JESSICA RUIVO MAXIMINO
Projetos de Pesquisa
Unidades Organizacionais
LIM/45 - Laboratório de Fisiopatologia Neurocirúrgica, Hospital das Clínicas, Faculdade de Medicina
17 resultados
Resultados de Busca
Agora exibindo 1 - 10 de 17
- Dysregulated expression of death, stress and mitochondrion related genes in the sciatic nerve of presymptomatic SOD1(G93A) mouse model of Amyotrophic Lateral Sclerosis(2015) ALVES, Chrystian J.; MAXIMINO, Jessica R.; CHADI, GersonSchwann cells are the main source of paracrine support to motor neurons. Oxidative stress and mitochondrial dysfunction have been correlated to motor neuron death in Amyotrophic Lateral Sclerosis (ALS). Despite the involvement of Schwann cells in early neuromuscular disruption in ALS, detailed molecular events of a dying-back triggering are unknown. Sciatic nerves of presymptomatic (60-day-old) SOD1(G93A) mice were submitted to a high-density oligonucleotide microarray analysis. DAVID demonstrated the deregulated genes related to death, stress and mitochondrion, which allowed the identification of Cell cycle, ErbB signaling, Tryptophan metabolism and Rig-l-like receptor signaling as the most representative KEGG pathways. The protein-protein interaction networks based upon deregulated genes have identified the top hubs (TRAF2, H2AFX, E2F1, FOXO3, MSH2, NGFR, TGFBR1) and bottlenecks (TRAF2, E2F1, CDKN1B, TWIST1, FOXO3). Schwann cells were enriched from the sciatic nerve of presymptomatic mice using flow cytometry cell sorting. qPCR showed the up regulated (Ngfr, Cdnkn1b, E2f1, Traf2 and Erbb3, H2afic, Cdkn1a, Hspa1, Prdx, Mapk10) and down-regulated (Foxo3, Mtor) genes in the enriched Schwann cells. In conclusion, molecular analyses in the presymptomatic sciatic nerve demonstrated the involvement of death, oxidative stress, and mitochondrial pathways in the Schwann cell non-autonomous mechanisms in the early stages of ALS.
- Evaluation of Neuronal Apoptosis Precursors in an Experimental Model of Acute Normovolemic Hemodilution(2014) FRAZILIO, Fabricio O.; OTSUKI, Denise Aya; NOEL-MORGAN, Jessica; MAXIMINO, Jessica Ruivo; OLIVEIRA, Gabriela Pintar; CHADI, Gerson; AULER JR., Jose Otavio Costa; FANTONI, Denise TabacchiBackground: The effects of acute anemia on neuronal cells and the safe limits of hematocrit are not well established. The objective of this study was to evaluate neuronal pro-and anti-apoptotic Bax and Bcl-x proteins, caspase-3 and -9 activity, and DNA fragmentation after acute normovolemic hemodilution (ANH). Methods: Twenty-four pigs were anesthetized and randomized into 4 groups: Sham, ANH to 15% hematocrit (ANH15%), ANH to 10% hematocrit (ANH10%) and hypoxia (Hx). ANH was achieved by simultaneous blood withdrawal and hydroxyethyl starch infusion. Hx consisted of ventilation with a 6% inspired oxygen fraction for 60 minutes. Bax and Bcl-x proteins as well as DNA fragmentation were evaluated in cortical nuclear and mitochondrial fractions. Caspase-3 and -9 activity was evaluated in the cortical mitochondrial and hippocampal cytosolic fractions. The data were compared using analysis of variance followed by Tukey's test (P<0.05). Results: No changes were observed in Bax protein expression after hemodilution in the ANH15% and ANH10% groups compared to the Sham group. Bax expression in the Hx group was increased in the nuclear and mitochondrial fractions compared to all other groups. No significant difference was observed in Bcl-x expression. Caspase-3 and -9 activity in the cytosolic and mitochondrial fractions was different in the Hx group compared to all other groups. No statistical significance in DNA fragmentation was found among the Sham, ANH15% or ANH10% groups. Conclusion: ANH to 10 and 15% hematocrit did not induce alterations in apoptosis precursors, suggesting that cerebral oxygenation was preserved during these anemic states.
- Clinical aspects of patients with sarcoglycanopathies under steroids therapy(2014) ALBUQUERQUE, Marco A. V.; ABATH-NETO, Osorio; MAXIMINO, Jessica R.; CHADI, Gerson; ZANOTELI, Edmar; REED, Umbertina C.Patients with sarcoglycanopathies, which comprise four subtypes of autosomal recessive limb-girdle muscular dystrophies, usually present with progressive weakness leading to early loss of ambulation and premature death, and no effective treatment is currently available. Objective: To present clinical aspects and outcomes of six children with sarcoglycanopathies treated with steroids for at least one year. Method: Patient files were retrospectively analyzed for steroid use. Results: Stabilization of muscle strength was noted in one patient, a slight improvement in two, and a slight worsening in three. In addition, variable responses of forced vital capacity and cardiac function were observed. Conclusions: No overt clinical improvement was observed in patients with sarcoglycanopathies under steroid therapy. Prospective controlled studies including a larger number of patients are necessary to determine the effects of steroids for sarcoglycanopathies.
- Effects of Lidocaine, Bupivacaine, and Ropivacaine on Calcitonin Gene-Related Peptide and Substance P Levels in the Incised Rat Skin(2016) LAPIN, Guilherme A. F.; HOCHMAN, Bernardo; MAXIMINO, Jessica R.; CHADI, Gerson; FERREIRA, Lydia M.OBJECTIVE: To evaluate the effect of 2% lidocaine, 0.5% bupivacaine, and 0.75% ropivacaine on the release of substance P (SP) and calcitonin gene-related peptide (CGRP) in skin wounds. DESIGN: A primary, experimental, analytical, prospective, self-controlled, blinded study. SETTING: The study is set in a university research center. INTERVENTIONS: Twenty-eight Wistar rats were randomly divided into 4 groups: lidocaine, bupivacaine, ropivacaine, and the control. After general anesthesia, a local anesthetic or 0.9% saline (control) was injected subdermally along a 2-cm line on the dorsal midline of each rat; 30 minutes later, an incision (nociceptive stimulus) was made along this line. The animals were euthanized, and skin samples were collected from the center of the incision line and sent for CGRP and SP quantification. MAIN OUTCOME MEASURES: Quantification of CGRP and SP by Western blotting. RESULTS: Substance P levels were similar in the lidocaine and ropivacaine groups but were significantly lower than those of the control group (P = .002); no significant difference in SP levels was found between the bupivacaine and control groups. Procalcitonin gene-related peptide levels were significantly lower in the experimental groups than those in control subjects (P = .009), with no significant differences among the experimental groups. No significant differences in CGRP levels were found among all groups. Lidocaine and ropivacaine inhibited SP release. All 3 local anesthetics inhibited the release of procalcitonin gene-related peptide, but not the release of CGRP in rat skin. CONCLUSIONS: Lidocaine and ropivacaine may inhibit neurogenic inflammation by biochemical pathways activated by SP, whereas bupivacaine seems to have no influence on this process.
- Motor Recovery and Cortical Plasticity After Functional Electrical Stimulation in a Rat Model of Focal Stroke(2014) CECATTO, Rebeca Boltes; MAXIMINO, Jessica Ruivo; CHADI, GersonObjective: The aim of this study was to investigate the functional responses and plastic cortical changes in a sample of animals with sequelae of cerebral ischemia that were subjected to a model of functional electrical stimulation (FES). Design: Rats received an ischemic cortical lesion (Rose Bengal method) and were randomized and submitted to an FES stimulation (1-2 mA, 30 Hz, 20-40 mins for 14 days) or sham stimulation. The Foot Fault Test was performed before inducing the cortical lesion and also before and after FES. Brain immunochemistry labeling with microtubule-associated protein-2 and neurofilament-200 markers was performed after FES. Results: The authors found a decreased percentage of errors in the Foot Fault Test (P < 0.001) in the stimulated group compared with the sham group after FES. FES has not altered the lesion size. Spontaneous motor parameters returned to basal values in both groups. The qualitative analysis showed an increased amount of radial microtubule-associated protein-2 immunoreactive fibers in the preserved cortex adjacent to stroke site in the stimulated animals. Regarding the measurements of neurofilament-200 immunostaining, there were no differences between the hemispheres or groups in area or intensity. Conclusions: Acute and short period of FES led to motor recovery of ankle joint neurodisability. The extent to which compensatory plasticity occurs after stroke or after FES and the extent to which it contributes to functional recovery are yet unclear. The changes induced by the stimulation may improve the ability of the nervous system to undergo spontaneous recovery, which is of substantial interest for neurorehabilitation strategies.
conferenceObject C9orf72 repeat expansions and TARDBP mutations in two Brazilian dementia research centers(2016) TAKADA, L.; BAHIA, V.; GUIMARAES, H.; SOUZA, L.; COSTA, T.; VALE, T.; RODRIGUEZ, R.; PORTO, F.; MACHADO, J.; BEATO, R.; CESAR, K.; SMID, J.; BRUCKI, S.; MAXIMINO, J.; CAMARGOS, S.; CHADI, G.; CARAMELLI, P.; NITRINI, R.- The Effects of Omega-3 Fatty Acid Supplementation on Dexamethasone-Induced Muscle Atrophy(2014) FAPPI, Alan; GODOY, Tiago S.; MAXIMINO, Jessica R.; RIZZATO, Vanessa R.; NEVES, Juliana de C.; CHADI, Gerson; ZANOTELI, EdmarCorticosteroids cause muscle atrophy by acting on proteasomal and lysosomal systems and by affecting pathways related to muscular trophysm, such as the IGF-1/PI-3k/Akt/mTOR. Omega-3 fatty acid (n-3) has been used beneficially to attenuate muscle atrophy linked to sepsis and cachexia; however, its effect on dexamethasone-induced muscle atrophy has not been evaluated. Objectives. We evaluated whether n-3 supplementation could mitigate the development of dexamethasone-induced muscle atrophy. Methods. Two groups of Wistar rats were orally supplemented with n-3 or vehicle solution for 40 days. In the last 10 days, dexamethasone, or saline solution, was administrated establishing four groups: control, dexamethasone, n-3, and dexamethasone + n-3. The cross-sectional areas of muscle fibers, gene expression (MyoD, Myogenin, MuRF-1, and Atrogin-1), and protein expression (Akt, GSK3 beta, FOXO3a, and mTOR) were assessed. Results. Dexamethasone induced a significant loss in body and muscle weight, atrophy in type 2B fibers, and decreased expression of P-Akt, P-GSK3 beta, and P-FOXO3a. N-3 supplementation did not attenuate the negative effects of dexamethasone on skeletal muscle; instead, it caused atrophy in type 1, 2A, reduced the expression of Myogenin, and increased the expression of Atrogin-1. Conclusion. Food supplements containing n-3 are usually healthful, but they may potentiate some of the side effects of glucocorticoids.
- Behavioral Improvement and Regulation of Molecules Related to Neuroplasticity in Ischemic Rat Spinal Cord Treated with PEDF(2014) BATISTA, Chary Marquez; BIANQUI, Leonardo Luis Torres; ZANON, Bruno Bonganha; IVO, Mauricio Menezes Aben Athar; OLIVEIRA, Gabriela Pintar de; MAXIMINO, Jessica Ruivo; CHADI, GersonPigment epithelium derived factor (PEDF) exerts trophic actions to motoneurons and modulates nonneuronal restorative events, but its effects on neuroplasticity responses after spinal cord (SC) injury are unknown. Rats received a low thoracic SC photothrombotic ischemia and local injection of PEDF and were evaluated behaviorally six weeks later. PEDF actions were detailed in SC ventral horn (motor) in the levels of the lumbar central pattern generator (CPG), far from the injury site. Molecules related to neuroplasticity (MAP-2), those that are able to modulate such event, for instance, neurotrophic factors (NT-3, GDNF, BDNF, and FGF-2), chondroitin sulfate proteoglycans (CSPG), and those associated with angiogenesis and antiapoptosis (laminin and Bcl-2) and Eph (receptor)/ephrin system were evaluated at cellular or molecular levels. PEDF injection improved motor behavioral performance and increased MAP-2 levels and dendritic processes in the region of lumbar CPG. Treatment also elevated GDNF and decreased NT-3, laminin, and CSPG. Injury elevated EphA4 and ephrin-B1 levels, and PEDF treatment increased ephrin A2 and ephrins B1, B2, and B3. Eph receptors and ephrins were found in specific populations of neurons and astrocytes. PEDF treatment to SC injury triggered neuroplasticity in lumbar CPG and regulation of neurotrophic factors, extracellular matrix molecules, and ephrins.
- GRN and MAPT Mutations in 2 Frontotemporal Dementia Research Centers in Brazil(2016) TAKADA, Leonel T.; BAHIA, Valeria S.; GUIMARAES, Henrique C.; COSTA, Thais V. M. M.; VALE, Thiago C.; RODRIGUEZ, Roberta D.; PORTO, Fabio H. G.; MACHADO, Joao C. B.; BEATO, Rogerio G.; CESAR, Karolina G.; SMID, Jerusa; NASCIMENTO, Camila F.; GRINBERG, Lea T.; BRUCKI, Sonia M. D.; MAXIMINO, Jessica R.; CAMARGOS, Sarah T.; CHADI, Gerson; CARAMELLI, Paulo; NITRINI, RicardoBackground: Mutations in GRN (progranulin) and MAPT (microtubule-associated protein tau) are among the most frequent causes of monogenic frontotemporal dementia (FTD), but data on the frequency of these mutations in regions such as Latin America are still lacking. Objective: We aimed to investigate the frequencies of GRN and MAPT mutations in FTD cohorts from 2 Brazilian dementia research centers, the University of Sao Paulo and the Federal University of Minas Gerais medical schools. Methods: We included 76 probands diagnosed with behavioral-variant FTD (n = 55), semantic-variant Primary Progressive Aphasia (PPA) (n = 11), or nonfluent-variant PPA (n = 10). Twenty-five percent of the cohort had at least 1 relative affected with FTD. Results: Mutations in GRN were identified in 7 probands, and in MAPT, in 2 probands. We identified 3 novel GRN mutations (p.Q130X, p.317Afs*12, and p.K259Afs*23) in patients diagnosed with nonfluent-variant PPA or behavioral-variant FTD. Plasma progranulin levels were measured and a cutoff value of 70 ng/mL was found, with 100% sensitivity and specificity to detect null GRN mutations. Conclusions: The frequency of GRN mutations was 9.6% and that of MAPT mutations was 7.1%. Among familial cases of FTD, the frequency of GRN mutations was 31.5% and that of MAPT mutations was 10.5%.
- C9ORF72 repeated expansion in patients with familial amyotrophic lateral sclerosis from a Brazilian research center. A preliminary report(2015) CHADI, G.; MAXIMINO, J. R.; JORGE, F. M. H.; CALLEGARO, D.