Search

Allancer DC Nunes,1 Laylla S Ramalho,2 Álvaro PS Souza,1 Elizabeth P Mendes,1,3 Diego B Colugnati,1 Nícholas Zufelato,2 Marcelo H Sousa,4 Andris F Bakuzis,2 Carlos H Castro1,3 1Department of Physiological Sciences, 2Physics Institute, Federal University of Goiás, Goiânia, Brazil; 3National Institute of Science and Technology in Nanobiopharmaceutics, Belo Horizonte, Brazil; 4Faculty of Ceilândia, University of Brasília, Brasília-DF, Brazil Abstract: Magnetic nanoparticles (MNPs) have been used for various biomedical applications. Importantly, manganese ferrite-based nanoparticles have useful magnetic resonance imaging characteristics and potential for hyperthermia treatment, but their effects in the cardiovascular system are poorly reported. Thus, the objectives of this study were to determine the cardiovascular effects of three different types of manganese ferrite-based magnetic nanoparticles: citrate-coated (CiMNPs); tripolyphosphate-coated (PhMNPs); and bare magnetic nanoparticles (BaMNPs). The samples were characterized by vibrating sample magnetometer, X-ray diffraction, dynamic light scattering, and transmission electron microscopy. The direct effects of the MNPs on cardiac contractility were evaluated in isolated perfused rat hearts. The CiMNPs, but not PhMNPs and BaMNPs, induced a transient decrease in the left ventricular end-systolic pressure. The PhMNPs and BaMNPs, but not CiMNPs, induced an increase in left ventricular end-diastolic pressure, which resulted in a decrease in a left ventricular end developed pressure. Indeed, PhMNPs and BaMNPs also caused a decrease in the maximal rate of left ventricular pressure rise (+dP/dt) and maximal rate of left ventricular pressure decline (–dP/dt). The three MNPs studied induced an increase in the perfusion pressure of isolated hearts. BaMNPs, but not PhMNPs or CiMNPs, induced a slight vasorelaxant effect in the isolated aortic rings. None of the MNPs were able to change heart rate or arterial blood pressure in conscious rats. In summary, although the MNPs were able to induce effects ex vivo, no significant changes were observed in vivo. Thus, given the proper dosages, these MNPs should be considered for possible therapeutic applications. Keywords: cardiac function, isolated heart, magnetic fluids, magnetic nanoparticles, nanomedicine

Exercise training leads to physiological cardiac hypertrophy and the protective axis of the renin-angiotensin system composed of angiotensin-converting enzyme 2, angiotensin-(1-7), and Mas receptor seems involved in this process. However, the role of the basal activity of the Mas receptor in exercise-induced physiological cardiac hypertrophy is still unclear. We evaluated the effects of the Mas receptor blockade on the left ventricular structure and function of rats submitted to running training. Rats were assigned to 4 groups: sedentary (S), sedentary + A-779 (Mas receptor antagonist, 120 µg/kg/day, i.p.; SA), trained (60-minute treadmill running sessions, five days a week, 8 weeks; T), and trained + A-779 (TA). Systolic blood pressure was higher in sedentary and trained rats treated with A-779 at the end of the experimental period. The A-779 treatment prevented the left ventricular hypertrophy evoked by physical exercise and increased collagen deposition in sedentary and trained rats. Cardiomyocytes from the SA group presented increased length and thickness of the sarcomeres, elongated mitochondria, glycogen deposits, and enlarged cisterns of the sarcoplasmic reticulum. TA group presented a reduced sarcomere thickness and cytoplasm with a degenerative aspect. These findings show that the basal activity of the Mas receptor is essential for the proper turnover of the extracellular matrix in the myocardium and the maintenance of the sarcomeric structure of cardiomyocytes., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

OSA is known to increase the risk for SUDEP in persons with epilepsy, but the relationship between these two factors is not clear. Also, there is no study showing the acute responses to obstructive apnea in a chronic epilepsy model. Therefore, this study aimed to characterize cardiorespiratory responses to obstructive apnea and chemoreceptor stimulation in rats. In addition, we analyzed respiratory centers in the brain stem by immunohistochemistry. Epilepsy was induced with pilocarpine. About 30-60 days after the first spontaneous seizure, tracheal and thoracic balloons, and electrodes for recording the electroencephalogram, electromyogram, and electrocardiogram were implanted. Intermittent apneas were made by inflation of the tracheal balloon during wakefulness, NREM sleep, and REM sleep. During apnea, respiratory effort increased, and heart rate fell, especially with apneas made during wakefulness, both in control rats and rats with epilepsy. Latency to awake from apnea was longer with apneas made during REM than NREM, but rats with epilepsy awoke more rapidly than controls with apneas made during REM sleep. Rats with epilepsy also had less REM sleep. Cardiorespiratory responses to stimulation of carotid chemoreceptors with cyanide were similar in rats with epilepsy and controls. Immunohistochemical analysis of Phox2b, tryptophan hydroxylase, and NK1 in brain stem nuclei involved in breathing and sleep (retrotrapezoid nucleus, pre-Bötzinger complex, Bötzinger complex, and caudal raphe nuclei) revealed no differences between control rats and rats with epilepsy. In conclusion, our study showed that rats with epilepsy had a decrease in the latency to awaken from apneas during REM sleep, which may be related to neuroplasticity in some other brain regions related to respiratory control, awakening mechanisms, and autonomic modulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Previous studies have suggested that the Angiotensin-(1-7) [(Ang-(1-7)] can change cardiac function by modulating the autonomic nervous system. However, it is unknown whether the Ang-(1-7) can modulate the effect of acetylcholine (ACh) in ventricular contractility. Thus, this study aimed to investigate whether Ang-(1-7) modifies the amplitude of the cardiac cholinergic effects and if these effects are intrinsic to the heart. In anesthetized Wistar rats, Ang-(1-7) attenuated the effect of ACh in decreasing the left ventricular end-systolic pressure (LVESP), dP/dt max , and dP/dt min , but did not modify the hypotensive effect of ACh. Similarly, Ang-(1-7) attenuated the reduction of the LVESP, dP/dt max , and dP/dt min evoked by ACh in isolated hearts. These effects were blocked by the Mas receptor antagonist, A-779, but not by the adenylyl cyclase inhibitor MDL-12,330 A. Ang-(1-7) also attenuated the reduction in the maximum contraction and relaxation speeds and the shortening promoted by ACh in isolated cardiomyocytes. These data show that Ang-(1-7) acting through Mas receptor counter-regulates the myocardial contractile response to ACh in an arterial pressure and heart rate-independent manner., Competing Interests: Declarations of interest None., (Copyright © 2022. Published by Elsevier Inc.)

Bombesin mediates several biological activities in the gastrointestinal (GI) tract and central nervous system in mammals, including smooth muscle contraction, secretion of GI hormones and regulation of homeostatic mechanisms. Here, we report a novel bombesin-like peptide isolated from Boana raniceps. Its amino acid sequence, GGNQWAIGHFM-NH 2 , was identified and structurally confirmed by HPLC, MS/MS and 454-pyrosequencing; the peptide was named BR-bombesin. The effect of BR-bombesin on smooth muscle contraction was assessed in ileum and esophagus, and its anti-secretory activity was investigated in the stomach. BR-bombesin exerted significant contractile activity with a concentration-response curve similar to that of commercially available bombesin in ileum strips of Wistar rats. In esophageal strips, BR-bombesin acted as an agonist, as many other bombesin-related peptides act, although with different behavior compared to the muscarinic agonist carbachol. Moreover, BR-bombesin inhibited stomach secretion by approximately 50% compared to the untreated control group. This novel peptide has 80% and 70% similarity with the 10-residue C-terminal domain of human neuromedin B (NMB) and human gastrin releasing peptide (GRP10), respectively. Molecular docking analysis revealed that the GRP receptor had a binding energy equal to - 7.3 kcal.mol -1 and - 8.5 kcal.mol -1 when interacting with bombesin and BR-bombesin, respectively. Taken together, our data open an avenue to investigate BR-bombesin in disorders that involve gastrointestinal tract motility and acid gastric secretion., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Cardiovascular alterations are frequently related to epilepsy in both clinical and experimental models, and have been hypothesized as a potential contributor to sudden unexpected death in epilepsy (SUDEP). Further, the frequency of generalized tonic-clonic seizures (GTCS) is a primary risk factor for SUDEP. Therefore, we aimed to evaluate the vascular response of rats subjected to the electrical amygdala kindling model of epilepsy. Male Wistar rats were randomly distributed into the following groups: without seizures (sham, n = 8), 5 GTCS (5 S, n = 5), and 10 GTCS (10 S, n = 6). One day after the last seizure, the rats were euthanized, and the thoracic aorta rings with (E + ) and without (E - ) endothelium were used to evaluate vascular reactivity ex vivo using the organ bath system. The maximum response to acetylcholine-induced vasorelaxation in the E + aortic ring was lower in the 5 S group than in the sham and 10 S groups. A reduced concentration of sodium nitroprusside was required to induce vasorelaxation in the E - aortic rings. These results suggest an impairment in endothelial function and alterations in the nitric oxide (NO) pathway. In conclusion, epilepsy altered the vasorelaxation of the aortic rings and the number of seizures influenced these alterations; therefore, an analysis of endothelial function in patients with a high risk of SUDEP may be beneficial., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Our aim with this study was to evaluate the consumption, performance, quantitative characteristics of carcasses, biochemical profile, plasma levels of ghrelin and leptin, expression of the receptor for ghrelin (GHS-R1a) in the hypothalamus and duodenum, and the number of goblet cells in the duodenum of calves subjected to milk volume restriction and supplemented with 2-hydroxy-4-(methylthio)butanoic acid (HMTBa). We used 21 Holstein mixed-breed calves, aged between 3 and 15 d with an average weight of 36.8 kg, and housed in pens with troughs for hay, concentrate, and water. The study included two consecutive experimental periods (first period [P1] and second period [P2]) of 21 d each, with 7 d of adaptation to the diet and facilities. The calves were distributed in a completely randomized design in three treatments with seven repetitions. 1) Control: 6 liters of milk/d during P1 and 6 liters of milk/day during P2; 2) RES (milk restriction): 3 liters of milk/day during P1 and 6 liters of milk/day during P2; and 3) RES + HMTBa: 3 liters of milk/day during P1 and 6 liters of milk/day during P2 + 3.3 g of HMTBa/day in both periods. HMTBa was supplied in milk, and the amount of concentrated ration and hay provided and leftovers were recorded daily to estimate dry matter (DM) and crude protein consumption. Mean daily weight gain (DWG), final weight (FW), and feed conversion (FC) were obtained at the beginning and at the end of each 21-d period. Plasma concentrations of ghrelin and leptin, triglycerides, total protein, urea, lactate, creatinine, alkaline phosphatase, and cholesterol were measured for P1 and P2 at the end of each 21-d period. At the end of P2, animals were slaughtered; sections of the duodenum were collected to evaluate the expression of GHS-R1a and quantity of goblet cells; hypothalamus was used to evaluate the expression of GHS-R1a; rumen was used to evaluate the thickness of epithelium and keratin and the density, height, and width of ruminal papillae. In P1, total DM consumption, FW, DWG, glucose, and triglycerides were lower in the RES and RES + HMTBa groups (P < 0.001). In P2, there was an improvement in the FC of the RES + HMTBa group (compared with Control and RES groups) and a lower urea concentration in the RES group (compared with Control and RES + HMTBa groups) (P < 0.001). No differences were observed among groups regarding hormonal concentrations, histological parameters, and GHS-R1a expression in the duodenum and hypothalamus. Therefore, milk restriction combined with HMTBa supplementation promoted greater compensatory gain by a mechanism independent of changes in GHS-R1a expression and hormone levels of ghrelin and leptin., (© The Author(s) 2021. Published by Oxford University Press on behalf of the American Society of Animal Science.)

Generalized tonic-clonic seizures (GTCS) are the main risk factor for sudden unexpected death in epilepsy (SUDEP). Also, among the several mechanisms underlying SUDEP there is the cardiac dysfunction. So, we aimed to evaluate the impact of the number of seizures on heart function and morphology in rats with epilepsy. Rats were randomized into three groups: Sham (without epilepsy), 5 S, and 10 S groups, referred as rats with epilepsy with a total of 5 or 10 GTCS, respectively. Epilepsy was induced by electrical amygdala kindling. The ventricular function was analyzed by the Langendorff technique and challenged by ischemia/reperfusion protocol. Cardiac fibrosis and hypertrophy were analyzed by histology. We also analyzed cardiac metalloproteinases (MMP2 and MMP9), ERK 1/2 and phosphorylated ERK1/2 (P-ERK) by western blot; microRNA-21 and -320 by RT-PCR; and oxidative stress (TBARS, catalase activity and nitrite) by biochemical analysis. Only the 5S group presented decreased values of ventricular function at before ischemia/reperfusion (baseline): intraventricular systolic pressure, developed intraventricular pressure, positive and negative dP/dt. During ischemia/reperfusion protocol, the variation of the ventricular function did not differ among groups. Both 5S and 10S groups had increased cardiomyocyte hypertrophy and fibrosis compared to Sham, but in the 5S group, these alterations were higher than in the 10S group. The 5S group increased in microRNA-21 and decreased in microRNA-320 expression compared to Sham and the 10S group. The 10S group increased in MMP9 and decreased in P-ERK/ERK expression, and increased in nitrite content compared to both Sham and the 5S group. Therefore, seizures impair cardiac function and morphology, probably through microRNA modulation. The continuation of seizures seems to exert a preconditioning-like stimulus that fails to compensate the cardiac tissue alteration., (Copyright © 2021 Elsevier Inc. All rights reserved.)

The effects of the renin-angiotensin system (RAS) on stem cells isolated from human dental apical papilla (SCAPs) are completely unknown. Therefore, the aim of this study was to identify RAS components expressed in SCAPs and the effects of angiotensin (Ang) II and Ang-(1-7) on cell proliferation. SCAPs were collected from third molar teeth of adolescents and maintained in cell culture. Messenger RNA expression and protein levels of angiotensin-converting enzyme (ACE), ACE2, and Mas, Ang II type I (AT1) and type II (AT2) receptors were detected in SCAPs. Treatment with either Ang II or Ang-(1-7) increased the proliferation of SCAPs. These effects were inhibited by PD123319, an AT2 antagonist. While Ang II augmented mTOR phosphorylation, Ang-(1-7) induced ERK1/2 phosphorylation. In conclusion, SCAPs produce the main RAS components and both Ang II and Ang-(1-7) treatments induced cell proliferation mediated by AT2 activation through different intracellular mechanisms., (© 2020 Wiley Periodicals LLC.)

Temporal lobe epilepsy (TLE) is the most frequent type of epilepsy and is often refractory to pharmacological treatment. In this scenario, extensive research has identified components of the renin-angiotensin system (RAS) as potential therapeutic targets. Therefore, the aim of the present study was to evaluate the effects of long-term treatment with angiotensin-(1-7) [Ang-(1-7)] in male Wistar rats with TLE induced by pilocarpine (PILO). Rats with TLE were submitted to intracerebroventricular (icv) infusion of Ang-(1-7) (200 ng/kg/h) for 28 days, starting at the first spontaneous motor seizure (SMS). Body weight, food intake, and SMS were evaluated daily. Behavioral tests and hippocampal protein levels were also evaluated at the end of the treatment. Ang-(1-7) treatment reduced the frequency of SMS and attenuated low anxiety levels, increased locomotion/exploration, and reduced body weight gain that was induced by TLE. Moreover, Ang-(1-7) positively regulated the hippocampal levels of antioxidant protein catalase and antiapoptotic protein B-cell lymphoma 2 (Bcl-2), as well as mammalian target of rapamycin (mTOR) phosphorylation, which were reduced by TLE. The hippocampal up-regulation of angiotensin type 1 receptor induced by TLE was also attenuated by Ang-(1-7), while the Mas receptor (MasR) was down-regulated compared with epilepsy. These data show that Ang-(1-7) presents an antiepileptic effect, increasing neuroprotection markers and reducing SMS frequency, body weight, and behavior impairments found in TLE. Therefore, Ang-(1-7) is a promising coadjutant therapeutic option for the treatment of TLE., (© 2020 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

The aim of this study was to investigate whether treatment with diminazene aceturate (DIZE), a putative ACE2 activator, or with angiotensin-(1-7) during pregnancy could attenuate the development of cardiovascular dysfunction in the adult offspring of spontaneously hypertensive rats (SHRs). For this, pregnant SHRs received DIZE or Ang-(1-7) throughout gestation. The systolic blood pressure (SBP) was measured in the male offspring from the 6th to16th weeks of age by tail-cuff plethysmography. Thereafter, the left ventricular contractile function and coronary reactivity were evaluated by the Langendorff technique. Samples of the left ventricles (LVs) and kidneys were collected for histology and western blot assay in another batch of adult rat offspring. Maternal treatment with DIZE or Ang-(1-7) during pregnancy attenuated the increase in SBP in adult offspring. In addition, both DIZE and Ang-(1-7) treatments reduced the cardiomyocyte diameter and fibrosis deposition in the LV, and treatment with Ang-(1-7) also reduced the fibrosis deposition in the kidneys. Maternal treatment with DIZE, as well as Ang-(1-7), improved the coronary vasodilation induced by bradykinin in isolated hearts from adult offspring. However, no difference was observed in the contractile function of the LVs of these animals. The expression levels of AT1 and Mas receptors, ACE, ACE2, SOD, and catalase in the LV were not modified by maternal treatment with Ang-(1-7), but this treatment elicited a reduction in AT2 expression. These data show that treatment with DIZE or Ang-(1-7) during gestation promoted beneficial effects of attenuating hypertension and cardiac remodeling in adult offspring.

Ghrelin is a recently discovered peptide, mainly produced in the stomach and involved in body's energy-maintenance processes. Ghrelin exerts its actions by activating the growth hormone secretagogue receptor (GHS-R). Recent analyses indicate that ghrelin targets the brain to regulate a wealth of functions, including behavioral responses that have been associated with stress and anxiety mechanisms. In this context, evidence shows the presence of GHS-R receptors in the dorsal raphe nucleus (DRN), the main source of serotonergic neurons that innervate encephalic structures involved in emotional control. Our study aims to evaluate the effects of the pharmacological manipulation of ghrelin receptors located in the DRN on the expression of the behavioral responses of Wistar rats. Such responses were assessed in the elevated T maze (ETM), an experimental model that allows the measurement, in the same animal, of two defensive tasks, inhibitory avoidance and escape. Our results showed that the intra-DRN infusion of ghrelin impaired the acquisition of inhibitory avoidance, an anxiolytic-like effect, and facilitated the expression of escape response in the ETM, indicating a panicogenic-like effect. The intra-DRN administration of the ghrelin receptor (GHS-R1a) antagonist PF-04628935 did not alter the behavioral tasks assessed in the ETM. Finally, our results revealed that intra-DRN infusions of PF-04628935 prior to the administration of ghrelin into this area neutralized the behavioral effects obtained in the ETM. Taken together, our data reveal the involvement of DRN GHS-R1a receptors in the regulation of defensive tasks that have been associated with generalized anxiety and panic disorders., (Copyright © 2019 Elsevier B.V. All rights reserved.)

We investigated the coronary arteries reactivity alterations in rats with epilepsy induced by pilocarpine. To do so, male Wistar rats weighing between 250 g and 300 g were used. Status epilepticus (SE) was induced in rats using 385 mg/kg (i.p.) of pilocarpine. After 60 days from the first spontaneous seizure, rats were submitted to heart rate measurements and then, one day after, euthanized, and the heart was dissected and submitted to constant flow Langendorff approaches to evaluate coronary reactivity. Rats with epilepsy showed higher resting heart rate and impairment of coronary vasodilation induced by bradykinin. Endothelial nitric oxide synthase (eNOS) and superoxide dismutase (SOD) presented a reduced staining in coronary arteries, and eNOS expression was also reduced in the left ventricle of rats with epilepsy. Our findings demonstrated, for the first time, that epilepsy can cause impairment of coronary arteries reactivity, probably because of an endothelial dependent mechanism., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The imbalance between antioxidant system and reactive oxygen species (ROS) generation is related to epileptogenesis, neuronal death, and seizure frequency. Treatment with vitamin E has been associated with neuroprotection and control of seizures. In most experimental studies, vitamin E treatment has short duration. Therefore, the aim of this study was to verify the role of long-term treatment with vitamin E in rats submitted to the pilocarpine model of epilepsy. Rats were divided into two main groups: control (Ctr) and pilocarpine (Pilo). Each one was subdivided according to treatment: vehicle (Ctr V and Pilo V) or vitamin E at dosages of 6 IU/kg/day (Ctr E6 and Pilo E6) or 60 IU/kg/day (Ctr E60 and Pilo E60). Treatment lasted 120 days from status epilepticus (SE). There were no statistical differences concerning treatment in the Ctr group for all variables, so the data were grouped. Carbonyl content in the hippocampus of Pilo V and Pilo E6 was higher compared with that of the Ctr group (8 ± 1.5, 7.1 ± 1, and 3.1 ± 0.3 nmol carbonyl/mg protein, respectively for Pilo V, Pilo E6, and Ctr; p < 0.05). Carbonyl content was restored to control values in Pilo E60 rats (4.2 ± 1.1 and 3.1 ± 0.3 nmol carbonyl/mg protein, respectively for Pilo E60 and Ctr; p > 0.05). The volume of the hippocampal formation (6.5 ± 0.3, 6.6 ± 0.4, 6.3 ± 0.3, and 7.4 ± 0.2, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) and subfields CA1 (1.6 ± 0.1, 1.4 ± 0.2, 1.5 ± 0.1, and 2 ± 0.05, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) and CA3 (1.7 ± 0.1, 1.5 ± 0.2, 1.4 ± 0.1, and 2 ± 0.1, respectively for Pilo V, Pilo E6, Pilo E60, and Ctr) was reduced in the Pilo group regardless of treatment. Parvalbumin immunostaining was increased in the hilus of the Pilo E60 group compared with that in the Ctr group (26 ± 2 and 39.6 ± 8.3 neurons, respectively for Ctr and Pilo E60). No difference was found in seizure frequency and Neo-Timm staining. Therefore, long-term treatment with 60 IU/kg/day of vitamin E prevented oxidative damage in the hippocampus and increased hilar parvalbumin expression in rats with epilepsy without a reduction in seizure frequency., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Aim: Many particularities concerning interhemispheric differences still need to be explored and unveiled. Functional and anatomical differential features found between left and right brain sides are best known as asymmetries and are consequence of the unilateral neuronal recruitment or predominance that is set to organize some function. The outflow from different neural pathways involved in the autonomic control of the cardiovascular system may route through asymmetrically relayed efferences (ipsilateral/lateralized and/or contralateral). In spite of this, the literature reporting on the role of central nuclei involved in the autonomic control is not always dedicated on these interhemispheric comparisons. Considering the recent reports demonstrating that asymmetries may set differential functional responses, it is worth checking differences between right and left sides of central regions. This review aims to inspire neuroscientists with the idea that studying the interhemispheric differences may deepen the understanding on several centrally controlled responses, with special regard to the autonomic functions underlying the cardiovascular regulation. Conclusions: Thus, an avenue of knowledge may unfold from a field of research that requires further exploration.

Sympathetic premotor neurons of the paraventricular hypothalamus (PVN) play a role in hemodynamics adjustments during changes in body fluid homeostasis. However, PVN contribution to the tonic control of cardiac function remains to be systematically studied. In this study, we assessed whether GABAergic and adrenergic synapses, known for being active in the PVN, are involved in the control of cardiac function. Adult male Wistar rats (250-350 g; n = 27) were anesthetized with urethane (1.2-1.4 g/kg i.p.) and underwent catheterization of femoral artery to record blood pressure and heart rate. The femoral vein was used to inject the vasoactive agents phenylephrine (10 μg/kg) and sodium nitroprusside (10 μg/kg) and to supplement anesthesia. The cardiac left ventricle was catheterized to record left ventricular pressure and its derivative. Craniotomy allowed for injections (100 nL) into the PVN of: muscimol (20 mM), bicuculline methiodide (0.4 mM), propranolol (10 mM), isoproterenol (100 μM), phentolamine (13 mM), phenylephrine (30 nM). We found that: (i) inhibition of PVN by muscimol, reduced arterial pressure, cardiac chronotropy and inotropy; (ii) disinhibition of PVN neurons by bicuculline evoked positive chronotropy and inotropy, and increase blood pressure; (iii) PVN alpha adrenergic receptors control cardiac chronotropy and inotropy; (iv) beta adrenergic receptors of the PVN do not influence cardiac function; (v) afterload does not contribute to the PVN-evoked inotropy. Our results indicate that the modulation of the activity of PVN neurons exerted by GABAergic and adrenergic mechanisms contribute to the control of cardiac function.

Prior evidence indicates that ghrelin is involved in the integration of cardiovascular functions and behavioral responses. Ghrelin actions are mediated by the growth hormone secretagogue receptor subtype 1a (GHS-R1a), which is expressed in peripheral tissues and central areas involved in the control of cardiovascular responses to stress., Aims: In the present study, we assessed the role of ghrelin - GHS-R1a axis in the cardiovascular reactivity to acute emotional stress in rats., Main Methods and Key Findings: Ghrelin potentiated the tachycardia evoked by restraint and air jet stresses, which was reverted by GHS-R1a blockade. Evaluation of the autonomic balance revealed that the sympathetic branch modulates the ghrelin-evoked positive chronotropy. In isolated hearts, the perfusion with ghrelin potentiated the contractile responses caused by stimulation of the beta-adrenergic receptor, without altering the amplitude of the responses evoked by acetylcholine. Experiments in isolated cardiomyocytes revealed that ghrelin amplified the increases in calcium transient changes evoked by isoproterenol., Significance: Taken together, our results indicate that the Ghrelin-GHS-R1a axis potentiates the magnitude of stress-evoked tachycardia by modulating the autonomic nervous system and peripheral mechanisms, strongly relying on the activation of cardiac calcium transient and beta-adrenergic receptors., (Copyright © 2018 Elsevier Inc. All rights reserved.)

This study investigated the influence of antihypertensive drugs, such as angiotensin-converting enzyme inhibitors (ACEIs), AT1 receptor blockers (ARBs), voltage-gated L-type calcium channel blockers, and mineralocorticoid receptor antagonists (MRAs), on the effects of angiotensin-(1-7) [Ang-(1-7)] on aorta and coronary arteries from pressure-overloaded rats. Pressure overload was induced by abdominal aortic banding (AB). To evaluate the role of antihypertensive drugs on the effect of Ang-(1-7), AB male Wistar rats weighing 250-300 g were treated with vehicle or low doses (5 mg·kg-1·day-1, gavage) of losartan, captopril, amlodipine, or spironolactone. Isolated aortic rings and isolated perfused hearts under constant flow were used to evaluate the effect of Ang-(1-7) in thoracic aorta and coronary arteries, respectively. Ang-(1-7) induced a significant relaxation in the aorta of sham animals, but this effect was reduced in the aortas of AB rats. Chronic treatments with losartan, captopril or amlodipine, but not with spironolactone, restored the Ang-(1-7)-induced aorta relaxation in AB rats. The coronary vasodilatation evoked by Ang-(1-7) in sham rats was blunted in hypertrophic rats. Only the treatment with losartan restored the coronary vasodilatory effect of Ang-(1-7) in AB rat hearts. These data support a beneficial vascular effect of an association of Ang-(1-7) and some antihypertensive drugs. Thus, this association may have potential as a new therapeutic strategy for cardiovascular diseases.

Previous studies have demonstrated a protective effect of the Ang-(1-7)/Mas receptor axis on pathological cardiac hypertrophy. Also, the involvement of Mas receptor in exercise-induced cardiac hypertrophy has been suggested. However, the role of the Ang-(1-7)/Mas receptor on pregnancy-induced cardiac remodelling remains unknown. The objective of the present study was to evaluate the participation of the Mas receptor in the development of the cardiac hypertrophy and fibrosis induced by gestation. Female Wistar rats were divided in three groups: control, pregnant and pregnant treated with Mas receptor antagonist A-779. Wild-type (WT) and Mas-knockout (KO) mice were distributed in non-pregnant and pregnant groups. Systolic blood pressure (SBP) was measured by tail-cuff plethysmography. The medial part of the left ventricle (LV) was collected for histological analysis. Echocardiographic analysis was used to evaluate cardiac function. SBP was not changed by pregnancy or A-779 treatment in the Wistar rats. Pharmacological blockade or genetic deletion of Mas receptor attenuates the pregnancy-induced myocyte hypertrophy. The treatment with A-779 or genetic deletion of the Mas receptor increased the collagen III deposition in LV from pregnant animals without changing fibroblast proliferation. KO mice presented a lower ejection fraction (EF), fractional shortening (FS) and stroke volume (SV) and higher end systolic volume (ESV) compared with WT. Interestingly, pregnancy restored these parameters. In conclusion, these data show that although Mas receptor blockade or deletion decreases physiological hypertrophy of pregnancy, it is associated with more extracellular matrix deposition. These alterations are associated with improvement of cardiac function through a Mas-independent mechanism., (© 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.)

Aims: Angiotensin-converting enzyme 2 (ACE2) is a key modulator of the renin-angiotensin system. Recent studies have shown that diminazene aceturate (DIZE) acts as an ACE2 activator. The aim of this study was to evaluate the cardiac effects of chronic treatment with DIZE in pressure-overloaded rats., Main Methods: Male Wistar rats were divided into 4 groups: (1) sham; (2) aortic banded rats (AB); (3) AB+DIZE (1mg/kg, gavage); and (4) AB+DIZE+A-779 (120μg/day, osmotic mini-pumps). Cardiac hypertrophy was evaluated by ventricular mass index and myocyte cross-sectional area. mRNA expression of atrial natriuretic peptide (ANP), B-type natriuretic peptide (BNP) and transforming growth factor beta 1 (TGF-β) was quantified by RT-PCR. Cardiac function was assessed according to the Langendorff technique. The ACE2 and Mas protein expression was examined by western blot analysis., Key Findings: DIZE treatment prevented the cardiomyocyte hypertrophy promoted by AB and A-779 inhibited this effect. Also, DIZE induced the expression of ANP and BNP mRNA in cardiac tissue from AB rats and attenuated the impairment in left ventricular end-systolic pressure and left ventricular developed pressure, +dP/dt and -dP/dt caused by AB. These effects were blocked by A-779. Moreover, DIZE prevented the increase in the expression of TGF-β mRNA in AB hearts, but it did not change the ACE2 and Mas protein expression., Significance: These results showed that DIZE was efficient in preventing the cardiomyocyte hypertrophy and attenuated the left ventricular contractile impairment induced by pressure overload. However, further studies are necessary to confirm whether these effects were due to ACE2 activation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Intrathecal injection of bombesin (BBS) promoted hypertensive and sympathoexcitatory effects in normotensive (NT) rats. However, the involvement of rostral ventrolateral medulla (RVLM) in these responses is still unclear. In the present study, we investigated: (1) the effects of BBS injected bilaterally into RVLM on cardiorespiratory and sympathetic activity in NT and spontaneously hypertensive rats (SHR); (2) the contribution of RVLM BBS type 1 receptors (BB1) to the maintenance of hypertension in SHR. Urethane-anesthetized rats (1.2 g · kg(-1), i.v.) were instrumented to record mean arterial pressure (MAP), diaphragm (DIA) motor, and renal sympathetic nerve activity (RSNA). In NT rats and SHR, BBS (0.3 mM) nanoinjected into RVLM increased MAP (33.9 ± 6.6 and 37.1 ± 4.5 mmHg, respectively; p < 0.05) and RSNA (97.8 ± 12.9 and 84.5 ± 18.1%, respectively; p < 0.05). In SHR, BBS also increased DIA burst amplitude (115.3 ± 22.7%; p < 0.05). BB1 receptors antagonist (BIM-23127; 3 mM) reduced MAP (-19.9 ± 4.4 mmHg; p < 0.05) and RSNA (-17.7 ± 3.8%; p < 0.05) in SHR, but not in NT rats (-2.5 ± 2.8 mmHg; -2.7 ± 5.6%, respectively). These results show that BBS can evoke sympathoexcitatory and pressor responses by activating RVLM BB1 receptors. This pathway might be involved in the maintenance of high levels of arterial blood pressure in SHR.

Sudden and unexpected death in epilepsy (SUDEP) is the most common type of death among patients with epilepsy. Here, we address the importance of the experimental models in search of the mechanisms underlying SUDEP. Most studies have investigated the cardiovascular responses in animal models of epilepsy. However, there are few proposed SUDEP models in literature. Hypoventilation, apnea, respiratory distress, pulmonary hypertension, autonomic dysregulation and arrhythmia are common findings in epilepsy models. Impairments on adenosinergic and serotonergic systems, brainstem spreading depolarization, seizure-activation of neural substrates related to cardiorespiratory control, altered autonomic control, and mutations on sodium and potassium channels are hypothesis suggested. Overall, current research highlights the evident multifactorial nature of SUDEP, which involves acute and chronic aspects ranging from systemic to molecular alterations. Thus, we are convinced that elucidation and prevention of SUDEP can be achieved only through the interaction between basic and clinical science.

Hypernatremia stimulates the secretion of oxytocin (OT), but the physiological role of OT remains unclear. The present study sought to determine the involvement of OT and renal nerves in the renal responses to an intravenous infusion of hypertonic saline. Male Wistar rats (280-350 g) were anesthetized with sodium thiopental (40 mg. kg(-1), i.v.). A bladder cannula was implanted for collection of urine. Animals were also instrumented for measurement of mean arterial pressure (MAP) and renal blood flow (RBF). Renal vascular conductance (RVC) was calculated as the ratio of RBF by MAP. In anesthetized rats (n = 6), OT infusion (0.03 µg • kg(-1), i.v.) induced renal vasodilation. Consistent with this result, ex vivo experiments demonstrated that OT caused renal artery relaxation. Blockade of OT receptors (OXTR) reduced these responses to OT, indicating a direct effect of this peptide on OXTR on this artery. Hypertonic saline (3 M NaCl, 1.8 ml • kg(-1) b.wt., i.v.) was infused over 60 s. In sham rats (n = 6), hypertonic saline induced renal vasodilation. The OXTR antagonist (AT; atosiban, 40 µg • kg(-1) • h(-1), i.v.; n = 7) and renal denervation (RX) reduced the renal vasodilation induced by hypernatremia. The combination of atosiban and renal denervation (RX+AT; n = 7) completely abolished the renal vasodilation induced by sodium overload. Intact rats excreted 51% of the injected sodium within 90 min. Natriuresis was slightly blunted by atosiban and renal denervation (42% and 39% of load, respectively), whereas atosiban with renal denervation reduced sodium excretion to 16% of the load. These results suggest that OT and renal nerves are involved in renal vasodilation and natriuresis induced by acute plasma hypernatremia.

Studies have demonstrated that median preoptic nucleus (MnPO) neurons play a role in organizing the cardiovascular responses induced by changes in the circulating blood volume. The present study examined whether the MnPO controls cardiovascular function. Male Wistar normotensive (NT) rats and spontaneously hypertensive rats (SHRs; 250-300 g) were anesthetized with urethane (1.2 g kg(-1), i.v.) and instrumented for recordings of mean arterial blood pressure (MAP) and renal blood flow (RBF). The renal vascular conductance (RVC) was calculated as the RBF:MAP ratio and was expressed as a percentage of the baseline value. In the NT rats (n=6), MnPO inhibition produced a MAP reduction (-8.1±1.1 mmHg, p<0.05). In the SHRs (n=6), the MAP response to MnPO inhibition was significantly greater (-22.3±4 mmHg, p<0.05) than in the NT rats. Furthermore, the increase in the RVC was higher in the SHRs (10.9±3.3%, p<0.05). Histological analyses confirmed that the injection sites were confined to the MnPO. We conclude that the MnPO is involved in the tonic regulation of blood pressure in NT rats. Moreover, the greater cardiovascular response to MnPO inhibition observed in the SHRs strongly suggests that the MnPO may contribute to the pathophysiology of essential hypertension., (Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.)

The aim of the present study was to investigate the coronary effects of Ang-(1-7) [angiotensin-(1-7)] in hypertrophic rat hearts. Heart hypertrophy was induced by abdominal aorta CoA (coarctation). Ang-(1-7) and AVE 0991, a non-peptide Mas-receptor agonist, at picomolar concentration, induced a significant vasodilation in hearts from sham-operated rats. These effects were blocked by the Mas receptor antagonist A-779. Pre-treatment with L-NAME (N(G)-nitro-L-arginine methyl ester) or ODQ (1H-[1,2,4]oxadiazolo[4,3-a]quinozalin-1-one) [NOS (NO synthase) and soluble guanylate cyclase inhibitors respectively] also abolished the effect of Ang-(1-7) in control hearts. The coronary vasodilation produced by Ang-(1-7) and AVE 0991 was completely blunted in hypertrophic hearts. Chronic oral administration of losartan in CoA rats restored the coronary vasodilation effect of Ang-(1-7). This effect was blocked by A-779 and AT2 receptor (angiotensin II type 2 receptor) antagonist PD123319. Acute pre-incubation with losartan also restored the Ang-(1-7)-induced, but not BK (bradykinin)-induced, coronary vasodilation in hypertrophic hearts. This effect was inhibited by A-779, PD123319 and L-NAME. Chronic treatment with losartan did not change the protein expression of Mas and AT2 receptor and ACE (angiotensin-converting enzyme) and ACE2 in coronary arteries from CoA rats, but induced a slight increase in AT2 receptor in aorta of these animals. Ang-(1-7)-induced relaxation in aortas from sham-operated rats was absent in aortas from CoA rats. In vitro pre-treatment with losartan restored the Ang-(1-7)-induced relaxation in aortic rings of CoA rats, which was blocked by the Mas antagonist A-779 and L-NAME. These data demonstrate that Mas is strongly involved in coronary vasodilation and that AT1 receptor (angiotensin II type 1 receptor) blockade potentiates the vasodilatory effects of Ang-(1-7) in the coronary beds of pressure-overloaded rat hearts through NO-related AT2- and Mas-receptor-dependent mechanisms. These data suggest the association of Ang-(1-7) and AT1 receptor antagonists as a potential therapeutic avenue for coronary artery diseases.

Noradrenergic neurons in the caudal ventrolateral medulla (CVLM; A1 group) contribute to cardiovascular regulation. The present study assessed whether specific lesions in the A1 group altered the cardiovascular responses that were evoked by hypertonic saline (HS) infusion in non-anesthetized rats. Male Wistar rats (280-340 g) received nanoinjections of antidopamine-β-hydroxylase-saporin (A1 lesion, 0.105 ng.nL(-1)) or free saporin (sham, 0.021 ng.nL(-1)) into their CVLMs. Two weeks later, the rats were anesthetized (2% halothane in O2) and their femoral artery and vein were catheterized and led to exit subcutaneously between the scapulae. On the following day, the animals were submitted to HS infusion (3 M NaCl, 1.8 ml • kg(-1), b.wt., for longer than 1 min). In the sham-group (n = 8), HS induced a sustained pressor response (ΔMAP: 35±3.6 and 11±1.8 mmHg, for 10 and 90 min after HS infusion, respectively; P<0.05 vs. baseline). Ten min after HS infusion, the pressor responses of the anti-DβH-saporin-treated rats (n = 11)were significantly smaller(ΔMAP: 18±1.4 mmHg; P<0.05 vs. baseline and vs. sham group), and at 90 min, their blood pressures reached baseline values (2±1.6 mmHg). Compared to the sham group, the natriuresis that was induced by HS was reduced in the lesioned group 60 min after the challenge (196±5.5 mM vs. 262±7.6 mM, respectively; P<0.05). In addition, A1-lesioned rats excreted only 47% of their sodium 90 min after HS infusion, while sham animals excreted 80% of their sodium. Immunohistochemical analysis confirmed a substantial destruction of the A1 cell group in the CVLM of rats that had been nanoinjected withanti-DβH-saporin. These results suggest that medullary noradrenergic A1 neurons are involved in the excitatory neural pathway that regulates hypertensive and natriuretic responses to acute changes in the composition of body fluid.

Since cardiovascular dysfunction may contribute to sudden unexpected death in epilepsy (SUDEP), the consumption of omega-3 fatty acids (omega-3 FAs) might be beneficial as an adjunctive therapy for SUDEP prevention. It is well recognized that omega-3 FAs exert positive effects on the cardiovascular system including heart rate (HR) reduction, a major risk factor to sudden death. Thus, we evaluated the effects of chronic supplementation of omega-3 FAs on the HR of rats with epilepsy. In agreement with our previous investigations, this study also showed that the HR of animals with epilepsy is higher than that of the control group. Quite interestingly, chronic supplementation with omega-3 FAs restored the HR of rats with epilepsy toward control values. In conclusion, although further investigations are still required, our preliminary results showed a potential preventive effect of omega-3 FA supplementation against SUDEP., (Copyright © 2013 Elsevier Inc. All rights reserved.)

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., (Copyright © 2011 Elsevier Inc. All rights reserved.)

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.

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.

Social behavior depends on the integrity of social brain circuitry. The temporal lobe is an important part of the social brain, and manifests morphological and functional alterations in autism spectrum disorders (ASD). Rats with temporal lobe epilepsy (TLE), induced with pilocarpine, were subjected to a social discrimination test that has been used to investigate potential animal models of ASD, and the results were compared with those for the control group. Rats with TLE exhibited fewer social behaviors than controls. No differences were observed in nonsocial behavior between groups. The results suggest an important role for the temporal lobe in regulating social behaviors. This animal model might be used to explore some questions about ASD pathophysiology.

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.

Epilepsy is the most common neurological disorder; approximately 1% of the population worldwide have epilepsy. Moreover, sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. 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 and AED number. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. Very recently, our research group was the first to annunciate that winter temperatures may lead a cardiac abnormalities and hence sudden death, become a new potential risk factor to SUDEP. Quite interesting, several mammalian species have evolved to develop a physiological phenomenon called hibernation as a strategy for survival under adverse cold conditions. From cardiovascular point of view, it has been established that hibernating mammals inherited a stable cardiovascular function as a result of adaptation to extreme external and internal environments during hibernation. For instance, hibernating mammals show resistance to hypothermia at a cellular level, the membrane potentials and excitability are more stable in the cardiac cells of these animals (action potentials (60 mV) have been recorded in hibernators myocardium at -5 degrees C), the aortic smooth muscle cells from hibernators are able to maintain ionic gradients upon prolonged exposure to low temperatures, and cardiac myocytes from hibernating mammals maintain constant levels of intracellular free calcium and forceful contractility at 10 degrees C or lower. Taken together, in this paper we postulate that hibernators have some cardiovascular particularities that confer heart protection that could positively influence the cardiovascular system of patients with epilepsy.

Epilepsy is the most common neurological disorder, approximately 1% of the population worldwide have epilepsy. Moreover, sudden unexpected death in epilepsy (SUDEP) is the most important direct epilepsy-related cause of death. 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, AED number and winter temperatures. Additionally, the cause of SUDEP is still unknown; however, the most commonly suggested mechanisms are cardiac abnormalities during and between seizures. Furthermore, the evidence from the last 10 years suggests that melatonin has an important role in the epileptogenesis process and influences the cardiovascular system as well. The positive effect of melatonin has been demonstrated against different convulsive stimuli in several rodents, including seizures induced by pentylenetetrazole kainate, glutamate, maximal electrical shock and electrically kindled stimulation of amygdala. Clinical studies have also demonstrated a positive role of melatonin on the seizure frequency in children and reduced spiking activity and seizure frequency in patients with intractable epilepsy. In the rat hearts, studies in vivo and in vitro using pharmacological concentrations of melatonin confirmed an anti-arrhythmic effect of this hormone and studies in humans have been shown that chronic heart disease patients have significantly lower melatonin levels in their blood stream than do normal individuals. Thus, caution should be taken in generalization of these findings to epileptic population. Moreover, it is important to note that when dealing with intractable epilepsy that do not respond to any conventional treatment, the additional of melatonin may be evaluated. Taken together, in this paper we suggested a possible relationship between cardiac abnormalities, melatonin and SUDEP.

Among the causes for sudden death in epilepsy, cardiac dysfunction has been an area of interest. Based on this, the aim of our study was to evaluate the heart rate (in vivo and in vitro) and ventricular pressure in vitro of rats with epilepsy induced by pilocarpine. Adult male Wistar rats (n=6) were given pilocarpine hydrochloride to induce status epilepticus. Control rats (n=6) received saline solution instead pilocarpine. Our results showed significant differences in the mean of heart rate in vivo between the groups. In contrast, we did not find differences during in vitro experiments. Our results suggest a central nervous system modulation on the heart, which could explain the sudden unexpected death in epilepsy.

Objective: To further characterize the capacity of lovastatin to prevent hippocampal neuronal loss after pilocarpine-induced status epilepticus (SE) METHOD: Adult male Wistar rats were divided into four groups: (A) control rats, received neither pilocarpine nor lovastatin (n=5); (B) control rats, received just lovastatin (n=5); (C) rats that received just pilocarpine (n=5); (D) rats that received pilocarpine and lovastatin (n=5). After pilocarpine injection (350 mg/kg, i.p.), only rats that displayed continuous, convulsive seizure activity were included in our study. Seizure activity was monitored behaviorally and terminated with an injection of diazepam (10 mg/kg, i.p.) after 4 h of convulsive SE. The rats treated with lovastatin received two doses of 20 mg/kg via an oesophagic probe immediately and 24 hours after SE induction. Seven days after pilocarpine-induced SE, all the animals were perfused and their brains were processed for histological analysis through Nissl method., Results: The cell counts in the Nissl-stained sections performed within the hippocampal formation showed a significant cell loss in rats that received pilocarpine and presented SE (CA1=26.8 +/- 13.67; CA3=38.1 +/- 7.2; hilus=43.8 +/- 3.95) when compared with control group animals (Group A: CA1=53.2 +/- 9.63; CA3=63.5 +/- 13.35; hilus=59.08 +/- 10.24; Group B: CA1=74.3 +/- 8.16; CA3=70.1 +/- 3.83; hilus=70.6 +/- 5.10). The average neuronal cell number of CA1 subfield of rats that present SE and received lovastatin (44.4 +/- 17.88) was statically significant increased when compared with animals that just presented SE., Conclusion: Lovastatin exert a neuroprotective role in the attenuation of brain damage after SE.