Documented growth of an intracranial capillary hemangioma: A case report.

Intracranial capillary hemangiomas in adults are rare, and diagnosis can be challenging. Hemangiomas, in general (and particularly in the skin), are more often noted in the pediatric population. Due to the lack of imaging undertaken in the presymptomatic phase, the literature provides few clues on the rate of growth of these unusual tumors. Therefore, we report a case of a 64-year-old man with a medical history of Lyme disease who presented with exhaustion and confusion. Imaging demonstrated an intra-axial lesion with vascularity in the posterior right temporal lobe, raising the possibility of a glioma. Imaging two years prior revealed a very small lesion in the same location. The patient underwent a craniectomy, total resection of the lesion was completed, and his symptoms of confusion resolved. Biopsy revealed a capillary hemangioma composed of small vascular channels lined by endothelial cells and pericytes without smooth muscle. Features of glioma, vascular neoplasms or neuroborreliosis (cerebral Lyme disease) were not identified. Our case documents the growth over two years of a rare intracranial capillary hemangioma in an older adult male.

A single brief stressful event time-dependently affects object recognition memory and promotes familiarity preference in marmoset monkeys.

A stressful experience can enhance information storage and impair memory retrieval in the rodent novel object recognition (NOR) task. However, recent conflicting results underscore the need for further investigation. Nonhuman primates may provide a unique, underexplored and more translational means to investigate stress-mediated changes in memory. Therefore, we assessed whether a single brief extrinsic stress event affects information encoding, storage and/or retrieval in adult marmoset monkeys submitted to the NOR task. This consisted of an initial 10 min familiarization period with two identical neutral objects. After a 6 h delay, a 10 min test trial was held where a new and familiar object could be explored. Stress was induced by a 15 min restraint event held before or after the encoding phase, or prior to retrieval. Pre-encoding stress had no effect on task performance, as this group displayed above-chance novelty preference similar to non-stressed controls. Post-encoding stress induced memory deficits, with both objects being explored equally. Interestingly, pre-retrieval stress induced an above-chance familiarity preference. A single brief stressful event thus affects recognition memory in a time-dependent manner. Also, negative discrimination ratios can be used as a measure of memory in the NOR task and a change in strategy may not mean memory failure in spontaneous learning paradigms.

The spatial layout of doorways and environmental boundaries shape the content of event memories.

Physical boundaries in our environment have been observed to define separate events in episodic memory. To date, however, there is little evidence that the spatial properties of boundaries exert any control over event memories. To examine this possibility, we conducted four experiments that took manipulations involving boundaries that have been demonstrated to influence spatial representations, and adapted them for use in an episodic object memory paradigm. Here, participants were given 15 min to freely explore an environment that contained 36 objects, equally dispersed among six discriminable buildings. In a subsequent test of object-location binding, participants were required to indicate where they remembered encountering the objects. In Experiment 1 the spatial properties of the building boundaries were identical; however, in Experiment 2 the boundaries were differentiated by their geometric shape and the location of the doorways in the buildings. In the test phases of these experiments, we observed a shift from a bias towards remembering the positions of objects within a building but not the building itself (Experiment 1), to a bias towards remembering which building an object was in but not the location within the building (Experiment 2). In Experiment 3, the buildings shared the same geometry but were differentiated by the locations of doorways, and we observed no significant differences between response types. Finally, in Experiment 4, the buildings were uniquely shaped but shared the same doorway location, and we observed a bias towards remembering the positions of objects within a building. In addition, exploratory analyses of non-spatial interference revealed more correct recall for objects housed in the first building a participant visited during exploration, compared to all other buildings. Together, our data indicates that the location of doorways in boundaries and, to a lesser extent, boundary geometries influence event models, and that a primacy effect can be observed in the recall of multiple object-location bindings.

Perirhinal cortex and the recognition of relative familiarity.

Spontaneous object recognition (SOR) is a widely used task of recognition memory in rodents which relies on their propensity to explore novel (or relatively novel) objects. Network models typically define perirhinal cortex as a region required for recognition of previously seen objects largely based on findings that lesions or inactivations of this area produce SOR deficits. However, relatively little is understood about the relationship between the activity of cells in the perirhinal cortex that signal novelty and familiarity and the behavioural responses of animals in the SOR task. Previous studies have used objects that are either highly familiar or absolutely novel, but everyday memory is for objects that sit on a spectrum of familiarity which includes objects that have been seen only a few times, or objects that are similar to objects which have been previously experienced. We present two studies that explore cellular activity (through c-fos imaging) within perirhinal cortex of rats performing SOR where the familiarity of objects has been manipulated. Despite robust recognition memory performance, we show no significant changes in perirhinal activity related to the level of familiarity of the objects. Reasons for this lack of familiarity-related modulation in perirhinal cortex activity are discussed. The current findings support emerging evidence that perirhinal responses to novelty are complex and that task demands are critical to the involvement of perirhinal cortex in the control of object recognition memory.

Impaired episodic simulation in a patient with visual memory deficit amnesia.

For the first time, we assess episodic simulation in a patient with visual memory deficit amnesia, following damage to visual association cortices. Compared to control participants, the patient with visual memory deficit amnesia shows severely restricted responses when asked to simulate different types of future episodic scenarios. Surprisingly, the patient's responses are more limited in cases where the scenarios require less reliance on visual information. We explain this counterintuitive finding through discussing how the severe retrograde amnesia in visual memory deficit amnesia limits the patient's access to episodic memories in which vision has not been a focus of their life. As a result, we argue that the deficits in visual memory deficit amnesia continue to distinguish it from amnesia after direct damage to the hippocampus.

Acetylcholine and Spontaneous Recognition Memory in Rodents and Primates.

Whilst acetylcholine has long been linked to memory, there have been significant questions about its specific role. In particular, the effects of cholinergic manipulations in primates and rodents has often been at odds. Here, we review the work in primates and rodents on the specific function of acetylcholine in memory, and episodic memory in particular. We propose that patterns of impairment can best be understood in terms of a role for hippocampal acetylcholine in resolving spatial interference and we discuss the benefits of new tasks of episodic memory in animals allowing clearer translation of findings to the clinic.

Changes in presynaptic calcium signalling accompany age-related deficits in hippocampal LTP and cognitive impairment.

The loss of cognitive function accompanying healthy aging is not associated with extensive or characteristic patterns of cell death, suggesting it is caused by more subtle changes in synaptic properties. In the hippocampal CA1 region, long-term potentiation requires stronger stimulation for induction in aged rats and mice and long-term depression becomes more prevalent. An age-dependent impairment of postsynaptic calcium homeostasis may underpin these effects. We have examined changes in presynaptic calcium signalling in aged mice using a transgenic mouse line (SyG37) that expresses a genetically encoded calcium sensor in presynaptic terminals. SyG37 mice showed an age-dependent decline in cognitive abilities in behavioural tasks that require hippocampal processing including the Barnes maze, T-maze and object location but not recognition tests. The incidence of LTP was significantly impaired in animals over 18 months of age. These effects of aging were accompanied by a persistent increase in resting presynaptic calcium, an increase in the presynaptic calcium signal following Schaffer collateral fibre stimulation, an increase in postsynaptic fEPSP slope and a reduction in paired-pulse facilitation. These effects were not caused by synapse proliferation and were of presynaptic origin since they were evident in single presynaptic boutons. Aged synapses behaved like younger ones when the extracellular calcium concentration was reduced. Raising extracellular calcium had little effect on aged synapses but altered the properties of young synapses into those of their aged counterparts. These effects can be readily explained by an age-dependent change in the properties or numbers of presynaptic calcium channels.

Cerebral Vasculitis in Ulcerative Colitis Is Predominantly Venular: Case Report and Review of the Literature.

Extraintestinal complications of ulcerative colitis include isolated case reports of cerebral vasculitis. In this case report, we describe autopsy findings in a 50-year-old female who died as a result of massive multifocal cerebral hemorrhage. Microscopic examination of the left colon showed findings typical for ulcerative colitis. Examination of the brain showed an extensive vasculitis. More affected vessels were noted in grey matter than in white matter. Many showed fibrinoid necrosis, invasion by neutrophils and thrombosis. There was extensive perivascular hemorrhage with associated infarction. Vessel analysis shows most of the vessels to have been venous rather than arterial. There were no perivascular sleeves of demyelination to suggest a primary demyelinating disorder, such as acute hemorrhagic leucoencephalitis. Our analysis shows that veins are the likely target of cerebral vasculitis in ulcerative colitis. This has clinical implications because venous occlusion generally causes massive intracerebral hemorrhage with a high mortality.

The NMDA receptor antagonist MK-801 fails to impair long-term recognition memory in mice when the state-dependency of memory is controlled.

NMDA receptor-dependent synaptic plasticity has been proposed to be important for encoding of memories. Consistent with this hypothesis, the non-competitive NMDA receptor antagonist, MK-801, has been found to impair performance on tests of memory. Interpretation of some of these findings has, however, been complicated by the fact that the drug-state of animals has differed during encoding and tests of memory. Therefore, it is possible that MK-801 may result in state-dependent retrieval or expression of memory rather than actually impairing encoding itself. We tested this hypothesis in mice using tests of object recognition memory with a 24-hour delay between the encoding and test phase. Mice received injections of either vehicle or MK-801 prior to the encoding phase and the test phase. In Experiment 1, a low dose of MK-801 (0.01 mg/kg) impaired performance when the drug-state (vehicle or MK-801) of mice changed between encoding and test, but there was no significant effect of MK-801 on encoding. In Experiment 2, a higher dose of MK-801 (0.1 mg/kg) failed to impair object recognition memory when mice received the drug prior to both encoding and test compared to mice that received vehicle. MK-801 did not affect object exploration, but it did induce locomotor hyperactivity at the higher dose. These results suggest that some previous demonstrations of MK-801 effects may reflect a failure to express or retrieve memory due to the state-dependency of memory rather than impaired encoding of memory.

Walking through doorways differentially affects recall and familiarity.

Previous research has reported that walking through a doorway to a new location makes memory for objects and events experienced in the previous location less accurate. This effect, termed the location updating effect, has been used to suggest that location changes are used to mark boundaries between events in memory: memories for objects encountered within the current event are more available than those from beyond an event boundary. Within a computer-generated memory task, participants navigated through virtual rooms, walking through doorways, and interacting with objects. The accuracy and their subjective experience of their memory for the objects (remember/know and confidence) were assessed. The findings showed that shifts in location decreased accurate responses associated with the subjective experience of remembering but not those associated with the experience of knowing, even when considering only the most confident responses in each condition. These findings demonstrate that a shift in location selectively impacts recollection and so contributes to our understanding of boundaries in event memory.

Continual Trials Spontaneous Recognition Tasks in Mice: Reducing Animal Numbers and Improving Our Understanding of the Mechanisms Underlying Memory.

Spontaneous recognition tasks are widely used as a laboratory measure of memory in animals but give rise to high levels of behavioral noise leading to a lack of reliability. Previous work has shown that a modification of the procedure to allow continual trials testing (in which many trials are run concurrently in a single session) decreases behavioral noise and thus significantly reduces the numbers of rats required to retain statistical power. Here, we demonstrate for the first time that this improved method of testing extends to mice, increasing the overall power of the approach. Moreover, our results show that the new continual trials approach provides the additional benefits of heightened sensitivity and thus provides greater insight into the mechanisms at play. Standard (c57) and transgenic Alzheimer model (TASTPM) mice were tested both at 7 and 10 months of age in both object recognition (OR) and object-location (OL) spontaneous recognition tasks using the continual trials methodology. Both c57 and TASTPM mice showed age-dependent changes in performance in OR. While c57 mice also showed age-related changes in performance of OL, TASTPM mice were unable to perform OL at either age. Significantly, we demonstrate that differences in OL performance in c57s and TASTPM animals is a result of proactive interference rather than an absolute inability to recognize OL combinations. We argue that these continual trials approaches provide overall improved reliability and better interpretation of the memory ability of mice, as well as providing a significant reduction in overall animal use.

Evidence for Cholinergic Dysfunction in Autosomal Dominant Kufs Disease.

OBJECTIVE: Neuronal ceroid-lipofuscinoses are a heterogeneous group of inherited disorders in which abnormal lipopigments form lysosomal inclusion bodies in neurons. Kufs disease is rare, and clinical symptoms include seizures, progressive cognitive impairment, and myoclonus. Most cases of Kufs disease are autosomal recessive; however, there have been a few case reports of an autosomal dominant form linked to mutations within the DNAJC5 gene. METHODS: We describe a family with Kufs disease in which the proband and three of her four children presented with cognitive impairment, seizures, and myoclonus. RESULTS: Genetic testing of all four children was positive for a c.346_348delCTC(p.L116del) mutation in the DNAJC5 gene. The proband brain had an abundance of neuronal lipofuscin in the cerebral cortex, striatum, amygdala, hippocampus, substantia nigra, and cerebellum. There were no amyloid plaques or neurofibrillary tangles. Immunohistochemistry demonstrated that the cholinergic neurons and cholinergic projection fibers were spared, but there was a profound loss of choline acetyltransferase within the caudate, putamen, and basal forebrain. This suggests a loss of choline acetyltransferase as opposed to a loss of the neurons. CONCLUSIONS: This report describes the clinical history of autosomal dominant Kufs disease, the genetic mutation within the DNAJC5 gene, and the neuropathological findings demonstrating depletion of choline acetyltransferase in the brain.

Surfen, a proteoglycan binding agent, reduces inflammation but inhibits remyelination in murine models of Multiple Sclerosis.

Proteoglycans are promising therapeutic targets in Multiple Sclerosis (MS), because they regulate many aspects of the immune response. This was studied using surfen, an agent that binds both heparan sulphate proteoglycans (HSPGs) and chondroitin sulphate proteoglycans (CSPGs). Initial cell culture work on bone marrow derived macrophages (BMDMs) found that surfen reduced concentrations of the chemokines CCL2, CCL4 and CCL5, with reduced messenger (m)RNA expression for Tumor Necrosis Factor, IL-6, IL-1ß and inducible nitric oxide synthase. These data were further explored using Experimental Autoimmune Encephalomyelitis (EAE) in mice. Surfen reduced clinical signs during EAE when administered from disease onset, and reduced infiltration by CD4 positive T cells and macrophages into the central nervous system. These mice also showed reduced mRNA expression for the chemokines CCL3 and CCL5, with reduced concentrations of CCL2, CCL3 and CCL5. During EAE, surfen treatment induced a persistent increase in Interleukin (IL)-4 concentrations which may enhance T helper 2 responses. During EAE, surfen treatment reduced mRNA expression for HSPGs (NDST1, agrin, syndecan-4, perlecan, serglycin, syndecan-1) and the CSPG versican. By contrast, surfen increased mRNA expression for the CSPG aggrecan, with no effect on neurocan. During EAE, significant positive correlations were found between mRNA expression and clinical score for syndecan-4, serglycin and syndecan-1 and a significant negative correlation for aggrecan. These correlations were absent in surfen treated mice. Repair in the later stages of MS involves remyelination, which was modeled by injecting lysolecithin (lysophosphatidylcholine, LPC) into mouse corpus callosum to create regions of demyelination. When surfen was injected 2 days after LPC, it delayed remyelination of the lesions, but had no effect when injected 7 days after LPC. The delayed remyelination was associated with local increases in CSPG expression. Therefore surfen suppresses inflammation but inhibits remyelination in these models. A mechanism in common may be increased CSPG expression.

Incidental context information increases recollection.

The current study describes a receiver-operating characteristic (ROC) task for human participants based on the spontaneous recognition memory paradigms typically used with rodents. Recollection was significantly higher when an object was in the same location and background as at encoding, a combination used to assess episodic-like memory in animals, but not when only one of these task-irrelevant cues was present. The results show that incidentally encoded cue information can determine the degree of recollection, and opens up the possibility of assessing recollection across species in a single experimental paradigm, allowing better understanding of the cognitive and biological mechanisms at play.

Human Brain Chemokine and Cytokine Expression in Sepsis: A Report of Three Cases.

BACKGROUND: Sepsis is a systemic response to infection that can affect brain function by inducing resident cells (including astrocytes and microglia) to generate brain chemokines and cytokines. However, there are few studies on the human brain. Since this information may shed further light on pathogenesis, our study objective was to measure the expression of 36 chemokines and cytokines in autopsied brain from 3 cases of sepsis and 10 controls, and to relate this to astrocyte and microglial activation. METHODS: The right frontal pole was removed at autopsy and chemokine and cytokine expression measured by multiplexed enzyme-linked immunosorbent assay and real-time quantitative polymerase chain reaction (qPCR). Immunohistochemistry and image analysis were carried out to determine the expression of glial fibrillary acidic protein (GFAP), a marker of activated astrocytes, and CD68 and CD45, markers of activated microglial cells. RESULTS: Concentrations of the chemokines CXCL8, CXCL10, CXCL12, CCL13 and CCL22 were increased in pooled data from the three cases of sepsis (p<0.05); however, their messenger RNA (mRNA) expression was unaltered. CXCL13, CXCL1, CXCL2, CCL1, CCL2, CCL8, CCL20, (interleukin) IL-16, IL-1ß and (tumour necrosis factor) TNF concentrations showed increases in two of three sepsis cases. Additionally, individual sepsis cases showed increases in mRNA expression for HDAC (histone deacetylase) 6 and EIF (eukaryotic translation initiation factor) 4A2. Brain GFAP expression was significantly increased (p<0.05) in pooled data from the three sepsis cases. Individual sepsis cases showed increases in CD68 or CD45 expression. CONCLUSIONS: These expression patterns add to our understanding of the pathogenesis of sepsis and its effects on the brain.