30 results on '"Coimbra NC"'
Search Results
2. A nationwide study on immunosenescence biomarkers profile in older adults: ELSI-Brazil.
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Lima-Silva ML, Torres KCL, Mambrini JVM, Brot NC, Santos SO, Martins-Filho OA, Teixeira-Carvalho A, Lima-Costa MF, and Peixoto SV
- Subjects
- Humans, Male, Female, Brazil epidemiology, Aged, Middle Aged, Aging immunology, Aging blood, Aged, 80 and over, Inflammation blood, Chemokines blood, Biomarkers blood, Immunosenescence, Cytokines blood
- Abstract
Immunosenescence is a phenomenon caused by changes in the immune system, and part of these changes involves an increase in circulating immunological biomarkers, a process known as "Inflammaging." Inflammaging can be associated with many diseases related to older people. As the older population continues to grow, understanding changes in the immune system becomes essential. While prior studies assessing these alterations have been conducted in countries with Caucasian populations, this investigation marks a pioneering effort. The object of the study is to describe for the first time that the distribution of cytokines, chemokines, and growth factors serum levels, assessed by Luminex platform, has been examined in a Brazilian population-based study of older adult females and males by age. Blood samples from 2111 participants (≥50 years old) were analyzed at the baseline (2015/2016) of the ELSI-Brazil study. The exploratory variables considered in the study were age, sex, educational level, residence area, geographic region, alcohol and smoking consumption, physical activity, and self-reported medical diagnoses of hypertension, diabetes, asthma, arthritis, and cancer. The association between serum biomarker levels and age was assessed by a quantile regression model adjusted in the total population and stratified by sex. The significance level considered in the analysis was 0.05. The mean age of the participants was 62.9 years, with a slight majority of female (52.7 %). Differences were found between the sexes in the median circulating levels of the CCL11, CXCL10, and FGF biomarkers. Eight biomarkers showed significant associations with age, including the pro-inflammatory CXCL10, TNF-α, IL-6, IL-17, and IL-2; and type 2/regulatory CCL11 and IL-4, showing positive associations, and anti-inflammatory IL-1Ra showing a negative association. The results suggest similar associations between the sexes, revealing an inflammatory profile characterized by types 1 and 2. Remarkably, these findings reinforce the concept of the Inflammaging process in Brazilian population. These findings add novel insights to about the immunosenescence aspects in middle-income countries and help define biomarkers capable of monitoring inflammation in older adults., Competing Interests: Declaration of competing interest The authors declare no conflict of interest and none of financial or personal interests appeared to influence the work reported in this article., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
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- 2024
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3. Paradoxical Kinesia Induced by Nightmare: Unique Case Report and Insights regarding the Neural Mechanism Based on Human and Rat Studies.
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Tostes JG, Fabbro MD, Pedrosa DJ, Coimbra NC, Schwarting R, and Melo-Thomas L
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Introduction: Bradykinesia, characterized by slowed movement, stands out as a primary symptom observed in individuals with Parkinson's disease (PD). Nonetheless, there are instances where PD patients exhibit sudden and effective movements despite the presence of bradykinesia. This phenomenon, referred to as paradoxical kinesia, has remained a subject of interest for neuroscientists, who have struggled to unravel its underlying neural mechanisms for decades., Case Presentation: We describe a patient who is suffering from advanced PD. The patient has severe motor limitations, including difficulty rising from bed and walking, as well as cognitive decline and visual impairment. However, an interesting occurrence took place during a nightmare episode. Surprisingly, the patient was able to get out of bed and quickly run away from the perceived threat within the nightmare, without any assistance., Conclusion: This report presents the first documented case of paradoxical kinesia induced by nightmares in a patient with PD. This phenomenon raises questions about the neurological mechanisms involved, which are still not fully understood. Based on existing research conducted on both animal and human subjects, we propose that after processing the emotion of fear, the brain aversive system activates motor outputs to generate appropriate behavior. Thus, the brain aversive system converts the emotion of fear into action through projections from the inferior colliculus to motor-related areas such as the mesencephalic locomotor region, pontine nuclei, and substantia nigra., Competing Interests: The authors have no conflicts of interest to declare., (© 2024 The Author(s). Published by S. Karger AG, Basel.)
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- 2024
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4. GABAergic and glutamatergic inputs to the medulla oblongata and locus coeruleus noradrenergic pathways are critical for seizures and postictal antinociception neuromodulation.
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Mendonça-Dos-Santos M, Gonçalves TCT, Falconi-Sobrinho LL, Dos Anjos-Garcia T, Matias I Jr, de Oliveira RC, Dos Santos Sampaio MF, Dos Santos Cardoso F, Dos Santos WF, Machado HR, and Coimbra NC
- Subjects
- Rats, Animals, Medulla Oblongata metabolism, Solitary Nucleus metabolism, Norepinephrine metabolism, Seizures metabolism, Locus Coeruleus physiology, Receptors, N-Methyl-D-Aspartate metabolism, Benzylamines
- Abstract
We investigated the participation of the nucleus of the tractus solitarius (NTS) in tonic‒clonic seizures and postictal antinociception control mediated by NMDA receptors, the role of NTS GABAergic interneurons and noradrenergic pathways from the locus coeruleus (LC) in these phenomena. The NTS-lateral nucleus reticularis paragigantocellularis (lPGi)-LC pathway was studied by evaluating neural tract tracer deposits in the lPGi. NMDA and GABAergic receptors agonists and antagonists were microinjected into the NTS, followed by pharmacologically induced seizures. The effects of LC neurotoxic lesions caused by DSP-4, followed by NTS-NMDA receptor activation, on both tonic‒clonic seizures and postictal antinociception were also investigated. The NTS is connected to lPGi neurons that send outputs to the LC. Glutamatergic vesicles were found on dendrites and perikarya of GABAergic interneurons in the NTS. Both tonic‒clonic seizures and postictal antinociception are partially dependent on glutamatergic-mediated neurotransmission in the NTS of seizing rats in addition to the integrity of the noradrenergic system since NMDA receptor blockade in the NTS and intrathecal administration of DSP-4 decrease the postictal antinociception. The GABA
A receptor activation in the NTS decreases both seizure severity and postictal antinociception. These findings suggest that glutamatergic inputs to NTS-GABAergic interneurons, in addition to ascending and descending noradrenergic pathways from the LC, are critical for the control of both seizures and postictal antinociception., (© 2024. The Author(s).)- Published
- 2024
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5. Neostriatum neuronal TRPV 1 -signalling mediates striatal anandamide at high concentration facilitatory influence on neostriato-nigral dishinhibitory GABAergic connections.
- Author
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da Silva JA, Almada RC, Falconi-Sobrinho LL, Pigatto GR, Hernandes PM, and Coimbra NC
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- Animals, Rats, Rats, Wistar, Bicuculline pharmacology, GABA-A Receptor Antagonists pharmacology, Neural Pathways physiology, Receptors, GABA-A metabolism, Substantia Nigra
- Abstract
Rationale: Several lines of evidence have demonstrated that the cannabinoid type 1 receptor (CB
1 ) is found in the caudate nucleus and putamen (CPu) in addition to the substantia nigra pars reticulata (SNpr). Here, we investigated the role of endocannabinoid neuromodulation of striato-nigral disinhibitory projections on the activity of nigro-collicular GABAergic pathways that control the expression of unconditioned fear-related behavioural responses elicited by microinjections of the GABAA receptor selective antagonist bicuculline (BIC) in the deep layers of the superior colliculus (dlSC)., Methods: Fluorescent neural tract tracers were deposited in either CPu or in SNpr. Wistar rats received injection of vehicle, anandamide (AEA), either at low (50 pmol) or high (100 pmol) concentrations in CPu followed by bicuculline microinjections in dlSC., Results: Connections between CPu, the SNpr and dlSC were demonstrated. The GABAA receptor blockade in dlSC elicited panic-like behaviour. AEA at the lowest concentration caused a panicolytic-like effect that was antagonised by the CPu pretreatment with AM251 at 100 pmol. AEA at the highest concentration caused a panicogenic-like effect that was antagonised by the CPu pretreatment with 6-iodonordihydrocapsaicin (6-I-CPS) at different concentrations (0.6, 6, 60 nmol)., Conclusion: These findings suggest that while pre-synaptic CB1-signalling subserves an indirect facilitatory effect of AEA on striato-nigral pathways causing panicolytic-like responses through midbrain tectum enhanced activity, post-synaptic TRPV1 -signalling in CPu mediates AEA direct activation of striato-nigral disinhibitory pathways resulting in increasing dlSC neurons activity and a panicogenic-like response. All these actions seem to depend on the interface with the nigro-collicular inhibitory GABAergic pathways., Competing Interests: Declaration of Competing Interest The authors declare that there are no conflicts of interest concerning the presented work., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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6. Photobiomodulation for the treatment of neuroinflammation: A systematic review of controlled laboratory animal studies.
- Author
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Cardoso FDS, Salehpour F, Coimbra NC, Gonzalez-Lima F, and Gomes da Silva S
- Abstract
Background: Neuroinflammation is a response that involves different cell lineages of the central nervous system, such as neurons and glial cells. Among the non-pharmacological interventions for neuroinflammation, photobiomodulation (PBM) is gaining prominence because of its beneficial effects found in experimental brain research. We systematically reviewed the effects of PBM on laboratory animal models, specially to investigate potential benefits of PBM as an efficient anti-inflammatory therapy., Methods: We conducted a systematic search on the bibliographic databases (PubMed and ScienceDirect) with the keywords based on MeSH terms: photobiomodulation, low-level laser therapy, brain, neuroinflammation, inflammation, cytokine, and microglia. Data search was limited from 2009 to June 2022. We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The initial systematic search identified 140 articles. Among them, 54 articles were removed for duplication and 59 articles by screening. Therefore, 27 studies met the inclusion criteria., Results: The studies showed that PBM has anti-inflammatory properties in several conditions, such as traumatic brain injury, edema formation and hyperalgesia, ischemia, neurodegenerative conditions, aging, epilepsy, depression, and spinal cord injury., Conclusion: Taken together, these results indicate that transcranial PBM therapy is a promising strategy to treat brain pathological conditions induced by neuroinflammation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Cardoso, Salehpour, Coimbra, Gonzalez-Lima and Gomes da Silva.)
- Published
- 2022
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7. Lateralization in hemi-parkinsonian rats is affected by deep brain stimulation or glutamatergic neurotransmission in the inferior colliculus.
- Author
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Melo-Thomas L, Tacken L, Richter N, Almeida D, Rapôso C, de Melo SR, Thomas U, de Paiva YB, Medeiros P, Coimbra NC, and Schwarting R
- Abstract
After unilateral lesion of the medial forebrain bundle (MFB) by 6-OHDA rats exhibit lateralized deficits in spontaneous behavior or apomorphine-induced rotations. We investigated whether such lateralization is attenuated by either deep brain stimulation (DBS) or glutamatergic neurotransmission in the inferior colliculus (IC) of Wistar rats. Intracollicular DBS did not affect spontaneous lateralization but attenuated apomorphine-induced rotations. Spontaneous lateralization disappeared after both glutamatergic antagonist MK-801 or the agonist NMDA microinjected in the IC. Apomorphine-induced rotations were potentiated by MK-801 but were not affected by NMDA intracollicular microinjection. After injecting a bidirectional neural tract tracer into the IC, cell bodies and/or axonal fibers were found in the periaqueductal gray, superior colliculus, substantia nigra, cuneiform nucleus and pedunculo-pontine tegmental nucleus, suggesting the involvement of these structures in the motor improvement after IC manipulation. Importantly, the side of the IC microinjection regarding the lesion (ipsi- or contralateral) is particularly important and this effect may not involve the neostriatum directly. Significance Statement The inferior colliculus, usually viewed as an auditory structure, when properly manipulated may counteract motor deficits in Parkinsonian rats. Indeed, the present study showed that 30 Hz deep brain stimulation or glutamatergic neural network in the inferior colliculus reduced body asymmetry induced by medial forebrain bundle unilateral 6-OHDA lesion in rats, an animal model of Parkinsonism. Understanding how glutamatergic mechanisms in the inferior colliculus influence motor control, classically attributed to the basal nuclei circuitry, could be useful in the development of new therapeutics to treat Parkinson's disease and other motor disorders., Competing Interests: Authors report no conflict of interests., (Copyright © 2022 Melo-Thomas et al.)
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- 2022
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8. Mitochondrial Photobiomodulation as a Neurotherapeutic Strategy for Epilepsy.
- Author
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Cardoso FDS, Gonzalez-Lima F, and Coimbra NC
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- 2022
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9. Functional activation of the periaqueductal gray matter during conditioned and unconditioned fear in guinea pigs confronted with the Boa constrictor constrictor snake.
- Author
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Paula BB, Vieira-Rasteli EB, Calvo F, Coimbra NC, and Leite-Panissi CRA
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- Animals, Fear physiology, Guinea Pigs, Immunohistochemistry, Male, Neurons physiology, Boidae, Periaqueductal Gray metabolism
- Abstract
The periaqueductal gray matter (PAG) is an essential structure involved in the elaboration of defensive responses, such as when facing predators and conspecific aggressors. Using a prey vs predator paradigm, we aimed to evaluate the PAG activation pattern evoked by unconditioned and conditioned fear situations. Adult male guinea pigs were confronted either by a Boa constrictor constrictor wild snake or by the aversive experimental context. After the behavioral test, the rodents were euthanized and the brain prepared for immunohistochemistry for Fos protein identification in different PAG columns. Although Fos-protein-labeled neurons were found in different PAG columns after both unconditioned and conditioned fear situations at the caudal level of the PAG, we found greater activation of the lateral column compared to the ventrolateral and dorsomedial columns after predator exposure. Moreover, the lateral column of the PAG showed higher Fos-labeled cells at the caudal level compared to the same area at the rostral level. The present results suggested that there are different activation patterns of PAG columns during unconditioned and conditioned fear in guinea pigs. It is possible to hypothesize that the recruitment of specific PAG columns depended on the nature of the threatening stimulus.
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- 2022
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10. Editorial: Classical and Modern Biotechnology Applied to the Treatment of Epilepsy and Anxiety Disorders.
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Beleboni RO, Mortari MR, Melo-Thomas L, and Coimbra NC
- Abstract
Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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- 2022
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11. The blockade of μ‑opioid receptors in the lateral hypothalamus enhances panic attack‑like behaviour and diminishes defensive antinociception.
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Maia Fernandes BF, de Avila DR, Santana VC, Pichinelli Maffei TH, Streg RV, Vale JS, de Araújo Berber RC, de Oliveira RC, Coimbra NC, and Oliveira R
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- Animals, Bicuculline pharmacology, Fear physiology, Naloxone analogs & derivatives, Naloxone pharmacology, Narcotic Antagonists pharmacology, Nociception, Panic physiology, Rats, Rats, Wistar, Behavior, Animal drug effects, Behavior, Animal physiology, Hypothalamic Area, Lateral drug effects, Hypothalamic Area, Lateral metabolism, Panic Disorder metabolism, Panic Disorder psychology, Receptors, Opioid, mu antagonists & inhibitors, Receptors, Opioid, mu metabolism
- Abstract
The lateral hypothalamus (LH) sends neural pathways to structures involved on predator‑related defensive behaviours, escape and antinociception. The aim of this study was to investigate the role played by μ-opioid receptors located on LH neurons in defensive behaviour and unconditioned fear‑induced antinociception elicited by electric stimulation of LH. To achieve the goals, the μ1-opioid receptor selective antagonist naloxonazine was administered at different concentrations in the LH, and the defensive behaviour and fear‑induced antinociception elicited by electrical stimulation of LH were evaluated. The electrical stimulation of LH caused escape behaviour followed by defensive antinociception. Microinjections of naloxonazine in a concentration of 5.0 μg/0.2 μL in the LH decreased the aversive stimulus‑induced escape behaviour thresholds, but diminished defensive antinociception. These findings suggest that μ-opioid receptors of LH can be critical to panic attack‑related symptoms and facilitate the unconditioned fear‑induced antinociception produced by LH neurons activation.
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- 2022
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12. Increased body sway in phobic patients exposed to images of spiders.
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Linares IMP, Nardi AE, Guimarães FS, Arrais KC, Chagas MH, Osório FL, Hallak JE, Zuardi AW, Coimbra NC, and Crippa JA
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- Animals, Anxiety, Anxiety Disorders, Heart Rate, Humans, Phobic Disorders, Spiders
- Abstract
Objective: The aim of the present study was to analyze the body sway response in specific phobia (SP) patients and healthy controls while viewing neutral, phobic, and disgusting images., Methods: The participants' heart rate (HR) and skin conductance were also recorded during the procedure. Nineteen patients with arachnophobia and 19 healthy volunteers matched by age, gender, and years of education underwent a postural control test on a stabilometric platform., Results: The platform recorded increased body sway in the SP group when exposed to spider images (SPI). The SP group presented increases in most parameters (SD, velocity, frequency, area, p ≤ 0.05) when viewing pictures of the SPI category. Psychometric measures of subjective anxiety (State-Trait Anxiety Inventory, STAI) and physiological states (HR; skin conductance responses; spontaneous fluctuations in skin conductance) showed increased anxiety (p ≤ 0.05) in the SP group compared to healthy volunteers. High anxiety levels were observed throughout the assessment, including the task of exposure to SPI (p ≤ 0.05). No significant effect or correlation was found between skin conductance and body sway measures (p > 0.05)., Conclusions: The results of the postural control test suggest the occurrence of a defensive escape response in SP, in agreement with previous evidence.
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- 2021
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13. Graphene oxide prevents lateral amygdala dysfunctional synaptic plasticity and reverts long lasting anxiety behavior in rats.
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Franceschi Biagioni A, Cellot G, Pati E, Lozano N, Ballesteros B, Casani R, Coimbra NC, Kostarelos K, and Ballerini L
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- Amygdala, Animals, Anxiety, Graphite, Rats, Synaptic Transmission, Fear, Neuronal Plasticity
- Abstract
Engineered small graphene oxide (s-GO) sheets were previously shown to reversibly down-regulate glutamatergic synapses in the hippocampus of juvenile rats, disclosing an unexpected translational potential of these nanomaterials to target selective synapses in vivo. Synapses are anatomical specializations acting in the Central Nervous System (CNS) as functional interfaces among neurons. Dynamic changes in synaptic function, named synaptic plasticity, are crucial to learning and memory. More recently, pathological mechanisms involving dysfunctional synaptic plasticity were implicated in several brain diseases, from dementia to anxiety disorders. Hyper-excitability of glutamatergic neurons in the lateral nucleus of the amygdala complex (LA) is substantially involved in the storage of aversive memory induced by stressful events enabling post-traumatic stress disorder (PTSD). Here we translated in PTSD animal model the ability of s-GO, when stereotaxically administered to hamper LA glutamatergic transmission and to prevent the behavioral response featured in long-term aversive memory. We propose that s-GO, by interference with glutamatergic plasticity, impair LA-dependent memory retrieval related to PTSD., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)
- Published
- 2021
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14. An Adapted Chronic Constriction Injury of the Sciatic Nerve Produces Sensory, Affective, and Cognitive Impairments: A Peripheral Mononeuropathy Model for the Study of Comorbid Neuropsychiatric Disorders Associated with Neuropathic Pain in Rats.
- Author
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Medeiros P, Dos Santos IR, Júnior IM, Palazzo E, da Silva JA, Machado HR, Ferreira SH, Maione S, Coimbra NC, and de Freitas RL
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- Animals, Constriction, Disease Models, Animal, Hyperalgesia epidemiology, Rats, Sciatic Nerve, Cognitive Dysfunction, Mononeuropathies, Neuralgia epidemiology, Neuralgia etiology
- Abstract
Background: Chronic constriction injury (CCI) is a model of neuropathic pain induced by four loose ligatures around the sciatic nerve. This work aimed to investigate the sensory, affective, cognitive, and motor changes induced by an adaptation of the CCI model by applying a single ligature around the sciatic nerve., Methods: Mechanical allodynia was measured from day 1 to day 28 postsurgery by the von Frey test. The beam walking test (BWT) was conducted weekly until 28 days after surgery. Anxiety- and depression-like behaviors, and cognitive performance were assessed through the open field (OF), forced swimming (FS), and novel object recognition (NOR) tests, respectively, 21 days after surgery., Results: The two CCI models, both Bennett and Xie's model (four ligatures of the sciatic nerve) and a modification of it (one ligature), induced mechanical allodynia, increased immobility in the FS, and reduced recognition index in the NOR. The exploratory behavior and time spent in the central part of the arena decreased, while the defensive behavior increased in the OF. The animals subjected to the two CCI models showed motor alterations in the BWT; however, autotomy was observed only in the group with four ligatures and not in the group with a single ligature., Conclusions: Overall these results demonstrate that our adapted CCI model, using a single ligature around the sciatic nerve, induces sensory, affective, cognitive, and motor alterations comparable to the CCI model with four ligatures without generating autotomy. This adaptation to the CCI model may therefore represent an appropriate and more easily performed model for inducing neuropathic pain and study underlying mechanisms and effective treatments., (© The Author(s) 2020. Published by Oxford University Press on behalf of the American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2021
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15. Effects of bone marrow mononuclear cells on induction of axonal sprouting in cortico-cortical and cortico-striatal pathways in an animal model of cortical ablation.
- Author
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Dos Santos Sampaio MF, Giraldi-Guimarães A, da Silva Lourenço C, Pereira MG, and Coimbra NC
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- Animals, Disease Models, Animal, Male, Neural Pathways, Neuroanatomical Tract-Tracing Techniques, Rats, Wistar, Axons physiology, Bone Marrow, Bone Marrow Transplantation, Brain Injuries therapy, Cerebral Cortex injuries, Corpus Striatum, Leukocytes, Mononuclear transplantation, Nerve Regeneration physiology
- Abstract
Objectives: Many therapies have been proposed in order to investigate the mechanisms of neural repair associated with neurological diseases, including bone marrow mononuclear cells (BMMC) transplantation. However, there is evidence that some encephalic injuries are less responsive to neural repair, such as, for example, cortical ablation. On the other hand, some models of cortical ablation have shown functional recovery after BMMC transplantation. Thus, it is relevant to expand the knowledge of BMMC transplantation-induced neuroplasticity in animal models, considering a promising approach for the rehabilitation of patients with neurological diseases. Using an experimental model of cerebral cortex ablation in adult male Wistar rats, which is known to be poorly responsive to neuroplasticity, the aim of this study was to investigate the effects of BMMC on axonal sprouting in cortico-cortical and cortico-striatal pathways synaptic fields. An anterograde neurotracer was used to evaluate the distribution of axonal fibres., Results: The results showed that BMMC were not able to significantly induce axonal sprouting in the evaluated synaptic fields. Our results reinforced the idea that cortical ablation may be less responsive to neuroplasticity and the beneficial effects of BMMC therapy depend on the particularities of a neural microenvironment intrinsic to a given cortical lesion.
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- 2020
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16. Anandamide in the anterior hypothalamus diminishes defensive responses elicited in mice threatened by Epicrates cenchria constrictor serpents.
- Author
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Dos Anjos-Garcia T and Coimbra NC
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- Animals, Male, Mice, Mice, Inbred C57BL, Receptor, Cannabinoid, CB1 drug effects, TRPV Cation Channels drug effects, Arachidonic Acids pharmacology, Bicuculline pharmacology, Endocannabinoids pharmacology, Escape Reaction drug effects, Hypothalamus, Anterior drug effects, Polyunsaturated Alkamides pharmacology
- Abstract
The purpose of this study was to investigate whether the panicolytic‑like effect of different doses of anandamide microinjected into the anterior hypothalamus (AH) follows the same pattern of a bell‑shaped dose‑response curve observed with the same dose treatment in dorsomedial and ventromedial hypothalamus. We investigated this assumption by administering the cannabinoid and vanilloid receptor agonist anandamide into the anterior hypothalamus of mice and exposing them to the real threatening situation by using our experimental model based on confrontations between rodents and wild snakes. Our findings showed a gradual decay of response, with a significant attenuation of the panic attack‑like responses with anandamide at the highest dose but no effect was found after anandamide at the lowest or intermediate doses. An immunohistochemical procedure showed a lower degree of TRPV1 receptor and moderate to higher degree of Cb1 receptors in anterior hypothalamus. In conclusion, the pattern of dose‑response curve of anandamide microinjected in the AH does not seem to be the same classical pattern compared with other hypothalamic nuclei.
- Published
- 2020
17. Indomethacin attenuates mechanical allodynia during the organization but not the maintenance of the peripheral neuropathic pain induced by nervus ischiadicus chronic constriction injury.
- Author
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Medeiros P, Dos Santos IR, Medeiros AC, da Silva JA, Ferreira SH, de Freitas RL, and Coimbra NC
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- Animals, Constriction, Disease Models, Animal, Male, Neuralgia etiology, Pain Threshold, Rats, Rats, Sprague-Dawley, Rats, Wistar, Indomethacin administration & dosage, Neuralgia drug therapy, Pain Measurement, Sciatic Nerve injuries
- Abstract
The neurochemical mechanisms underlying neuropathic pain (NP) are related to peripheral and central sensitization caused by the release of inflammatory mediators in the peripheral damaged tissue and ectopic discharges from the injured nerve, leading to a hyperexcitable state of spinal dorsal horn neurons. The aim of this work was to clarify the role played by cyclooxygenase (COX) in the lesioned peripheral nerve in the development and maintenance of NP by evaluating at which moment the non-steroidal anti-inflammatory drug indomethacin, a non-selective COX inhibitor, attenuated mechanical allodynia after placing one loose ligature around the nervus ischiadicus, an adaptation of Bennett and Xie's model in rodents. NP was induced in male Wistar rats by subjecting them to chronic constriction injury (CCI) of the nervus ischiadicus, placing one loose ligature around the peripheral nerve, and a sham surgery (without CCI) was used as control. Indomethacin (2 mg/kg) or vehicle was intraperitoneally and acutely administered in each group of rats and at different time windows (1, 2, 4, 7, 14, 21, and 28 days) after the CCI or sham surgical procedures, followed by von Frey's test for 30 min. The data showed that indomethacin decreased the mechanical allodynia threshold of rats on the first, second, and fourth days after CCI (P<0.05). These findings suggested that inflammatory mechanisms are involved in the induction of NP and that COX-1 and COX-2 are involved in the induction but not in the maintenance of NP.
- Published
- 2020
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18. Stimulation of the Nigrotectal Pathway at the Level of the Superior Colliculus Reduces Threat Recognition and Causes a Shift From Avoidance to Approach Behavior.
- Author
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Almada RC, Genewsky AJ, Heinz DE, Kaplick PM, Coimbra NC, and Wotjak CT
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- Animals, Anxiety drug therapy, Behavior, Animal drug effects, Bicuculline pharmacology, Choice Behavior drug effects, Fear drug effects, Fear physiology, Mice, Inbred C57BL, Neural Pathways drug effects, Neurons drug effects, Neurons physiology, Superior Colliculi drug effects, Behavior, Animal physiology, Choice Behavior physiology, Neural Pathways physiology, Superior Colliculi physiology
- Abstract
Defensive behavioral responses are essential for survival in threating situations. The superior colliculus (SC) has been implicated in the generation of defensive behaviors elicited by visual, tactile and auditory stimuli. Furthermore, substantia nigra pars reticulata (SNr) neurons are known to exert a modulatory effect on midbrain tectum neural substrates. However, the functional role of this nigrotectal pathway in threating situations is still poorly understood. Using optogenetics in freely behaving mice, we activated SNr projections at the level of the SC, and assessed consequences on behavioral performance in an open field test (OFT) and the beetle mania task (BMT). The latter confronts a mouse with an erratic moving robo-beetle and allows to measure active and passive defensive responses upon frequent encounter of the threatening object. Channelrhodopsin-2 (ChR2)-mediated activation of the inhibitory nigrotectal pathway did not affect anxiety-like and exploratory behavior in the OFT, but increased the number of contacts between robo-beetle and test mouse in the BMT. Depending on the size of the arena, active avoidance responses were reduced, whereas tolerance and close following of the robo-beetle were significantly increased. We conclude from the data that the nigrotectal pathway plays holds the potential to modulate innate fear by attenuating threat recognition and causing a shift from defensive to approach behavior.
- Published
- 2018
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19. Critical neuropsychobiological analysis of panic attack- and anticipatory anxiety-like behaviors in rodents confronted with snakes in polygonal arenas and complex labyrinths: a comparison to the elevated plus- and T-maze behavioral tests.
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Coimbra NC, Paschoalin-Maurin T, Bassi GS, Kanashiro A, Biagioni AF, Felippotti TT, Elias-Filho DH, Mendes-Gomes J, Cysne-Coimbra JP, Almada RC, and Lobão-Soares B
- Subjects
- Animals, Fear physiology, Fear psychology, Maze Learning, Predatory Behavior, Rats, Rats, Wistar, Anxiety Disorders psychology, Behavior, Animal physiology, Instinct, Panic Disorder psychology, Snakes
- Abstract
Objective:: To compare prey and snake paradigms performed in complex environments to the elevated plus-maze (EPM) and T-maze (ETM) tests for the study of panic attack- and anticipatory anxiety-like behaviors in rodents., Methods:: PubMed was reviewed in search of articles focusing on the plus maze test, EPM, and ETM, as well as on defensive behaviors displayed by threatened rodents. In addition, the authors' research with polygonal arenas and complex labyrinth (designed by the first author for confrontation between snakes and small rodents) was examined., Results:: The EPM and ETM tests evoke anxiety/fear-related defensive responses that are pharmacologically validated, whereas the confrontation between rodents and snakes in polygonal arenas with or without shelters or in the complex labyrinth offers ethological conditions for studying more complex defensive behaviors and the effects of anxiolytic and panicolytic drugs. Prey vs. predator paradigms also allow discrimination between non-oriented and oriented escape behavior., Conclusions:: Both EPM and ETM simple labyrinths are excellent apparatuses for the study of anxiety- and instinctive fear-related responses, respectively. The confrontation between rodents and snakes in polygonal arenas, however, offers a more ethological environment for addressing both unconditioned and conditioned fear-induced behaviors and the effects of anxiolytic and panicolytic drugs.
- Published
- 2017
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20. NMDA and AMPA/kainate glutamatergic receptors in the prelimbic medial prefrontal cortex modulate the elaborated defensive behavior and innate fear-induced antinociception elicited by GABAA receptor blockade in the medial hypothalamus.
- Author
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de Freitas RL, Salgado-Rohner CJ, Biagioni AF, Medeiros P, Hallak JE, Crippa JA, and Coimbra NC
- Subjects
- Animals, Behavior, Animal drug effects, Bicuculline pharmacology, Excitatory Amino Acid Antagonists pharmacology, Fear drug effects, GABA-A Receptor Antagonists pharmacology, Hypothalamus, Middle drug effects, Isoquinolines pharmacology, Male, Nociceptive Pain drug therapy, Nociceptive Pain physiopathology, Pain Perception drug effects, Panic drug effects, Prefrontal Cortex drug effects, Quinoxalines pharmacology, Rats, Wistar, Receptors, AMPA antagonists & inhibitors, Receptors, AMPA metabolism, Receptors, GABA-A metabolism, Receptors, N-Methyl-D-Aspartate antagonists & inhibitors, Receptors, N-Methyl-D-Aspartate metabolism, Synaptic Transmission drug effects, Synaptic Transmission physiology, Behavior, Animal physiology, Fear physiology, Hypothalamus, Middle physiology, Pain Perception physiology, Panic physiology, Prefrontal Cortex physiology
- Abstract
The aim of the present study was to investigate the involvement of N-methyl-d-aspartate (NMDA) and amino-3-hydroxy-5-methyl-isoxazole-4-proprionate (AMPA)/kainate receptors of the prelimbic (PL) division of the medial prefrontal cortex (MPFC) on the panic attack-like reactions evoked by γ-aminobutyric acid-A receptor blockade in the medial hypothalamus (MH). Rats were pretreated with NaCl 0.9%, LY235959 (NMDA receptor antagonist), and NBQX (AMPA/kainate receptor antagonist) in the PL at 3 different concentrations. Ten minutes later, the MH was treated with bicuculline, and the defensive responses were recorded for 10 min. The antagonism of NMDA receptors in the PL decreased the frequency and duration of all defensive behaviors evoked by the stimulation of the MH and reduced the innate fear-induced antinociception. However, the pretreatment of the PL cortex with NBQX was able to decrease only part of defensive responses and innate fear-induced antinociception. The present findings suggest that the NMDA-glutamatergic system of the PL is critically involved in panic-like responses and innate fear-induced antinociception and those AMPA/kainate receptors are also recruited during the elaboration of fear-induced antinociception and in panic attack-related response. The activation of the glutamatergic neurotransmission of PL division of the MPFC during the elaboration of oriented behavioral reactions elicited by the chemical stimulation of the MH recruits mainly NMDA receptors in comparison with AMPA/kainate receptors.
- Published
- 2014
- Full Text
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21. Involvement of prelimbic medial prefrontal cortex in panic-like elaborated defensive behaviour and innate fear-induced antinociception elicited by GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei: role of the endocannabinoid CB1 receptor.
- Author
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Freitas RL, Salgado-Rohner CJ, Hallak JE, Crippa JA, and Coimbra NC
- Subjects
- Analysis of Variance, Animals, Bicuculline pharmacology, Bicuculline therapeutic use, Disease Models, Animal, Dose-Response Relationship, Drug, GABA Antagonists pharmacology, GABA Antagonists therapeutic use, Hyperalgesia drug therapy, Hyperalgesia pathology, Hypothalamus physiology, Instinct, Male, Microinjections, Pain Threshold drug effects, Piperidines pharmacology, Prefrontal Cortex drug effects, Pyrazoles pharmacology, Rats, Rats, Wistar, Receptor, Cannabinoid, CB1 antagonists & inhibitors, Defense Mechanisms, Hypothalamus drug effects, Pain Measurement drug effects, Panic drug effects, Prefrontal Cortex physiopathology, Receptor, Cannabinoid, CB1 metabolism, Receptors, GABA-A metabolism
- Abstract
It has been shown that GABAA receptor blockade in the dorsomedial and ventromedial hypothalamic nuclei (DMH and VMH, respectively) induces elaborated defensive behavioural responses accompanied by antinociception, which has been utilized as an experimental model of panic attack. Furthermore, the prelimbic (PL) division of the medial prefrontal cortex (MPFC) has been related to emotional reactions and the processing of nociceptive information. The aim of the present study was to investigate the possible involvement of the PL cortex and the participation of local cannabinoid CB1 receptors in the elaboration of panic-like reactions and in innate fear-induced antinociception. Elaborated fear-induced responses were analysed during a 10-min period in an open-field test arena. Microinjection of the GABAA receptor antagonist bicuculline into the DMH/VMH evoked panic-like behaviour and fear-induced antinociception, which was decreased by microinjection of the non-selective synaptic contact blocker cobalt chloride in the PL cortex. Moreover, microinjection of AM251 (25, 100 or 400 pmol), an endocannabinoid CB1 receptor antagonist, into the PL cortex also attenuated the defensive behavioural responses and the antinociception that follows innate fear behaviour elaborated by DMH/VMH. These data suggest that the PL cortex plays an important role in the organization of elaborated forward escape behaviour and that this cortical area is also involved in the elaboration of innate fear-induced antinociception. Additionally, CB1 receptors in the PL cortex modulate both panic-like behaviours and fear-induced antinociception elicited by disinhibition of the DMH/VMH through microinjection of bicuculline.
- Published
- 2013
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22. Neuroanatomical and neuropharmacological approaches to postictal antinociception-related prosencephalic neurons: the role of muscarinic and nicotinic cholinergic receptors.
- Author
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de Freitas RL, Bolognesi LI, Twardowschy A, Corrêa FM, Sibson NR, and Coimbra NC
- Abstract
Several studies have suggested the involvement of the hippocampus in the elaboration of epilepsy. There is evidence that suggests the hippocampus plays an important role in the affective and motivational components of nociceptive perception. However, the exact nature of this involvement remains unclear. Therefore, the aim of this study was to determine the role of muscarinic and nicotinic cholinergic receptors in the dorsal hippocampus (dH) in the organization of postictal analgesia. In a neuroanatomical study, afferent connections were found from the somatosensory cortex, the medial septal area, the lateral septal area, the diagonal band of Broca, and the dentate gyrus to the dH; all these areas have been suggested to modulate convulsive activity. Outputs to the dH were also identified from the linear raphe nucleus, the median raphe nucleus (MdRN), the dorsal raphe nucleus, and the locus coeruleus. All these structures comprise the endogenous pain modulatory system and may be involved either in postictal pronociception or antinociception that is commonly reported by epileptic patients. dH-pretreatment with cobalt chloride (1.0 mmol/L CoCl2/0.2 μL) to transiently inhibit local synapses decreased postictal analgesia 10 min after the end of seizures. Pretreatment of the dH with either atropine or mecamylamine (1.0 μg/0.2 μL) attenuated the postictal antinociception 30 min after seizures, while the higher dose (5.0 μg/0.2 μL) decreased postictal analgesia immediately after the end of seizures. These findings suggest that the dH exerts a critical role in the organization of postictal analgesia and that muscarinic and nicotinic cholinergic receptor-mediated mechanisms in the dH are involved in the elaboration of antinociceptive processes induced by generalized tonic-clonic seizures.
- Published
- 2013
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23. Panic-like defensive behavior but not fear-induced antinociception is differently organized by dorsomedial and posterior hypothalamic nuclei of Rattus norvegicus (Rodentia, Muridae).
- Author
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Biagioni AF, Silva JA, and Coimbra NC
- Subjects
- Animals, Bicuculline pharmacology, Dorsomedial Hypothalamic Nucleus drug effects, GABA-A Receptor Antagonists pharmacology, Hypothalamus, Posterior drug effects, Male, Maze Learning, Pain Threshold drug effects, Panic Disorder etiology, Rats, Dorsomedial Hypothalamic Nucleus physiology, Escape Reaction physiology, Hypothalamus, Posterior physiology, Panic Disorder metabolism
- Abstract
The hypothalamus is a forebrain structure critically involved in the organization of defensive responses to aversive stimuli. Gamma-aminobutyric acid (GABA)ergic dysfunction in dorsomedial and posterior hypothalamic nuclei is implicated in the origin of panic-like defensive behavior, as well as in pain modulation. The present study was conducted to test the difference between these two hypothalamic nuclei regarding defensive and antinociceptive mechanisms. Thus, the GABA(A) antagonist bicuculline (40 ng/0.2 µL) or saline (0.9% NaCl) was microinjected into the dorsomedial or posterior hypothalamus in independent groups. Innate fear-induced responses characterized by defensive attention, defensive immobility and elaborate escape behavior were evoked by hypothalamic blockade of GABA(A) receptors. Fear-induced defensive behavior organized by the posterior hypothalamus was more intense than that organized by dorsomedial hypothalamic nuclei. Escape behavior elicited by GABA(A) receptor blockade in both the dorsomedial and posterior hypothalamus was followed by an increase in nociceptive threshold. Interestingly, there was no difference in the intensity or in the duration of fear-induced antinociception shown by each hypothalamic division presently investigated. The present study showed that GABAergic dysfunction in nuclei of both the dorsomedial and posterior hypothalamus elicit panic attack-like defensive responses followed by fear-induced antinociception, although the innate fear-induced behavior originates differently in the posterior hypothalamus in comparison to the activity of medial hypothalamic subdivisions.
- Published
- 2012
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24. Anti-aversive effects of cannabidiol on innate fear-induced behaviors evoked by an ethological model of panic attacks based on a prey vs the wild snake Epicrates cenchria crassus confrontation paradigm.
- Author
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Uribe-Mariño A, Francisco A, Castiblanco-Urbina MA, Twardowschy A, Salgado-Rohner CJ, Crippa JA, Hallak JE, Zuardi AW, and Coimbra NC
- Subjects
- Animals, Anti-Anxiety Agents pharmacology, Anti-Anxiety Agents therapeutic use, Cannabidiol therapeutic use, Humans, Male, Mice, Snakes, Cannabidiol pharmacology, Disease Models, Animal, Fear drug effects, Instinct, Panic Disorder drug therapy
- Abstract
Several pharmacological targets have been proposed as modulators of panic-like reactions. However, interest should be given to other potential therapeutic neurochemical agents. Recent attention has been given to the potential anxiolytic properties of cannabidiol, because of its complex actions on the endocannabinoid system together with its effects on other neurotransmitter systems. The aim of this study was to investigate the effects of cannabidiol on innate fear-related behaviors evoked by a prey vs predator paradigm. Male Swiss mice were submitted to habituation in an arena containing a burrow and subsequently pre-treated with intraperitoneal administrations of vehicle or cannabidiol. A constrictor snake was placed inside the arena, and defensive and non-defensive behaviors were recorded. Cannabidiol caused a clear anti-aversive effect, decreasing explosive escape and defensive immobility behaviors outside and inside the burrow. These results show that cannabidiol modulates defensive behaviors evoked by the presence of threatening stimuli, even in a potentially safe environment following a fear response, suggesting a panicolytic effect.
- Published
- 2012
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25. Evaluation of the neuroprotective effect of ketoprofen on rats submitted to permanent focal brain ischemia.
- Author
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Silva MN, Colli BO, Coimbra NC, and Coutinho Netto J
- Subjects
- Animals, Brain drug effects, Brain metabolism, Brain pathology, Glutamic Acid analysis, Infarction, Middle Cerebral Artery metabolism, Infarction, Middle Cerebral Artery surgery, Rats, Rats, Wistar, Time Factors, Anti-Inflammatory Agents, Non-Steroidal therapeutic use, Infarction, Middle Cerebral Artery pathology, Ketoprofen therapeutic use, Neuroprotective Agents therapeutic use
- Abstract
Objective: To study the neurobehavioral, biochemical and histopathological consequences of permanent focal brain ischemia, and the putative neuroprotective action of ketoprofen., Method: One-hundred-and-three Wistar rats divided into groups A and B were respectively submitted to 48 hours and 15 days of ischemia. Each group was divided into 4 subgroups: ischemic not treated, ischemic treated, sham not treated, and sham treated. Ischemic animals had the left middle cerebral artery coagulated. Ketoprofen was administered to treated subgroups 15 minutes before arterial coagulation (manipulation in the sham group)., Results: Exploratory activity and defecation were reduced in all ischemic animals in the first postoperative days and constant histopathological changes were observed in each group. The total brain glutamate levels were higher in treated animals 48 hours after surgery., Conclusion: No clear parallelism among behavioral, biochemical and histopathological findings was observed. Ketoprofen demonstrated no neuroprotective effect on the behavioral or histopathological aspects of focal permanent brain ischemia.
- Published
- 2007
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26. Inhibition of acute nociceptive responses in rats after i.c.v. injection of Thr6-bradykinin, isolated from the venom of the social wasp, Polybia occidentalis.
- Author
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Mortari MR, Cunha AO, Carolino RO, Coutinho-Netto J, Tomaz JC, Lopes NP, Coimbra NC, and Dos Santos WF
- Subjects
- Analgesics administration & dosage, Animals, Bradykinin administration & dosage, Bradykinin isolation & purification, Bradykinin pharmacology, Chromatography, High Pressure Liquid, Dose-Response Relationship, Drug, Injections, Intraventricular, Kallikrein-Kinin System, Male, Morphine administration & dosage, Morphine pharmacology, Pain physiopathology, Pain Measurement, Rats, Rats, Wistar, Receptor, Bradykinin B2 drug effects, Receptor, Bradykinin B2 metabolism, Spectrometry, Mass, Electrospray Ionization, Tandem Mass Spectrometry, Analgesics pharmacology, Bradykinin analogs & derivatives, Pain drug therapy, Wasp Venoms chemistry
- Abstract
Background and Purpose: In this work, a neuroactive peptide from the venom of the neotropical wasp Polybia occidentalis was isolated and its anti-nociceptive effects were characterized in well-established pain induction models., Experimental Approach: Wasp venom was analysed by reverse-phase HPLC and fractions screened for anti-nociceptive activity. The structure of the most active fraction was identified by electron-spray mass spectrometry (ESI-MS/MS) and it was further assessed in two tests of anti-nociceptive activity in rats: the hot plate and tail flick tests., Key Results: The most active fraction contained a peptide whose structure was Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg-OH, which corresponds to that of Thr(6)-BK, a bradykinin analogue. This peptide was given by i.c.v. injection to rats. In the tail flick test, Thr(6)-BK induced anti-nociceptive effects, approximately twice as potent as either morphine or bradykinin also given i.c.v. The anti-nociceptive activity of Thr(6)-BK peaked at 30 min after injection and persisted for 2 h, longer than bradykinin. The primary mode of action of Thr(6)-BK involved the activation of B(2) bradykinin receptors, as anti-nociceptive effects of Thr(6)-BK were antagonized by a selective B(2) receptor antagonist., Conclusions and Implications: Our data indicate that Thr(6)-BK acts through B(2) bradykinin receptors in the mammalian CNS, evoking antinociceptive behaviour. This activity is remarkably different from that of bradykinin, despite the structural similarities between both peptides. In addition, due to the increased metabolic stability of Thr(6)-BK, relative to that of bradykinin, this peptide could provide a novel tool in the investigation of kinin pathways involved with pain.
- Published
- 2007
- Full Text
- View/download PDF
27. Compliance with maintenance treatment of asthma (ADERE study).
- Author
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Chatkin JM, Cavalet-Blanco D, Scaglia NC, Tonietto RG, Wagner MB, and Fritscher CC
- Subjects
- Adult, Albuterol therapeutic use, Drug Combinations, Female, Fluticasone, Humans, Male, Multivariate Analysis, Prospective Studies, Regression Analysis, Salmeterol Xinafoate, Severity of Illness Index, Albuterol analogs & derivatives, Androstadienes therapeutic use, Asthma drug therapy, Bronchodilator Agents therapeutic use, Patient Compliance statistics & numerical data
- Abstract
Objective: To determine the rate of compliance with preventive treatment of moderate and severe persistent asthma., Methods: Physicians at various medical centers across the country were invited to nominate patients for participation in the study. Inclusion criteria were being over the age of 12 and presenting moderate or severe persistent asthma. Participating patients received salmeterol/fluticasone 50/250 microg by dry powder inhaler for 90 days and were instructed to return the empty packages at the end of the study as a means of determining the total quantity used. In order to evaluate compliance, a member of the research team contacted each patient via telephone at the study outset and again at the end of the 90-day study period. Asthma patients were considered compliant with the treatment if they used at least 85% of the prescribed dose. The following variables were studied: gender, age, race, marital status, years of schooling, smoking habits, other atopic conditions, comorbidities, asthma severity, use of other medication and number of hospital admissions for asthma., Results: A total of 131 patients from fifteen states were included. The overall rate of compliance was found to be 51.9%. There was a significant difference in compliance in relation to asthma severity: compliance was greater among patients with severe persistent asthma than among those with moderate persistent asthma (p = 0.02). There were no statistically significant differences among any of the other variables., Conclusion: The overall rate of compliance with maintenance treatment of asthma was low.
- Published
- 2006
28. Thermoeffector neuronal pathways in fever: a study in rats showing a new role of the locus coeruleus.
- Author
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Almeida MC, Steiner AA, Coimbra NC, and Branco LG
- Subjects
- Animals, Catecholamines physiology, Denervation, Dinoprostone physiology, Lipopolysaccharides pharmacology, Male, Neural Pathways, Rats, Rats, Wistar, Fever physiopathology, Locus Coeruleus cytology, Locus Coeruleus physiology
- Abstract
It is known that brain noradrenaline (norepinephrine) mediates fever, but the neuronal group involved is unknown. We studied the role of the major noradrenergic nucleus, the locus coeruleus (LC), in lipopolysaccharide (LPS)-induced fever. Male Wistar rats had their LC completely ablated electrolytically or their catecholaminergic LC neurones selectively lesioned by microinjection of 6-hydroxydopamine; the controls were sham-operated. Both lesions resulted in a marked attenuation of LPS (1 or 10 microg kg(-1), i.v.) fever at a subneutral (23 degrees C) ambient temperature (Ta). Because electrolytic and chemical lesions produced similar effects, the role of the LC in fever was further investigated using electrolytic lesions only. The levels of prostaglandin (PG) E2, the terminal mediator of fever, were equally raised in the anteroventral third ventricular region of LC-lesioned and sham-operated rats during the course of LPS fever, indicating that LC neurones are not involved in febrigenic signalling to the brain. To investigate the potential involvement of the LC in an efferent thermoregulatory neuronal pathway, the thermoregulatory response to PGE(2) (25 ng, i.c.v.) was studied at a subneutral (23 degrees C, when fever is brought about by thermogenesis) or neutral (28 degrees C, when fever is brought about by tail skin vasoconstriction) Ta. The PGE2-induced increases in metabolic rate (an index of thermogenesis) and fever were attenuated in LC-lesioned rats at 23 degrees C, whereas PGE2-induced skin vasoconstriction and fever normally developed in LC-lesioned rats at 28 degrees C. The LC-lesioned rats had attenuated PGE2 thermogenesis despite the fact that they were fully capable of activating thermogenesis in response to noradrenaline and cold exposure. It is concluded that LC neurones are part of a neuronal network that is specifically activated by PGE2 to increase thermogenesis and produce fever.
- Published
- 2004
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29. Purification of a neuroprotective component of Parawixia bistriata spider venom that enhances glutamate uptake.
- Author
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Fontana AC, Guizzo R, de Oliveira Beleboni R, Meirelles E Silva AR, Coimbra NC, Amara SG, dos Santos WF, and Coutinho-Netto J
- Subjects
- Animals, Brazil, Carbon Isotopes, Cerebral Cortex cytology, Chromatography, High Pressure Liquid methods, Chromatography, Ion Exchange, Disease Models, Animal, Dose-Response Relationship, Drug, Glaucoma drug therapy, Glaucoma physiopathology, Glutamic Acid drug effects, Glutamic Acid metabolism, Ion Channels drug effects, Ion Channels metabolism, Ion Channels physiopathology, Male, Neuroprotective Agents chemistry, Rats, Rats, Wistar, Receptors, Metabotropic Glutamate drug effects, Receptors, Metabotropic Glutamate physiology, Retina drug effects, Retina pathology, Retina ultrastructure, Spider Venoms chemistry, Spider Venoms pharmacology, Spiders, Synaptosomes drug effects, Synaptosomes metabolism, Tritium, gamma-Aminobutyric Acid drug effects, gamma-Aminobutyric Acid metabolism, gamma-Aminobutyric Acid pharmacokinetics, Glutamic Acid pharmacokinetics, Neuroprotective Agents isolation & purification, Neuroprotective Agents pharmacology, Spider Venoms isolation & purification, Tissue Extracts pharmacology
- Abstract
(1) In this study, we examined the effects of crude venom from the spider Parawixia bistriata on glutamate and GABA uptake into synaptosomes prepared from rat cerebral cortex. Addition of venom to cortical synaptosomes stimulated glutamate uptake and inhibited GABA uptake in a concentration-dependent manner. (2) The venom was fractionated using reverse-phase high-performance liquid chromatography on a preparative column. The fraction that retained glutamate uptake-stimulating activity was further purified on a reverse-phase analytical column followed by ion-exchange chromatography. (3) The active fraction, referred to as PbTx1.2.3, stimulated glutamate uptake in synaptosomes without changing the K(M) value, and did not affect GABA uptake. Additional experiments showed that the enhancement of glutamate uptake by PbTx1.2.3 occurs when ionotropic glutamate receptors or voltage-gated sodium and calcium channels are completely inhibited or when GABA receptors and potassium channels are activated, indicating that the compound may have a direct action on the transporters. (4) In an experimental model for glaucoma in which rat retinas are subjected to ischemia followed by reperfusion, PbTx1.2.3 protected neurons from excitotoxic death in both outer and inner nuclear layers, and ganglion cell layers. (5) This active spider venom component may serve as a basis for designing therapeutic drugs that increase glutamate clearance and limit neurodegeneration.
- Published
- 2003
- Full Text
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30. Sucrose ingestion causes opioid analgesia.
- Author
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Segato FN, Castro-Souza C, Segato EN, Morato S, and Coimbra NC
- Subjects
- Animals, Male, Naloxone pharmacology, Pain Measurement drug effects, Rats, Rats, Wistar, Analgesia, Opioid Peptides drug effects, Sucrose pharmacology
- Abstract
The intake of saccharin solutions for relatively long periods of time causes analgesia in rats, as measured in the hot-plate test, an experimental procedure involving supraspinal components. In order to investigate the effects of sweet substance intake on pain modulation using a different model, male albino Wistar rats weighing 180-200 g received either tap water or sucrose solutions (250 g/l) for 1 day or 14 days as their only source of liquid. Each rat consumed an average of 15.6 g sucrose/day. Their tail withdrawal latencies in the tail-flick test (probably a spinal reflex) were measured immediately before and after this treatment. An analgesia index was calculated from the withdrawal latencies before and after treatment. The indexes (mean +/- SEM, N = 12) for the groups receiving tap water for 1 day or 14 days, and sucrose solution for 1 day or 14 days were 0.09 +/- 0.04, 0.10 +/- 0.05, 0.15 +/- 0.08 and 0.49 +/- 0.07, respectively. One-way ANOVA indicated a significant difference (F(3, 47) = 9.521, P < 0.001) and the Tukey multiple comparison test (P < 0.05) showed that the analgesia index of the 14-day sucrose-treated animals differed from all other groups. Naloxone-treated rats (N = 7) receiving sucrose exhibited an analgesia index of 0.20 +/- 0.10 while rats receiving only sucrose (N = 7) had an index of 0.68 +/- 0.11 (t = 0.254, 10 degrees of freedom, P < 0.03). This result indicates that the analgesic effect of sucrose depends on the time during which the solution is consumed and extends the analgesic effects of sweet substance intake, such as saccharin, to a model other than the hot-plate test, with similar results. Endogenous opioids may be involved in the central regulation of the sweet substance-produced analgesia.
- Published
- 1997
- Full Text
- View/download PDF
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