Maria da Graça Naffah-Mazzacoratti | Universidade Federal de São Paulo (UNIFESP) (original) (raw)

Papers by Maria da Graça Naffah-Mazzacoratti

Developmental Neuroscience, 2011

Malnutrition during the earliest stages of life may result in innumerable brain problems. Moreove... more Malnutrition during the earliest stages of life may result in innumerable brain problems. Moreover, this condition could increase the chances of developing neurological diseases, such as epilepsy. We analyzed the effects of early-life malnutrition on susceptibility to epileptic seizures induced by the pilocarpine model of epilepsy. Wistar rat pups were kept on a starvation regimen from day 1 to day 21 after birth. At day 60, 16 animals (8 = well-nourished; 8 = malnourished) were exposed to the pilocarpine experimental model of epilepsy. Age-matched well-nourished (n = 8) and malnourished (n = 8) rats were used as controls. Animals were video-monitored over 9 weeks. The following behavioral parameters were evaluated: first seizure threshold (acute period of the pilocarpine model); status epilepticus (SE) latency; first spontaneous seizure latency (silent period), and spontaneous seizure frequency during the chronic phase. The cell and mossy fiber sprouting (MFS) density were evaluate...

Neuroscience and Medicine, 2012

Hypertension Research, 2018

The underlying mechanisms by which renal denervation (RD) decreases blood pressure (BP) remain in... more The underlying mechanisms by which renal denervation (RD) decreases blood pressure (BP) remain incompletely understood. In this study, we investigated the effects of ischemic kidney denervation on different sympathetic outflows, brain and renal expression of angiotensin-II receptors, oxidative stress and renal function markers in the 2-kidney, 1-clip (2K-1C) rat model. Surgical RD was performed in Wistar male rats 4-5 weeks after clip implantation. After 10 days of RD, BP, and the activity of sympathetic nerves projecting to the contralateral kidney (rSNA) and splanchnic region were partially reduced in 2K-1C rats, with no change in systemic renin-angiotensin system (RAS). To distinguish the effects of RD from the reduction in BP, 2K-1C rats were treated with hydralazine by oral gavage (25 mg/kg/day for 1 week). RD, but not hydralazine, normalized oxidative stress in the sympathetic premotor brain regions and improved intrarenal RAS, renal injury, and proteinuria. Furthermore, different mechanisms led to renal injury and oxidative stress in the ischemic and contralateral kidneys of 2K-1C rats. Injury and oxidative stress in the ischemic kidney were driven by the renal nerves. Although RD attenuated rSNA, injury and oxidative stress persisted in the contralateral kidney, probably due to increased BP. Therefore, nerves from the ischemic kidney at least partially contribute to the increase in BP, sympathetic outflows, brain oxidative stress, and renal alterations in rats with renovascular hypertension. Based on these findings, the reduction in oxidative stress in the brain is a central mechanism that contributes to the effects of RD on Goldblatt hypertension.

Frontiers in Neuroscience

Interest in the use of anticholinergics to prevent the development of epilepsy after traumatic br... more Interest in the use of anticholinergics to prevent the development of epilepsy after traumatic brain injury (TBI) has grown since recent basic studies have shown their effectiveness in modifying the epileptogenic process. These studies demonstrated that treatment with anticholinergics, in the acute phase after brain injury, decreases seizure frequency, and severity, and the number of spontaneous recurrent seizures (SRS). Therefore, anticholinergics may reduce the risk of developing posttraumatic epilepsy (PTE). In this brief review, we summarize the role of the cholinergic system in epilepsy and the key findings from using anticholinergic drugs to prevent PTE in animal models and new clinical trial protocols. Furthermore, we discuss why treatment with anticholinergics is more likely to prevent PTE than treatment for other epilepsies.

Clinical Neurology and Neurosurgery, Jul 1, 2020

This is a PDF file of an article that has undergone enhancements after acceptance, such as the ad... more This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Alzheimers & Dementia, Jun 1, 2023

Arquivos De Neuro-psiquiatria, Oct 1, 2018

The aim of this work was to evaluate patients with chronic migraine treated with botulinum toxin ... more The aim of this work was to evaluate patients with chronic migraine treated with botulinum toxin A (BT-A) and compare this with low level laser therapy (LLLT), referencing: pain days, pain intensity, intake of drugs/self-medication, anxiety and sleep disorders. Methods: Patients were randomized into two groups: BT-A group (n = 18) and LLLT group (n = 18). Each patient kept three pain diaries: one before (baseline) (30 days), one during treatment (30 days) and one after the post-treatment phase (30 days). Repeated ANOVA plus the Bonferroni post-test, Student's t test, and factorial analysis were applied, and p < 0.05 was accepted as significant. Results: Our data showed that both treatments were able to reduce headache days, acute medication intake and decrease the intensity of pain. Anxiety was reduced in the BT-A group, while sleep disturbance was reduced in the LLLT group. Conclusion: Our data showed that both treatments can be used to treat chronic migraine, without notable differences between them.

Cephalalgia, 2008

Chronic migraine (CM) has been associated with idiopathic intracranial hypertension without papil... more Chronic migraine (CM) has been associated with idiopathic intracranial hypertension without papilloedema (IIHWOP), a significant percentage of these cases occurring in obese patients with intractable headache. A prospective study from February 2005 to June 2006 was made of 62 CM patients who fulfilled International Headache Society diagnostic criteria and had cerebral magnetic resonance venography (MRV) and lumbar puncture (LP) done. Two patients were excluded, six (10%) with elevated cerebrospinal fluid (CSF) open pressure (OP), five with body mass index (BMI) > 25. None of the patients had papilloedema or abnormal MRV. BMI and CSF OP were significantly correlated ( r = 0.476, P < 0.001, Pearson's correlation test). Obesity (defined as BMI > 30) was a predictor of increase in intracranial pressure (defined as OP > 200 mmH2O) ( f = 17.26, 95% confidence interval 6.0, 8.6; P < 0.001). From our study we strongly recommend that not only intractable CM patients with h...

Oxidative medicine and cellular longevity, 2018

Neuroprotection is a desirable process in many neurological disorders, yet complex mechanisms inv... more Neuroprotection is a desirable process in many neurological disorders, yet complex mechanisms involved in this field are not completely understood. The pilocarpine epilepsy model causes potent, seizure-induced excitotoxicity cell death and mitochondria impairment. The present study is aimed at investigating the role of UCP2, a ROS negative regulator, in the neuroprotection after cholinergic insult. Our data demonstrated that UCP2 expression was augmented in the rat hippocampus 3 days after (SE), reaching a peak on the fifth day, then returning to basal levels. Concomitantly, phospho-AKT expression levels were higher in the hippocampus during the early silent phase (5 days after SE). Additionally, it was demonstrated that the blockade of UCP2 by antisense oligonucleotides (ASO) in SE rats successfully diminished both UCP2 mRNA and protein contents. SE ASO rats presented increased mitochondrial proapoptotic factor expression, caspase-3 activity, inflammatory cytokine expression, and R...

Journal of Equine Veterinary Science, Feb 1, 2016

Catecholamines and arginine vasopressin (AVP) release can affect arterial blood pressure (ABP) an... more Catecholamines and arginine vasopressin (AVP) release can affect arterial blood pressure (ABP) and hemodynamic stability in standing, sedated horses. Six mature horses were included in this prospective, randomized, crossover, blinded, experimental study. All the horses were sedated with detomidine (DET) alone (0.01 mg/kg, IV) or combined with methadone (MET) (0.01 mg/kg DET and 0.2 mg/kg MET, IV). Cardiopulmonary data and blood samples were collected 30 minutes before (prebaseline and baseline) and for 120 minutes postinjection. The combination DET/MET produced a significant increase (31%) in mean ABP (MAP) 5 minutes after drug administration which lasted for 120 minutes. Detomidine alone induced only a short-term increase in MAP (15%) at 5 minutes compared with baseline. There were significant differences between groups at 5, 15, and from 60 to 120 minutes. Plasma AVP concentrations were higher in horses receiving the treatment DET from 60 to 120 minutes than those in the combination group, for the same period. There were no significant differences in norepinephrine and epinephrine serum concentrations respect to baseline and between treatments. Detomidine induces a short-term MAP increase, and this effect was prolonged and potentiated by MET association. There is no evidence of AVP, norepinephrine, and epinephrine involvement in this effect.

Headache Medicine

Background: The hypothalamus is a key brain region in the control of energy metabolism, sleep and... more Background: The hypothalamus is a key brain region in the control of energy metabolism, sleep and circadian rhythms, stress and anxiety, food intake, sexual and reproductive behaviors. Orexin-A (hypocretin-1) is a neuropeptide, synthesized in the hypothalamus extensively linked to sleep/wake states, particularly excessive daytime sleepiness. Chronic migraine is comorbid with several conditions but little is known about its mechanisms. We aimed to study the role of orexin-A in the mechanism of chronic migraine and comorbid conditions. Methods: We studied orexin-A levels in the CSF of 60 chronic migraine patients, comparing with age and sex matched controls, and comorbidity with anxiety, depression and excessive daytime sleepiness, using appropriate scales. Results: Orexin-A levels were inversively correlated with anxiety levels (r=-308, p=0,03), but not depression and excessive daytime sleepiness. Orexin levels in CM patients were not different than controls. Discussion/Conclusion: A...

Journal of Andrology

ABSTRACTIn the present work, histochemical and biochemical studies were conducted to analyze chan... more ABSTRACTIn the present work, histochemical and biochemical studies were conducted to analyze changes in the pattern of autonomic innervation during sexual maturation, using the rat epididymis as a model. Glyoxylic acid histochemistry and immunohistochemical studies against dopamine β‐hydroxylase (DβH) and acetylcholinesterase (AChE) indicated a reduction in the amount of catecholaminergic and AChE‐positive neurons, fibers, and puncta detected in the cauda epididymis of adult rats (120 days old), when compared to immature (40 days) and young adult (60 days) animals. No obvious age‐related variations were detected in the few catecholaminergic and AChE‐positive fibers and puncta present in the caput region. AChE‐positive fibers were found sorting out among epithelial cells and ending free upon the epithelial surface or into the tubular lumen of the cauda region of adult rats. Furthermore, a positive staining for AChE in epithelial cells was also detected in the caput and cauda epididym...

Journal of Epilepsy and Clinical Neurophysiology, 2010

Background and Purpose: Rasmussen Encephalitis (RE) is characterized by intractable epilepsy, pro... more Background and Purpose: Rasmussen Encephalitis (RE) is characterized by intractable epilepsy, progressive hemiparesis and unilateral hemispheric atrophy. The progression of the symptoms usually occurs within months to few years. Antiepileptic drugs are usually not effective to control disease progression and epilepsy surgery in the form of hemispheric disconnection has been considered the treatment of choice. This work describes the clinical and electrographic analyses, as well as the post-operative evolution of patients with RE. Patients and Methods: This work includes all the patients with RE evaluated from January 1995 to January 2008 by the Ribeirão Preto Epilepsy Surgery Program (CIREP) considering demographic data, interictal and ictal electroencephalographic (EEG) findings; anatomo-pathological findings and clinical outcome. Results: Twenty-five patients were evaluated, thirteen were female. Mean age of epilepsy onset was 4.4±2.0 years. There were no differences between patients with slow and fast evolution with respect to age of epilepsy onset (p=0.79), age at surgery (p=0.24), duration of epilepsy (0.06), and follow-up (p=0.40). There were no correlations between the presence of bilateral EEG abnormalities or the absence of spikes and post-operative seizure outcome (p=0.06). Twenty-three patients underwent surgery. The mean follow-up was 75.3 months. Eleven patients had total seizure control. Twelve individuals persisted with seizures consisting of mild facial jerks (6 patients), occasional hemigeneralized tonic-clonic seizures (3 patients), and frequent tonic-clonic seizures (3 patients). Mental and language impairment was observed in 15 and 12 patients, after surgery, respectively. Conclusions: This retrospective study reported the clinical and electrographic analysis, as well as the evolution of 23 patients with RE. Fourteen patients achieved satisfactory seizure control, three patients had partial response to surgery, and five patients had maintenance of the pre-operative condition. All patients with left side involvement presented with some language and cognitive disturbance.

Scientific Reports, Dec 2, 2020

The Amazon rodent Proechimys guyannensis is widely studied for hosting various pathogens, though ... more The Amazon rodent Proechimys guyannensis is widely studied for hosting various pathogens, though rarely getting sick. Previous studies on male Proechimys have revealed an endogenous resistance to epilepsy. Here, we assess in female Proechimys, whether sex hormones and biochemical aspects can interfere with the induction of status epilepticus (SE). The lithium-pilocarpine ramp-up protocol was used to induce SE, and blood sera were collected at 30 and 90 min after SE, alongside brains, for biochemical, western blot and immunohistochemical analyses. Results from non-ovariectomised (NOVX) Proechimys were compared to ovariectomised (OVX) animals. Data from female Wistars were used as a positive control of SE inductions. SE latency was similar in NOVX, OVX, and female Wistars groups. However, the pilocarpine dose required to induce SE in Proechimys was higher (25-to 50-folds more). Despite a higher dose, Proechimys did not show strong SE like Wistars; they only reached stage 2 of the Racine scale. These data suggest that female Proechimys are resistant to SE induction. Glucose and progesterone levels increased at 30 min and returned to normal at 90 min after SE. A relevant fact because in humans and rodents, SE leads to hypoglycaemia after 30 min of SE and does not return to normal levels in a short time, a typical adverse effect of SE. In OVX animals, a decrease in GABAergic receptors within 90 min of SE may suggest that ovariectomy produces changes in the hippocampus, including a certain vulnerability to seizures. We speculate that progesterone and glucose increases form part of the compensatory mechanisms that provide resistance in Proechimys against SE induction. Status epilepticus (SE) a condition characterised by is a prolonged seizure activity resulting from the failure of mechanisms responsible for ending seizures or from mechanisms that lead to seizures with a prolonged duration 1. In humans and experimental animal models, sustained SE lead to neuronal loss in selective regions of the brain that can cause epilepsy or death. The transition to SE can be preceded by biochemical changes and the gradual development of pathological brain electrical activity characterised by the involvement of an epileptogenic focus usually located in the hippocampus. Studies have shown that susceptibility to SE can be analysed by measuring biochemical and brain dynamics (i.e., neurochemical and electrical activities) 2,3. Susceptibility to SE in women is related to hormonal fluctuations during the menstrual cycle phases 4. Traditionally, in the follicular phase, oestrogen is produced, a hormone classified as a proconvulsant as it reduces the convulsive threshold. In contrast, in the luteal phase, progesterone, a hormone considered an anticonvulsant agent due to its neuroprotective role, reaches high levels 4,5. In rodent brain, oestradiol decreases gamma-aminobutyric acid (GABA)ergic inhibition 6 , whereas progesterone, via allopregnanolone, binds to GABA receptors

The FASEB Journal, Apr 1, 2012

Neuroscience Letters, Aug 1, 2004

An increase in intra-neuronal Ca(2+) concentration has been associated to status epilepticus (SE)... more An increase in intra-neuronal Ca(2+) concentration has been associated to status epilepticus (SE). Ca(2+) is stored in the endoplasmic reticulum, mediated by the Ca(2+)-ATPases (SERCAs). Here we studied the Ca(2+)-ATPase activity and the SERCA2b distribution in the hippocampus of rats submitted to 5h of SE. The Ca(2+)-uptake was measured using [45Ca]CaCl(2) and the hippocampal distribution of SERCA2b was analyzed by immunohistochemistry. A reduction in the amount of cells expressing SERCA2b in CA1, CA3 and dentate gyrus was observed. However, the surviving cells of these regions increased the SERCA2b immunoreactivity, when compared with control tissues. The Ca(2+)-ATPase activity measured in all hippocampal formation was not modified by SE. These results suggest that SE promotes a redistribution of SERCA2b in the hippocampus as a compensatory Ca(2+)-transport mechanism.

Neuroscience Letters, Mar 1, 2018

Research highlights  Status epilepticus changes the levels of inflammatory cytokines in the brai... more Research highlights  Status epilepticus changes the levels of inflammatory cytokines in the brain of Wistar rats.  In Wistar rats, cortical and hippocampal levels of IL-1β, IL-6, and VEGF are found increased 24h after status epilepticus induced by pilocarpine;  In Amazon Proechimys rodents, no significant change in hippocampal and cortical inflammatory response (IL-1β, IL-6, IL-10, TNF-α and VEGF) was observed 24h after status epilepticus induced by pilocarpine.