Marmosets have a greater diversity of c-Fos response after hyperstimulation in distinct cortical regions as compared to rats.

Previous evidence indicated a potential mechanism that might support the fact that primates exhibit greater neural integration capacity as a result of the activation of different structures of the central nervous system, as compared to rodents. The current study aimed to provide further evidence to confirm previous findings by analyzing the patterns of c-Fos expression in more neocortical structures of rats and marmosets using a more robust quantitative technique and evaluating a larger number of brain areas. Nineteen Wistar rats and 21 marmosets (Callithrix jacchus) were distributed among control groups (animals without injections) and animals injected with pentylenetetrazol (PTZ) and euthanized at different time points after stimulus. Immunohistochemical detection of c-Fos was quantified using unbiased and efficient stereological cell counting in eight neocortical regions. Marmosets had a c-Fos expression that was notably more widely expressed (5× more cells) and longer lasting (up to 3 hr) than rats. c-Fos expression in rats presented similar patterns of expression according to the function of the brain cortical structures (associative, sensorial, and motor functions), which was not observed for marmosets (in which no clear pattern could be drawn, and a more diverse profile emerged). Our results provide evidence that the marmoset brain has a greater neuronal activation after intense stimulation by means of PTZ and a more complex pattern of brain activation. We speculate that these functional differences may contribute for the understanding of the different neuronal processing capacities of the neocortex in these mammals' orders.

c-Jun expression after cerebral hyperstimulation differs between rats and marmosets.

Immediate early genes (IEGs) are a fundamental element in the way we respond and adapt to a variety of stimuli. We have recently reported that IEG response, as measured by c-Fos expression, is different between rodents and primates. Here, we further extend this analysis by assessing the expression of c-Jun, one of the main complements of c-Fos, under the same stimulation protocol. For this, we investigated the immunohistochemical expression of c-Jun (and compared with that previously shown for c-Fos) after stimulation with pentylenetetrazol in the cingulate gyrus, motor cortex, piriform cortex, inferior temporal cortex, and visual cortex of rats and marmosets (Callithrix jacchus), both male and female. Overall the immunohistochemical expression of c-Jun was more intense but remained elevated for a shorter duration in marmosets as compared to rats. These results are in contrast to what we had previously shown for c-Fos. Furthermore, in terms of the temporal profile, c-Fos and c-Jun expression occurred in a complementary manner in rats-the peak of c-Fos expression coincided with low levels of c-jun expression-and in a superimposed manner in marmosets-the peak of c-Fos expression coincided with the peak of c-Jun expression. Since Fos proteins may form dimers with Jun proteins and together control late gene expressions in the cell nucleus, this different expression profile between primates and rodents may bear meaningful impact for how the nervous system reacts and adapts to stimulation.

Seizures triggered by pentylenetetrazol in marmosets made chronically epileptic with pilocarpine show greater refractoriness to treatment.

The efficiency of most of the new antiepileptic drugs (AEDs) on clinical trials still falls short the success reported in pre-clinical studies, possibly because the validity of the animal models is insufficient to fully represent the human pathology. To improve the translational value for testing AEDs, we propose the use of non-human primates. Here, we suggest that triggering limbic seizures with low doses of PTZ in pilocarpine-treated marmosets might provide a more effective basis for the development of AED. Marmosets with epileptic background were more susceptible to seizures induced by PTZ, which were at least 3 times longer and more severe (about 6 times greater frequency of generalized seizures) in comparison to naïve peers. Accordingly, PTZ-induced seizures were remarkably less attenuated by AEDs in epileptic than naïve marmosets. While phenobarbital (40mg/kg) virtually abolished seizures regardless of the animal's background, carbamazepine (120mg/kg) and valproic acid (400mg/kg) could not prevent PTZ-induced seizures in epileptic animals with the same efficiency as observed in naïve peers. VPA was less effective regarding the duration of individual seizures in epileptic animals, as assessed in ECoG (p=0.05). Similarly following CBZ treatment, the behavioral manifestation of generalized seizures lasted longer in epileptic (p<0.05), which were also more frequent than in the naïve group (p<0.05). As expected, epileptic marmosets experiencing stronger seizures showed more NPY- and ΔFosB-immunostained neurons in a number of brain areas associated with the generation and spread of limbic seizures. Our results suggest that PTZ induced seizures over an already existing epileptic background constitutes a reliable and controllable mean for the screening of new AEDs.

Role of adenosine in the antiepileptic effects of deep brain stimulation.

Despite the effectiveness of anterior thalamic nucleus (AN) deep brain stimulation (DBS) for the treatment of epilepsy, mechanisms responsible for the antiepileptic effects of this therapy remain elusive. As adenosine modulates neuronal excitability and seizure activity in animal models, we hypothesized that this nucleoside could be one of the substrates involved in the effects of AN DBS. We applied 5 days of stimulation to rats rendered chronically epileptic by pilocarpine injections and recorded epileptiform activity in hippocampal slices. We found that slices from animals given DBS had reduced hippocampal excitability and were less susceptible to develop ictal activity. In live animals, AN DBS significantly increased adenosine levels in the hippocampus as measured by microdialysis. The reduced excitability of DBS in vitro was completely abolished in animals pre-treated with A1 receptor antagonists and was strongly potentiated by A1 receptor agonists. We conclude that some of the antiepileptic effects of DBS may be mediated by adenosine.

Effects of anterior thalamic nucleus deep brain stimulation in chronic epileptic rats.

Deep brain stimulation (DBS) has been investigated for the treatment of epilepsy. In rodents, an increase in the latency for the development of seizures and status epilepticus (SE) has been reported in different animal models but the consequences of delivering stimulation to chronic epileptic animals have not been extensively addressed. We study the effects of anterior thalamic nucleus (AN) stimulation at different current intensities in rats rendered epileptic following pilocarpine (Pilo) administration. Four months after Pilo-induced SE, chronic epileptic rats were bilaterally implanted with AN electrodes or had sham-surgery. Stimulation was delivered for 6 h/day, 5 days/week at 130 Hz, 90 µsec. and either 100 µA or 500 µA. The frequency of spontaneous recurrent seizures in animals receiving stimulation was compared to that recorded in the preoperative period and in rats given sham treatment. To investigate the effects of DBS on hippocampal excitability, brain slices from animals receiving AN DBS or sham surgery were studied with electrophysiology. We found that rats treated with AN DBS at 100 µA had a 52% non-significant reduction in the frequency of seizures as compared to sham-treated controls and 61% less seizures than at baseline. Animals given DBS at 500 µA had 5.1 times more seizures than controls and a 2.8 fold increase in seizure rate as compared to preoperative values. In non-stimulated controls, the average frequency of seizures before and after surgery remained unaltered. In vitro recordings have shown that slices from animals previously given DBS at 100 µA had a longer latency for the development of epileptiform activity, shorter and smaller DC shifts, and a smaller spike amplitude compared to non-stimulated controls. In contrast, a higher spike amplitude was recorded in slices from animals given AN DBS at 500 µA.

Therapeutic effects of the transplantation of VEGF overexpressing bone marrow mesenchymal stem cells in the hippocampus of murine model of Alzheimer's disease.

Alzheimer's disease (AD) is clinically characterized by progressive memory loss, behavioral and learning dysfunction and cognitive deficits, such as alterations in social interactions. The major pathological features of AD are the formation of senile plaques and neurofibrillary tangles together with neuronal and vascular damage. The double transgenic mouse model of AD (2xTg-AD) with the APPswe/PS1dE9 mutations shows characteristics that are similar to those observed in AD patients, including social memory impairment, senile plaque formation and vascular deficits. Mesenchymal stem cells (MSCs), when transplanted into the brain, produce positive effects by reducing amyloid-beta (Aß) deposition in transgenic amyloid precursor protein (APP)/presenilins1 (PS1) mice. Vascular endothelial growth factor (VEGF), exhibits neuroprotective effects against the excitotoxicity implicated in the AD neurodegeneration. The present study investigates the effects of MSCs overexpressing VEGF in hippocampal neovascularization, cognitive dysfunction and senile plaques present in 2xTg-AD transgenic mice. MSC were transfected with vascular endothelial growth factor cloned in uP vector under control of modified CMV promoter (uP-VEGF) vector, by electroporation and expanded at the 14th passage. 2xTg-AD animals at 6, 9 and 12 months old were transplanted with MSC-VEGF or MSC. The animals were tested for behavioral tasks to access locomotion, novelty exploration, learning and memory, and their brains were analyzed by immunohistochemistry (IHC) for vascularization and Aß plaques. MSC-VEGF treatment favored the neovascularization and diminished senile plaques in hippocampal specific layers. Consequently, the treatment was able to provide behavioral benefits and reduce cognitive deficits by recovering the innate interest to novelty and counteracting memory deficits present in these AD transgenic animals. Therefore, this study has important therapeutic implications for the vascular damage in the neurodegeneration promoted by AD.

Grafting of GABAergic precursors rescues deficits in hippocampal inhibition.

gamma-Aminobutyric acid (GABA) has an important role in the mechanism of epilepsy. Cell grafts from different sources have been performed to modulate local circuits or increase GABAergic inhibition in animal models of epilepsy. Among the different transplanted cell types, the medial ganglionic eminence (MGE)-derived cells present the best properties to be used in cell-based therapy. In this work we review previous experiences with these cells. In addition, we present new evidence showing their ability to modulate the levels of inhibition in the host brain of mice with alterations in the GABAergic system, caused by the specific ablation of hippocampal interneurons. Grafted GFP(+) MGE-derived cells occupied the area of ablation and differentiated into mature NK-1-, SOM-, PV-, CR-, and NPY-expressing interneurons. Inhibitory postsynaptic current (IPSC) frequency and amplitude on CA1 pyramidal cells of the ablated hippocampus significantly increased after transplantation, reaching levels similar to controls. Our data strongly suggest the suitability of MGE-derived cells for the treatment of neurologic conditions for which an increase or modulation of synaptic inhibition is required.

Effect of neuronal precursor cells derived from medial ganglionic eminence in an acute epileptic seizure model.

Most of the gamma-aminobutyric acid (GABA)ergic interneurons in the cerebral cortex originate from restricted regions of the ventral telencephalon known as the caudal and medial ganglionic eminence (MGE) and from the preoptic area. It is well established that dysfunction of GABAergic interneurons can lead to epilepsy. During the last decade new approaches to prevent, reduce, or reverse the epileptic condition have been studied, including cell-based therapy from different sources. Recent studies have shown that transplanted neuronal precursor cells derived from MGE have the ability to migrate, differentiate into inhibitory GABAergic interneurons, and integrate into cortical and hippocampal networks, modifying the inhibitory tone in the host brain. Therefore, transplantation of neuronal precursors derived from MGE into the postnatal central nervous system (CNS) could modify the neuronal circuitry in neurologic diseases in which inhibitory synaptic function is altered, such as in epilepsy. Here, we evaluated the seizure susceptibility of mice transplanted with MGE-derived cells in the maximum electroconvulsive shock (MES) model and we review some data from different studies using GABAergic precursor or GABA-releasing cell grafts in animal models of seizure and epilepsy.

Distribution and proliferation of bone marrow cells in the brain after pilocarpine-induced status epilepticus in mice.

The distribution of bone marrow cells in brain areas during the acute period after pilocarpine-induced status epiepticus (SE) was investigated here. To achieve this, we generated chimeric mice by engrafting bone marrow cells from enhanced green fluorescent protein (eGFP) transgenic mice. GFP(+) bone marrow-derived cells were found throughout the brain, predominantly in the hippocampus. As expected, these cells exhibited the characteristics of microglia. The pattern of distribution, proliferation, and differentiation of GFP(+)cells changes as a function of intensity and time following SE. This pattern is also a consequence of the inflammatory response, which is followed by the progressive neuronal damage that is characteristic of the pilocarpine model.

Effects of FGF-2 and EGF removal on the differentiation of mouse neural precursor cells.

Cell therapy for neurological disorders has advanced, and neural precursor cells (NPC) may become the ideal candidates for neural transplantation in a wide range of diseases. However, additional work has to be done to determine either the ideal culture environment for NPC expansion in vitro, without altering their plasticity, or the FGF-2 and EGF mechanisms of cell signaling in neurospheres growth, survival and differentiation. In this work we evaluated mouse neurospheres cultured with and without FGF-2 and EGF containing medium and showed that those growth factors are responsible for NPC proliferation. It is also demonstrated that endogenous production of growth factors shifts from FGF-2 to IGF-1/PDGFb upon EGF and FGF-2 withdrawal. Mouse NPC cultured in suspension showed different patterns of neuronal localization (core versus shell) for both EGF and FGF-2 withdrawal and control groups. Taken together, these results show that EGF and FGF-2 removal play an important role in NPC differentiation and may contribute to a better understanding of mechanisms of NPC differentiation. Our findings suggest that depriving NPC of growth factors prior to grafting might enhance their chance to effectively integrate into the host.

Effects of FGF-2 and EGF removal on the differentiationof mouse neural precursor cells

Cell therapy for neurological disorders has advanced, and neural precursor cells (NPC) may become the ideal candidates for neural transplantation in a wide range of diseases. However, additional work has to be done to determine either the ideal culture environment for NPC expansion in vitro, without altering their plasticity, or the FGF-2 and EGF mechanisms of cell signaling in neurospheres growth, survival and differentiation. In this work we evaluated mouse neurospheres cultured with and without FGF-2 and EGF containing medium and showed that those growth factors are responsible for NPC proliferation. It is also demonstrated that endogenous production of growth factors shifts from FGF-2 to IGF-1/PDGFb upon EGF and FGF-2 withdrawal. Mouse NPC cultured in suspension showed different patterns of neuronal localization (core versus shell) for both EGF and FGF-2 withdrawal and control groups. Taken together, these results show that EGF and FGF-2 removal play an important role in NPC differentiation and may contribute to a better understanding of mechanisms of NPC differentiation. Our findings suggest that depriving NPC of growth factors prior to grafting might enhance their chance to effectively integrate into the host.

As terapias celulares para doenças neurológicas têm avançado e células precursoras neurais (NPC) surgem como candidatas ideais para o transplante de células neurais em muitas doenças. No entanto, trabalhos adicionais devem ser feitos para determinar o ambiente de cultivo ideal para a expansão in vitro das NPC, sem alterar sua plasticidade, e os mecanismos de sinalização celular do fator de crescimento epidérmico (EGF) e fator de crescimento de fibroblasto 2 (FGF-2) no crescimento, sobrevivência e diferenciação da neuroesfera. Nesse trabalho avaliamosNPCcultivadas na presença e na ausência de FGF-2 e EGF e mostramos que esses fatores de crescimento são responsáveis pela proliferação das NPC. Também foi demonstrado que a produção endógena de fatores de crescimento alterna de FGF-2 a fator de crescimento de insulina 1 (IGF-1) e fator de crescimento derivado de plaquetas b (PDGFb) após remoção de EGF e FGF-2. NPC de camundongo cultivadas em suspensão mostraram padrões de localização neuronal distintos (centro versus borda) tanto no grupo controle como no grupo sem EGF e FGF-2. Juntos, esses resultados mostram que a remoção de EGF e FGF-2 exerce importante ação na diferenciação de NPC e possivelmente contribui para melhor compreensão dos mecanismos envolvidos na diferenciação. Nossos achados sugerem que, privando as NPC de fatores de crescimento antes do transplante, talvez aumente as chances de que as células efetivamente se integrem ao hospedeiro.

Chemically-induced RAT mesenchymal stem cells adopt molecular properties of neuronal-like cells but do not have basic neuronal functional properties.

Induction of adult rat bone marrow mesenchymal stem cells (MSC) by means of chemical compounds (beta-mercaptoethanol, dimethyl sulfoxide and butylated hydroxyanizole) has been proposed to lead to neuronal transdifferentiation, and this protocol has been broadly used by several laboratories worldwide. Only a few hours of MSC chemical induction using this protocol is sufficient for the acquisition of neuronal-like morphology and neuronal protein expression. However, given that cell death is abundant, we hypothesize that, rather than true neuronal differentiation, this particular protocol leads to cellular toxic effects. We confirm that the induced cells with neuronal-like morphology positively stained for NF-200, S100, beta-tubulin III, NSE and MAP-2 proteins. However, the morphological and molecular changes after chemical induction are also associated with an increase in the apoptosis of over 50% of the plated cells after 24 h. Moreover, increased intracellular cysteine after treatment indicates an impairment of redox circuitry during chemical induction, and in vitro electrophysiological recordings (patch-clamp) of the chemically induced MSC did not indicate neuronal properties as these cells do not exhibit Na(+) or K(+) currents and do not fire action potentials. Our findings suggest that a disruption of redox circuitry plays an important role in this specific chemical induction protocol, which might result in cytoskeletal alterations and loss of functional ion-gated channels followed by cell death. Despite the neuronal-like morphology and neural protein expression, induced rat bone marrow MSC do not have basic functional neuronal properties, although it is still plausible that other methods of induction and/or sources of MSC can achieve a successful neuronal differentiation in vitro.

Bilateral anterior thalamic nucleus lesions are not protective against seizures in chronic pilocarpine epileptic rats.

AIMS: To investigate whether anterior thalamic nucleus (AN) lesions are protective against spontaneous recurrent seizures in the chronic phase of the pilocarpine model of epilepsy. METHODS: Two groups of rats were treated with bilateral AN radiofrequency thalamotomies or sham surgery 2 weeks after pilocarpine-induced status epilepticus. After the lesions, animals were videotaped from the 2nd to the 8th week after status epilepticus (total 180 h). RESULTS: During the 6 weeks of observation, no differences in the frequency of spontaneous seizures were found between animals that had bilateral AN lesions (n = 26; 3.1 +/- 0.6 seizures per animal) and controls (n = 25; 3.0 +/- 0.6 seizures per animal; p = 0.8). CONCLUSIONS: We conclude that AN thalamotomies were not effective in reducing the frequency of seizures during the chronic phase of the pilocarpine model of epilepsy.

Short-term withdrawal of mitogens prior to plating increases neuronal differentiation of human neural precursor cells.

BACKGROUND: Human neural precursor cells (hNPC) are candidates for neural transplantation in a wide range of neurological disorders. Recently, much work has been done to determine how the environment for NPC culture in vitro may alter their plasticity. Epidermal growth factor (EGF) and fibroblast growth factor-2 (FGF-2) are used to expand NPC; however, it is not clear if continuous exposure to mitogens may abrogate their subsequent differentiation. Here we evaluated if short-term removal of FGF-2 and EGF prior to plating may improve hNPC differentiation into neurons. PRINCIPAL FINDINGS: We demonstrate that culture of neurospheres in suspension for 2 weeks without EGF-FGF-2 significantly increases neuronal differentiation and neurite extension when compared to cells cultured using standard protocols. In this condition, neurons were preferentially located in the core of the neurospheres instead of the shell. Moreover, after plating, neurons presented radial rather than randomly oriented and longer processes than controls, comprised mostly by neurons with short processes. These changes were followed by alterations in the expression of genes related to cell survival. CONCLUSIONS: These results show that EGF and FGF-2 removal affects NPC fate and plasticity. Taking into account that a three dimensional structure is essential for NPC differentiation, here we evaluated, for the first time, the effects of growth factors removal in whole neurospheres rather than in plated cell culture.

Kinin-B2 receptor expression and activity during differentiation of embryonic rat neurospheres.

Neural progenitor cells were isolated from rat fetal telencephalon and proliferate as neurospheres in the presence of EGF, FGF-2, and heparin. In the absence of these growth factors, neurospheres differentiate into neurons, astrocytes, and oligodendrocytes. Using an embryonal carcinoma cell line as in vitro differentiation model, we have already demonstrated the presence of an autocrine loop system between kinin-B2 receptor activity and secretion of its ligand bradykinin (BK) as prerequisites for final neuronal differentiation (Martins et al., J Biol Chem 2005; 280: 19576-19586). The aim of this study was to verify the activity of the kallikrein-kinin system (KKS) during neural progenitor cell differentiation. Immunofluorescence studies and flow cytometry analysis revealed increases in glial fibrillary acidic protein and beta-3 tubulin expression and decrease in the number of nestin-positive cells along neurospheres differentiation, indicating the transition of neural progenitor cells to astrocytes and neurons. Kinin-B2 receptor expression and activity, secretion of BK into the medium, and presence of high-molecular weight kininogen suggest the participation of the KKS in neurosphere differentiation. Functional kinin-B2 receptors and BK secretion indicate an autocrine loop during neurosphere differentiation to neurons, astrocytes, and oligodendrocytes, reflecting events occurring during early brain development.

Predicting malignant involvement in a thyroid nodule: role of ultrasonography.

OBJECTIVE: To assess how ultrasonography can contribute during the evaluation of a thyroid nodule and whether this technique can have a role in predicting malignant involvement. METHODS: In this retrospective study, data were analyzed on 220 consecutive patients (with 348 thyroid nodules) who underwent thyroidectomy and had previously undergone assessment by high-resolution thyroid ultrasonography. Nodule size, echogenicity, regularity of margins, halo sign, presence or absence of calcifications, and invasion of surrounding tissues were evaluated. The nodules were classified as low, medium, or high risk for malignant involvement on the basis of nodule characteristics found on ultrasonography. All nodules were submitted to cytologic examination by fine-needle aspiration (FNA) before thyroidectomy. Ultrasound, FNA, and pathologic postoperative results were compared. RESULTS: Among the 348 thyroid nodules, 56 were ultrasonographically classified as low risk, 268 as medium risk, and 24 as high risk for malignant potential. Fifty of 56 (89.3%) low-risk nodules and 213 of 268 (79.5%) medium-risk nodules were diagnosed as benign at pathologic postoperative examination. In contrast, however, only 6 of 24 (25%) high-risk nodules were diagnosed as benign. Among the 18 high-risk nodules of 1-cm diameter or larger, FNA showed a 20% false-negative result. CONCLUSION: High-risk classification of a thyroid nodule on ultrasonography had a positive predictive value for malignant involvement of 75%. Nodule characteristics analyzed by ultrasonography should be considered at the time of surgical intervention.

Consequences of prolonged caffeine administration and its withdrawal on pilocarpine- and kainate-induced seizures in rats.

PURPOSE: To investigate the consequences of caffeine consumption on epileptic seizures, we used the pilocarpine and the kainate models of epilepsy. We hypothesized that prolonged caffeine consumption or its withdrawal would alter adenosine levels and hence alter seizure susceptibility. METHODS: We administered a 0.1% caffeine solution in the drinking water of adult male Wistar rats over a 2-week period. We challenged another group of animals with the same doses of pilocarpine or kainate 12 h after the withdrawal of the same caffeine-administration protocol. RESULTS: This did not alter the threshold for the induction of seizures by a subconvulsant dose of pilocarpine (200 mg/kg, i.p.) or kainic acid (8 mg/kg, i.p.). Similarly, challenging another group of animals with the same doses of pilocarpine or kainate 12 h after the withdrawal of the same caffeine-administration protocol did not lead to any significant changes in seizures. CONCLUSIONS: With the pilocarpine model of epilepsy, we were not able to find any significant difference in seizure profile that could stem from either caffeine administration or its withdrawal. Despite the extensive laboratory evidence on the convulsant properties of xanthine derivatives in animal models of epilepsy, such strong evidence is lacking in clinical settings. Our current findings with the administration of caffeine at doses similar to those of daily life both support and confirm the clinical experience.

Onset of estrogen replacement has a critical effect on synaptic density of CA1 hippocampus in ovariectomized adult rats.

OBJECTIVES: The aim of this study was to evaluate differences between estrogen replacement therapy initiated either 4 or 12 days after ovariectomy on the synaptic density of the hippocampal CA1 field in rats. DESIGN: Female, adult, Wistar rats were ovariectomized bilaterally under ether anesthesia and divided among the following groups: 1) estrogen (conjugated equine estrogen 50 microg in 0.5 mL of propylene glycol, daily, p.o. gavage, for 60 days), starting 4 days after ovariectomy (n = 5); 2) propylene glycol (0.5 mL daily, p.o. gavage, for 60 days), starting 4 days after ovariectomy (n = 4); 3) estrogen (conjugated equine estrogen 50 microg in 0.5 mL of propylene glycol, daily, p.o. gavage, for 45 days), starting 12 days after ovariectomy (n = 3); 4) propylene glycol (0.5 mL daily, p.o. gavage, for 45 days), starting 12 days after ovariectomy (n = 3). At the end of the treatment, the rats were processed for electron microscopy and light analysis. RESULTS: Synaptic density in all of the CA1 strata subjected to evaluation was significantly higher in animals in which estrogen replacement was initiated 4 days after ovariectomy as compared with controls. In contrast, initiation of treatment after a 12-day interval did not result in recovery of synaptic density in any of the CA1 strata and was significantly lower than that of the animals subjected to hormone replacement after a 4-day delay (P < 0.01). CONCLUSION: The delay for hormone replacement therapy might have critical implications for modulating synaptic density.

Convulxin does not induce convulsions when injected into the rat dorsal hippocampus

La convulxina, una neurotoxina extraída del veneno de Crotalus durissus terrificus, ejerce un efecto convulsivante cuando se inyecta por vía endovenosa en ratones y gatos. En la búsqueda de nuevos compuestos más efectivos selectivos, diversos estudios se han desarrollado en el campo de las neurotoxinas. En consecuencia, el objetivo de este trabajo fue analizar los efectos comportamentales, electroencefalograficos y neuropatológicos desencadenados por la inyección intrahipocampal de convulxina. En otra secuencia experimental, fue utilizada una mexcla de convulxina y plasma rico en plaquetas, como tentativa de testar la hipótesis de la acción indirecta de la convulxina. Los resultados han demostrado que tanto la convulxina como la mexcla de convulxina y plasma rico en plaquetas fueron incapaces de desencadenar convulsione o de causar lesiones celulares específicas