RESUMO
The perception of control over a stressful experience may determine its impacts and generate resistance against future stressors. Although the medial prefrontal cortex (PFC) and the hippocampus (HPC) are implicated in the encoding of stressor controllability, the neural dynamics underlying this process are unknown. Here, we recorded HPC and PFC neural activities in male rats during the exposure to controllable, uncontrollable, or no shocks and investigated electrophysiological predictors of escape performance upon exposure to subsequent uncontrollable shocks. We were able to accurately discriminate stressed from nonstressed animals and predict resistant (R) or helpless (H) individuals based on hippocampal-cortical oscillatory dynamics. Remarkably, R animals exhibited an increase in theta power during CS, while H exhibited a decrease. Furthermore, R exhibited higher HPC to PFC θ synchronization during stress. Notably, HPC-PFC θ connectivity in the initial stress exposure showed strong correlations with escape performance evaluated days later. R rats also showed stronger θ coupling to both γ oscillations and neuronal firing in the PFC. Finally, we found that these distinct features of network dynamics collectively formed a pattern that accurately predicted learned resistance and was lacking in H individuals. Our findings suggest that hippocampal-prefrontal network θ activity supports cognitive mechanisms of stress coping, whose impairment may underlie vulnerability to stress-related disorders.SIGNIFICANCE STATEMENT The appraisal of adversities as controllable or uncontrollable is key in determining resilience or risk for stress-related disorders. Here, we performed the first electrophysiological investigation during controllable or uncontrollable stress. Pharmacological studies showed that the prefrontal cortex (PFC) and the hippocampus (HPC) encode stressor controllability, and here we identified the neural activity underlying this process. This "neural signature of stressor controllability" accurately predicted resistance to future stressors and was characterized by increased HPC-PFC oscillatory activity in the θ frequency (4-10 Hz). Our findings suggest a new role of frontal θ oscillations in adaptive stress coping, integrating its emotional and cognitive functions. We also endorse the potential of this biomarker to guide neurophysiologically-informed and rhythm-based stimulation therapies for depression.
Assuntos
Adaptação Psicológica/fisiologia , Desamparo Aprendido , Hipocampo/fisiologia , Vias Neurais/fisiologia , Córtex Pré-Frontal/fisiologia , Animais , Masculino , Ratos , Ratos Wistar , Estresse Psicológico/complicações , Ritmo Teta/fisiologiaRESUMO
Synchronous activity of cortical inhibitory interneurons expressing parvalbumin (PV) underlies expression of cortical γ rhythms. Paradoxically, deficient PV inhibition is associated with increased broadband γ power in the local field potential. Increased baseline broadband γ is also a prominent characteristic in schizophrenia and a hallmark of network alterations induced by NMDAR antagonists, such as ketamine. Whether enhanced broadband γ is a true rhythm, and if so, whether rhythmic PV inhibition is involved or not, is debated. Asynchronous and increased firing activities are thought to contribute to broadband power increases spanning the γ band. Using male and female mice lacking NMDAR activity specifically in PV neurons to model deficient PV inhibition, we here show that neuronal activity with decreased synchronicity is associated with increased prefrontal broadband γ power. Specifically, reduced spike time precision and spectral leakage of spiking activity because of higher firing rates (spike "contamination") affect the broadband γ band. Desynchronization was evident at multiple time scales, with reduced spike entrainment to the local field potential, reduced cross-frequency coupling, and fragmentation of brain states. Local application of S(+)-ketamine in (control) mice with intact NMDAR activity in PV neurons triggered network desynchronization and enhanced broadband γ power. However, our investigations suggest that disparate mechanisms underlie increased broadband γ power caused by genetic alteration of PV interneurons and ketamine-induced power increases in broadband γ. Our study confirms that enhanced broadband γ power can arise from asynchronous activities and demonstrates that long-term deficiency of PV inhibition can be a contributor.SIGNIFICANCE STATEMENT Brain oscillations are fundamental to the coordination of neuronal activity across neurons and structures. γ oscillations (30-80 Hz) have received particular attention through their association with perceptual and cognitive processes. Synchronous activity of inhibitory parvalbumin (PV) interneurons generates cortical γ oscillation, but, paradoxically, PV neuron deficiency is associated with increases in γ oscillations. We here reconcile this conundrum and show how deficient PV inhibition can lead to increased and asynchronous excitatory firing, contaminating the local field potential and manifesting as increased γ power. Thus, increased γ power does not always reflect a genuine rhythm. Further, we show that ketamine-induced γ increases are caused by separate network mechanisms.
Assuntos
Potenciais de Ação/fisiologia , Encéfalo/metabolismo , Ritmo Gama/fisiologia , Interneurônios/metabolismo , Rede Nervosa/metabolismo , Animais , Química Encefálica/fisiologia , Feminino , Interneurônios/química , Masculino , Camundongos , Camundongos Knockout , Camundongos Transgênicos , Rede Nervosa/química , Parvalbuminas/análise , Parvalbuminas/metabolismo , Receptores de N-Metil-D-Aspartato/análise , Receptores de N-Metil-D-Aspartato/metabolismoRESUMO
Glial cells and extracellular matrix (ECM) molecules are crucial for the maintenance of brain homeostasis. Especially because of their actions regarding neurotransmitter and ionic control, and synaptic function, these cells can potentially contribute to the hyperexcitability seen in the epileptogenic, while ECM changes are linked to synaptic reorganization. The present review will explore glial and ECM homeostatic roles and their potential contribution to tissue plasticity. Finally, we will address how glial, and ECM changes in the epileptogenic zone can be seen in magnetic resonance imaging (MRI), pointing out their importance as markers for the extension of the epileptogenic area. This article is part of the Special Issue "NEWroscience 2018".
Assuntos
Matriz Extracelular , Neuroglia , Biomarcadores , Encéfalo/diagnóstico por imagem , Humanos , Imageamento por Ressonância MagnéticaRESUMO
Memory impairment is the most common cognitive deficit in patients with temporal lobe epilepsy (TLE). This type of epilepsy is currently regarded as a network disease because of its brain-wide alterations in functional connectivity between temporal and extra-temporal regions. In patients with TLE, network dysfunctions can be observed during ictal states, but are also described interictally during rest or sleep. Here, we examined the available literature supporting the hypothesis that hippocampal-cortical coupling during sleep is hijacked in TLE. First, we look at studies showing that the coordination between hippocampal sharp-wave ripples (100-200â¯Hz), corticothalamic spindles (9-16â¯Hz), and cortical delta waves (1-4â¯Hz) during nonrapid eye movement (NREM) sleep is critical for spatial memory consolidation. Then, we reviewed studies showing that animal models of TLE display precise coordination between hippocampal interictal epileptiform discharges (IEDs) and spindle oscillations in the prefrontal cortex. This aberrant oscillatory coupling seems to surpass the physiological ripple-delta-spindle coordination, which could underlie memory consolidation impairments. We also discuss the role of rapid eye movement (REM) sleep for local synaptic plasticity and memory. Sleep episodes of REM provide windows of opportunity for reactivation of expression of immediate early genes (i.e., zif-268 and Arc). Besides, hippocampal theta oscillations during REM sleep seem to be critical for memory consolidation of novel object place recognition task. However, it is still unclear which extend this particular phase of sleep is affected in TLE. In this context, we show some preliminary results from our group, suggesting that hippocampal theta-gamma phase-amplitude coupling is exacerbated during REM in a model of basolateral amygdala fast kindling. In conclusion, there is an increasing body of evidence suggesting that circuits responsible for memory consolidation during sleep seem to be gradually coopted and degraded in TLE. This article is part of the Special Issue "NEWroscience 2018".
Assuntos
Epilepsia do Lobo Temporal , Consolidação da Memória , Sono de Ondas Lentas , Animais , Eletroencefalografia , Epilepsia do Lobo Temporal/complicações , Hipocampo , Humanos , SonoRESUMO
Brazil has a higher rate of dysphagia in stroke patients compared to developed countries, but does not have a fully validated method for early identification of dysphagia in this population. The aim of this study is to translate the TOR-BSST© into Brazilian Portuguese and assess the newly translated version for reliability and validity with Brazilian adult patients with stroke. The translation of the TOR-BSST© followed a multi-step process, according to the International Quality of Life Assessment project. For validation, we included patients with age ≥ 18 years and stroke diagnosis confirmed by neuroimaging and tolerance for videofluoroscopic swallowing assessment. The BR-PTfinal TOR-BSST© was administered by two trained screeners within two hours of videofluoroscopy. All assessors were independent and blinded. Estimates for reliability used the intraclass correlation coefficient (ICC) and for accuracy both sensitivity (SN) and negative predictive (NP) values were used, along with 95% confidence intervals (CI). Sixty patients were enrolled and tested for a mean (SD) of 14.4 (6.9) days from last seen normal. Of all the patients, 41 (68.3%) failed the BR-PTfinal TOR-BSST© and 21 (35%) were scored to have dysphagia on videofluoroscopy, of which 11 (52.4%) had mild dysphagia. The overall reliability between screeners was satisfactory (ICC = 0.59; 95% CI 0.32 to 0.76). The SN and NP values for the BR-PTfinal TOR-BSST© were 85.7% (95% CI 0.62-0.96) and 84.2% (95% CI 0.72-0.95), respectively. The TOR-BSST© was successfully translated to Brazilian Portuguese with the BR-PTfinal TOR-BSST© proven to have high sensitivity and negative predictive values when compared to gold standard videofluoroscopy.
Assuntos
Acidente Vascular Cerebral , Inquéritos e Questionários , Traduções , Adulto , Brasil , Humanos , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/complicaçõesRESUMO
Background and Purpose- Sleep apnea has been associated with a poor outcome in acute stroke patients. Polysomnography is the gold standard diagnostic method for sleep apnea, but it is not feasible as a routine in the acute stroke setting. The current generation of positive airway pressure (PAP) devices can detect the different types of respiratory events. This study aimed to compare the algorithms used in PAP device to manually scored events on polysomnography in patients with acute stroke. Methods- A sleep study was performed with standard polysomnography and PAP device, simultaneously, within the first 48 hours after acute stroke onset. Results- We prospectively evaluated 29 patients with acute stroke (59.5±12.1 years). The area under the receiver operating characteristic curve for each apnea-hypopnea index value was above 0.90 by PAP device. There was a good correlation of apnea-hypopnea index (rs=0.92; P<0.001), hypopnea index (rs=0.89; P<0.001), and apnea index (rs=0.70; P<0.001) between device-detected events and manually scored polysomnography. Conclusions- Given the high frequency of sleep apnea during the acute phase of stroke and the complexity of a full polysomnography study in this setting, PAP device on diagnostic mode can be used as an alternative tool for sleep apnea detection in acute stroke patients.
Assuntos
Algoritmos , Pressão Positiva Contínua nas Vias Aéreas , Polissonografia , Síndromes da Apneia do Sono , Acidente Vascular Cerebral , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Síndromes da Apneia do Sono/diagnóstico , Síndromes da Apneia do Sono/fisiopatologia , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologiaRESUMO
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.
Assuntos
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
OBJECTIVE: The objective of this study was to analyze the impact of pediatric epilepsy surgery on the quality of life (QOL), determining whether patients improve, worsen, or maintain their preoperative patterns, as it relates to the burden of caregivers, as well as evaluating potential related factors, from both the children and caregivers perspectives. MATERIAL AND METHODS: This is a retrospective study of children and adolescents who underwent epilepsy surgery and were evaluated through clinical data, videoelectroencephalogram (V-EEG), neuroimaging findings, neuropsychological testing, and aspects of QOL. These assessments were performed prior to surgery and after six months and two years of follow-up. Quality of life was assessed with epilepsy-specialized questionnaires, namely Questionnaire health-related quality of life for children with epilepsy (QVCE-50), Autoquestionnaire Qualité de Vie Enfant Image Scale (AUQUEI), Quality of life in epilepsy inventory for adolescents (QOLEI-AD-48); and burden of caregivers with Burden Interview - ZARIT scale. Postoperative changes in QVCE-50 were quantified using measures of the analysis of variance (ANOVA MR) for comparison of the difference between the three times of the scale and domains. RESULTS: Fifty patients were enrolled. Of these, 27 (54%) were male, with a mean age at surgery of 8.2â¯years (range: 1-18â¯years). Thirty-five patients (70%) were Engel I and one was Engel II (2%) at six months of follow-up, whereas 28 (56%) were Engel I and 32 (64%) were Engel I or II at two years of follow-up. Preoperatively, 21 (42%) presented with moderate or severe intellectual disability. Postoperative cognitive evaluations at the two-year follow-up showed 18 (36%) maintained similar deficits. The QVCE-50 showed postoperative improvement in the two-year follow-up period, but not at six months after surgery. Postoperative improvements were associated mainly with better seizure outcome. Autoperception evaluations were limited because of the clinical and cognitive severity of patients. The burden of caregivers was quoted as mild to moderate and remained unchanged postoperatively. CONCLUSIONS: Children and adolescents with surgically treated epilepsy reach a good seizure outcome, stabilize in intellectual and adaptive functions, and have an increase in QOL, from the caregiver's perspective. Nevertheless, their burden remains unchanged. Seizure outcome is the main factor for improvement in the QOL. The upgrading of structured questionnaires and QOL instruments specific to pediatric epilepsy can be helpful to assess patient- and caregiver-reported surgical outcomes, allowing for better planning of therapeutic approaches.
Assuntos
Cuidadores/psicologia , Efeitos Psicossociais da Doença , Epilepsia Resistente a Medicamentos/psicologia , Epilepsia Resistente a Medicamentos/cirurgia , Qualidade de Vida/psicologia , Adolescente , Criança , Pré-Escolar , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Lactente , Masculino , Neuroimagem/métodos , Testes Neuropsicológicos , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: Increased T2 relaxation time is often seen in temporal lobe epilepsy (TLE) with hippocampal sclerosis. Water content directly affects the effective T2 in a voxel. Our aim was to evaluate the relation between T2 values and two molecules associated with brain water homeostasis aquaporin 4 (AQP4) and chondroitin sulfate proteoglycan (CSPG), as well as cellular populations in the hippocampal region of patients with TLE. METHODS: Hippocampal T2 imaging and diffusion tensor imaging (DTI) were obtained from 42 drug-resistant patients with TLE and 20 healthy volunteers (radiologic controls, RCs). A similar protocol (ex vivo) was applied to hippocampal sections from the same TLE cases and 14 autopsy control hippocampi (histologic and radiologic controls, HRCs), and each hippocampal subfield was evaluated. Hippocampal sections from TLE cases and HRC controls were submitted to immunohistochemistry for neurons (neuron nuclei [NeuN]), reactive astrocytes (glial fibrillary acidic protein [GFAP]), activated microglia (human leukocyte antigen-D-related [HLA-DR]), polarized AQP4, and CSPG. RESULTS: Patients with TLE had higher in vivo and ex vivo hippocampal T2 relaxation time. Hippocampi from epilepsy cases had lower neuron density, higher gliosis, decreased AQP4 polarization, and increased CSPG immunoreactive area. In vivo relaxation correlated with astrogliosis in the subiculum and extracellular CSPG in the hilus. Ex vivo T2 relaxation time correlated with astrogliosis in the hilus, CA4, and subiculum, and with microgliosis in CA1. The difference between in vivo and ex vivo relaxation ratio correlated with mean diffusivity and with the immunopositive area for CSPG in the hilus. SIGNIFICANCE: Our data indicate that astrogliosis, microgliosis, and CSPG expression correlate with the increased T2 relaxation time seen in the hippocampi of patients with TLE.
Assuntos
Aquaporina 4/metabolismo , Proteoglicanas de Sulfatos de Condroitina/metabolismo , Epilepsia do Lobo Temporal/patologia , Gliose/etiologia , Hipocampo/metabolismo , Hipocampo/patologia , Adulto , Estudos de Casos e Controles , Imagem de Tensor de Difusão , Epilepsia do Lobo Temporal/complicações , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Gliose/patologia , Antígenos HLA/metabolismo , Hipocampo/diagnóstico por imagem , Humanos , Masculino , Pessoa de Meia-Idade , Neuroglia/metabolismo , Neurônios/metabolismo , Fosfopiruvato Hidratase/metabolismo , Esclerose/diagnóstico por imagem , Estatística como Assunto , Fatores de TempoRESUMO
OBJECTIVE: Patients with temporal lobe epilepsy caused by hippocampal sclerosis (TLE-HS) have episodic memory impairment. Memory has rarely been evaluated using an ecologic measure, even though performance on these tests is more related to patients' memory complaints. We aimed to measure everyday memory of patients with TLE-HS to age- and gender-matched controls. METHODS: We evaluated 31 patients with TLE-HS and 34 healthy controls, without epilepsy and psychiatric disorders, using the Rivermead Behavioral Memory Test (RBMT), Visual Reproduction (WMS-III) and Logical Memory (WMS-III). We evaluated the impact of clinical variables such as the age of onset, epilepsy duration, AED use, history of status epilepticus, and seizure frequency on everyday memory. Statistical analyses were performed using MANCOVA with years of education as a confounding factor. RESULTS: Patients showed worse performance than controls on traditional memory tests and in the overall score of RBMT. Patients had more difficulties to recall names, a hidden belonging, to deliver a message, object recognition, to remember a story full of details, a previously presented short route, and in time and space orientation. Clinical epilepsy variables were not associated with RBMT performance. Memory span and working memory were correlated with worse performance on RBMT. SIGNIFICANCE: Patients with TLE-HS demonstrated deficits in everyday memory functions. A standard neuropsychological battery, designed to assess episodic memory, would not evaluate these impairments. Impairment in recalling names, routes, stories, messages, and space/time disorientation can adversely impact social adaptation, and we must consider these ecologic measures with greater attention in the neuropsychological evaluation of patients with memory complaints.
Assuntos
Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/psicologia , Hipocampo/patologia , Transtornos da Memória/diagnóstico , Transtornos da Memória/psicologia , Memória Episódica , Adolescente , Adulto , Epilepsia do Lobo Temporal/complicações , Feminino , Humanos , Masculino , Transtornos da Memória/etiologia , Pessoa de Meia-Idade , Testes Neuropsicológicos , Esclerose/complicações , Esclerose/patologia , Esclerose/psicologia , Adulto JovemRESUMO
BACKGROUND: Brazil is a developing country struggling to reduce its extreme social inequality, which is reflected on shortage of health-care infrastructure, mainly to the low-income class, which depends exclusively on the public health system. In Brazil, less than 1% of stroke patients have access to intravenous thrombolysis in a stroke unit, and constraints to the development of mechanical thrombectomy in the public health system increase the social burden of stroke. OBJECTIVE: Report the feasibility of mechanical thrombectomy as part of routine stroke care in a Brazilian public university hospital. METHODS: Prospective data were collected from all patients treated for acute ischemic stroke with mechanical thrombectomy from June 2011 to March 2016. Combined thrombectomy was performed in eligible patients for intravenous thrombolysis if they presented occlusion of large artery. For those patients ineligible for intravenous thrombolysis, primary thrombectomy was performed as long as there was no evidence of significant ischemia for anterior circulation stroke (Alberta Stroke Program Early CT score >6) within a 6-hour time window, and also for those patients with wake-up stroke or posterior circulation stroke, regardless of the time of symptoms onset. RESULTS: A total of 161 patients were evaluated, resulting in an overall successful recanalization rate of 76% and symptomatic intracranial hemorrhage rate of 6.8%. At 3 months, 36% of the patients had modified Rankin Scale score less than or equal to 2. The overall mortality rate was 23%. CONCLUSION: Our study, the first ever large series of mechanical thrombectomy in Brazil, demonstrates acceptable efficacy and safety results, even under restricted conditions outside the ideal scenario of trial studies.
Assuntos
Hospitais Universitários , Trombólise Mecânica/métodos , Acidente Vascular Cerebral/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Encéfalo/diagnóstico por imagem , Brasil/epidemiologia , Feminino , Humanos , Hemorragias Intracranianas/etiologia , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estatísticas não Paramétricas , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico por imagem , Tomógrafos Computadorizados , Adulto JovemRESUMO
BACKGROUND: Decision-making abilities have rarely been examined in patients with temporal lobe epilepsy related to hippocampal sclerosis (TLE-HS). We aimed to investigate the ability to delay gratification, a decision-making subdomain, in patients with intractable TLE-HS and to verify the association of delay gratification performance and cool executive function tests. METHODS: We evaluated 27 patients with TLE-HS (mean age: 35.46 [±13.31] years; 7 males) and their cognitive performance was compared with that of 27 age- and gender-matched healthy controls (mean age: 35.33 [±12.05] years; 7 males), without epilepsy and psychiatric disorders. Patients were assessed using the delay discounting task (DDT) and tests of attention, shifting, inhibitory control, and concept formation. Results were correlated with clinical epilepsy variables such as age of onset, epilepsy duration, AED use, history of status epilepticus, febrile seizures, and the presence of generalized seizures. Statistical analysis was performed using one-way ANCOVA with years of education as a confounding factor. RESULTS: Patients and controls demonstrated similar performance on DDT, showing similar discount rate (p=0.935) and probability rate (p=0.585). Delay gratification was not related to cool executive function tests (Digit Span, Stroop Color Test, Trail Making Test, Wisconsin Card Sorting Test, and Connors' CPT). History of status epilepticus, presence of generalized seizures and higher seizure frequency, age at onset, and epilepsy duration had a significant impact on DDT. CONCLUSION: Patients with intractable TLE-HS showed unimpaired delay gratification abilities, being able to accept a higher delay and a lower amount of chance for receiving a higher reward in the future. Clinical variables related to the epilepsy severity impacted the performance on delay gratification. Impairment on cool aspects of executive function was unrelated to this decision-making domain.
Assuntos
Tomada de Decisões , Desvalorização pelo Atraso , Epilepsia do Lobo Temporal/diagnóstico , Epilepsia do Lobo Temporal/psicologia , Hipocampo/patologia , Adolescente , Adulto , Função Executiva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Esclerose/patologia , Adulto JovemRESUMO
Intracranial pressure (ICP) monitoring is sometimes required in clinical pictures of stroke, as extensive intraparenchymal hematomas and intracranial bleeding may severely increase ICP, which can lead to irreversible conditions, such as dementia and cognitive derangement. ICP monitoring has been accepted as a procedure for the safe diagnosis of increased ICP, and for the treatment of intracranial hypertension in some diseases. In this work, we evaluated ICP behavior during the induction of an experimental model of autologous blood injection in rats, simulating a hemorrhagic stroke. Rats were subjected to stereotactic surgery for the implantation of a unilateral cannula into the left striatal region of the brain. Autologous blood was infused into the left striatal region with an automatic microinfusion pump. ICP monitoring was performed throughout the procedure of hemorrhagic stroke induction. Analyses consisted of short-time Fourier transform for ICP before and after stroke induction and the histological processing of the animals' brains. Short-time Fourier transform analysis demonstrated oscillations in the ICP frequency components throughout time after the microinjections compared with data before them. Histological analysis revealed neuropathological changes in the striatum in all microinjected animals.
Assuntos
Hemorragia Cerebral/fisiopatologia , Pressão Intracraniana/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Animais , Hemorragia Cerebral/complicações , Hemorragia Cerebral/patologia , Corpo Estriado/patologia , Modelos Animais de Doenças , Análise de Fourier , Homeostase , Masculino , Monitorização Fisiológica , Ratos , Ratos Wistar , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/patologiaRESUMO
BACKGROUND: Despite the strong association between epilepsy and psychiatric comorbidities, few biological substrates are currently described. We have previously reported neuropathological alterations in mesial temporal lobe epilepsy (MTLE) patients with major depression and psychosis that suggest a morphological and neurochemical basis for psychopathological symptoms. Neuroinflammatory-related structures and molecules might be part of the altered neurochemical milieu underlying the association between epilepsy and psychiatric comorbidities, and such features have not been previously investigated in humans. METHODS: MTLE hippocampi of subjects without psychiatric history (MTLEW), MTLE + major depression (MTLE + D), and MTLE + interictal psychosis (MTLE + P) derived from epilepsy surgery and control necropsies were investigated for reactive astrocytes (glial fibrillary acidic protein (GFAP)), activated microglia (human leukocyte antigen, MHC class II (HLA-DR)), glial metallothionein-I/II (MT-I/II), and aquaporin 4 (AQP4) immunohistochemistry. RESULTS: We found an increased GFAP immunoreactive area in the molecular layers, granule cell layer, and cornus ammonis region 2 (CA2) and cornus ammonis region 1 (CA1) of MTLEW and MTLE + P, respectively, compared to MTLE + D. HLA-DR immunoreactive area was higher in cornus ammonis region 3 (CA3) of MTLE + P, compared to MTLE + D and MTLEW, and in the hilus, when compared to MTLEW. MTLEW cases showed increased MT-I/II area in the granule cell layer and CA1, compared to MTLE + P, and in the parasubiculum, when compared to MTLE + D and MTLE + P. Differences between MTLE and control, such as astrogliosis, microgliosis, increased MT-I/II, and decreased perivascular AQP4 in the epileptogenic hippocampus, were in agreement to what is currently described in the literature. CONCLUSIONS: Neuroinflammatory-related molecules in MTLE hippocampus show a distinct pattern of expression when patients present with a comorbid psychiatric diagnosis, similar to what is found in the pure forms of schizophrenia and major depression. Future studies focusing on inflammatory characteristics of MTLE with psychiatric comorbidities might help in the design of better therapeutic strategies.
Assuntos
Citocinas/metabolismo , Transtorno Depressivo Maior/epidemiologia , Epilepsia do Lobo Temporal/epidemiologia , Hipocampo/metabolismo , Adolescente , Aquaporina 4/metabolismo , Criança , Pré-Escolar , Comorbidade , Transtorno Depressivo Maior/patologia , Epilepsia do Lobo Temporal/patologia , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Antígenos HLA-DR/metabolismo , Humanos , Masculino , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/patologia , Índice de Gravidade de Doença , Estatísticas não ParamétricasRESUMO
BACKGROUND: Better treatments for schizophrenia are urgently needed. The therapeutic use of the nitric oxide (NO)-donor sodium nitroprusside (SNP) in patients with schizophrenia has shown promising results. The role of NO in schizophrenia is still unclear, and NO modulation is unexplored in ketamine (KET) animal models to date. In the present study, we compared the behavioral effects of pre- and post-treatment with SNP, glyceryl trinitrate (GTN), and methylene blue (MB) in the acute KET animal model of schizophrenia. The present study was designed to test whether acute SNP, GTN, and MB treatment taken after (therapeutic effect) or before (preventive effect) a single KET injection would influence the behavior of rats in the sucrose preference test, object recognition task and open field. RESULTS: The results showed that KET induced cognitive deficits and hyperlocomotion. Long- term memory improvement was seen with the therapeutic GTN and SNP treatment, but not with the preventive one. MB pretreatment resulted in long-term memory recovery. GTN pre-, but not post-treatment, tended to increase vertical and horizontal activity in the KET model. Therapeutic and preventive SNP treatment consistently decreased KET-induced hyperlocomotion. CONCLUSION: NO donors - especially SNP - are promising new pharmacological candidates in the treatment of schizophrenia. In addition, we showed that the potential impact of NO-related compounds on KET-induced behavioral changes may depend on the temporal window of drug administration.
Assuntos
Antipsicóticos/farmacologia , Azul de Metileno/farmacologia , Nitroglicerina/farmacologia , Nitroprussiato/farmacologia , Esquizofrenia/tratamento farmacológico , Doença Aguda , Animais , Transtornos Cognitivos/tratamento farmacológico , Transtornos Cognitivos/fisiopatologia , Sacarose Alimentar/administração & dosagem , Modelos Animais de Doenças , Comportamento Exploratório/efeitos dos fármacos , Masculino , Atividade Motora , Doadores de Óxido Nítrico/farmacologia , Ratos Wistar , Reconhecimento Psicológico/efeitos dos fármacos , Esquizofrenia/fisiopatologia , Psicologia do Esquizofrênico , Percepção Gustatória/efeitos dos fármacos , Resultado do TratamentoRESUMO
OBJECTIVE: Hippocampal sclerosis is a common finding in patients with temporal lobe epilepsy (TLE), and magnetic resonance imaging (MRI) studies associate the reduction of hippocampal volume with the neuron loss seen on histologic evaluation. Astrogliosis and increased levels of chondroitin sulfate, a major component of brain extracellular matrix, are also seen in hippocampal sclerosis. Our aim was to evaluate the association between hippocampal volume and chondroitin sulfate, as well as neuronal and astroglial populations in the hippocampus of patients with TLE. METHODS: Patients with drug-resistant TLE were subdivided, according to hippocampal volume measured by MRI, into two groups: hippocampal atrophy (HA) or normal volume (NV) cases. Hippocampi from TLE patients and age-matched controls were submitted to immunohistochemistry to evaluate neuronal population, astroglial population, and chondroitin sulfate expression with antibodies against neuron nuclei protein (NeuN), glial fibrillary acidic protein (GFAP), and chondroitin sulfate (CS-56) antigens, respectively. RESULTS: Both TLE groups were clinically similar. NV cases had higher hippocampal volume, both ipsilateral and contralateral, when compared to HA. Compared to controls, NV and HA patients had reduced neuron density, and increased GFAP and CS-56 immunopositive area. There was no statistical difference between NV and HA groups in neuron density or immunopositive areas for GFAP and CS-56. Hippocampal volume correlated positively with neuron density in CA1 and prosubiculum, and with immunopositive areas for CS-56 in CA1, and negatively with immunopositive area for GFAP in CA1. Multiple linear regression analysis indicated that both neuron density and CS-56 immunopositive area in CA1 were statistically significant predictors of hippocampal volume. SIGNIFICANCE: Our findings indicate that neuron density and chondroitin sulfate immunopositive area in the CA1 subfield are crucial for the hippocampal volume, and that chondroitin sulfate is important for the maintenance of a normal hippocampal volume in some cases with severe neuron loss.
Assuntos
Sulfatos de Condroitina/metabolismo , Epilepsia do Lobo Temporal/patologia , Hipocampo/metabolismo , Hipocampo/patologia , Neuroglia/metabolismo , Neurônios/patologia , Estudos de Casos e Controles , Feminino , Proteína Glial Fibrilar Ácida/metabolismo , Humanos , Imageamento por Ressonância Magnética , Masculino , Neurônios/metabolismo , Fosfopiruvato Hidratase/metabolismo , Análise de RegressãoRESUMO
INTRODUCTION: Early carotid revascularization (≤ 14 days) is recommended for symptomatic carotid stenosis. Carotid artery stenting (CAS) has become an alternative to carotid endarterectomy (CEA); however, safety data on early CAS is controversial. The study aims to compare early versus late CAS, when CAS is performed as a first intention revascularization strategy. METHODS: A retrospective analysis of all symptomatic patients admitted to our stroke unit who underwent CAS was conducted. Patients were divided between two groups: patients who had undergone CAS within 14 days after symptoms and those who had undergone CAS later. Primary endpoints were ipsilateral ischemic stroke or ipsilateral parenchymal hemorrhage (iPH) at 30 days. The secondary endpoints were major adverse cardiac and cerebrovascular events (MACCE) at the 30-day and at the 12-month follow-up. RESULTS: One hundred twenty-seven consecutive patients were evaluated. Primary endpoints obtained in the early and late CAS groups were, respectively, ipsilateral stroke (2.0% vs. 2.6%, P = 1.00) and iPH (2.0% vs. 0.0%, P = 0.40). The rates of MACCE between the early and the late CAS groups were, respectively, (7.8% vs. 2.6%, P = 0.21) at the 30-day follow-up, and (12.2% vs. 10.5%, P = 0.77) at the 12-month follow-up. CONCLUSIONS: In this study, CAS seems to be safe when used as first intention revascularization treatment within 2 weeks of symptoms, if infarcted area is less than one third of the middle cerebral artery territory. Our results need to be confirmed by larger studies.
Assuntos
Angioplastia com Balão/métodos , Estenose das Carótidas/cirurgia , Endarterectomia das Carótidas , Stents , Adulto , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/etiologia , Isquemia Encefálica/cirurgia , Estenose das Carótidas/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Medição de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Fatores de Tempo , Resultado do TratamentoRESUMO
Temporal lobe epilepsy (TLE) and psychosis coexist more frequently than chance would predict. In this short review, clinical and neuropathological findings of schizophrenia, TLE, and psychosis of epilepsy are described to enhance our understanding of the noncoincidental association between these conditions. In addition, psychosis of epilepsy was included for the first time in the Diagnostic and Statistical Manual of Mental Disorders (DSM), in the recently launched 5th edition, and improvement in diagnostic criteria was highlighted. Since the hippocampus has long been considered an anatomical area involved in the pathophysiology of TLE and schizophrenia, neuropathological studies of psychoses of epilepsy may contribute to our understanding of the pathophysiology of psychosis in general. The discovery of shared mechanisms and/or affected neurochemicals in TLE and schizophrenia might disclose important clues on the vulnerability of patients with TLE to psychotic symptoms and be an opportunity for new treatment development.
Assuntos
Comorbidade , Epilepsia do Lobo Temporal/fisiopatologia , Hipocampo/fisiopatologia , Transtornos Psicóticos/fisiopatologia , Esquizofrenia/fisiopatologia , Epilepsia do Lobo Temporal/epidemiologia , Epilepsia do Lobo Temporal/etiologia , Humanos , Transtornos Psicóticos/epidemiologia , Transtornos Psicóticos/etiologiaRESUMO
Clinical depression is characterized by multiple concurrent symptoms, manifesting as a complex heterogeneous condition. Although some well-established classical behavioral assessments are widespread in rodent models, it remains uncertain whether rats also display stress-induced depression-related phenotypes in a multidimensional manner, i.e., simultaneous alterations in multiple behavioral tests. Here, we investigated multivariate patterns and profiles of depression-related behavioral traits in male Wistar rats subjected to inescapable footshocks (IS) or no-shocks (NS), followed by a comprehensive battery of behavioral tests and ethological characterization. We observed generalized stronger intra-test but weaker inter-test correlations. However, feature clustering of behavioral measures successfully delineated variables linked to resilience and susceptibility to stress. Accordingly, a noteworthy covariation pattern emerged, characterized by increased open field locomotion, reduced time in the elevated plus maze open arms, lower sucrose preference, and increased shuttle box escape failures that consistently differentiated IS from NS. Surprisingly there is little contribution from forced swim. In addition, individual clustering revealed a diversity of behavioral profiles, naturally separating NS and IS, including subpopulations entirely characterized by resilience or susceptibility. In conclusion, our study elucidates intricate relationships among classical depression-related behavioral measures, highlighting multidimensional individual variability. Our work emphasizes the importance of a multivariate framework for behavioral assessment in animal models to understand stress-related neuropsychiatric disorders.
Assuntos
Comportamento Animal , Depressão , Ratos Wistar , Estresse Psicológico , Animais , Masculino , Ratos , Resiliência Psicológica , Modelos Animais de Doenças , Suscetibilidade a DoençasRESUMO
Tinnitus is a conscious attended awareness perception of sourceless sound. Widespread theoretical and evidence-based neurofunctional and psychological models have tried to explain tinnitus-related distress considering the influence of psychological and cognitive factors. However, tinnitus models seem to be less focused on causality, thereby easily misleading interpretations. Also, they may be incapable of individualization. This study proposes a Conceptual Cognitive Framework (CCF) providing insight into cognitive mechanisms involved in the predisposition, precipitation, and perpetuation of tinnitus and consequent cognitive-emotional disturbances. The current CCF for tinnitus relies on evaluative conditional learning and appraisal, generating negative valence (emotional value) and arousal (cognitive value) to annoyance, distress, and distorted perception. The suggested methodology is well-defined, reproducible, and accessible, which can help foster future high-quality clinical databases. Perceived tinnitus through the perpetual-learning process can always lead to annoyance, but only in the clinical stage directly cause annoyance. In the clinical stage, tinnitus perception can lead indirectly to distress only with experiencing annoyance either with (" I n d - 1 C " = 1.87; 95% CI 1.18-2.72)["1st indirect path in the Clinical stage model": Tinnitus Loudness â Attention Bias â Cognitive-Emotional Value â Annoyance â Clinical Distress]or without (" I n d - 2 C "= 2.03; 95% CI 1.02-3.32)[ "2nd indirect path in the Clinical stage model": Tinnitus Loudness â Annoyance â Clinical Distress] the perpetual-learning process. Further real-life testing of the CCF is expected to express a meticulous, decision-supporting platform for cognitive rehabilitation and clinical interventions. Furthermore, the suggested methodology offers a reliable platform for CCF development in other cognitive impairments and supports the causal clinical data models. It may also enhance our knowledge of psychological disorders and complicated comorbidities by supporting the design of different rehabilitation interventions and comprehensive frameworks in line with the "preventive medicine" policy.