Papers by Maria Graca Naffah Mazzacoratti
Arquivos de Neuro-Psiquiatria, 2009
OBJECTIVE: Nestin is temporarily expressed in several tissues during development and it is replac... more OBJECTIVE: Nestin is temporarily expressed in several tissues during development and it is replaced by other protein types during cell differentiation process. This unique property allows distinguishing between undifferentiated and differentiated cells. This study was delineated to analyze the temporal pattern of nestin expression in cortical radial glial cells of rats during normal development and of rats submitted to recurrent status epilepticus (SE) in early postnatal life (P). METHOD: Experimental rats were submitted to pilocarpine-induced SE on P7-9. The cortical temporal profile of nestin was studied by immunohistochemistry at multiple time points (P9, P10, P12, P16, P30 and P90). RESULTS: We observed delayed nestin down-regulation in experimental rats of P9, P10, P12 and P16 groups. In addition, few radial glial cells were still present only in P21 experimental rats. CONCLUSION: Our results suggested that SE during early postnatal life alters normal maturation during a critic...
Spontaneous periodic episodes of hypothermia still defy medical knowledge. In 1969, Shapiro et al... more Spontaneous periodic episodes of hypothermia still defy medical knowledge. In 1969, Shapiro et al. described the first two cases of spontaneous periodic hypothermia associated with agenesis of the corpus callosum. Recently, Dundar et al. reported a case of spontaneous periodic hypother-mia and hyperhidrosis without corpus callosum agenesis, suggesting that the periodic episodes of hypothermia might be of epileptiform origin. Here we describe two paediatric patients with spontaneous periodic hypothermia without corpus callosum agenesis and demonstrate, to our knowledge for the first time, altered levels of neurotransmitter metabolites within the cerebro-spinal fluid.
duced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS... more duced by a psychoactive beverage ayahuasca in the hippocampus and amygdala of naive rats. METHODS: The level of monoamines, their main me-tabolites and amino acid neurotransmitters concentrations were quantified using high performance liquid chromatography (HPLC). Four groups of rats were employed: saline-treated and rats receiving 250, 500 and 800 mg/kg of ayahuasca infusion (gavage). Animals were killed 40 minutes after drug ingestion and the structures stored at-80 ℃ until HPLC assay. The data from all groups were compared using Analysis of variance and Scheffé as post test and P < 0.05 was accepted as significant. RESULTS: The results showed decreased concentrations of glycine (GLY) (0.13 ± 0.03 vs 0.29 ± 0.07, P < 0.001) and γ-aminobutyric acid (GABA) (1.07 ± 0.14 vs 1.73 ± 0.25, P < 0.001) in the amygdala of rats that received 500 of ayahuasca. Animals that ingested 800 mg/kg of ayahuasca also showed a reduction of GLY level (0.11 ± 0.01 vs 0.29 ± 0.07, P < 0.001) and GABA (0.98 ± 0.06 vs 1.73 ± 0.25, P < 0.001). In the hippocampus, increased GABA levels were found in rats that received all ayahuasca doses: 250 mg/kg (1.29 ± 0.19 vs 0.84 ± 0.21, P < 0.05); 500 mg/kg (2.23 ± 038 vs 084 ± 0.21, P < 0.05) and 800 mg/kg (1.98 ± 0.92 vs 0.84 ± 0.21, P < 0.05). In addition, an increased utilization rate of all monoamines was found in the amygdala after ayahuasca administration in doses: 250 mg/kg (noradrenaline: 0.16 ± 0.02 vs 0.36 ± 0.06, P < 0.01; dopamine-0.39 ± 0.012 vs 2.39 ± 0.84, P < 0.001; serotonin: 1.02 ± 0.22 vs 4.04 ± 0.91, P < 0.001), 500 mg/kg (noradrenaline: 0.08 ± 0.02 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.33 ± 0.19 vs 2.39 ± 0.84, P < 0.001, serotonin-0.59 ± 0.08 vs 4.04 ± 0.91, P < 0.001) and 800 mg/kg (noradrenaline: 0.16 ± 0.04 vs 0.36 ± 0.06, P < 0.001; dopamine: 0.84 ± 0.65 vs Abstract AIM: To evaluate changes in neurotransmission in
The treatment of epilepsy with antiepileptic drugs (AEDs) is generally a chronic procedure and ma... more The treatment of epilepsy with antiepileptic drugs (AEDs) is generally a chronic procedure and may be lifelong. Although necessary to decrease the number of seizures, AEDs have been associated with significant adverse effects on several tissues. Thus, the purpose of this study was to identify in 100 patients the prevalence of gingival hypertrophy due to AEDs used to treat seizures. The frequency of dental fracture in these patients as well as other oral alterations was also investigated. Around 50% of patients treated with polytherapy showed gingival hypertrophy being 22% fibrous and 28% inflammatory. Among all patients with inflammatory gingival hypertrophy, 25% have been treated with a cocktail containing PHT and PB. In addition, the highest incidence (27%) of fibrous hypertrophy was observed in those patients using PB, CBZ and CLB. The prevalence of gingival hypertrophy was higher in patients treated with polytherapy, when compared with monotherapy (Qui-Square test p= 0.004).
Parkinson's disease is a neurodegenerative disorder where the main hallmark is the dopaminergic n... more Parkinson's disease is a neurodegenerative disorder where the main hallmark is the dopaminergic neuronal loss. Besides motor symptoms, PD also causes cognitive decline. Although current therapies focus on the restoration of dopamine levels in the striatum, prevention or disease-modifying therapies are urgently needed. Valproic acid (VA) is a wide spectrum antiepileptic drug, exerting many biochemical and physiological effects. It has been shown to inhibit histone deacetylase which seems to be associated with the drug neuroprotective action. The objectives were to study the neuroprotective properties of VA in a model of Parkinson's disease, consisting in the unilateral striatal injection of the neurotoxin 6-OHDA. For that, male Wistar rats (250 g) were divided into the groups: sham-operated (SO), untreated 6-OHDA-lesioned, and 6-OHDA-lesioned treated with VA (25 or 50 mg/kg). Oral treatments started 24 h after the stereotaxic surgery and continued daily for 2 weeks, when the animals were subjected to behavioral evaluations (apomorphine-induced rotations and open-field tests). Then, they were sacrificed and had their mesencephalon, striatum, and hippocampus dissected for neurochemical (DA and DOPAC determinations), histological (Fluoro-Jade staining), and immunohistochemistry evaluations (TH, OX-42, GFAP, TNF-alpha, and HDAC). The results showed that VA partly reversed behavioral and neurochemical alterations observed in the untreated 6-OHDA-lesioned rats. Besides, VA also decreased neuron degeneration in the striatum and reversed the TH depletion observed in the mesencephalon of the untreated 6-OHDA groups. This neurotoxin increased the OX-42 and GFAP immunoreactivities in the mesencephalon, indicating increased microglia and astrocyte reactivities, respectively, which were reversed by VA. In addition, the immunostainings for TNF-alpha and HDAC demonstrated in the untreated 6-OHDA-lesioned rats were also decreased after VA treatments. These results were observed not only in the CA1 and CA3 subfields of the hippocampus, but also in the temporal cortex. In conclusion, we showed that VA partly reversed the behavioral, neurochemical, histological, and immunohistochemical alterations observed in the untreated 6-OHDA-lesioned animals. These effects are probably related to the drug anti-inflammatory activity and strongly suggest that VA is a potential candidate to be included in translational studies for the treatment of neurodegenerative diseases as PD.
which inactivate bradykinin were partially purified fram the fresh exsanguinated liver of rat, ma... more which inactivate bradykinin were partially purified fram the fresh exsanguinated liver of rat, man, dog, gUinea-pig, chicKen,
Keywords: C-reactive protein Cytokines Epileptogenesis Omega-3 fatty acid Temporal lobe epilepsy ... more Keywords: C-reactive protein Cytokines Epileptogenesis Omega-3 fatty acid Temporal lobe epilepsy Pilocarpine During the epileptogenic process, several events may occur, such as an important activation of the immune system in the central nervous system. The response to seizure activity results in an inflammation in the brain as well as in the periphery. Moreover, CRP and cytokines may be able to interact with numerous ligands in response to cardiac injury caused by sympathetic stimulation in ictal and postictal states. Based on this, we measured the serum levels of C-reactive protein (CRP) and cytokines during acute, silent, and chronic phases of rats submitted to the pilocarpine model of epilepsy. We have also analyzed the effect of a chronic treatment of these rats with omega-3 fatty acid in CRP and cytokine levels, during an epileptic focus generation. C-reactive protein and cyto-kines such as IL-1β, IL-6, and TNF-α presented high concentration in the blood of rats, even well after the occurrence of SE. We found reduced levels of CRP and all proinflammatory cytokines in the blood of animals with chronic seizures, treated with omega-3, when compared with those treated with vehicle solution. Taken together, our results strongly suggest that the omega-3 is an effective treatment to prevent SUDEP occurrence due to its capability to act as an anti-inflammatory compound, reducing the systemic inflammatory parameters altered by seizures.
Anais da Academia Brasileira de Ciências, 2009
Epilepsy & Behavior, 2010
We investigated the effect of epileptic seizures during pregnancy on hippocampal expression of ca... more We investigated the effect of epileptic seizures during pregnancy on hippocampal expression of calciumbinding proteins in the offspring. Female Wistar rats were submitted to the pilocarpine model and mated during the chronic period. Seizure frequency was monitored over the entire pregnancy. Pups were perfused at postnatal days 6 and 13, and the brains processed for Nissl staining and immunohistochemistry for NeuN, calbindin, calretinin, and parvalbumin. Number of stained cells in the hippocampus was estimated through stereological methods. Our results showed a decrease in epileptic seizure frequency during pregnancy. No differences were observed in NeuN-positive, CR-positive cells, and Nissl-stained hippocampal neurons between the groups. However, there was a significant decrease in calbindin-positive cells (P = 0.005) and a significant increase in parvalbumin-positive cells (P = 0.02) in the experimental group when compared with the control group. These results suggest that seizures during pregnancy affect the development of specific hippocampal interneurons of the offspring.
Epilepsy & Behavior, 2010
To evaluate a potential insult in the cerebellum of pups exposed to maternal epileptic seizures d... more To evaluate a potential insult in the cerebellum of pups exposed to maternal epileptic seizures during intrauterine life, female rats were subjected to pilocarpine-induced epilepsy. Pups from different litters were sacrificed at 1, 3, 7 and 14 post-natal days (PN) and neuroglobin (Ngb) and gliosis were analyzed in the cerebellum by Western blotting (WB) and RT-PCR. 14 C-l-leucine-[ 14 C-Leu] incorporation was used to analyze protein synthesis at PN1. Nitric Oxide (NO) and thiobarbituric acid-reactive substances (TBARS) levels were also measured. Pups from naive mothers were used as controls. The mRNA level of Ngb was increased in experimental animals at PN1 ( ** p ≤ 0.001) and PN3 ( ** p ≤ 0.001), at PN7 ( *** p ≤ 0.0001) and at PN14 ( ** p ≤ 0.001) compared to the respective controls. The protein level of Ngb increased significantly in the experimental pups at PN1 ( * p ≤ 0.05) and at PN3 ( ** p ≤ 0.001), when compared to the control pups at PN1 and PN3. At PN7 and PN14 no difference was found. The mRNA level of GFAP increased significantly about two times at PN3 ( * p ≤ 0.05) and PN7 ( * p ≤ 0.05) in the experimental pups when compared to the respective controls, but was unchanged in the other studied ages. Data showed that experimental pups at PN1 exhibited reduced (about 2 times, * p ≤ 0.05) total protein synthesis in the cerebellum when compared to control. No differences were found in the NO and TBARS levels. Our data support the hypothesis that an up-regulation of Ngb could be a compensatory mechanism in response to the hypoxic-ischemic insults caused by seizures in pups during intrauterine life.
Objective: The goal of this study was to verify the effects of treatment with melatonin and N-ace... more Objective: The goal of this study was to verify the effects of treatment with melatonin and N-acetylserotonin on the pilocarpine-induced epilepsy model. Methods: The animals were divided into four groups: (1) animals treated with saline (Saline); (2) animals that received pilocarpine and exhibited SE (SE); (3) animals that exhibited SE and were treated with N-acetylserotonin (30 minutes and 1, 2, 4, 6, 12, 24, 36, and 48 hours) after SE onset (SE + NAS); (4) animals that exhibited SE and were treated with melatonin at the same time the SE + NAS group (SE + MEL). Behavioral (latency to first seizure, frequency of seizures, and mortality) and histological (Nissl and neo-Timm) parameters were analyzed. Results: The animals treated with melatonin (SE + MEL) had a decreased number of spontaneous seizures during the chronic period (P b 0.05), a reduction in mossy fiber sprouting, and less cell damage than the SE group. Animals treated with N-acetylserotonin did not exhibit any kind of significant change. Conclusion: Melatonin exerts an important neuroprotective effect by attenuating SE-induced postlesion and promoting a decrease in the number of seizures in epileptic rats. This suggests, for the first time, that melatonin could be used co-therapeutically in treatment of patients exhibiting SE to minimize associated injuries in these situations.
Developmental Neuroscience, 2011
fiber sprouting (MFS) density were evaluated in the hippocampal formation. Our results showed tha... more fiber sprouting (MFS) density were evaluated in the hippocampal formation. Our results showed that the malnourished animals required a lower pilocarpine dose in order to develop SE (200 mg/kg), lower latency to reach SE, less time for the first spontaneous seizure and higher seizure frequency, when compared to well-nourished pilocarpine rats. Histopathological findings revealed a significant cell density reduction in the CA1 region and intense MFS among the malnourished animals. Our data indicate that early malnutrition greatly influences susceptibility to seizures and behavioral manifestations in adult life. These findings suggest that malnutrition in infancy reduces the threshold for epilepsy and promotes alterations in the brain that persist into adult life.
Epilepsy Research, 2002
Previous studies have shown that the susceptibility to pilocarpine-induced status epilepticus (SE... more Previous studies have shown that the susceptibility to pilocarpine-induced status epilepticus (SE) in female rats changes according to estrous cycle phases. These studies have also shown that following pilocarpine administration changes occur in gonadal, hypophyseal and hypothalamic hormones that could contribute for the sequence of the epileptic events. Accordingly, the present work aimed to investigate the role of sexual hormones withdrawal on the development of the pilocarpine model of epilepsy in female rats. With this purpose, castrated and non-castrated adult female Wistar rats were injected with pilocarpine and some characteristic parameters of the experimental model were observed. The results showed increased mortality after pilocarpine injection in the castrated rats when compared with non-castrated females. The latency period for SE onset and for the first spontaneous seizure was decreased in castrated when compared with non-castrated animals. The mossy fiber sprouting measured by neo-Timm scale during the chronic period, reached grade 3 for castrated epileptic rats while the non-castrated epileptic rats showed grade 2.
Menopause, 1999
. Hormonal and gestational parameters in female rats submitted to the pilocarpine model of epilep... more . Hormonal and gestational parameters in female rats submitted to the pilocarpine model of epilepsy. Epilepsy Res. 32,[266][267][268][269][270][271][272][273][274], studying the establishment of the pilocarpine epilepsy model in female rats observed that the estrous cycle was dramatically altered during the three periods of this experimental model. This work was delineated to study the function of sexual hormones in the development of the epilepsy model induced by pilocarpine in ovariectomized rats. Experimental groups were: (a) control animals during estrus phase of the estrous cycle (E) and ovariectomized female rats (OVX) treated with saline instead of pilocarpine in the same volume, (b) experimental animals, that developed status epilepticus (SE) and were studied during the chronic phase of this model: intact chronic rats (CHRON) and ovariectomized chronic rats (OVX + CHRON) and (c) ovariectomized chronic rats, that were submitted to hormonal replacement therapy treated with: medroxyprogesterone (OVX + CHRON + MPA); 17-estradiol (OVX + CHRON + E2), or both (OVX + CHRON + E2 + MPA). All ovariectomized animals showed genital atrophy 4 days after the surgical procedure. Moreover, all animals that developed SE and survived showed spontaneous recurrent seizures during the chronic phase. Concerning to seizure frequency, animals receiving medroxyprogesterone associated with 17-estradiol * Hormonal replacement therapy in ovariectomized epileptic female rats 47 showed decreased seizures' number. However, animals that received only medroxyprogesterone therapy also showed reduction in the number of seizures. In addition, hormonal treatment was also able to stabilize the mossy fibers sprouting process, showing the importance of these hormones in the development of the epilepsy in female rats.
Brain Research Bulletin, 2002
Extracellular matrix proteoglycans (PGs) and glycosaminoglycans (GAGs) play a crucial role in cel... more Extracellular matrix proteoglycans (PGs) and glycosaminoglycans (GAGs) play a crucial role in cell differentiation and synaptogenesis by modulating neurite outgrowth. The chondroitin sulfate (CS)-rich PG, the receptor protein tyrosine phosphatase ζ /β (RPTPζ /β), has been related to neural morphogenesis and axon guidance. Hippocampal sclerosis is the most frequent pathologic finding in patients with intractable mesial temporal lobe epilepsy (MTLE), which is associated with neuron loss, reactive gliosis, and mossy fiber sprouting. In the present study, we investigated the concentration of CS, heparan sulfate (HS) and hyaluronic acid (HA) in the hippocampus and temporal neocortex as well as RPTPζ /β expression in the hippocampus of patients with MTLE. Compared to autopsy control tissue, epileptic hippocampi showed a significantly increased concentration of CS (224%; p = 0.0109) and HA (146%; p = 0.039). HS was instead similar to control values. No differences were found in the concentration of CS, HS, or HA in the temporal neocortex of epileptic patients when compared to control values. In contrast, RPTPζ /β immunoreactivity was induced in astrocytes of the inner molecular layer of the dentate gyrus of the sclerotic hippocampus. Because matrix compounds have been associated with tissue injury and repair, the present findings suggest that changes in PGs and GAGs might be related to damage-induced gliosis and neuronal reorganization in the hippocampus of MTLE patients.
Epilepsy Research, 1997
Since its original description over 10 years ago, the pilocarpine model of status epilepticus (SE... more Since its original description over 10 years ago, the pilocarpine model of status epilepticus (SE) has gained considerable attention. Much work has been done with the model in order to characterize the involvement of different brain structures in seizure genesis and spread. Electrophysiological studies of temporal lobe epileptic slices of both human and animal models, have failed to reveal hyperexcitability, unless blockade of GABAergic inhibition is performed. Thus, we have decided to evaluate potential contributions of picrotoxin, a GABAA channel blocker, on pilocarpine-induced SE. Animals injected with three-specific dose combinations (pilocarpine dose/picrotoxin dose), 150/0.5, 75/1.5 and 50/2.0 mg/kg, evoked status epilepticus (SE) within 23, 31 and 27 min, respectively. Ictal events and EEG spikes were initially observed either in the amygdala or in the hippocampus, with a later spread to cerebral cortex. Neuropathological analysis, performed 5-7 days after SE, has shown a high degree of cell loss predominantly in the piriform cortex, amygdala, hippocampus, thalamus and substantia nigra. Mortality rates for 150/0.5, 75/1.5 and 50/2.0 mg/kg (pilocarpine dose/picrotoxin dose) were 53, 42 and 51%, respectively. Single injections of 150 mg/kg of pilocarpine or 3 mg/kg of picrotoxin did not evoke any form of sustained epileptic activity. Previous studies in which simultaneous injections of other GABAA antagonists (i.e. bicuculline) and pilocarpine were performed, did not show clear evidences of a synergistic action between these two systems. The present study reveals a proconvulsant role for picrotoxin when co-administered with subconvulsant doses of pilocarpine. Possible mechanisms that might account for the interactions between the cholinergic and GABAergic systems in regard to epileptogenesis are discussed.
Uploads
Papers by Maria Graca Naffah Mazzacoratti