Mechanism of the medium‐duration afterhyperpolarization in rat serotonergic neurons

Most serotonergic neurons display a prominent medium‐duration afterhyperpolarization (mAHP), which is mediated by small‐conductance Ca²⁺‐activated K⁺ (SK) channels. Recent ex vivo and in vivo experiments have suggested that SK channel blockade increases the firing rate and/or bursting in these neurons. The purpose of this study was therefore to characterize the source of Ca²⁺ which activates the mAHP channels in serotonergic neurons. In voltage‐clamp experiments, an outward current was recorded at ?60 mV after a depolarizing pulse to +100 mV. A supramaximal concentration of the SK channel blockers apamin or (‐)‐bicuculline methiodide blocked this outward current. This current was also sensitive to the broad Ca²⁺ channel blocker Co²⁺ and was partially blocked by both ω‐conotoxin and mibefradil, which are blockers of N‐type and T‐type Ca²⁺ channels, respectively. Neither blockers of other voltage‐gated Ca²⁺ channels nor DBHQ, an inhibitor of Ca²⁺‐induced Ca²⁺ release, had any effect on the SK current. In current‐clamp experiments, mAHPs following action potentials were only blocked by ω‐conotoxin and were unaffected by mibefradil. This was observed in slices from both juvenile and adult rats. Finally, when these neurons were induced to fire in an in vivo‐like pacemaker rate, only ω‐conotoxin was able to increase their firing rate (by ~30%), an effect identical to the one previously reported for apamin. Our results demonstrate that N‐type Ca²⁺ channels are the only source of Ca²⁺ which activates the SK channels underlying the mAHP. T‐type Ca²⁺ channels may also activate SK channels under different circumstances.     

Regionally selective atrophy of subcortical structures in prodromal HD as revealed by statistical shape analysis

Huntington disease (HD) is a neurodegenerative disorder that involves preferential atrophy in the striatal complex and related subcortical nuclei. In this article, which is based on a dataset extracted from the PREDICT‐HD study, we use statistical shape analysis with deformation markers obtained through “Large Deformation Diffeomorphic Metric Mapping” of cortical surfaces to highlight specific atrophy patterns in the caudate, putamen, and globus pallidus, at different prodromal stages of the disease. On the basis of the relation to cortico‐basal ganglia circuitry, we propose that statistical shape analysis, along with other structural and functional imaging studies, may help expand our understanding of the brain circuitry affected and other aspects of the neurobiology of HD, and also guide the most effective strategies for intervention. Hum Brain Mapp 35:792–809, 2014. © 2012 Wiley Periodicals, Inc.     

How do we process event‐based and time‐based intentions in the brain? an fMRI study of prospective memory in healthy individuals

Prospective memory (PM) refers to the ability to remember to do something in the future, either in response to an event (event‐based) or after a certain amount of time has elapsed (time‐based). While the distinction between event‐ and time‐based PM is widely acknowledged in the literature, little is known about the processes they share and those they do not. This is particularly true concerning their brain substrates, as almost all neuroimaging studies so far have focused on event‐based PM. We proposed a functional magnetic resonance imaging paradigm assessing both event‐based and time‐based PM to 20 healthy young individuals. Analyses revealed that event‐ and time‐based PM both induced activation in the posterior frontal and parietal cortices, and deactivation in the medial rostral prefrontal cortex. In addition, activation more specific to each condition, which may underlie differences in strategic monitoring, was highlighted. Thus, occipital areas were more activated during event‐based PM, probably reflecting target‐checking, while a network comprising the dorsolateral prefrontal cortex, the cuneus/precuneus and, to a lesser extent, the inferior parietal lobule, superior temporal gyrus, and the cerebellum, was more activated in time‐based PM, which may reflect the involvement of time‐estimation processes. These results confirm the allocation of attentional resources to the maintenance of intention for event‐based and time‐based PM, as well as the engagement of distinct mechanisms reflecting the monitoring strategies specific to each condition. Hum Brain Mapp 35:3066–3082, 2014. © 2013 Wiley Periodicals, Inc.     

Brain networks disconnection in early multiple sclerosis cognitive deficits: An anatomofunctional study

Severe cognitive impairment involving multiple cognitive domains can occur early during the course of multiple sclerosis (MS). We investigated resting state functional connectivity changes in large‐scale brain networks and related structural damage underlying cognitive dysfunction in patients with early MS. Patients with relapsing MS (3–5 years disease duration) were prospectively assigned to two groups based on a standardized neuropsychological evaluation: (1) cognitively impaired group (CI group, n = 15), with abnormal performances in at least 3 tests; (2) cognitively preserved group (CP group, n = 20) with normal performances in all tests. Patients and age‐matched healthy controls underwent a multimodal 3T magnetic resonance imaging (MRI) including anatomical T1 and T2 images, diffusion imaging and resting state functional MRI. Structural MRI analysis revealed that CI patients had a higher white matter lesion load compared to CP and a more severe atrophy in gray matter regions highly connected to networks involved in cognition. Functional connectivity measured by integration was increased in CP patients versus controls in attentional networks (ATT), while integration was decreased in CI patients compared to CP both in the default mode network (DMN) and ATT. An anatomofunctional study within the DMN revealed that functional connectivity was mostly altered between the medial prefrontal cortex (MPFC) and the posterior cingulate cortex (PCC) in CI patients compared to CP and controls. In a multilinear regression model, functional correlation between MPFC and PCC was best predicted by PCC atrophy. Disconnection in the DMN and ATT networks may deprive the brain of compensatory mechanisms required to face widespread structural damage. Hum Brain Mapp 35:4706–4717, 2014. © 2014 Wiley Periodicals, Inc .     

Aneurysmal remodeling in the circle of Willis after carotid occlusion in an experimental model

Carotid occlusions are associated with de novo intracranial aneurysm formation in clinical case reports, but this phenomenon is not widely studied. We performed bilateral carotid ligation (n=9) in rabbits to simulate carotid occlusion, and sham surgery (n=3) for control. Upon euthanasia (n=3 at 5 days, n=6 at 6 months post ligation, and n=3 at 5 days after sham operation), vascular corrosion casts of the circle of Willis (CoW) were created. Using scanning electron microscopy, we quantified gross morphologic, macroscopic, and microscopic changes on the endocasts and compared findings with histologic data. At 5 days, CoW arteries of ligated animals increased caliber. The posterior communicating artery (PCom) increased length and tortuosity, and the ophthalmic artery (OA) origin presented preaneurysmal bulges. At 6 months, calibers were unchanged from 5 days, PComs further increased tortuosity while presenting segmental dilations, and the OA origin and basilar terminus presented preaneurysmal bulges. This exploratory study provides evidence that flow increase after carotid occlusion produces both compensatory arterial augmentation and pathologic remodeling such as tortuosity and saccular/fusiform aneurysm. Our findings may have considerable clinical implications, as these lesser-known consequences should be considered when managing patients with carotid artery disease or choosing carotid ligation as a therapeutic option.     

Unusual features of Creutzfeldt–Jakob disease followed-up in a memory clinic

Sporadic Creutzfeldt–Jakob disease (sCJD) generally manifests itself by cognitive or rapidly progressive motor symptoms. An atypical onset or an unusual evolution may delay the diagnosis. Among patients with a confirmed diagnosis of sCJD following a post-mortem neuropathological examination at the Neuropathology Centre of Lille, France, those who had presented with atypical cognitive disorders at onset were included in the study. Four patients were included. The first patient (64-years-old) presented early language disorders, later accompanied by apathy and behavioral disorders. The prolonged course suggested a diagnosis of progressive primary aphasia. The second patient (68-years-old) presented with aphasia, apraxia, and ataxia of the right upper limb with parkinsonian syndrome, suggesting corticobasal degeneration. In the two last patients (58- and 61-years-old), the onset was marked by an anxiety–depression syndrome, falls, visual hallucinations, extra-pyramidal syndrome, and fluctuating cognitive decline. The diagnosis raised was probable Lewy body dementia. The 14.3.3 protein was found in two of the four cases. The clinical elements found may initially suggest focal atrophy or Lewy body dementia. A very rapid clinical deterioration generally suggests sCJD, but in the last case, the evolution was particularly slow. The diagnosis of sCJD must be considered in cases of rapid-onset dementia, even if all of the clinical criteria are not present. The detection of the 14.3.3 protein and multifold increase in total-Tau with normal or slightly increased phosphorylated-Tau in the CSF are additional arguments to reinforce the diagnosis. The post-mortem neuropathological examination is important to confirm the diagnosis.     

The efficiency of glutamate uptake differs between neonatal and adult cortical microvascular endothelial cells

Glutamate transporters (excitatory amino-acid transporters (EAATs)) are essential for brain homeostasis. While previous studies indicate that the vascular endothelium contributes to glutamate efflux in the adult brain, little information is available regarding glutamate uptake in the immature brain. The present study shows a differential expression pattern of EAATs between cortical microvessels in adults and newborns. In addition, adult cortical endothelial cells take up glutamate more efficiently than neonatal cells. Our findings indicate age-specific changes in extracellular glutamate regulation by brain endothelial cells, suggesting differences in the efficiency of glutamate efflux during an excitotoxic process that, in turn, may contribute to age-specific brain vulnerability.     

Multiple bowel perforation and necrotising fasciitis secondary to abdominal liposuction in a patient with bilateral lumbar hernia

We present a rare complication of abdominal liposuction: bowel perforation and necrotizing fasciitis. Because of bilateral lumbar hernia, a 56-year-old woman had caecum and descending colon perforation during lipoplasty. She had septic shock syndrome at her admission. The authors treated this complex wound with several debridement, omental flap, NPWT and split-thickness skin graft. The incidence of abdominal wall perforation with visceral injury is 14 in 100,000 liposuctions performed. There are only 12 cases of bowel perforation in literature but this complication is probably underestimated. Prompt surgical debridement is absolutely mandatory in this life threatening scenario. Lumbar hernia is very rare and should be ruled out before every abdominal liposuction clinically or with imaging modalities.KEY WORDS: Bowel perforation, liposuction, lumbar hernia, necrotizing fasciitis, negative pressure large wound therapy