Simvastatin Prevents Long-Term Cognitive Deficits in Sepsis Survivor Rats by Reducing Neuroinflammation and Neurodegeneration

Abstract We previously showed that developmental 3,4-methylenedioxymethamphetamine (MDMA) treatment induces long-term spatial and egocentric learning and memory deficits and serotonin (5-HT) reductions. During brain development, 5-HT is a neurotrophic factor influencing neurogenesis, synaptogenesis, migration, and target field organization. MDMA (10 mg/kg × 4/d at 2 h intervals) given on post-natal day (PD) 11–20 in rats (a period of limbic system development that approximates human third trimester brain development) induces 50% reductions in 5-HT during treatment and 20% reductions when assessed as adults. To determine whether the 5-HT reduction is responsible for the cognitive deficits, we used citalopram (Cit) pretreatment to inhibit the effects of MDMA on 5-HT reuptake in a companion study. Cit attenuated MDMA-induced 5-HT reductions by 50% (Schaefer et al., 2012). Here we tested whether Cit (5 or 7.5 mg/kg × 2/d) pretreatment attenuates the cognitive effects of MDMA. Within each litter, different offspring were treated on PD11–20 with saline (Sal) + MDMA, Cit + MDMA, Cit + Sal or Sal + Sal. Neither spatial nor egocentric learning/memory was improved by Cit pretreatment. Unexpectedly, Cit + Sal (at both doses) produced spatial and egocentric learning deficits as severe as those caused by Sal + MDMA. These are the first data showing cognitive deficits resulting from developmental exposure to a selective serotonin reuptake inhibitor. These data indicate the need for further research on the long-term safety of antidepressants during pregnancy.

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Maternal Overnutrition Induces Long-Term Cognitive Deficits across Several Generations

Nutrients ◽

10.3390/nu11010007 ◽

2018 ◽

Vol 11 (1) ◽

pp. 7 ◽

Cited By ~ 8

Author(s):

Gitalee Sarker ◽

Daria Peleg-Raibstein

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Cognitive Deficits ◽

Maternal Obesity ◽

Cognitive Impairments ◽

Long Term Effects ◽

Ample Evidence ◽

Increased Risk ◽

Maternal Overnutrition

Ample evidence from epidemiological studies has linked maternal obesity with metabolic disorders such as obesity, cardiovascular disease, and diabetes in the next generation. Recently, it was also shown that maternal obesity has long-term effects on the progeny’s central nervous system. However, very little is known regarding how maternal overnutrition may affect, in particular, the cognitive abilities of the offspring. We reported that first-generation offspring exposed to a maternal high-fat diet (MHFD) displayed age-dependent cognitive deficits. These deficits were associated with attenuations of amino acid levels in the medial prefrontal cortex and the hippocampus regions of MHFD offspring. Here, we tested the hypothesis that MHFD in mice may induce long-term cognitive impairments and neurochemical dysfunctions in the second and third generations. We found that MHFD led to cognitive disabilities and an altered response to a noncompetitive receptor antagonist of the N-Methyl-D-aspartic acid (NMDA) receptor in adult MHFD offspring in both second and third generations in a sex-specific manner. Our results suggest that maternal overnutrition leads to an increased risk of developing obesity in subsequent generations as well as to cognitive impairments, affecting learning and memory processes in adulthood. Furthermore, MHFD exposure may facilitate pathological brain aging which is not a consequence of obesity. Our findings shed light on the long-term effects of maternal overnutrition on the development of the central nervous system and the underlying mechanisms which these traits relate to disease predisposition.

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Incidence of Delirium in Hospitalized Children with Cancer

Journal of Pediatrics & Neonatal Biology ◽

10.33140/jpnb.04.02.07 ◽

2019 ◽

Vol 4 (2) ◽

Keyword(s):

Cognitive Deficits ◽

Pediatric Intensive Care ◽

Limited Data ◽

Statistical Manual ◽

Diagnostic And Statistical Manual ◽

Dsm V ◽

Increased Risk ◽

Short Period ◽

Fluctuating Course

Delirium is defined in the Diagnostic and Statistical Manual of Mental Disorders: Fifth edition (DSM-V) as a “disturbance and change in attention and awareness from baseline that develops over a short period of time, with fluctuating course” [1]. Delirium occurs as a result of factors related to primary illness, the treatment of that illness, and stressful and disorientating environment of the hospital [2]. There are limited data to describe the incidence of delirium in children hospitalized with cancer [3]. Delirium occurs frequently in adults and is an independent predictor of mortality, increased length of stay, and increased risk for long-term cognitive deficits [3]. The prevalence of delirium in hospitalized adults ages 18-56 with cancer ranges from 18%-44% [4]. Most pediatric studies on delirium focus on the critically ill child in the pediatric intensive care unit (PICU). It is estimated that the incidence of delirium in this population is as high as 29% [5].

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A-158 Case Study: Cognitive Deficits Associated with Postoperative Intracranial Hemorrhage Following Meningioma Resection

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acab062.176 ◽

2021 ◽

Vol 36 (6) ◽

pp. 1212-1212

Author(s):

Khushnoo K Indorewalla ◽

Richard Phenis

Keyword(s):

Intracranial Hemorrhage ◽

Cognitive Deficits ◽

Vision Loss ◽

Tumor Resection ◽

Inpatient Rehabilitation ◽

Neuropsychological Deficits ◽

Resection Cavity ◽

Neurocognitive Profile

Abstract Objective Postoperative intracranial hemorrhages (PIH) are an infrequent complication following cranial tumor resection and associated with prolonged hospitalization as well as long-term neurologic deficits. There is limited research examining the neuropsychological deficits resulting from PIH following meningioma resection, especially with neuropsychological data. Here, we present the neurocognitive profile of a patient who underwent a meningioma resection surgery and subsequently suffered a PIH within the resection cavity. Method Mr. Doe is a bilingual male in his late 40s who developed right-side vision loss and an isolated incidence of disorientation, resulting in discovery of a left anterior clinoid meningioma. He underwent a left frontotemporal craniotomy for gross total resection of the mass a month after discovery. Postoperative neuroimaging the following day revealed the appearance of a hematoma and intracranial hemorrhage within the resection cavity, resulting in right hemiplegia, aphasia, and ophthalmoplegia. He underwent neuropsychological evaluation 15 months post-resection, to assess residual cognitive deficits following his hospitalization and subsequent inpatient rehabilitation. Results In the context of average premorbid intellectual functioning, Mr. Doe’s neurocognitive profile was notable for deficits in processing speed, receptive and expressive language, and executive functioning associated with speed/verbally mediated tasks. Testing revealed lateralized deficits indicative of left (language-dominant) hemisphere dysfunction secondary to meningioma resection and subsequent PIH within the resection cavity. Conclusion The current poster aims to contribute to the limited body of literature examining residual neuropsychological deficits resulting from PIH following intracranial resection of meningioma. This is especially crucial given that long-term cognitive deficits can negatively impact patients’ quality of life over time.

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The Hyperfocusing Hypothesis: A New Account of Cognitive Dysfunction in Schizophrenia

Schizophrenia Bulletin ◽

10.1093/schbul/sbz063 ◽

2019 ◽

Vol 45 (5) ◽

pp. 991-1000 ◽

Cited By ~ 6

Author(s):

Steven J Luck ◽

Britta Hahn ◽

Carly J Leonard ◽

James M Gold

Keyword(s):

Working Memory ◽

Cognitive Processes ◽

Cognitive Deficits ◽

Term Outcome ◽

Long Term Outcome ◽

Good Target ◽

Processing Resources ◽

Nonspecific Factors ◽

New Treatments

Abstract Impairments in basic cognitive processes such as attention and working memory are commonly observed in people with schizophrenia and are predictive of long-term outcome. In this review, we describe a new theory—the hyperfocusing hypothesis—which provides a unified account of many aspects of impaired cognition in schizophrenia. This hypothesis proposes that schizophrenia involves an abnormally narrow but intense focusing of processing resources. This hyperfocusing impairs the ability of people with schizophrenia to distribute attention among multiple locations, decreases the number of representations that can simultaneously be maintained in working memory, and causes attention to be abnormally captured by irrelevant inputs that share features with active representations. Evidence supporting the hyperfocusing hypothesis comes from a variety of laboratory tasks and from both behavioral and electrophysiological measures of processing. In many of these tasks, people with schizophrenia exhibit supranormal effects of task manipulations, which cannot be explained by a generalized cognitive deficit or by nonspecific factors such as reduced motivation or poor task comprehension. In addition, the degree of hyperfocusing in these tasks is often correlated with the degree of impairment in measures of broad cognitive function, which are known to be related to long-term outcome. Thus, the mechanisms underlying hyperfocusing may be a good target for new treatments targeting cognitive deficits in schizophrenia.

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Deficits in motor and cognitive functions in an adult mouse model of hypoxia-ischemia induced stroke

Scientific Reports ◽

10.1038/s41598-020-77678-8 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Li Feng ◽

Chun-Xia Han ◽

Shu-Yu Cao ◽

He-Ming Zhang ◽

Gang-Yi Wu

Keyword(s):

Cognitive Deficits ◽

Neuronal Loss ◽

Behavioral Changes ◽

Morris Water Maze Test ◽

Functional Deficits ◽

Stroke Research ◽

Ipsilateral Striatum ◽

Histological Data ◽

The Right

AbstractIschemic strokes cause devastating brain damage and functional deficits with few treatments available. Previous studies have shown that the ischemia-hypoxia rapidly induces clinically similar thrombosis and neuronal loss, but any resulting behavioral changes are largely unknown. The goal of this study was to evaluate motor and cognitive deficits in adult HI mice. Following a previously established procedure, HI mouse models were induced by first ligating the right common carotid artery and followed by hypoxia. Histological data showed significant long-term neuronal losses and reactive glial cells in the ipsilateral striatum and hippocampus of the HI mice. Whereas the open field test and the rotarod test could not reliably distinguish between the sham and HI mice, in the tapered beam and wire-hanging tests, the HI mice showed short-term and long-term deficits, as evidenced by the increased number of foot faults and decreased hanging time respectively. In cognitive tests, the HI mice swam longer distances and needed more time to find the platform in the Morris water maze test and showed shorter freezing time in fear contextual tests after fear training. In conclusion, this study demonstrates that adult HI mice have motor and cognitive deficits and could be useful models for preclinical stroke research.

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