Aline Priscila Pansani

Whole transcriptome analysis of the hippocampus: toward a molecular portrait of epileptogenesis

BackgroundUncovering the molecular mechanisms involved in epileptogenesis is critical to better understand the physiopathology of epilepsies and to help develop new therapeutic strategies for this prevalent and severe neurological condition that affects millions of people worldwide.ResultsChanges in the transcriptome of hippocampal cells from rats subjected to the pilocarpine model of epilepsy were evaluated by microarrays covering 34,000 transcripts representing all annotated rat genes to date. Using such genome-wide approach, differential expression of nearly 1,400 genes was detected during the course of epileptogenesis, from the early events post status epilepticus (SE) to the onset of recurrent spontaneous seizures. Most of these genes are novel and displayed an up-regulation after SE. Noteworthy, a group of 128 genes was found consistently hyper-expressed throughout epileptogenesis, indicating stable modulation of the p38MAPK, Jak-STAT, PI3K, and mTOR signaling pathways. In particular, up-regulation of genes from the TGF-beta and IGF-1 signaling pathways, with opposite effects on neurogenesis, correlate with the physiopathological changes reported in humans.ConclusionsA consistent regulation of genes functioning in intracellular signal transduction regulating neurogenesis have been identified during epileptogenesis, some of which with parallel expression patterns reported in patients with epilepsy, strengthening the link between these processes and development of epilepsy. These findings reveal dynamic molecular changes occurring in the hippocampus that may serve as a starting point for designing alternative therapeutic strategies to prevent the development of epilepsy after acquired brain insults.

Preventing tomorrow's sudden cardiac death in epilepsy today: what should physicians know about this?

Approximately 1% of the population has epilepsy, the most common neurological disorder. Moreover, people with epilepsy are more likely to die prematurely than those without epilepsy, and the most common epilepsy-related category of death is sudden unexpected death in epilepsy (SUDEP). Information concerning risk factors for SUDEP is conflicting, but potential risk factors include: age, early onset of epilepsy, duration of epilepsy, uncontrolled seizures, seizure frequency, number of antiepileptic drugs and winter temperatures. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. This review discusses the epidemiology, risk factors, etiology, and preventative measures in the management of SUDEP.

Acute strength exercise and the involvement of small or large muscle mass on plasma brain-derived neurotrophic factor levels

OBJECTIVE: Blood neurotrophins, such as the brain‐derived neurotrophic factor, are considered to be of great importance in mediating the benefits of physical exercise. In this study, the effect of acute strength exercise and the involvement of small versus large muscle mass on the levels of plasma brain‐derived neurotrophic factor were evaluated in healthy individuals. METHODS: The concentric strengths of knee (large) and elbow (small) flexor and extensor muscles were measured on two separate days. Venous blood samples were obtained from 16 healthy subjects before and after exercise. RESULTS: The levels of brain‐derived neurotrophic factor in the plasma did not significantly increase after both arm and leg exercise. There was no significant difference in the plasma levels of the brain‐derived neurotrophic factor in the arms and legs. CONCLUSION: The present results demonstrate that acute strength exercise does not induce significant alterations in the levels of brain‐derived neurotrophic factor plasma concentrations in healthy individuals. Considering that its levels may be affected by various factors, such as exercise, these findings suggest that the type of exercise program may be a decisive factor in altering peripheral brain‐derived neurotrophic factor.

Expression of vitamin D receptor mRNA in the hippocampal formation of rats submitted to a model of temporal lobe epilepsy induced by pilocarpine.

Vitamin D (VD), is a steroid hormone with multiple functions in the central nervous system (CNS), producing numerous physiological effects mediated by its receptor (VDR). Clinical and experimental studies have shown a link between VD dysfunction and epilepsy. Along these lines, the purpose of our work was to analyze the relative expression of VDR mRNA in the hippocampal formation of rats during the three periods of pilocarpine-induced epilepsy. Male Wistar rats were divided into five groups: (1) control group; rats that received saline 0.9%, i.p. and were killed 7 days after its administration (CTRL, n=8), (2) SE group; rats that received pilocarpine and were killed 4h after SE (SE, n=8), (3) Silent group--7 days; rats that received pilocarpine and were killed 7 days after SE (SIL 7d, n=8), (4) Silent group--14 days; rats that received pilocarpine and were killed 14 days after SE (SIL 14d, n=8), (5) Chronic group; rats that received pilocarpine and were killed 60 days after the first spontaneous seizure, (chronic, n=8). The relative expression of VDR mRNA was determined by real-time PCR. Our results showed an increase of the relative expression of VDR mRNA in the SIL 7 days, SIL 14 days and Chronic groups, respectively (0.060+/-0.024; 0.052+/-0.035; 0.085+/-0.055) when compared with the CTRL and SE groups (0.019+/-0.017; 0.019+/-0.025). These data suggest the VDR as a possible candidate participating in the epileptogenesis process of the pilocarpine model of epilepsy.

Repeated amygdala-kindled seizures induce ictal rebound tachycardia in rats

It is thought that cardiovascular changes may contribute to sudden death in patients with epilepsy. To examine cardiovascular alterations that occur during epileptogenesis, we measured the heart rate of rats submitted to the electrical amygdala kindling model. Heart rate was recorded before, during, and after the induced seizures. Resting heart rate was increased in stages 1, 3, and 5 as compared with the unstimulated control condition. In the initial one third of the seizures, we observed bradycardia, which increased in intensity with increasing stage and was blocked by injecting methyl atropine. During stage 5 seizures, a rebound tachycardia was observed that also increased in intensity with increasing number of seizures. This study demonstrated the influence of seizure frequency on cardiac autonomic modulation, providing a basis for discussion of potential mechanisms that cause patients with epilepsy to die suddenly.

Increased basal plasma brain-derived neurotrophic factor levels in sprint runners.

ObjectiveExercise is known to enhance circulating brain-derived neurotrophic factor (BDNF) levels in healthy humans. BDNF changes have been measured in endurance but not in strength exercise. The present study aimed to investigate whether anaerobic activity such as sprinting differentially alters basal plasma BDNF concentration.MethodsBrazilian sprinters (100 m) at either the international (Olympics and Outdoor World Championships) (n = 14) or the domestic level (n = 8), and sedentary subjects (n = 15), were recruited. Plasma BDNF concentrations were analyzed by enzyme-linked immunosorbent assay.ResultsThe basal plasma BDNF concentrations were significantly higher in the international and the domestic sprinters than in the sedentary subjects. In addition, sprinters at the international level had higher plasma BDNF concentrations than those at the domestic level.ConclusionOur findings suggest that increased basal plasma BDNF level is related to enhanced exercise performance.摘要目的目前研究发现锻炼能增强健康人血液中脑源性神经营养因子(BDNF)的水平。 BDNF水平的改变常发现于耐力运动而非力量锻炼。 本研究旨在探讨厌氧型活动(如短跑)是否能改变人血浆中BDNF的浓度。方法对22名巴西100米短跑运动员, 包括14名过去4年间参加过国际级奥林匹克及户外世锦赛的运动员(国际级)和8名只参加过本国比赛的运动员(国内级), 以及15名此前从未参加过任何运动比赛的健康对照人群, 用ELISA法检测其血浆中BDNF的水平。结果与对照组相比, 国际级和国内级短跑运动员血浆中BDNF的水平均显著升高。 此外, 国际级短跑运动员血浆中BDNF的水平显著高于国内级运动员。结论血浆中BDNF水平的升高可能与运动加强有关。

IS COLD THE NEW HOT IN SUDDEN UNEXPECTED DEATH IN EPILEPSY? Effect of low temperature on heart rate of rats with epilepsy

Sudden unexpected death in epilepsy (SUDEP) is the commonest cause of seizure-related mortality in people with refractory epilepsy. Several risk factors for SUDEP are described; however, the importance of including low temperatures as risk factor for SUDEP was never explored. Based on this, the aim of this study was to evaluate the heart rate of rats with epilepsy during low temperature exposure. Our results showed that low temperature clearly increased the heart rate of rats with epilepsy. Taken together, we concluded that exposure to low temperatures could be considered important risk factors from cardiovascular abnormalities and hence sudden cardiac death in epilepsy.

Hippocampal plasticity in rats submitted to a gastric restrictive procedure

Abstract Bariatric surgery has been the most effective therapeutic intervention for morbidly obese patients. However, recent evidence has shown that this procedure may cause serious neurological complications such as Wernicke encephalopathy, depression, and memory impairment. With this in mind, we conducted an experimental study to investigate whether weight-reduction surgery would promote morphological changes in the hippocampal formation, a brain region linked to cognitive and emotional processes. To do so, the present study evaluated the hippocampal expression of parvalbumin interneurons in rats submitted to a gastric restrictive procedure (experimental phytobezoar). Our results demonstrated that rats with gastric-reduced capacity presented a significant increase in the expression of the parvalbumin interneurons in the hippocampal CA1 and CA3 subfields. These data are the first experimental evidence that restrictive bariatric surgery may alter hippocampal cytoarchitecture.

Níveis cardíacos de troponina I em pacientes com epilepsia do lobo temporal refratária após cortico-amígdalo-hipocampectomia

PURPOSE: Sudden unexpected death in epilepsy (SUDEP) is the main cause of death in patients with epilepsy. Morphologic and functional changes in the heart are related to SUDEP. The aim of our study was to verify the concentration of troponin I, an important marker of myocardium damage, in patients with temporal lobe epilepsy who were submitted to surgical resection and were not seizure-free after the procedure. METHODS: Eleven non-consecutive patients participated in the study and all of them presented poor seizure control after surgical procedure. Troponin I levels higher then 1 ng/ml indicate myocardium damage. The detection level of the kit used in our study was 0,15 ng/ml. RESULTS: Only three patients showed detectable troponin I levels. The troponin I levels found in our study is not related with sex, age or side of the lesion. CONCLUSIONS: In spite of we did not find positive results in our study, an active role of the heart in SUDEP cannot be discarded, since some injuries, even so not being capable to modify troponin I levels, can be enough to generate arrhythmogenic foci.

Carbamazepine does not alter the intrinsic cardiac function in rats with epilepsy

Among the causes for sudden unexpected death (SUDEP) in epilepsy, the effects of antiepileptic drugs on the heart have been poorly explored. Based on this, the aim of our study was to evaluate the heart rate (in vivo and isolated ex vivo) and ventricular pressure (isolated ex vivo) of rats with and without epilepsy treated with carbamazepine. Four groups of adult, male Wistar rats (200-250 g) were studied: [A] control rats (n=8), received neither pilocarpine nor carbamazepine [B] carbamazepine-treated rats (n=8), received a daily dose of 120 mg/Kg, i.p. of carbamazepine for two weeks; [C] rats with epilepsy that received just saline solution (n=8); [D] rats with epilepsy that received a daily dose of 120 mg/Kg, i.p. of carbamazepine for two weeks (n=8). Our results showed significant increase in heart rate in animals with epilepsy (with and without the use of carbamazepine) when compared to the control groups in vivo. In contrast, we did not find differences during isolated ex vivo experiments comparing animals with and without epilepsy and despite the use of carbamazepine. Our results suggest that, in isolation, carbamazepine may not be a potential risk factor for sudden unexpected death in epilepsy.