes the current research results on the background of older data and gives recommendations regarding diagnostic and therapeutic procedures in RE patients.     

对传导阻滞的新认识

经典理论认为有髓神经传导是跳跃式的 ,假设髓鞘是高电阻的绝缘体 ,在郎飞结之间没有电活动通过膜内外。传导阻滞被认为是髓鞘绝缘性破坏 ,电流泄漏所致。活动电流通过钠离子通道在被兴奋的郎飞结处进入 ,它就向邻近的结流去造成其向外的电流 ,引起邻近结的兴奋。这个去极化过程使郎飞结处膜上的离子通道到达开放的阈值并驱动另一轮的电流进入。动作电流从一个结到启动下一个结的时间称为“结间传导时间”。传导安全因子大于1,才能成功地传导。正常的有髓纤维安全因子为 5或大于 5。如果到达下一结处的电流不足以达到下一结处膜上的离子通道…     

线粒体与阿尔茨海默病的研究进展

阿尔茨海默病(Alzheimer's disease,AD)是一种主要在老年期发生的以进行性痴呆为主要特征的神经元退行性疾病,其主要临床表现为进行性认知功能障碍、记忆力衰退、性格和行为改变等.     

Alternating vigilance states: new insights regarding neuronal networks and mechanisms

Since the discovery of rapid eye movement (REM) sleep (also known as paradoxical sleep; PS), it is accepted that sleep is an active process. PS is characterized by EEG rhythmic activity resembling that of waking with a disappearance of muscle tone and the occurrence of REMs, in contrast to slow-wave sleep (SWS, also known as non-REM sleep) identified by the presence of delta waves. Here, we review the most recent data on the mechanisms responsible for the genesis of SWS and PS. Based on these data, we propose an updated integrated model of the mechanisms responsible for the sleep–wake cycle. This model introduces for the first time the notion that the entrance and exit of PS are induced by different mechanisms. We hypothesize that the entrance from SWS to PS is due to the intrinsic activation of PS-active GABAergic neurons localized in the posterior hypothalamus (co-containing melanin-concentrating hormone), ventrolateral periaqueductal gray and the dorsal paragigantocellular reticular nucleus. In contrast, the exit from PS is induced by the inhibition of these neurons by a PS-gating system composed of GABAergic neurons localized in the ventrolateral periaqueductal gray and just ventral to it, and waking systems such as the pontine and medullary noradrenergic neurons and the hypothalamic hypocretin neurons. Finally, we review human neurological disorders of the network responsible for sleep and propose hypotheses on the mechanisms responsible for REM behavior disorder and narcolepsy.     

Molecular insights into neurodevelopmental and neurodegenerative diseases

Magnetic resonance spectroscopy (MRS) is a non-invasive physical technique that is routinely used to determine the quantity and structure of organic molecules in solution. Technical advances that have expanded the usefulness of this technique include: (1) high resolution MRS to identify and quantify individual molecules present in complex mixtures of tissue extracts; (2) in vivo MRS techniques to non-invasively monitor metabolites in humans; (3) structure determination of proteins of moderate size; and (4) improved structure characterization of solids and liquid crystals, such as the detection of phase changes in membranes. The focus of this review is on the first two technical advances mentioned above. The strengths of MRS as a research tool to investigate molecular alterations in disease states include ease of sample preparation, minimum sample manipulation, avoidance of the preparation of derivatives, and the ability to analyze an unfractionated sample. The strengths of MRS in the clinic are its ability to measure neuronal metabolite levels non-invasively in humans and its potential for disease diagnosis, monitoring disease progression, and assessing the efficacy of experimental therapies.     

Dissecting functional connectivity of neuronal microcircuits: experimental and theoretical insights

Structure-function studies of neuronal networks have recently benefited from considerable progress in different areas of investigation. Advances in molecular genetics and imaging have allowed for the dissection of neuronal connectivity with unprecedented detail whereas in vivo recordings are providing much needed clues as to how sensory, motor and cognitive function is encoded in neuronal firing. However, bridging the gap between the cellular and behavioral levels will ultimately require an understanding of the functional organization of the underlying neuronal circuits. One way to unravel the complexity of neuronal networks is to understand how their connectivity emerges during brain maturation. In this review, we will describe how graph theory provides experimentalists with novel concepts that can be used to describe and interpret these developing connectivity schemes.     

中枢神经系统损伤后神经再生的策略

中枢神经系统（central nervous system，CNS）损伤后神经细胞受损、缺失或死亡，常使神经功能严重受损而导致偏瘫、失语、智力障碍或昏迷，甚至死亡。传统的药物治疗及功能性电刺激虽然显示了一定的效果，但是要修复受损的神经环路，重建神经功能，至关重要的是解决神经再生这一难题。由于CNS损伤后复杂的病理生理变化，单一的治疗措施难以获得良好的再生效果，因此，促进CNS损伤后的神经再生需要“多管齐下”。目前，我们认为促进神经再生的策略主要有下述几个方面。[第一段]