Neuronal excitability and calcium/calmodulin-dependent protein kinase type II: location, location, location

Calcium/calmodulin-dependent protein kinase type II (CaMKII) is a highly abundant serine/threonine kinase comprising a significant fraction of total protein in mammalian forebrain and forming a major component of the postsynaptic density. CaMKII is essential for certain forms of synaptic plasticity and memory consolidation and this is mediated through substrate binding and intramolecular phosphorylation of holoenzyme subunits. CaMKII is multifunctional; it targets a variety of cellular substrates, and this diversity depends on holoenzyme subunit composition. CaMKII comprises homooligomeric and heterooligomeric complexes generated from four subunits (α, β, δ, and γ) encoded by separate genes that are further expanded by extensive alternative splicing to more than 30 different isoforms. Much attention has been paid to understanding the regulation of CaMKII function through its structural diversity and/or substrate specificity. However, given the importance of subunit composition to holoenzyme activity, it is likely that specificity of cellular expression of CaMKII isoforms also plays a major role in regulation of enzyme function. Herein we review the cellular colocalization of CaMKII isoforms with special regard to the cell-type specificity of isoform expression in brain. In addition, we highlight the remarkable specificity of subcellular localization by the CaMKIIα isoform. In addition, we discuss the role that this cellular specificity of expression might play in propagating the type of recurrent neuronal activity associated with disorders such as temporal lobe epilepsy.     

Heterogeneity of nervous system mitochondria: Location, location, location!

Mitochondrial impairments have been associated with many neurological disorders, from inborn errors of metabolism or genetic disorders to age and environmentally linked diseases of aging (DiMauro S., Schon E.A. 2008. Mitochondrial disorders in the nervous system. Annu. Rev., Neurosci. 31, 91–123.). In these disorders, specific nervous system components or brain regions appear to be initially more susceptible to the triggering event or pathological process. Such regional variation in susceptibility to multiple types of stressors raises the possibility that inherent differences in mitochondrial function may mediate some aspect of pathogenesis. Regional differences in the distribution or number of mitochondria, mitochondrial enzyme activities, enzyme expression levels, mitochondrial genes or availability of necessary metabolites become attractive explanations for selective vulnerability of a nervous system structure. While regionally selective mitochondrial vulnerability has been documented, regional variations in other cellular and tissue characteristics may also contribute to metabolic impairment. Such environmental variables include high tonic firing rates, neurotransmitter phenotype, location of mitochondria within a neuron, or the varied tissue perfusion pressure of different cerebral arterial branches. These contextual variables exert regionally distinct regulatory influences on mitochondria to tune their energy production to local demands. Thus to understand variations in mitochondrial functioning and consequent selective vulnerability to injury, the organelle must be placed within the context of its cellular, functional, developmental and neuroanatomical environment.     

Location, location, location: a spatial view of neurotrophin signal transduction

Neurotrophins were originally identified as target-derived factors that regulate the survival and differentiation of innervating neurons. However, neurotrophins can also be released by presynaptic cells to stimulate postsynaptic neurons. Recent studies indicate that differences exist between the signaling pathways activated by neurotrophin stimulation of nerve terminals (retrograde signaling) and neurotrophin stimulation of cell bodies. Retrograde signaling relies on the formation of signaling endosomes, vesicles containing activated Trk receptors and their ligands. Signaling endosomes travel from the nerve terminals to remote cell bodies, where they selectively activate a novel MAP kinase, Erk5, as well as PI3 kinase, and thereby stimulate neuronal survival. The differences in the signaling pathways activated by neurotrophins, which depends on the location of stimulation, provide a mechanism by which neurons can interpret the 'where' as well as the 'what' of growth factor stimulation.     

Right-hemisphere deficits,lesion size and location

Abstract

Thirty-seven patients with single right-hemisphere infarcts localized on CT or isotope scans were examined on tests of constructional apraxia, neglect, visuospatial problem solving, motor praxis, and language. The patients were placed, according to the anatomical location of their lesions, into five groups: frontal, central cortical, central deep, parietal, and occipital. Mean scores for drawing, Block Design and Raven's Coloured Progressive Matrices were not significantly different across the groups, but measures of neglect and perseveration appeared significantly worse in the frontal and extensive central lesion groups. Lesion size did not correlate significantly with any of the parameters. The previously emphasized parietal locus of lesions in constructional apraxia, visuospatial difficulty, and neglect was not confirmed, suggesting a more diffusely organized right hemisphere.     

Housing type,housing location and mental health

A number of studies have suggested a connection between the type of dwellings which people occupy and their mental health. People who live in flats are usually shown to be more prone to mental illness than those who live in houses. Those who live in high-rise accommodation are shown to be particularly vulnerable. These conclusions were examined by comparing rates on an indicator of psychological distress, in different dwelling types located in good and bad council housing areas. The results suggest that psychological distress is more closely associated with the location of a dwelling than with dwelling type. High-rise flats located on inner-city problem estates are associated with high levels of psychological distress, while low levels are found in similar dwelling types located in the suburbs. These findings are consistent when the effect of age, health, sex and household class are taken into consideration.     

The wandering psychiatric emergency room--design, location and transformations

We describe the changes in location and philosophy of a psychiatric emergency room over a period of 20 years. Four phases are described in which location, size, modes of access as well as internal and external boundaries reflect philosophies of treatment and the evolving identity of a psychiatric emergency room. The four phases include an early embryonic stage, a second stage involving rapid development of services, a third stage involving regression and consolidation and a fourth stage representing a fully developed independent service. The authors stress both external and rational considerations, such as mental health policies and budget, as well as unconscious irrational processes, which reflect the dynamic forces within the organization.     

Brain spectrin: Structure,location, and function. A symposium overview

On November 12, 1986 a symposium was held at the 16th Annual Meeting of the Society for Neuroscience which brought together the pioneers and leaders in the brain spectrin field to discuss the structure, location, and function of this important cytoskeletal protein. In this brief overview, we summarize the major new concepts which emerged from this symposium.     

Spike morphology, location, and frequency in benign epilepsy with centrotemporal spikes

The literature on benign epilepsy with centrotemporal spikes reports a constellation of neurophysiologic features in selected populations with heterogeneous methodologies. The aim of this study was to determine the specific electroencephalographic (EEG) features (spike morphology, location, and frequency and associated background slowing) in a broad population-based cohort identified through EEG laboratories. The mean spike frequency in the awake state was 9.3 per minute (95% confidence interval 6.5-12.0), in drowsiness, 21.2 per minute (16.7-25.6); and in sleep, 45.6 per minute (38.3-52.8), where 60% of patients had > 40 discharges per minute. In five patients, spike train rates occupied > 80% of the sleep record, and in nine patients, they occupied 61% to 80%. An ambulatory overnight record did not add new information comparing early-onset sleep with a mean spike frequency of 37.1 per minute (27.3-46.9) with slow-wave sleep, 36.0 per minute (27.3-44.7). Patients with benign epilepsy with centrotemporal spikes have a high spike burden, which can impact on cognitive function.     

Childhood meningioma: unusual location, atypical radiological findings, and favorable treatment outcome

OBJECTS: To investigate the characteristics of childhood meningioma, especially, locations, radiological findings, pathological features (including proliferative potential) and outcome, 11 children with meningiomas were retrospectively analyzed. RESULTS: Unusual location, large size, frequent calcification, and cyst formation were characteristic radiological findings. Gross total resection was achieved in 8 patients, and there was recurrence in 2. Gamma knife radiosurgery was performed on residual and recurrent tumors. MIB-1 indices tended to be high in large tumors. Nine patients had a Karnofsky Performance Scale of more than 70 during the follow-up period of 10 months to 19.5 years. Surgical treatment rendered 4 of 5 epileptic patients seizure free. The childhood meningiomas examined had unusual locations, atypical radiological findings, and various proliferative potentials. CONCLUSIONS: Complete resection is the treatment of choice. Gamma knife radiosurgery can be a good alternative for residual tumors and small recurrent tumors. The outcome of childhood meningiomas is good after surgery.     

Ectosylvian visual area of the cat: location, retinotopic organization, and connections

We have mapped out the ectosylvian visual area (EVA) of the cat in a series of single- and multiunit recording studies. EVA occupies 10-20 mm2 of cortex at the posterior end of the horizontal limb of the anterior ectosylvian sulcus. EVA borders on somatosensory cortex anteriorly, auditory cortex posteriorly, and nonresponsive cortex laterally. EVA exhibits limited retinotopic organization, as indicated by the fact that receptive fields shift gradually with tangential travel of the microelectrode through cortex. However, a point-to-point representation of the complete visual hemifield is not present. We have characterized the afferent and efferent connections of EVA by placing retrograde and anterograde tracer deposits in EVA and in other cortical visual areas. The strongest transcortical fiber projection to EVA arises in the lateral suprasylvian visual areas. Area 20, the granular insula, and perirhinal cortex provide additional sparse afferents. The projection from lateral suprasylvian cortex to EVA arises predominantly in layer 3 and terminates in layer 4. EVA projects reciprocally to all cortical areas from which it receives input. The projection from EVA to the lateral suprasylvian areas arises predominantly in layers 5 and 6 and terminates in layer 1. EVA is linked reciprocally to a thalamic zone encompassing the lateromedial-suprageniculate complex and the adjacent medial subdivision of the latero-posterior nucleus. We conclude that EVA is an exclusively visual area confined to the anterior ectosylvian sulcus and bounded by nonvisual cortex. EVA is distinguished from other visual areas by its physical isolation from those areas, by its lack of consistent global retinotopic organization, and by its placement at the end of a chain of areas through which information flows outward from the primary visual cortex.     

Hemangioblastoma of supra-tentorial location

A case of hemangioblastoma with supra-tentorial localization is reported. General considerations are made.     

Glomangiomas of atypical location

Glomangiomas are most frequently situated on fingers and toes, especially in the vicinity of the ungual plate. The authors report five cases of glomangiomas of atypical location/in the knee joint, in the vicinity of femoral and tibial epiphyses, and in the subcutaneous tissue on the forearm. The clinical findings are described, stressing the lack of parallelism between the intensity of symptoms and the size of the tumour which rarely exceeds the size of a millet grain. Complete removal of the tumour produces complete disappearance of pain and recurrences are not observed.     

Intracerebral hemorrhage in young people: analysis of risk factors, location, causes, and prognosis

BACKGROUND AND PURPOSE: The frequency of intracerebral hemorrhages (ICHs) in people aged 31 years (odds ratio, 3.48), and those with ICH that resulted from arteriovenous malformations were aged <20 years (odds ratio, 2.80). The final outcome was considered favorable in 60%. CONCLUSIONS: ICHs in young people are mainly lobar in location and result from vascular malformation. Hypertension causes most cases in which the ICH is located in the basal ganglia. Mortality and morbidity in the acute phase are low and are related to hypertension as the cause of ICH.     

Epidermal innervation: changes with aging, topographic location, and in sensory neuropathy.

In previous work we demonstrated little effect of aging on the density and spatial pattern of epidermal innervation, however, this was restricted to two sites proximal and distal in the leg. To expand on these observations, we used punch skin biopsy in ten healthy controls to examine the variation in intra-epidermal nerve fiber (IENF) density at multiple specific sites in the leg. There was a consistent gradient in IENF from proximal to distal sites in all subjects, but minimal effect of age was noted. In the older age group (> or =70 years), the IENF densities ranged from 28.6+/-1.9 IENF/mm at the trunk to 15.5+/-1.5 at the distal leg. In a group of six patients with painful sensory neuropathy, we confirmed a length-dependent reduction in IENF. We observed what may be a predegenerative change, namely increased branching of epidermal nerve fibers at clinically unaffected sites. These data suggest little age-related change in IENF, at least up to age 75 years, in healthy normals. The increased branching complexity noted in unaffected sites in patients with sensory neuropathies implies that this may be a predegenerative change, preceding the actual loss of nerve fibers. Skin biopsy may be a useful tool for assessing the topographic extent and degree of nerve fiber damage in sensory neuropathies and its quantitative interpretation should be little affected by aging changes.     

卒中类型、卒中部位与卒中后癫痫的多因素关系

目的探讨卒中类型、卒中部位与卒中后癫痫的多因素关系,为卒中后癫痫的防治提供参考。方法以1804例卒中患者为研究对象,收集其性别、年龄、卒中类型、卒中部位、卒中后癫痫发生的时间等资料,根据卒中后是否发生癫痫,将患者分为卒中后无癫痫组(n=1487)和卒中后癫痫组(n=317),分析卒中后癫痫发作的危险因素。结果共317例卒中后癫痫发作患者,其中早发性癫痫141例(44.48%),迟发性癫痫176例(55.52%)。不同卒中部位及卒中类型的癫痫发病率为17.57%。多因素logistic回归分析显示,卒中部位中的顶叶合并蛛网膜下腔、额叶合并颞叶、额叶合并颞叶和枕叶、单一颞叶是卒中后发生癫痫的危险因素(P<0.01),其中单一颞叶是卒中后早发性癫痫的危险因素(P<0.01)。脑梗死患者常见早发性癫痫(23.66%),脑出血患者常见迟发性癫痫(47.95%)。结论卒中类型中的脑梗死、脑出血、蛛网膜下腔出血与卒中后癫痫有关;卒中部位中顶叶合并蛛网膜下腔、额叶合并颞叶、额叶合并颞叶和枕叶、单一颞叶与卒中后癫痫有关。