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Vision specialists will benefit from increased awareness of posterior cortical atrophy (PCA) syndrome. Failure to adequately identify the chief complaint as a visual symptom may lead to incorrect diagnosis or diagnostic delay. A previously healthy, 59-year-old woman presented with a 5-year history of 'losing her stuff'. Upon psychiatric and neuro-ophthalmological evaluation, this symptom was better recognised as a feature of visual agnosia and simultanagnosia. She also presented with multiple previously unrecognised symptoms indicative of higher visual processing dysfunction, such as alexia without agraphia, ocular motor apraxia, optic ataxia, prosopagnosia, akinetopsia and topographagnosia, so further assessment to investigate for PCA was carried out. After a work-up including cognitive assessment, brain structural/functional imaging, and laboratory tests she was diagnosed with visual-variant Alzheimer's disease. Patients with PCA merit a detailed review of their symptoms, as well as the use of office tests such as cognitive evaluation tools, different types of perimetry, colour vision tests, and non-delayed psychiatric consultation for correct management and assessment. This report will emphasise five key aspects to be considered when evaluating patients with PCA.
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SUMMARY STATEMENT: In utero exposure to ZIKV leads to decreased number of neurons in adult mice. Female mice exposed to ZIKV in utero exhibit lower levels of BDNF, a decrease in synaptic markers, memory deficits, and risk-taking behavior during adulthood.
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Infecção por Zika virus , Zika virus , Animais , Feminino , Masculino , Transtornos da Memória/etiologia , Camundongos , Neurônios , Infecção por Zika virus/complicaçõesRESUMO
Sports-related concussions are particularly common during adolescence, and there is insufficient knowledge about how recurrent concussions in this phase of life alter the metabolism of essential structures for memory in adulthood. In this sense, our experimental data revealed that seven recurrent concussions (RC) in 35-day-old rats decreased short-term and long-term memory in the object recognition test (ORT) 30 days after injury. The RC protocol did not alter motor and anxious behavior and the immunoreactivity of brain-derived neurotrophic factor (BDNF) in the cerebral cortex. Recurrent concussions induced the inflammatory/oxidative stress characterized here by increased glial fibrillary acidic protein (GFAP), interleukin 1ß (IL 1ß), 4-hydroxynonenal (4 HNE), protein carbonyl immunoreactivity, and 2',7'-dichlorofluorescein diacetate oxidation (DCFH) levels and lower total antioxidant capacity (TAC). Inhibited Na+,K+-ATPase activity (specifically isoform α2/3) followed by Km (Michaelis-Menten constant) for increased ATP levels and decreased immunodetection of alpha subunit of this enzyme, suggesting that cognitive impairment after RC is caused by the inability of surviving neurons to maintain ionic gradients in selected targets to inflammatory/oxidative damage, such as Na,K-ATPase activity.
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Concussão Encefálica , Disfunção Cognitiva , Hipocampo , Transtornos da Memória , Doenças Neuroinflamatórias , Estresse Oxidativo/fisiologia , ATPase Trocadora de Sódio-Potássio/metabolismo , Memória Espacial/fisiologia , Fatores Etários , Animais , Concussão Encefálica/complicações , Concussão Encefálica/imunologia , Concussão Encefálica/metabolismo , Concussão Encefálica/fisiopatologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/imunologia , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/fisiopatologia , Modelos Animais de Doenças , Hipocampo/imunologia , Hipocampo/metabolismo , Hipocampo/fisiopatologia , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/imunologia , Transtornos da Memória/metabolismo , Transtornos da Memória/fisiopatologia , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/metabolismo , Doenças Neuroinflamatórias/fisiopatologia , Ratos , Ratos WistarRESUMO
OBJECTIVE: We investigated the influence of dietary omega-3 polyunsaturated fatty acids (n-3 PUFAs) on glutamatergic system modulation after a single episode of neonatal seizures and their possible effects on seizure-induced long-lasting behavioral deficits. METHODS: Male Wistar rats receiving an omega-3 diet (n-3) or an n-3 deficient diet (D) from the prenatal period were subjected to a kainate-induced seizure model at P7. Glutamate transporter activity and immunocontents (GLT-1 and GLAST) were assessed in the hippocampus at 12, 24, and 48 h after the seizure episode. Fluorescence intensity for glial cells (GFAP) and neurons (NeuN) was assessed 24â h after seizure in the hippocampus. Behavioral analysis (elevated-plus maze and inhibitory avoidance memory task) was performed at 60 days of age. RESULTS: The D group showed a decrease in glutamate uptake 24â h after seizure. In this group only, the GLT1 content increased at 12â h, followed by a decrease at 24â h. GLAST increased up to 24â h after seizure. GFAP fluorescence was higher, and NeuN fluorescence decreased, in the D group independent of seizures. In adulthood, the D group presented memory deficits independent of seizures, but short-term memory (1.5â h after a training session) was abolished in the D group treated with kainate. SIGNIFICANCE: N-3 PUFA positively influenced the glutamatergic system during seizure and prevented seizure-related memory deficits in adulthood.
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Epilepsia , Ácidos Graxos Ômega-3 , Animais , Dieta , Ácidos Graxos Ômega-3/efeitos adversos , Feminino , Ácido Glutâmico , Hipocampo , Ácido Caínico , Masculino , Transtornos da Memória/prevenção & controle , Gravidez , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/prevenção & controleRESUMO
Aging is associated both with an increase in memory loss and with comorbidities such as Osteoporosis, which could be causatively linked. In the present study, a deleterious effect on bone is demonstrated for the first time in a model of aged rats with impaired memory. We show that bone marrow progenitor cells obtained from rats with memory deficit have a decrease in their osteogenic capacity, and an increase both in their osteoclastogenic profile and adipogenic capacity, when compared to aged rats with preserved memory. Rats with impaired (versus preserved) memory also show alterations in long-bone micro-architecture (decreased trabecular bone and osteocyte density, increased TRAP-positive osteoclasts), lower bone quality (decreased trabecular bone mineral content and density) and an increase in bone marrow adiposity. Interestingly, the development of bone alterations and memory deficit in old rats is associated with significantly higher levels of serum oxidative stress (versus unaffected aged rats). In conclusion, we have found for the first time in an aged rat model, a relationship between alterations in bone quality and memory impairment, with increased systemic oxidative stress as a possible unifying mechanism.
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Disfunção Cognitiva , Osteoporose , Animais , Densidade Óssea , Disfunção Cognitiva/etiologia , Osteogênese , Estresse Oxidativo , RatosRESUMO
OBJECTIVE: We aimed to evaluate whether human immunodeficiency virus (HIV)-positive patients with and without clinically significant memory deficits and healthy control participants differ on in vivo hydrogen-1 magnetic resonance spectroscopy (H-MRS) in the posterior cingulate gyri. MATERIALS AND METHODS: In total, 21 HIV-positive patients with memory deficit (HIV+wMD) were compared with 15 HIV-positive patients without memory deficit (HIV+wOMD) and 22 sex-, age-, and education-matched control participants. Memory impairments were classified based on the participants' performance on the Rey Auditory Verbal Learning Test. Short echo time (30 ms), single-voxel H-MRS was performed using a 1.5-T magnetic resonance scanner. RESULTS: The HIV+wMD and HIV+wOMD groups had higher choline/creatine ratio in the posterior cingulate gyri than the control group. There were no significant metabolite ratio differences between the HIV+wMD and HIV+wOMD groups. CONCLUSION: HIV-positive patients with and without memory deficits had significantly higher choline/creatine ratios than controls in the posterior cingulate gyri, which may reflect cerebral inflammation, altered cell membrane metabolism, microgliosis, and/or astrocytosis.
OBJETIVO: Nós avaliamos se os pacientes HIV-positivos com e sem déficits de memória clinicamente significativos e controles saudáveis diferem na espectroscopia de prótons do giro do cíngulo posterior, por ressonância magnética (RM) cerebral. MATERIAIS E MÉTODOS: Vinte e um pacientes HIV-positivos com déficit de memória foram comparados com 15 pacientes HIV-positivos sem déficit de memória e 22 controles, pareados por sexo, idade e escolaridade. As deficiências de memória foram classificadas por meio do desempenho no Teste de Aprendizagem Auditivo-Verbal de Rey. A espectroscopia de prótons foi realizada com tempo de eco curto (30 ms), por voxel único, no giro do cíngulo posterior, utilizando aparelho de RM de 1,5 T. RESULTADOS: Os pacientes HIV-positivos com e sem déficit de memória apresentaram aumento da relação colina/creatina no giro do cíngulo posterior, comparados aos controles. Não houve diferenças significativas nas relações metabólicas no grupo HIV-positivo com déficit de memória, em relação ao grupo de pacientes HIV-positivo sem déficit. CONCLUSÃO: Pacientes HIV-positivos com e sem déficits de memória apresentaram relações colina/creatina significativamente aumentadas em relação aos controles, no giro do cíngulo posterior, o que pode refletir inflamação cerebral, alteração do metabolismo da membrana celular, microgliose e/ou astrocitose.
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Abstract Objective: We aimed to evaluate whether human immunodeficiency virus (HIV)-positive patients with and without clinically significant memory deficits and healthy control participants differ on in vivo hydrogen-1 magnetic resonance spectroscopy (H-MRS) in the posterior cingulate gyri. Materials and Methods: In total, 21 HIV-positive patients with memory deficit (HIV+wMD) were compared with 15 HIV-positive patients without memory deficit (HIV+wOMD) and 22 sex-, age-, and education-matched control participants. Memory impairments were classified based on the participants' performance on the Rey Auditory Verbal Learning Test. Short echo time (30 ms), single-voxel H-MRS was performed using a 1.5-T magnetic resonance scanner. Results: The HIV+wMD and HIV+wOMD groups had higher choline/creatine ratio in the posterior cingulate gyri than the control group. There were no significant metabolite ratio differences between the HIV+wMD and HIV+wOMD groups. Conclusion: HIV-positive patients with and without memory deficits had significantly higher choline/creatine ratios than controls in the posterior cingulate gyri, which may reflect cerebral inflammation, altered cell membrane metabolism, microgliosis, and/or astrocytosis.
Resumo Objetivo: Nós avaliamos se os pacientes HIV-positivos com e sem déficits de memória clinicamente significativos e controles saudáveis diferem na espectroscopia de prótons do giro do cíngulo posterior, por ressonância magnética (RM) cerebral. Materiais e Métodos: Vinte e um pacientes HIV-positivos com déficit de memória foram comparados com 15 pacientes HIV-positivos sem déficit de memória e 22 controles, pareados por sexo, idade e escolaridade. As deficiências de memória foram classificadas por meio do desempenho no Teste de Aprendizagem Auditivo-Verbal de Rey. A espectroscopia de prótons foi realizada com tempo de eco curto (30 ms), por voxel único, no giro do cíngulo posterior, utilizando aparelho de RM de 1,5 T. Resultados: Os pacientes HIV-positivos com e sem déficit de memória apresentaram aumento da relação colina/creatina no giro do cíngulo posterior, comparados aos controles. Não houve diferenças significativas nas relações metabólicas no grupo HIV-positivo com déficit de memória, em relação ao grupo de pacientes HIV-positivo sem déficit. Conclusão: Pacientes HIV-positivos com e sem déficits de memória apresentaram relações colina/creatina significativamente aumentadas em relação aos controles, no giro do cíngulo posterior, o que pode refletir inflamação cerebral, alteração do metabolismo da membrana celular, microgliose e/ou astrocitose.
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OBJECTIVE: Drebrins are crucial for synaptic function and dendritic spine development, remodeling, and maintenance. In temporal lobe epilepsy (TLE) patients, a significant hippocampal synaptic reorganization occurs, and synaptic reorganization has been associated with hippocampal hyperexcitability. This study aimed to evaluate, in TLE patients, the hippocampal expression of drebrin using immunohistochemistry with DAS2 or M2F6 antibodies that recognize adult (drebrin A) or adult and embryonic (pan-drebrin) isoforms, respectively. METHODS: Hippocampal sections from drug-resistant TLE patients with hippocampal sclerosis (HS; TLE, n = 33), of whom 31 presented with type 1 HS and two with type 2 HS, and autopsy control cases (n = 20) were assayed by immunohistochemistry and evaluated for neuron density, and drebrin A and pan-drebrin expression. Double-labeling immunofluorescences were performed to localize drebrin A-positive spines in dendrites (MAP2), and to evaluate whether drebrin colocalizes with inhibitory (GAD65) and excitatory (VGlut1) presynaptic markers. RESULTS: Compared to controls, TLE patients had increased pan-drebrin in all hippocampal subfields and increased drebrin A-immunopositive area in all hippocampal subfields but CA1. Drebrin-positive spine density followed the same pattern as total drebrin quantification. Confocal microscopy indicated juxtaposition of drebrin-positive spines with VGlut1-positive puncta, but not with GAD65-positive puncta. Drebrin expression in the dentate gyrus of TLE cases was associated negatively with seizure frequency and positively with verbal memory. TLE patients with lower drebrin-immunopositive area in inner molecular layer (IML) than in outer molecular layer (OML) had a lower seizure frequency than those with higher or comparable drebrin-immunopositive area in IML compared with OML. SIGNIFICANCE: Our results suggest that changes in drebrin-positive spines and drebrin expression in the dentate gyrus of TLE patients are associated with lower seizure frequency, more preserved verbal memory, and a better postsurgical outcome.
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Epilepsia Resistente a Medicamentos/metabolismo , Epilepsia do Lobo Temporal/metabolismo , Hipocampo/metabolismo , Neuropeptídeos/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Lobectomia Temporal Anterior , Região CA1 Hipocampal/metabolismo , Região CA2 Hipocampal/metabolismo , Região CA3 Hipocampal/metabolismo , Estudos de Casos e Controles , Dendritos/metabolismo , Dendritos/patologia , Giro Denteado/metabolismo , Epilepsia Resistente a Medicamentos/patologia , Epilepsia Resistente a Medicamentos/cirurgia , Epilepsia do Lobo Temporal/patologia , Epilepsia do Lobo Temporal/cirurgia , Feminino , Glutamato Descarboxilase/metabolismo , Hipocampo/patologia , Hipocampo/cirurgia , Humanos , Imuno-Histoquímica , Masculino , Microscopia Confocal , Proteínas Associadas aos Microtúbulos/metabolismo , Pessoa de Meia-Idade , Plasticidade Neuronal , Esclerose , Proteína Vesicular 1 de Transporte de Glutamato/metabolismoRESUMO
Abnormalities in the thyroid hormones, like in hypothyroidism, are closely related to dementia and Alzheimer's disease demonstrating the main symptom of these disorders: memory deficit. In this study we evaluated the effect of chrysin on deficit spatial and aversive memories and the contribution of glutamatergic, cholinergic pathways and Na+, K+-ATPase activity on hippocampus and prefrontal cortex in hypothyroid adult female mice C57BL/6. Hypothyroidism was induced by the continuous exposure to 0.1% methimazole (MTZ) in drinking water for 31 days. The exposure to MTZ was associated to low plasma levels of thyroid hormones (TH) compared to the control group on the 32nd. Subsequently, euthyroid and MTZ-induced hypothyroid mice received (intragastrically) either vehicle or chrysin (20 mg/kg) once a day for 28 consecutive days. After treatments mice performed the following behavioral assessments: open-field test (OFT), morris water maze (MWM) and passive avoidance test. Additionally, plasma TH levels were measured again, as well as glutamate levels, Na+,K+-ATPase and acetylcholinesterase (AChE) activities were analyzed in the hippocampus and prefrontal cortex of mice. Mice with hypothyroidism showed a deficit of spatial and aversive memory and chrysin treatment reversed these deficits. It also reduced the levels of glutamate and decreased Na+,K+-ATPase activity in both cerebral structures in the hypothyroid mice compared with the euthyroid ones, with the exception of glutamate in the hippocampus, which was a partial reversal. AChE activity was not altered by treatments. Together, our results demonstrate that chrysin normalized hippocampal glutamate levels and Na+,K+-ATPase activity, which could be involved in the reversal of memory deficit.
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Ácido Glutâmico , Hipotireoidismo , Animais , Feminino , Flavonoides , Hipocampo/metabolismo , Hipotireoidismo/induzido quimicamente , Hipotireoidismo/tratamento farmacológico , Camundongos , Camundongos Endogâmicos C57BL , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
PURPOSE: Cognitive dysfunction is common in neuropsychiatric systemic lupus erythematosus (SLE). Memory is a commonly affected cognitive domain. Clinically, however, it is difficult to detect memory deficits. The objective of this study is to evaluate whether normal controls and SLE patients with and without memory deficit differ in terms of white-matter integrity. METHODS: Twenty SLE patients with memory deficit were compared to 47 SLE patients without memory deficit and 22 sex-, age-, and education-matched control individuals. Diffusion tensor imaging (DTI) was performed in a 1.5-Tesla scanner. For tract-based spatial statistics analysis, a white-matter skeleton was created. A permutation-based inference with 5000 permutations with a threshold of p < 0.05 was used to identify abnormalities in fractional anisotropy (FA). The mean diffusivity (MD), radial diffusivity (RD) and axial diffusivity (AD) were also projected onto the mean FA skeleton. RESULTS: Compared to controls, SLE patients with and without memory deficit had decreased FA in: bilateral anterior thalamic radiation, inferior fronto-occipital fasciculus, superior longitudinal fasciculus, uncinate fasciculus, corticospinal tract, genu, and body of the corpus callosum. SLE patients with and without memory deficit also presented increased MD and RD values compared to controls in these areas. Comparison between SLE patients with and without memory deficit did not present significant differences in DTI parameters. CONCLUSION: DTI can detect extensive abnormalities in the normal-appearing white matter of SLE patients with and without memory deficit, compared to controls. However, there was no difference, in terms of white-matter integrity, between the groups of SLE patients.
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Imagem de Difusão por Ressonância Magnética/métodos , Lúpus Eritematoso Sistêmico/patologia , Transtornos da Memória/patologia , Substância Branca/diagnóstico por imagem , Adulto , Anisotropia , Mapeamento Encefálico , Estudos de Casos e Controles , Transtornos Cognitivos/diagnóstico por imagem , Transtornos Cognitivos/etiologia , Corpo Caloso/diagnóstico por imagem , Feminino , Humanos , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Masculino , Transtornos da Memória/diagnóstico por imagem , Pessoa de Meia-Idade , Fibras Nervosas/patologia , Testes Neuropsicológicos , Estudos RetrospectivosRESUMO
Temporal lobe epilepsy (TLE) is a highly prevalent syndrome among people with epilepsy, and is usually refractory to drug treatment. Structural and physiological changes, such as hippocampal sclerosis, are often present in TLE patients. The objective of this study is to evaluate the feasibility and safety of intra-arterial infusion of autologous bone marrow mononuclear cells (BMMC) in adults with medically refractory mesial TLE (MTLE) and unilateral hippocampal sclerosis (HS). We enrolled 20 patients who had been diagnosed with MTLE-HS and were refractory to medical treatment. All patients underwent a neurological evaluation, magnetic resonance imaging with hippocampal volumetry, video-electroencephalography (EEG) with ictal recording, and a neuropsychological test battery focusing on verbal and nonverbal memory domains. After bone marrow aspiration and subsequent cell preparation, the BMMC were infused by selective posterior cerebral artery catheterization. Patients were followed for 6 months. Safety of the procedure, seizure frequency, neuropsychological evaluation, EEG variables, routine brain magnetic resonance imaging and hippocampal volumetry were considered measurements of outcome. Any serious intercurrent clinical event or adverse effects related to the procedure were reported. No additional lesions and no significant hippocampal volumetric changes were observed. EEG recordings showed a decrease in theta activity and spike density. At 6 months, eight patients (40%) were seizure free. A significant increase in the memory scores over time was observed. The BMMC autologous transplant for the treatment of temporal lobe epilepsy is feasible and safe. The seizure control achieved in this novel study supports the therapeutic potential of stem cell transplants in MTLE-HS patients. Copyright © 2016 John Wiley & Sons, Ltd.
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Células da Medula Óssea/citologia , Transplante de Medula Óssea/efeitos adversos , Epilepsia do Lobo Temporal/terapia , Leucócitos Mononucleares/transplante , Convulsões/terapia , Adulto , Eletroencefalografia , Epilepsia do Lobo Temporal/fisiopatologia , Feminino , Seguimentos , Humanos , Processamento de Imagem Assistida por Computador , Injeções Intra-Arteriais , Masculino , Memória , Pessoa de Meia-Idade , Convulsões/patologia , Convulsões/fisiopatologia , Transplante Autólogo , Gravação em Vídeo , Adulto JovemRESUMO
Preconditioning can induce a cascade of cellular events leading to neuroprotection against subsequent brain insults. In this study, we investigated the chronic effects of hypoxic preconditioning on spontaneous recurrent seizures (SRS), neuronal death, and spatial memory performance in rats subjected to pilocarpine (Pilo)-induced status epilepticus (SE). Rats underwent a short hypoxic episode (7% O2+93% N2; 30min on two consecutive days) preceding a 4-h SE (HSE group). Control groups were rats submitted to SE only (SE), rats subjected to hypoxia only (H) or normoxia-saline (C). Animals were monitored for the occurrence of SRS, and spatial memory performance was evaluated in the radial-arm maze. Hippocampal sections were analyzed for cell death and mossy fiber sprouting at 1 or 60days after SE. Compared to SE group, HSE had increased SE latency, reduced number of rats with SRS, reduced mossy fiber sprouting at 60days, and reduced cell death in the hilus and the CA3 region 1 and 60days after SE. Additionally, HSE rats had better spatial memory performance than SE rats. Our findings indicated that short hypoxic preconditioning preceding SE promotes long-lasting protective effects on neuron survival and spatial memory.
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Hipocampo/patologia , Precondicionamento Isquêmico , Transtornos da Memória/prevenção & controle , Neurônios/patologia , Estado Epiléptico/terapia , Animais , Modelos Animais de Doenças , Masculino , Transtornos da Memória/patologia , Neuroproteção , Pilocarpina , Ratos Wistar , Memória Espacial , Estado Epiléptico/patologia , Estado Epiléptico/psicologiaRESUMO
We previously reported that long-term treatment with fish oil (FO) facilitates memory recovery after transient, global cerebral ischemia (TGCI), despite the presence of severe hippocampal damage. The present study tested whether this antiamnesic effect resulted from an action of FO on behavioral performance itself, or whether it resulted from an anti-ischemic action. Different treatment regimens were used that were distinguished from each other by their initiation or duration with regard to the onset of TGCI and memory assessment. Naive rats were trained in an eight-arm radial maze, subjected to TGCI (4-VO model, 15 min), and tested for memory performance up to 6 weeks after TGCI. Fish oil (docosahexaenoic acid, 300 mg/kg/day) was given orally according to one of the following regimens: regimen 1 (from 3 days prior to ischemia until 4 weeks post-ischemia), regimen 2 (from 3 days prior to ischemia until 1 week post-ischemia), and regimen 3 (from week 2 to week 5 post-ischemia). When administered according to regimens 1 and 2, FO abolished amnesia completely. This effect persisted for at least 5 weeks after discontinuing the treatment. Such an effect did not occur, however, in the group treated according to regimen 3. Hippocampal and cortical damage was not alleviated by FO. The present results demonstrate that FO-mediated memory recovery (or preservation) following TGCI is a reproducible, robust, and long-lasting effect. Moreover, such an effect was found with a relatively short period of treatment, provided it covered the first days prior to and after ischemia. This suggests that FO prevented amnesia by changing some acute, ischemia/reperfusion-triggered process and not by stimulating memory performance on its own.