Immunohistochemistry of resorption and inflammation factors in the periodontal ligament of human deciduous teeth.

The understanding of the biological mechanisms involved in root resorption in deciduous teeth is important to the future development of preventive measures and treatments of this condition. The aim of the present study was to compare the expression and immunostaining of iNOS, MMP-9, OPG and RANKL in the periodontal ligament (PDL) of deciduous teeth with physiologic root resorption (GI), inflammatory pathological root resorption (GII) and permanent teeth (GIII), the negative control. Teeth in GI (n = 10), GII (n = 10) and (GIII) (n = 10) were submitted to immunohistochemical analysis to determine the expression of iNOS, MMP-9, OPG, and RANKL. The immunostaining was analysed by optical density. Statistical analysis included one-way ANOVA, followed by Student-Newman-Keuls post hoc test (p < 0.05). The results showed that iNOS, MMP-9 and RANKL expression in the PDL was higher in GII compared to GI and GIII (p < 0.05). Moreover, RANKL expression was higher in GI compared to GIII (p < 0.001), while OPG immunolabelling was lower in GII compared to GI and GIII (p < 0.001). The PDL of deciduous teeth bearing inflammatory processed exhibited upregulation of resorption-associated factors as well as enzymes related to tissue degradation which, in turn explains the exacerbation and greater susceptibility of those teeth to root resorption process.

Worst spasticity in patients post-stroke associated with MNSOD ALA16VAL polymorphism and interleukin-1ß.

The MnSOD Ala16Val single nucleotide polymorphism (SNP) has shown to be associated to risk factors of several metabolic and vascular diseases. However, little is known about interaction between MnSOD Ala16Val SNP in stroke, a frequent neurologic disease that involves clinic manifestations such as motor deficits and spasticity. In this sense, we decided to investigate the relationship between MnSOD Ala16Val SNP with spasticity in stroke and also its influence on interleukin levels, BDNF, and glycolipid parameters. Eighty post-stroke subjects and 80 healthy controls were investigated. We showed a higher spasticity, levels of total cholesterol, LDL, IL-1ß, IL-6, and INF-γ in VV post-stroke group. Interesting, we found a correlation between IL-1ß levels and spasticity in VV post-stroke. Triglycerides, glucose levels and caspases (1 and 3) activation were significantly higher, as well as BDNF levels were lower in VV and AV post-stroke. DNA damage was higher in post-stroke group. Thus, we can suggest that the V allele has a worse glycolipid profile, which would facilitate changes in neurovascular homeostasis. These events associated with an increase in inflammatory markers and a reduction in BDNF can contribute with the stroke and a worse clinical evolution in relation to spasticity in patients with VV genotype.

The antinociceptive effect of manual acupuncture in the auricular branch of the vagus nerve in visceral and somatic acute pain models and its laterality dependence.

AIMS: The vagus nerve provides an important route to the central nervous system, and its brain projections are involved in nociceptive control and pain perception. We investigated the effect of ABVN stimulation on the inhibition of nociceptive signaling and the role of the cholinergic system in its neurobiological effects in models of visceral-somatic pain in rats, as well as the potential difference in stimulus laterality. MATERIALS AND METHODS: Male and female Wistar rats were pretreated with auricular acupuncture in the ABVN and submitted to the visceral-somatic nociception model by acetic acid or somatic nociception by formalin. Vagotomy and pharmacological tools were used to verify the participation of the cholinergic system in the experiments. KEY FINDINGS: Acupuncture on the left, but not the right, in the ABVN inhibited nociceptive signaling in the visceral-somatic nociception model in male and female rats. Acupuncture on the left ABVN reduced the response time in the formalin test. The cervical vagotomy of the left branch, but not the right, also inhibited nociceptive signaling in the visceral-somatic nociception model and reduced the effect of ABVN stimulation. Furthermore, cholinergic antagonists reduced the left ABVN stimulation effects in the same model. SIGNIFICANCE: Our data show that only the stimulation in the left ABVN is capable of producing antinociceptive effect in acute pain models in rats, and that it is dependent on the activation of the vagus nerve caudal to the nodose ganglion, as well as the muscarinic and nicotinic cholinergic receptors.

Estratégia digital para aproximar neurociência e reabilitação: relato de experiência profissional / Digital strategy to bring neuroscience and rehabilitation closer together: report of a professional experience / Estrategia digital para acercar la neurociencia y la rehabilitación: informe de una experiencia professional

Objetivo: Descrever a operacionalização do I Webinar NeuroRehab com o tema de "Neurociências com foco em Reabilitação" desenvolvido em meio ao distanciamento social em decorrência dos efeitos da pandemia COVID-19. Métodos: Estudo descritivo, do tipo relato de experiência, realizado on-line pela plataforma Conference web.RNP, desenvolvido no dia 18 junho de 2020. Nesse projeto de ação extensionista participaram 205 inscritos, 10 experts convidados e três organizadores. Resultados: Tendo como tema de conhecimento a neurociência com foco em reabilitação, os pesquisadores utilizaram a tecnologia digital para discutir, despertar e disseminar saberes, bem como promover reflexões do tempo de distanciamento social e uso de tecnologias para ampliar conhecimentos, otimizar a criatividade e potencializar a discussão sobre a temática ainda incipiente na literatura. Conclusão: A construção desse trabalho reforça e justifica o uso de tecnologia digital como meio profícuo para a discussão sobre o conhecimento de bancada da neurociência e problematização do cuidado assistencial da reabilitação. O distanciamento social em decorrência da pandemia COVID-19 trouxe um redescobrimento da globalização, e revelou a urgência de abrir as janelas da ciência em saúde, da periferia à centralidade da reabilitação. (AU)

Objective: To describe the I NeuroRehab Webinar's operationalization with the theme of "Neurosciences focusing on Rehabilitation" developed during social isolation due to the effects of the COVID-19 pandemic. Methods: Descriptive study, an experience report type, carried out on the platform Conference web.RNP and developed from May to June 2020. In this extension project, 205 participants, 10 invited experts, and three organizers participated. Results: Based on the title "Digital technology for the dissemination of knowledge about neuroscience and rehabilitation," the researchers endeavored to discuss the social influence of technology in awakening to neuroscience and rehabilitation, as well as promoting reflections on the time of social distance and the use of technologies to expand knowledge, optimize creativity and enhance the discussion on this topic, that is still incipient in the literature. Conclusion: The construction of this work responds to the challenge of implementing digital technology to discuss the neuroscience research bench and the problematization of rehabilitation assistance care. The social distance resulting from the COVID-19 pandemic brought a rediscovery of globalization. It revealed the urgency to open the windows of health and science from the periphery to rehabilitation's centrality. (AU)

Objetivo: Describir la operacionalización del I Webinar NeuroRehab con el tema "Neurociencias con enfoque en Rehabilitación" desarrollado en medio del distanciamiento social por los efectos de la pandemia COVID-19. Métodos: Estudio descriptivo, tipo relato de experiencia, realizado en la plataforma Conference web.RNP, desarrollado de mayo a junio de 2020. En este proyecto de extensión participaron 205 inscritos, 10 expertos invitados y tres organizadores. Resultados: Con el título "Tecnología digital para la difusión del conocimiento sobre neurociencia y rehabilitación", los investigadores se propusieron discutir la influencia social de la tecnología en el despertar de la neurociencia y la rehabilitación, así como promover reflexiones sobre el tiempo de distancia y uso social de las tecnologías para ampliar conocimientos, optimizar la creatividad y potenciar la discusión sobre el tema, aún incipiente en la literatura. Conclusión: La construcción de este trabajo responde al desafío de implementar tecnología digital para la discusión sobre el banco de conocimientos de neurociencias y problematización de la atención asistencial rehabilitadora. La distancia social resultante de la pandemia de COVID-19 há traído un redescubrimiento de la globalización y reveló la urgencia de abrir las ventanas de la ciencia e salud, desde la periferia a la centralidad de la rehabilitación (AU)

Preclinical Pharmacokinetic and Pharmacodynamic Investigation of 5'-Methoxynobiletin from Ageratum conyzoides: In vivo and In silico Approaches.

PURPOSE: 5'-methoxynobiletin (5'-MeONB), a polymethoxyflavone isolated from A. conyzoides, has shown anti-inflammatory property. Nevertheless, the antinociceptive activity and pre-clinical pharmacokinetics (PK) characteristics of 5'-MeONB remain unknown. Considering the anti-inflammatory potential of the 5'-MeONB, this study aimed to investigate the pre-clinical PK behavior of 5'-MeONB, as well as its time course antinociceptive activity. METHODS: 5'-MeONB plasma concentrations were determined in Wistar rats after intravenous (i.v.) (10 mg/kg) and oral (50 mg/kg) administration, and in Swiss mice after oral administration (100 mg/kg). Plasma samples were deproteinization and 5'-MeONB quantified by a validated UPLC-MS method. Additionally, the antinociceptive activity of 5'-MeONB was evaluated after 15, 30, 60, 180 and 360 min following oral administration on the acute nocifensive behavior of mice induced by formalin. RESULTS: 5'-MeONB rats and mice plasma concentration-time profiles were best one-compartment model. After i.v. administration to rats, a short half-life, a high clearance and moderate volume of distribution at steady state were observed. Similar results were obtained after oral administration. The oral bioavailability ranged from 8 to 11%. Additionally, 5'-MeONB exhibited antinociceptive activity in both formalin phases, especially in the inflammatory phase of the model, inhibiting 68% and 91% of neurogenic and inflammatory responses, respectively, after 30 min of oral administration. CONCLUSIONS: The results described here provide novel insights on 5'-MeONB pharmacokinetics and pharmacodynamic effect, serving as support for future studies to confirm this compound as anti-nociceptive and anti-inflammatory effective agent.

Aerobic Exercise Attenuates Kidney Injury, Improves Physical Performance, and Increases Antioxidant Defenses in Lungs of Adenine-Induced Chronic Kidney Disease Mice.

The association between chronic kidney disease (CKD) and pulmonary pathophysiological changes is well stablished. Nevertheless, the effects of aerobic exercise (AE) on lungs of CKD need further clarification. Thus, Swiss mice were divided in control, AE, CKD, and CKD + AE groups. CKD was induced by 0.2% adenine intake during 8 weeks (4 weeks of CKD induction and 4 weeks of AE). AE consisted in running on treadmill, at moderate intensity, 30 min/day, 5 days/week, during 4 weeks. Twenty-four hours after the last training day, functional capacity test was performed, and 48 h after the test, mice were euthanized. CKD mice showed a significant increase in urine output, serum urea, and creatinine concentrations, and decreased body weight and urine density, besides oxidative damage (p = 0.044), edema area (p < 0.001), leukocyte infiltration (p = 0.040), and collagen area in lung tissue (p = 0.004). AE resulted in an increase of distance traveled (p = 0.049) and maximum speed (p = 0.046), increased activity of catalase (p = 0.031) and glutathione peroxidase (p = 0.048) in lungs, increased levels of nitric oxide (NOx) in serum (p = 0.001) and bronchoalveolar lavage fluid (p = 0.047), and decreased kidney histological injury (p = 0.018) of CKD mice. However, AE also increased oxidative damage (p = 0.003) and did not change collagen content or perivascular edema in lungs (p > 0.05) of CKD mice. Therefore, AE attenuated kidney injury and improved antioxidants defenses in lungs. Despite no significant changes in pulmonary damage, AE significantly improved physical performance in CKD mice.

Immunohistochemistry of resorption and inflammation factors in the periodontal ligament of human deciduous teeth

Abstract: The understanding of the biological mechanisms involved in root resorption in deciduous teeth is important to the future development of preventive measures and treatments of this condition. The aim of the present study was to compare the expression and immunostaining of iNOS, MMP-9, OPG and RANKL in the periodontal ligament (PDL) of deciduous teeth with physiologic root resorption (GI), inflammatory pathological root resorption (GII) and permanent teeth (GIII), the negative control. Teeth in GI (n = 10), GII (n = 10) and (GIII) (n = 10) were submitted to immunohistochemical analysis to determine the expression of iNOS, MMP-9, OPG, and RANKL. The immunostaining was analysed by optical density. Statistical analysis included one-way ANOVA, followed by Student-Newman-Keuls post hoc test (p < 0.05). The results showed that iNOS, MMP-9 and RANKL expression in the PDL was higher in GII compared to GI and GIII (p < 0.05). Moreover, RANKL expression was higher in GI compared to GIII (p < 0.001), while OPG immunolabelling was lower in GII compared to GI and GIII (p < 0.001). The PDL of deciduous teeth bearing inflammatory processed exhibited upregulation of resorption-associated factors as well as enzymes related to tissue degradation which, in turn explains the exacerbation and greater susceptibility of those teeth to root resorption process.

Characterization of biopsychosocial factors of patients with chronic nonspecific low back pain / Caracterização de fatores biopsicossociais de pacientes com dor lombar crônica inespecífica

ABSTRACT BACKGROUND AND OBJECTIVES: Low back pain is considered a public health problem worldwide and has a personal, social, occupational and economic impact. Psychosocial signs such as inappropriate beliefs about pain, fear of movement, anxiety, stress, depression and low job satisfaction are characteristics of individuals with low back pain. These clinical signs are mediators of chronic pain and disability. The present study aimed to assess psychological comorbidities in patients with chronic non-specific low back pain who are undergoing physical therapy and patients awaiting physical therapy; in addition to characterizing the psychosocial profile of these individuals. METHODS: This research was carried out with 31 individuals recruited from physical therapy clinics in the region of greater Florianópolis. They were divided into two groups: Treatment (TG) and non-treatment (CG). The following self-report instruments were applied: Hospital Anxiety and Depression Scale (HADS), Health Status Questionnaire (SF-36V2), Visual Analog Scale (VAS), Oswestry Low Back Pain Disability Index (OLBPDI), Fear-Avoidance Belief Questionnaire (FABQ) and Pain Castatrophizing Scale (PCS). RESULTS: Significant differences (p<0.05) were observed in the scores of the instruments applied between the groups. The CG had higher averages than the GT. CONCLUSION: The results obtained in this study support previous findings about the benefits of physical therapy for individuals with chronic nonspecific low back pain, suggesting that, in addition to reducing pain and disability, there are benefits related to psychosocial factors.

RESUMO JUSTIFICATIVA E OBJETIVOS A dor lombar é considerada um problema de saúde pública em todo o mundo e gera impacto pessoal, social, ocupacional e econômico. Os sinais psicossociais como crenças inapropriadas sobre a dor, medo do movimento, ansiedade, estresse, depressão e baixa satisfação no trabalho são características de indivíduos com lombalgia. Esses sinais clínicos são mediadores da dor crônica e incapacidade. O presente estudo teve como objetivo avaliar as comorbidades psicológicas em pacientes com dor lombar crônica inespecífica que estão em atendimento fisioterapêutico e pacientes que aguardam o atendimento de fisioterapia; além de caracterizar o perfil psicossocial desses indivíduos. MÉTODOS Estudo realizado com 31 indivíduos, recrutados em clínicas de fisioterapia na região da grande Florianópolis. Foram divididos em dois grupos: tratamento (GT/n=16) e não tratamento (GC/n=15). Foram aplicados os seguintes instrumentos de autorrelato: Hospital Anxiety and Depression Scale (HADS), Health Status Questionnaire (SF-36V2), Escala Analógica Visual (EAV), Oswestry Low Back Pain Disability Index (OLBPDI), Fear-Avoidance Belief Questionnaire (FABQ) and Pain Castatrophizing Scale (PCS). RESULTADOS: Foram observadas diferenças significativas (p<0,05) nos escores dos instrumentos aplicados entre os grupos. Sendo que o GC apresentou médias maiores que o GT. CONCLUSÃO Os resultados obtidos neste estudo apoiam descobertas anteriores sobre os benefícios da fisioterapia para indivíduos com dor lombar crônica inespecífica, sugerindo que, além da redução da dor e incapacidade, há benefícios relacionados aos fatores psicossociais.

Mood disorders are associated with the reduction of brain derived neurotrophic factor in the hypocampus in rats submitted to the hipercaloric diet.

Adipose tissue accumulation, resulting from the consumption of hypercaloric foods, can cause a dysfunction of the endocrine system. Such endocrine changes can influence the expression of various neurochemicals including brain-derived neurotrophic factor (BDNF) - associated with cognitive and emotional problems. Here, we investigated the effects of a hypercaloric diet on depression- and anxiety-like behaviors in young rats along with concomitant changes in BDNF expression levels in the hippocampus. Eight week-old Wistar rats (n = 20) were divided in: control diet (CD) group which received industrial food (n = 8) and hypercaloric diet (HD) group which received animal fat and soybean oil (n = 12). After 45 days on the diet, the animals were evaluated: body weight and blood biochemical analisys. Changes in mood disposition were evaluated using forced swim test and the elevated plus-maze, whereas hippocampal BDNF expression levels were quantified by ELISA. After 45 weeks, the CD group showed a significant increase in body weight relative to the HD group. However, the HD rats had a body fat percentage and exhibited increased level of the biochemical markers. Furthermore, the animals in the HD group presented increased immobility time in the forced swimming test, as well as reduced response to plus-maze test suggesting a depression- and anxiety-like emotional state. In addition, the HD group also showed lower BDNF expression levels in the hippocampus. This study demonstrates that a hypercaloric diet induced increase in adipose tissue concentration in young rats was associated with reduced hippocampal BDNF expression and resulted in an increase in depression- and anxiety-like behaviors. Graphical abstract.

Simple and fast UPLC-MS method for quantifying the anti-inflammatory candidate 5'-methoxynobiletin in rat plasma: Validation and application in a preliminary pharmacokinetic study.

This study presents the development and validation of a fast and simple bioanalytical ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS) method intended for quantifying the anti-inflammatory candidate 5'-methoxynobiletin (5'-MeONB) in rat plasma. Standard of 5'-MeONB was purified from A. conyzoides extract by using preparative HPLC. After a pretreatment of plasma samples with acetonitrile, chromatographic separations were efficiently achieved with a C18 column using a 9 min gradient system of 0.1% aqueous formic acid and acetonitrile as eluent. Drug candidate 5'-MeONB and chrysin (internal standard, IS) detection were carried out using ESI+ through the extracted ion chromatograms approach, monitored at m/z 433.1494 (for 5'-MeONB, tR:1.78 min) and m/z 255.0657 (for IS, tR:1.57 min). Method was validated according to US FDA guidelines, presenting linearity (R2 > 0.999) over concentration range of 30-750 ng/mL. Relative standard deviation (RSD) of repeatability and intermediary precision respectively ranged between 1.93-3.65% and 2.16-7.54%, considering lower limit of quantitation (30 ng/mL) and quality control (90, 360 and 600 ng/mL) samples, while accuracy was between 82.51 and 109.44%. Moreover, no interference from plasma endogenous substances, no carryover effect, and no influence of extraction method even in hemolyzed blood samples were observed. Sample stability in auto-sampler and long-term -80 °C storage, as well as matrix effect were within acceptable limits. For the first time, using the validated UPLC-MS bioanalytical method, the plasma pharmacokinetics of 5'-MeONB following 2 mg/kg intravenous bolus dosing to Wistar rats was characterized allowing the determination of the parameters describing drug distribution and elimination.

Sustained glial reactivity induced by glutaric acid may be the trigger to learning delay in early and late phases of development: Involvement of p75NTR receptor and protection by N-acetylcysteine.

Degeneration of striatal neurons and cortical atrophy are pathological characteristics of glutaric acidemia type I (GA-I), a disease characterized by accumulation of glutaric acid (GA). The mechanisms that lead to neuronal loss and cognitive impairment are still unclear. The purpose of this study was to verify if acute exposure to GA during the neonatal period is sufficient to trigger apoptotic processes and lead to learning delay in early and late period. Besides, whether N-acetylcysteine (NAC) would protect against impairment induced by GA. Pups mice received a dose of GA (2.5 µmol/ g) or saline, 12 hs after birth, and were treated with NAC (250 mg/kg) or saline, up to 21th day of life. Although GA exhibited deficits in the procedural and working memories in 21 and 40-day-old mice, NAC protected against cognitive impairment. In striatum and cortex, NAC prevented glial cells activation (GFAP and Iba-1), decreased NGF, Bcl-2 and NeuN, the increase of lipid peroxidation and PARP induced by GA in both ages. NAC protected against increased p75NTR induced by GA, but not in cortex of 21-day-old mice. Thus, we showed that the integrity of striatal and cortical pathways has an important role for learning and suggested that sustained glial reactivity in neonatal period can be an initial trigger for delay of cognitive development. Furthermore, NAC protected against cognitive impairment induced by GA. This work shows that early identification of the alterations induced by GA is important to avoid future clinical complications and suggest that NAC could be an adjuvant treatment for this acidemia.

Capsaicin-sensitive fibers mediate periorbital allodynia and activation of inflammatory cells after traumatic brain injury in rats: Involvement of TRPV1 channels in post-traumatic headache.

Post-traumatic headache (PTH) is a condition that frequently affects individuals after traumatic brain injury (TBI). Inflammation is one of the major causes of this disability. However, little is known about the trigger for, and endurance of, this painful process. Thus, the involvement of fibers containing the transient receptor potential vanilloid 1 (TRPV1) channels on the PTH and inflammation after TBI through neonatal treatment with capsaicin are investigated. Fluid percussion injury (FPI) in adult male Wistar rats caused periorbital allodynia in one, three and seven days after injury, and the neonatal treatment reversed the painful sensation in seven days. The lack of TRPV1 channels reduced the activation of macrophages and glial cells induced by TBI in the trigeminal system, which were characterized by glial fibrillary acidic protein (GFAP) and ionized calcium binding adapter molecule-1 (IBA-1) immune content in the ipsilateral trigeminal ganglion, brainstem, and perilesional cortex. Immunofluorescence analyses of the ipsilateral Sp5C nucleus demonstrated a hypertrophic astrocytes profile after TBI which was reduced with treatment. Moreover, effects of succinate sumatriptan (SUMA - 1 mg/kg), TRPV1 selective antagonist capsazepine (CPZ - 2 mg/kg), and TRP non-selective antagonist ruthenium red (RR - 3 mg/kg) were evaluated. Although all mentioned drugs reduced the painful sensation, SUMA and CPZ demonstrated a stronger effect compared to the RR treatment, reinforcing the involvement of TRPV1 channels in periorbital allodynia after TBI. Hence, this report suggests that TRPV1-containing fibers and TRPV1 channels are able to induce inflammation of the trigeminal system and maintain the painful sensation after TBI.

Hydroalcoholic extract of leaf of Arachis hypogaea L. (Fabaceae) did not induce toxic effects in the repeated-dose toxicity study in rats.

Arachis hypogaea L. (peanut) leaf is traditionally used for the treatment of insomnia in Asia. However, studies describing the safety and toxicity profile for this plant preparation are limited. Thus, the goal of this study was to investigate the toxicity of peanut leaf hydroalcoholic extract (PLHE) repeated treatment. The extract was administered orally (100, 300 or 1000 mg/kg) in male and female Wistar rats for 28 days (OECD guideline 407). PLHE treatment did not cause mortality or weight variation in the animals. Also, there was no alteration on locomotor activity (open field test), motor coordination (rotarod test), or anxiety behaviour (elevated plus-maze test). Male rats had a reduction in relative liver weight (100 mg/kg) and an increase in total kidney weight (1000 mg/kg), but there was no change in biochemical and haematological parameters after PLHE treatment. Free extracellular double-stranded DNA (dsDNA) levels was also evaluated, but PLHE treatment did not increase this parameter in rat organs. Also, the dose of 1000 mg/kg of PLHE significantly increased the total thiols in the liver of females compared with the control animals. Thus, PLHE did not induce toxicity after repeated exposure for 28 days in rats.

Machaerium hirtum (Vell.) Stellfeld Alleviates Acute Pain and Inflammation: Potential Mechanisms of Action.

:Machaerium hirtum (Vell.) Stellfeld (Fabaceae) known in Brazil as "jacaranda de espinho" or "espinheira santa nativa" is a medicinal plant commonly used in folk medicine to treat ulcers, cough and diarrhea. This study aimed to investigate the anti-inflammatory and antinociceptive effects of hydroalcoholic extracts from M. hirtum twig (HEMh) using in vivo experimental models of nociception through the involvement of transient receptor potential channels, acid-sensing ion channel (ASIC), nitrergic, opioidergic, glutamatergic, and supraspinal pathways. Our results revealed an antinociceptive effect of HEMh mediated by the opioidergic, L-arginine-nitric oxide and glutamate systems, as well as by interactions with TRPA1/ASIC channels. The anti-inflammatory effect of HEMh evaluated with a xylene-induced ear edema and by the involvement of arachidonic acid and prostaglandin E2 (PGE2) showed involvement of the COX pathway, based on observed decreases in PGE2 levels. A phytochemical investigation of the HEMh led to the isolation of α-amyrin, ß-amyrin, allantoin, apigenin-7-methoxy-6-C-ß-D-glucopyranoside, and apigenin-6-C-ß-D-glucopyranosyl-8-C-ß-D-xylopyranoside. In conclusion, the acute oral administration of HEMh inhibits the nociceptive behavioral response in animals through the nitrergic, opioid, glutamatergic pathways, and by inhibition of the TRPA1 and ASIC channels, without causing locomotor dysfunction. In addition, its anti-inflammatory effect is associated with the COX pathway and decreased PGE2 levels.

Predictors of Pain Recurrence After Lumbar Facet Joint Injections.

INTRODUCTION: Facet joint injections (FJIs) of anesthetic and corticosteroids are useful for the diagnosis and treatment of low back pain (LBP). In the current study, we evaluated the efficacy of FJI on LBP treatment and the predictive variables of pain recurrence after FJI. METHODS: We included and followed prospectively forty-three consecutive patients with chronic LBP treated with FJI. Clinical assessments were carried out at a baseline 1 week before FJIs and after a 6-month follow-up visit using the visual analog scale (VAS) for pain, Oswestry Disability Index (ODI) for disability-specific measure and MacNab criteria for global effectiveness, and compared through analysis using paired-samples "t" tests. Multiple cox-regression analysis was used to identify the presurgical variables independently associated with pain recurrence anytime during the follow-up. In addition to the demographic, clinical, and surgical data, we also analyzed psychometric scales: Pain Catastrophizing Scale (PCS), Beck Anxiety Inventory (BAI), and Beck Depression Inventory (BDI). RESULTS: After a 6-month follow-up, thirty-two patients (74.4%) showed a clinically significant reduction of pain and twenty-seven (62.8%) reported a clinically significant improvement of disability. Presurgical catastrophizing (PCS score ≥ 5, adjusted HR 4.4, CI 95% 1.7-11.3, p = 0.002) and smoking (Adjusted HR 12.5, CI 95% 1.1-138.9, p = 0.04) remains associated with pain recurrence. CONCLUSION: FJI reduces LBP and disability of patients with unresponsive LBP. Pain-related cognitive and behavioral factors determined by pain catastrophizing and smoking were independently associated with pain recurrence after lumbar FJI. The results support the need of a multidisciplinary approach for presurgical evaluation of patients with chronic pain.

Functional Recovery Occurs Even After Partial Remyelination of Axon-Meshed Median and Ulnar Nerves in Mice.

Upper limb nerve injuries are common, and their treatment poses a challenge for physicians and surgeons. Experimental models help in minimum exploration of the functional characteristics of peripheral nerve injuries of forelimbs. This study was conducted to characterize the functional recovery (1, 3, 7, 10, 14, and 21 days) after median and ulnar nerve crush in mice and analyze the histological and biochemical markers of nerve regeneration (after 21 days). Sensory-functional impairments appeared after 1 day. The peripheral nerve morphology, the nerve structure, and the density of myelin proteins [myelin protein zero (P0) and peripheral myelin protein 22 (PMP22)] were analyzed after 21 days. Cold allodynia and fine motor coordination recovery occurred on the 10th day, and grip strength recovery was observed on the 14th day after injury. After 21 days, there was partial myelin sheath recovery. PMP22 recovery was complete, whereas P0 recovery was not. Results suggest that there is complete functional recovery even with partial remyelination of median and ulnar nerves in mice.

Overground gait training promotes functional recovery and cortical neuroplasticity in an incomplete spinal cord injury model.

AIM: Evidence suggests that task-specific gait training improves locomotor impairments in people with incomplete spinal cord injury (SCI); however, plastic changes in brain areas remain poorly understood. The aim of this study was to examine the possible effects of a task-specific overground gait training on locomotor recovery and neuroplasticity markers in the cortex, cerebellum, and lumbar spinal cord in an experimental model of incomplete-SCI. MAIN METHODS: Using a blind, basic experimental design, 24 adult Wistar rats underwent a surgical procedure and were allocated into sham, non-trained SCI (SCI), and trained SCI (Tr-SCI) groups. On postoperative day 14, trained animals started a 4-week overground gait training program. All groups were subjected to weekly assessment of locomotor recovery of the hind limbs. On postoperative day 40, brain and lumbar spinal cord structures were dissected and processed for biochemical analysis of the synaptophysin, microtubule-associated protein 2 (MAP-2), and brain-derived neurotrophic factor (BDNF). KEY FINDINGS: Tr-SCI group showed greater locomotor function recovery compared with non-trained SCI from the postoperative day 21 (p < 0.05). The training was able to improve the neuroplasticity markers synaptophysin, MAP-2, and BDNF expressions in motor cortex (p < 0.05), but not in the cerebellum and in the spinal cord for trained SCI group compared to non-trained. SIGNIFICANCE: Task-specific overground gait training improves locomotor recovery in a rat model of incomplete thoracic-SCI. Furthermore, training promotes motor cortex plasticity, evidenced for increasing expression of the neuroplasticity markers that may support the functional recovery.

Galangin Prevents Increased Susceptibility to Pentylenetetrazol-Stimulated Seizures by Prostaglandin E2.

Epilepsy is one of the most common chronic neurological diseases. It is characterized by recurrent epileptic seizures, where one-third of patients are refractory to existing treatments. Evidence revealed the association between neuroinflammation and increased susceptibility to seizures since there is a pronounced increase in the expression of key inflammatory mediators, such as prostaglandin E2 (PGE2), during seizures. The purpose of this study was to investigate whether PGE2 increases susceptibility to pentylenetetrazol-induced (PTZ) seizures. Subsequently, we evaluated if the flavonoid isolated from the plant Piper aleyreanum (galangin) presented any anticonvulsive effects. Our results demonstrated that the group treated with PGE2 increased susceptibility to PTZ and caused myoclonic and generalized seizures, which increased seizure duration and electroencephalographic wave amplitudes. Furthermore, treatment with PGE2 and PTZ increased IBA-1 (microglial marker), GFAP (astrocytic marker), 4-HNE (lipid peroxidation marker), VCAM-1 (vascular cell adhesion molecule 1), and p-PKAIIα (phosphorylated cAMP-dependent protein kinase) immunocontent. Indeed, galangin prevented behavioral and electroencephalographic seizures, reactive species production, decreased microglial and astrocytic immunocontent, as well as decreased VCAM-1 immunocontent and p-PKA/PKA ratio induced by PGE2/PTZ. Therefore, this study suggests galangin may have an antagonizing role on PGE2-induced effects, reducing cerebral inflammation and protecting from excitatory effects evidenced by administrating PGE2 and PTZ. However, further studies are needed to investigate the clinical implications of the findings and their underlying mechanisms.

Modulation of Na+/K+- ATPase activity by triterpene 3ß, 6ß, 16ß-trihidroxilup-20 (29)-ene (TTHL) limits the long-term secondary degeneration after traumatic brain injury in mice.

Traumatic brain injury (TBI) is a public health problem characterized by a combination of immediate mechanical dysfunction of the brain tissue, and secondary damage. Based on the hypothesis that selected targets, such as Na+ K+-ATPase are involved in the secondary damage after TBI and modulation of this enzyme activity by triterpene 3ß, 6ß, 16ß-trihidroxilup-20 (29)-ene (TTHL) supports the ethnomedical applications of this plant, we decided to investigate whether previous TTHL treatment interrupts the progression of pathophysiology induced by TBI. Statistical analyses revealed that percussion fluid injury (FPI) increased Na+,K+-ATPase activity in all isoform (α1 and α2/3) 15 min after neuronal injury. The FPI protocol inhibited Na+,K+-ATPase activity total and α1 isoform, increased [3H]MK-801 binding but did not alter Dichloro-dihydro-fluorescein diacetate (DCFH-DA) oxidation, carbonylated proteins and free -SH groups 60 min after injury. The increase of immunoreactivity of protein PKC and state of phosphorylation of at Ser16 of Na+,K+-ATPase 60 min after FPI suggest the involvement of PKC on Na+,K+-ATPase activity oscillations characterized by inhibition of total and α1 isoform. Our experimental data also revealed that natural product rich in compounds such as triterpenes (TTHL; 30 mg/kg) attenuates [3H]MK-801 binding increase, phosphorylation of the PKC and the Na+,K+-ATPase alpha 1 subunit (Ser16) induced by FPI. The previous TTHL treatment had not effect on motor disability but protected against spatial memory deficit, BDNF, TrKB expression decrease, protein carbonylation and hippocampal cell death 7 days after FPI. These data suggest that TTHL-induced reduction on initial damage limits the long-term secondary degeneration and supports neural repair or behavioral compensation after neuronal injury.

Spinal cord injury by clip-compression induces anxiety and depression-like behaviours in female rats: The role of the inflammatory response.

Traumatic spinal cord injury (SCI) promotes long-term disability that affects mobility and functional independence. The spinal cord inflammatory response after the initial mechanical insult substantially impacts locomotor impairment and development of neuropsychiatric disorders, including anxiety and depression. However, these psychiatric events are scarcely investigated in females. This study investigated the anxiety/depression-like behaviours and inflammatory responses related to the production/release of pro- and anti-inflammatory cytokines in female adult Wistar rats submitted to severe clip-compression SCI. Data showed that SCI impaired the locomotor performance assessment by the BBB scale, but did not alter exploratory activity in open-field test. Animals' locomotor impairment was associated with anxious and depressive-like behaviours characterised by a decreased amount of time in the open arms of the elevated plus-maze test, and the motivational reduction of social interaction and anhedonia assessed by social exploration and sucrose preference tests. By contrast, SCI decreased the immobility time in the forced swimming test. Moreover, SCI caused a significant increase in local and systemic proinflammatory cytokines (TNF-α, INF-γ, IL-1ß, and IL-6) and a reduction in the anti-inflammatory cytokine IL-10. Finally, there were significant negative correlations between depression-like behaviour, but not anxiety, and increased plasma concentrations of TNF-α, IL-1ß, IL-6, and INF-γ. Additionally, the laminectomy procedure provoked the inflammatory response associated with reduced sucrose intake in Sham animals, although less expressively than in the SCI group. Collectively, these results indicate that SCI by clip-compression in female rats promotes a neuropsychiatric-like profile associated with an imbalance in the production/release of pro- and anti-inflammatory cytokines.