Neuroprotective effects and improvement of learning and memory elicited by erythravine and 11α-hydroxy-erythravine against the pilocarpine model of epilepsy.

Deficits in cognitive functions are often observed in epileptic patients, particularly in temporal lobe epilepsy (TLE). Evidence suggests that this cognitive decline can be associated with the occurrence of focal brain lesions, especially on hippocampus and cortex regions. We previously demonstrated that the erythrinian alkaloids, (+)-erythravine and (+)-11α-hydroxy-erythravine, inhibit seizures evoked in rats by different chemoconvulsants. AIMS: The current study evaluated if these alkaloids would be acting in a neuroprotective way, reducing hippocampal sclerosis, and consequently, improving learning/memory performance. MAIN METHODS: Here we confirmed the anticonvulsant effect of both alkaloids by means of the pilocarpine seizure-induced model and also showed that they enhanced spatial learning of rats submitted to the Morris Water Maze test reverting the cognition deficit. Additionally, immunohistochemistry assays showed that neuronal death and glial activation were prevented by the alkaloids in the hippocampus CA1, CA3 and dentate gyrus regions at both hemispheres indistinctly 15 days after status epilepticus induction. KEY FINDINGS: Our results show, for the first-time, the improvement on memory/learning elicited by these erythrinian alkaloids. Furthermore, data presented herein explain, at least partially, the cellular mechanism of action of these alkaloids. Together, (+)-erythravine and (+)-11α-hydroxy-erythravine seem to be a promising protective strategy against TLE, comprising three main aspects: neuroprotection, control of epileptic seizures and cognitive improvement. SIGNIFICANCE: Moreover, our findings on neuroprotection corroborate the view that seizure frequency and severity, hippocampal lesions and memory deficits are interconnected events.

Neuropharmacological profile of FrPbAII, purified from the venom of the social spider Parawixia bistriata (Araneae, Araneidae), in Wistar rats.

The aims of the present study were to investigate the anticonvulsant activity and behavioral toxicity of FrPbAII using freely moving Wistar rats. Moreover, the effectiveness of this compound against chemical convulsants was compared to that of the inhibitor of the GABAergic uptake, nipecotic acid. Our results show that FrPbAII was effective against seizures induced by the i.c.v. injection of pilocarpine (ED(50) = 0.05 microg/animal), picrotoxin (ED(50) = 0.02 microg/animal), kainic acid (ED(50) = 0.2 microg/animal) and the systemic administration of PTZ (ED(50) = 0.03 microg/animal). The anticonvulsant effect of FrPbAII differed from that of nipecotic acid in potency, as the doses needed to block the seizures were more than 10 folds lower. Toxicity assays revealed that in the rotarod, the toxic dose of the FrPbAII is 1.33 microg/animal, and the therapeutic indexes were calculated for each convulsant. Furthermore, the spontaneous locomotor activity of treated animals was not altered when compared to control animals but differed from the animals treated with nipecotic acid. Still, FrPbAII did not induce changes in any of the behavioral parameters analyzed. Finally, when tested for cognitive impairments in the Morris water maze, the i.c.v. injection of FrPbAII did not alter escape latencies of treated animals. These findings indicate that the novel GABA uptake inhibitor is a potent anticonvulsant with mild side-effects when administered to Wistar rats.

Anticonvulsant and behavioural effects of the denatured venom of the social wasp Polybia occidentalis (Polistinae, Vespidae).

Several investigations demonstrate that neurotoxins isolated from venoms of spiders and wasps may exert specific and selective activity on structures of the mammalian CNS. In the present work we examine the neurological effects of the low molecular weight compounds of the denatured venom of the neotropical social wasp Polybia occidentalis in freely moving rats. Central administration of denatured venom decreased the duration of exploratory, elevation and grooming behaviours on the open field. Moreover, denatured venom inhibited convulsing action of bicuculline (ED50 57 microg/microl), picrotoxin (ED50 75 microg/microl) and kainic acid (ED50 44 microg/microl), although it was ineffective against pentylenetetrazole-induced seizures. Despite of its inhibitory activity, toxic effects on motor performance examined in the rotarod test were not found, not even in extremely high doses. Also, denatured venom moderately reduced the spontaneous locomotor activity at anticonvulsant doses. These findings may indicate that the denatured venom has anticonvulsant activity with scarce propensity to cause neurological side-effects. Further studies are necessary to isolate the active compound and establish its mechanism of action.

Anxiety: a systematic review of neurobiology, traditional pharmaceuticals and novel alternatives from medicinal plants.

Pathologic anxiety is a disproportional reaction of individuals to anticipation or misinterpretation of a potential danger, which affects individual social and personal life. Despite the advances already accomplished, further studies are still necessary in order to understand the mechanisms involved in anxiety. These may provide more effective and safer treatments to aid in the control of anxiety and improve patient quality of life. In this work, we review the current issue about anxiety disorders, covering general aspects such as basic epidemiology and classification, an overview of the pharmacological treatments employed and the current search for natural anxiolytics. Also, a compilation of data investigating the neurobiology that underlies anxiety disorders and a brief discussion evolving the most usual animal experimental models to study anxiety is presented.