Víctor Manuel Magdaleno-Madrigal

Vagus nerve prolonged stimulation in cats: effects on epileptogenesis (amygdala electrical kindling): behavioral and electrographic changes.

Summary: Purpose: To analyze the effect of prolonged (daily) electrical vagus nerve stimulation (VNS) on daily amygdaloid kindling (AK) in freely moving cats.

Effect of electrical stimulation of the nucleus of the solitary tract on the development of electrical amygdaloid kindling in the cat.

Summary:  Purpose: This work analyzed the effect of electrical stimulation of the nucleus of the solitary tract (NTS) on the development of electrical amygdaloid kindling (AK) in freely moving cats.

Chronic stimulation of the cat vagus nerve Effect on sleep and behavior

The effect of electrical vagus nerve stimulation (VNS) on sleep and behavior was analyzed in freely moving cats. Eight cats were prepared for 23-h sleep recordings. The left vagus nerve of four of them was stimulated during 1 min, five times at 1-h intervals, for 5 days. The VNS induces: ipsilateral myosis, blinking, licking, abdominal contractions, upward gaze, swallowing, and eventually yawning and compulsive eating, as well as an increase of ponto-geniculate-occipital (PGO) wave density and of the number of stages and total amount of rapid eye movement (REM) sleep. Besides, there was a sudden transition from waking stage to REM sleep. The present results suggest that VNS modifies sleep in the cat. This effect could be explained by an activation of the areas involved in the physiological mechanisms of sleep.

Preemptive effect of nucleus of the solitary tract stimulation on amygdaloid kindling in freely moving cats

Purpose:  The nucleus of the solitary tract (NTS) is a primary site where vagal afferents terminate. The aim of this study was to analyze the preemptive effect of NTS electrical stimulation on daily amygdaloid kindling (AK) in freely moving cats.

Electroencephalographic activity in neonatal ventral hippocampus lesion in adult rats

A neonatal ventral hippocampal lesion (NVHL) in rats has been commonly used as a neurodevelopmental model to mimic schizophrenia‐like behaviors. Recently, we reported that NVHL resulted in dendritic retraction and spine loss in pyramidal neurons of the prefrontal cortex (PFC). In addition, the hippocampus and PFC are important structures in the regulation of the electroencephalographic (EEG) activity. Patients with PFC lesions show deficits in the EEG activity. This study aimed to determine whether the EEG activity was altered in NVHL rats. In addition, we also analyzed the locomotor activity induced by a novel environment and exploratory behavior using the hole‐board test. Consistent with the behavioral findings, the EEG analysis of the cortical regions showed that the NVHL rats displayed a lower power in cortical bands. At 1–8 Hz, 9–14 Hz, and 15–30 Hz bands, our findings showed a decrease in the absolute power of the parietal and occipital cortices recordings. In addition, the NVHL rats also showed a reduction in the exploratory behavior tested using the hole‐board test. In conclusion, this study demonstrated that the EEG activity was reduced in adult NVHL rats and suggests that this may play a role in the behavioral changes observed in this neurodevelopmental model of schizophrenia. Synapse, 2012.

Long-term changes in sleep and electroencephalographic activity by chronic vagus nerve stimulation in cats.

We previously reported the effect of vagus nerve electrical stimulation (VNS) on sleep and behavior in cats. The aim of the present study is to analyze the long-term effects of VNS on the electroencephalographic (EEG) power spectrum and on the different stages of the sleep-wakefulness cycle in the freely moving cat. To achieve this, six male cats were implanted with electrodes on the left vagal nerve and submitted to 15 rounds of 23 h continuous sleep recordings in three categories: baseline (BL), VNS and post-stimulus recording (PSR). The following parameters were analyzed: EEG power spectrum, total time and number of sleep phases, ponto-geniculo-occipital (PGO) wave density of the rapid eye movement (REM) sleep, and the number of times the narcoleptic reflex was present (sudden transition from wakefulness to REM sleep). Significant changes were detected, such as an enhancement of slow-wave sleep (SWS) stage II; a power increase in the bands corresponding to sleep spindles (8-14 Hz) and delta waves (1-4 Hz) with VNS and PSR; an increase in the total time, number of stages, and density of PGO wave in REM sleep with VNS; a decrease of wakefulness in PSR, and the eventual appearance of the narcoleptic reflex with VNS. The results show that the effect of the VNS changes during different stages of the sleep-wakefulness cycle. In REM sleep, the effect was present only during VNS, while the SWS II was affected beyond VNS periods. This suggests that ponto-medullar and thalamic mechanisms of slow EEG activity may be due to plastic changes elicited by vagal stimulation.

Anti-epileptogenic effect of high-frequency stimulation in the thalamic reticular nucleus on PTZ-induced seizures.

BACKGROUND Deep brain stimulation, specifically high-frequency stimulation (HFS), is an alternative and promising treatment for intractable epilepsies; however, the optimal targets are still unknown. The thalamic reticular nucleus (TRN) occupies a key position in the modulation of the cortico-thalamic and thalamo-cortical pathways. OBJECTIVE We determined the efficacy of HFS in the TRN against tonic-clonic generalized seizures (TCGS) and status epilepticus (SE), which were induced by scheduled pentylenetetrazole (PTZ) injections. METHODS Male Wistar rats were stereotactically implanted and assigned to three experimental groups: Control group, which received only PTZ injections; HFS-TRN group, which received HFS in the left TRN prior to PTZ injections; and HFS-Adj group, which received HFS in the left adjacent nuclei prior to PTZ injections. RESULTS The HFS-TRN group reported a significant increase in the latency for development of TCGS and SE compared with the HFS-Adj and Control groups (P < 0.009). The number of PTZ-doses required for SE was also significantly increased (P < 0.001). Spectral analysis revealed a significant decrease in the frequency band from 0.5 Hz to 4.5 Hz of the left motor cortex in the HFS-TRN and HFS-Adj groups, compared to the Control group. Conversely, HFS-TRN provoked a significant increase in all frequency bands in the TRN. EEG asynchrony was observed during spike-wave discharges by HFS-TRN. CONCLUSION These data indicate that HFS-TRN has an anti-epileptogenic effect and is able to modify seizure synchrony and interrupt abnormal EEG recruitment of thalamo-cortical and, indirectly, cortico-thalamic pathways.

Propylparaben applied after pilocarpine-induced status epilepticus modifies hippocampal excitability and glutamate release in rats

&NA; Propylparaben (PPB) induces cardioprotection after ischemia–reperfusion injury by inhibiting voltage‐dependent Na+ channels. The present study focuses on investigating whether the i.p. application of 178 mg/kg PPB after pilocarpine‐induced status epilepticus (SE) reduces the acute and long‐term consequences of seizure activity. Initially, we investigated the effects of a single administration of PPB after SE. Our results revealed that compared to rats receiving diazepam (DZP) plus vehicle after 2 h of SE, animals receiving a single dose of PPB 1 h after DZP injection presented 126% (p < 0.001) lower extracellular levels of glutamate in the hippocampus. This effect was associated with an increased potency of low‐frequency oscillations (0.1–13 Hz bands, p < 0.001), a reduced potency of 30–250 Hz bands (p < 0.001) and less neuronal damage in the hippocampus. The second experiment examined whether the subchronic administration of PPB during the post‐SE period is able to prevent the long‐term consequences of seizure activity. In comparison to animals that were treated subchronically with vehicle after SE, rats administered with PPB for 5 days presented lower hippocampal excitability and interictal glutamate release, astrogliosis, and neuroprotection in the dentate gyrus. Our data indicate that PPB, when applied after SE, can be used as a therapeutic strategy to reduce the consequences of seizure activity. Graphical abstract Figure. No caption available. HighlightsPropylparaben reduces high glutamate release evoked by seizures.Propylparaben decreases hippocampal neuronal damage.Propylparaben diminishes hippocampal high‐frequency oscillations.Propylparaben reduces hippocampal excitability in rats with epilepsy.

Effects of electrical stimulation of the vagus nerve on the development of visual habituation in the cat

The vagus nerve participates in the control and regulation of important autonomous functions, emotional tasks, and neural activity. Electrical vagus nerve stimulation (VNS) is an approved procedure for the treatment of refractory epilepsy in humans. VNS has also been shown to improve mood complaints and cognitive function in both human patients and animals. Thus, the purpose of this study was to analyse and describe the effects of VNS on the development and establishment of sensory habituation and electrographic activity of the visual pathway in freely moving cats. Six cats had implants placed in the optic chiasm (OC), lateral geniculate body (LGB), mesencephalic reticular formation (MRF), primary visual cortex (VC) of the left hemisphere, and left vagus nerve. Immediately after surgery, all cats presented anisocoria and relaxation of the left nictitant membrane. Also showed vegetative-type responses such as myosis, licking, and swallowing during VNS. Animals were then subjected to repeated luminous stimuli at intervals of 1 and 3s to cause habituation. The effect of VNS on the frequency and latency of the habituation episodes and the electrographic changes in the registered brain structures were analysed. Latency analysis showed that VNS delayed the first habituation episode. VNS had transitory effects on the neural activity of the primary visual pathway structures, which caused a small but measurable delay in the establishment of habituation. In conclusion, VNS interferes with the development and establishment of visual habituation, an elementary form of non-associative learning, in freely moving cats.

Acute deep brain stimulation in the thalamic reticular nucleus protects against acute stress and modulates initial events of adult hippocampal neurogenesis.

Deep brain stimulation (DBS) is used as an alternative therapeutic procedure for pharmacoresistant psychiatric disorders. Recently the thalamic reticular nucleus (TRN) gained attention due to the description of a novel pathway from the amygdala to this nucleus suggesting that may be differentially disrupted in mood disorders. The limbic system is implicated in the regulation of these disorders that are accompanied by neuroplastic changes. The hippocampus is highly plastic and shows the generation of new neurons, process affected by stress but positively regulated by antidepressant drugs. We explored the impact of applying acute DBS to the TRN (DBS-TRN) in male Wistar rats exposed to acute stress caused by the forced-swim Porsolts test (FST) and on initial events of hippocampal neurogenesis. After the first session of forced-swim, rats were randomly subdivided in a DBS-TRN and a Sham group. Stimulated rats received 10min of DBS, thus the depressant-like behavior reflected as immobility was evaluated in the second session of forced-swim. Locomotricity was evaluated in the open field test. Cell proliferation and doublecortin-associated cells were quantified in the hippocampus of other cohorts of rats. No effects of electrode implantation were found in locomotricity. Acute DBS-TRN reduced immobility in comparison to the Sham group (p<0.001). DBS-TRN increased cell proliferation (Ki67 or BrdU-positive cells; p=0.02, p=0.02) and the number of doublecortin-cells compared to the Sham group (p<0.02). Similar effects were found in rats previously exposed to the first session of forced-swim. Our data could suggest that TRN brain region may be a promising target for DBS to treat intractable depression.