Neuroestimulación del nervio vago, hipocampal y de núcleos anteriores y centromedianos del tálamo en epilepsia temporal: revisión de la literatura / Neurostimulation of the vagus nerve, hippocampal and anterior and centromedian nuclei of the thalamus in temporal epilepsy: literature review

Introducción: En pacientes con epilepsia del lóbulo temporal refractarios que no son candidatos a cirugía, se debe considerar la estimulación eléctrica cerebral como una opción. Contenido: La estimulación eléctrica cerebral es la administración directa de pulsos eléctricos al tejido nervioso que permite modular un sustrato patológico, interrumpir la manifestación clínica de las crisis y reducir la gravedad de estas. Así, dada la importancia de estos tratamientos para los pacientes con epilepsia del lóbulo temporal refractaria, se hace una revisión de cuatro tipos de estimulación eléctrica. La primera, la del nervio vago, es una buena opción en crisis focales y crisis generalizadas o multifocales. La segunda, la del hipocampo, es más útil en pacientes no candidatos a lobectomía por riesgo de pérdida de memoria, con resonancia magnética normal o sin esclerosis mesial temporal. La tercera, la del núcleo anterior, es pertinente principalmente en pacientes con crisis focales, pero debe realizarse con precaución en pacientes con alto riesgo de cambios cognitivos, como los ancianos, o en los que presentan alteración del estado de ánimo basal, y, por último, la del núcleo centromediano se recomienda para el tratamiento crisis focales en el síndrome de Rasmussen y crisis tónico-clónicas en el síndrome de Lennox-Gastaut. Conclusiones: El interés por la estimulación eléctrica cerebral ha venido aumentando, al igual que las estructuras diana en las cuales se puede aplicar, debido a que es un tratamiento seguro y eficaz en pacientes con epilepsia del lóbulo temporal para controlar las crisis, pues disminuye la morbimortalidad y aumenta la calidad de vida.

Introduction: In patients with refractory temporal lobe epilepsy who are not candidates for surgery, electrical brain stimulation should be considered as another option. Contents: Electrical brain stimulation is the direct administration of electrical pulses to nerve tissue that modulates a pathological substrate, interrupts the clinical manifestation of seizures, and reduces their severity. Thus, given the importance of these treatments for patients with refractory temporal lobe epilepsy, four types of electrical stimulation are reviewed. The first, vagus nerve stimulation, is a good option in focal seizures and generalized or multifocal seizures. The second, hippocampal stimulation, is more useful in patients who are not candidates for lobectomy due to the risk of memory loss, with normal MRI or without mesial temporal sclerosis. The third, the anterior nucleus, is mainly in patients with focal seizures, but with caution in patients at high risk of cognitive changes such as the elderly, or in those with baseline mood disturbance and, finally, the centromedian nucleus is recommended for the treatment of focal seizures in Rasmussen's syndrome and tonic-clonic seizures in Lennox-Gastaut syndrome. Conclusions: the interest in brain electrical stimulation has been increasing as well as the target structures in which it can be applied because it is a safe and effective treatment in patients with temporal lobe epilepsy to control seizures, decreasing morbidity and mortality and increasing quality of life

Arousal mechanism after sevoflurane anesthesia in rats: orexinergic modulation in dorsal raphe nucleus by optogenetic and chemogenetic techniques / 中华麻醉学杂志

Objective:To investigate the arousal mechanism after sevoflurane anesthesia using orexinergic modulation in dorsal raphe nucleus(DRN) by optogenetic and chemogenetic techniques in rats.Methods:Forty-five healthy male Hcrt-Cre rats, aged 10-12 weeks, weighing 220-250 g, were divided into 6 groups by the random number table method: optical-excitatory group (CHR2 group, n=5), optical-inhibitory group (eNpHR group, n=5), optical-control group (O-CON group, n=5); chemogenetic-excitatory group (hm3Dq group, n=10), chemogenetic-inhibitory group (hm4Di group, n=10) and chemogenetic-control group (C-CON group, n=10). The optogenetic or chemogenetic techniques were used in each group. Three weeks after injecting the rat virus, anesthesia was induced and maintained with 2.7% sevoflurane anesthesia in 1.5 L/min O 2, and the EEG data were continuously recorded throughout the process. The burst suppression ratio (%BSR) was recorded at 2 min before and of laser stimulation. Combining optogenetic and chemogenetic strategies, it was investigated that whether activation of orexinergic projection to DRN could modulate anesthetic behaviors during sevoflurane anesthesia. Results:Compared with C-CON group, the recovery of righting reflex (RORR) time was significantly shortened after sevoflurane anesthesia in hm3Dq group ( P<0.05), and the RORR time was significantly prolonged after sevoflurane anesthesia in hm4Di group and eNpHR group ( P<0.05). Compared with O-CON group or the baseline at 2 min before light stimulation, the %BSR was significantly decreased during 473nm laser stimulation in CHR2 group ( P<0.05), and no statistically significant change was found in the %BSR during 473nm laser stimulation in eNpHR group ( P>0.05). Compared with O-CON group, the RORR time was significantly shortened after sevoflurane anesthesia in CHR2 group ( P<0.05). Conclusions:Lateral hypothalamic area orexin-DRN neural circuit plays a key role in promoting arousal from general anesthesia in rats.

Acoustic response characteristics of posterior intralaminar nucleus of auditory thalamus in mice / 中华耳鼻咽喉头颈外科杂志

Objective@#To study the response characteristics of the posterior intralaminar nucleus (PIN) of auditory thalamus in VGluT2-Cre transgenic adult mice when exposed to white noise and 10K pure tone stimulation.@*Methods@#All adult male Vglut2-Cre mice (8-12 weeks) were used in this study between Oct, 2017 and Oct, 2018. Using the calcium signal fiber photometry method, optic fiber was employed to locate on PIN by injecting AAV-hSyn-DIO-GCaMP6m virus, and thereafter, the activity of the target cluster neurons during different acoustic stimuli was recorded. Matlab was used for data processing and statistical analysis.@*Results@#(1)In both white noise and 10 kHz pure tone as a continuous three-second stimulation, the peak amplitude of calcium signal activity generated in PIN by white noise was superior to that of pure tone, the statistic result showed significantly difference (n=6, t=2.404, P=0.037 1) . (2)In addition, when white noise and 10K pure tone played as consecutive 3 or 5 pips within three-second stimulation, the stimulus-following ability in a consecutive 3 pulses play within 3 seconds was far better than a consecutive 5 pips play within 3 seconds (in both white noise and 10 kHz pure tone), yet consecutive 3 pips play showed greater signal attenuation speed than that in consecutive 5 pips play, the statistic result showed significantly difference (n=6, t=2.748 P=0.033 4) .(3)Regardless of the intra-group comparisons between white noise and 10 kHz pure tone stimulation, PIN showed better signal response in a consecutive 3 pips play than consecutive 5 pips play or a continuous three-second stimulation. When came to the statistical analysis, the acoustic response degree of a continuous three-second stimulation was an intermediate between two others, both consecutive 3 or 5 pips play showed significantly difference.@*Conclusions@#The results suggest that under the same acoustic intensity, VGluT2-Cre transgenic adult mice′s PIN shows greater signal response in white noise than pure tone. PIN shows greater signal attenuation to repetition play of 10 kHz pure tone, which implies PIN shows stronger adaptation to 10 kHz pure tone than to white noise. Lastly, PIN is more responsive to a complex sound information (white noise) than to simple sound information (pure tone).

Thalamic paraventricular nucleus mediates orexinergic neurons-induced promotion of emergence from general anesthesia in mice: evaluation using optogenetics method / 中华麻醉学杂志

Objective To evaluate whether the thalamic paraventricular nucleus mediates orexiner-gic ( orexin ) neurons-induced promotion of emergence from general anesthesia by using the optogenetics method in mice. Methods Twenty healthy male Hcrt-cre mice, aged 8-10 weeks, weighing 20-25 g, were divided into 4 groups ( n=5 each) using a random number table method: retrograde labeled viruses channelrhodopsin group ( R group) , anterograde labeled viruses channelrhodopsin group ( A group) , retro-grade labeled viruses control group ( RC group ) , and anterograde labeled viruses control group ( AC group) . The optogenetics technique was used in each group. Anesthesia was induced and maintained through inhaling 1％ isoflurane and pure oxygen 1. 0 L∕min. Electroencephalogram was monitored througout the procedure with the PowerLab monitoring system. The burst suppression ratio ( BSR) was recorded at 1 min before light stimulation and during light stimulation. Results Compared with RC group or the baseline at 1 min before light stimulation, the BSR was significantly decreased during light stimulation in R group ( P<0. 05) . Compared with AC group or the baseline at 1 min before light stimulation, the BSR was signifi-cantly decreased during light stimulation in group A ( P<0. 05) . Conclusion Optogenetics technique ap-plication once again confirms that orexin neurons can promote emergence from general anesthesia through thalamic paraventricular nucleus in mice.

Prudently applying the therapy of anterior thalamic stimulation for refractory epilepsy: present situation and thinking / 中华神经科杂志

Recently,the U.S.Food and Drug Administration has granted premarket approval for bilateral anterior thalamic nucleus stimulation as adjunctive treatment for reducing the frequency of partial-onset seizures in adults who are refractory to three or more antiepileptic medications.The anterior nucleus of the thalamus (ANT) is a primary component of the limbic system (the Papez circuit),which represents a fundamental pathway for seizure propagation.Scholars speculated that ANT is an anatomic target that may halt or influence seizure propagation or epileptogenic foci originating within the limbic system.Some suggestions on the possible factors associated with the efficacy of ANT stimulation put forward by experts are helpful.However,given the limited clinical data,there is a lack of valid predictors of individual treatment response.Most importantly,rational patient selection relies on a detailed and careful anatomo-electro-clinical analysis for individualized treatment.

AAV-Mediated Astrocyte-Specific Gene Expression under Human ALDH1L1 Promoter in Mouse Thalamus

Adeno-associated virus (AAV)-mediated gene delivery has been proposed to be an essential tool of gene therapy for various brain diseases. Among several cell types in the brain, astrocyte has become a promising therapeutic target for brain diseases, as more and more contribution of astrocytes in pathophysiology has been revealed. Until now, genetically targeting astrocytes has been possible by utilizing the glial fibrillary acidic protein (GFAP) promoter. In some brain areas including thalamus, however, the GFAP expression in astrocytes is reported to be low, making it difficult to genetically target astrocytes using GFAP promoter. To study the function of astrocytes in thalamus, which serves as a relay station, there is a great need for identifying an alternative astrocyte-specific promoter in thalamus. Recently, a new astrocyte-specific promoter of ALDH1L1 has been identified. However, it has not been examined in thalamus. Here we developed and characterized an AAV vector expressing Cre recombinase under the human ALDH1L1 promoter, AAV-hALDH1L1-Cre. To test the cell-type specific expression of AAV-hALDH1L1-Cre, AAV virus was injected into several brain regions of Ai14 (RCL-tdTomato) mouse, which reports Cre activity by tdTomato expression. In thalamus, we observed that tdTomato was found mostly in astrocytes (91.71%), with minimal occurrence in neurons (2.67%). In contrast, tdTomato signal was observed in both neurons and astrocytes of the amygdala (neuron: 68.13%, astrocyte: 28.35%) and hippocampus (neuron: 76.25%, astrocyte: 18.00%), which is consistent with the previous report showing neuronal gene expression under rat ALDH1L1 promoter. Unexpectedly, tdTomato was found mostly in neurons (91.98%) with minimal occurrence in astrocytes (6.66%) of the medial prefrontal cortex. In conclusion, hALDH1L1 promoter shows astrocyte-specificity in thalamus and may prove to be useful for targeting thalamic astrocytes in mouse.

Neural Mechanisms and Delayed Gastric Emptying of Liquid Induced Through Acute Myocardial Infarction in Rats / Mecanismos Neurais e Retardo do Esvaziamento Gástrico de Liquido Induzido no Infarto Agudo do Miocárdio em Ratos

Background: In pathological situations, such as acute myocardial infarction, disorders of motility of the proximal gut can trigger symptoms like nausea and vomiting. Acute myocardial infarction delays gastric emptying (GE) of liquid in rats. Objective: Investigate the involvement of the vagus nerve, α 1-adrenoceptors, central nervous system GABAB receptors and also participation of paraventricular nucleus (PVN) of the hypothalamus in GE and gastric compliance (GC) in infarcted rats. Methods: Wistar rats, N = 8-15 in each group, were divided as INF group and sham (SH) group and subdivided. The infarction was performed through ligation of the left anterior descending coronary artery. GC was estimated with pressure-volume curves. Vagotomy was performed by sectioning the dorsal and ventral branches. To verify the action of GABAB receptors, baclofen was injected via icv (intracerebroventricular). Intravenous prazosin was used to produce chemical sympathectomy. The lesion in the PVN of the hypothalamus was performed using a 1mA/10s electrical current and GE was determined by measuring the percentage of gastric retention (% GR) of a saline meal. Results: No significant differences were observed regarding GC between groups; vagotomy significantly reduced % GR in INF group; icv treatment with baclofen significantly reduced %GR. GABAB receptors were not conclusively involved in delaying GE; intravenous treatment with prazosin significantly reduced GR% in INF group. PVN lesion abolished the effect of myocardial infarction on GE. Conclusion: Gastric emptying of liquids induced through acute myocardial infarction in rats showed the involvement of the vagus nerve, alpha1- adrenergic receptors and PVN. .

Fundamento: Distúrbios da motilidade do intestino proximal no infarto agudo do miocárdio podem desencadear sintomas digestivos como náuseas e vômitos. O infarto do miocárdio ocasiona retardo do esvaziamento gástrico (EG) de líquido em ratos. Objetivo: Investigar se existe a influência do nervo vago (VGX), adrenoreceptores α-1, receptores GABAB do sistema nervoso central e participação do núcleo paraventricular (NPV) do hipotálamo no esvaziamento gástrico (EG) e complacência gástrica (CG) em ratos infartados. Métodos: Ratos Wistar (n = 8-15) foram divididos em: grupo infarto (INF), sham (SH) e subdivididos. O infarto foi realizado por ligadura da artéria coronária descendente anterior. A complacência gástrica foi estimada com curvas pressão-volume. Realizada vagotomia por secção dos ramos dorsal e ventral. Para verificar a ação dos receptores GABAB foi injetado baclofeno por via intra ventrículo-cerebral. Simpatectomia química foi realizada com prazosina intravenosa (iv), e na lesão do núcleo paraventricular do hipotálamo foi utilizada corrente elétrica de 1mA/10s, com esvaziamento gástrico determinado por medição da retenção gástrica (% RG) de uma refeição salina. Resultados: Não houve diferença significativa na CG. A vagotomia (VGX) reduziu significativamente a %RG; no grupo INF, o tratamento intra ventrículo-cerebral (ivc) com baclofeno reduziu significativamente a % RG; não houve conclusivamente envolvimento dos receptores GABAB em retardar o EG; o tratamento intravenoso com prazosina reduziu significativamente a %RG no grupo INF. A lesão do NPV aboliu o efeito do infarto do miocárdio no EG. Conclusão: O nervo vago, receptores α-adrenérgicos e núcleo paraventricular estão envolvidos no retardo do esvaziamento gástrico no infarto agudo do miocárdio em ratos. .

NMDA receptors in central medial thalamus participate in propofol-induced unconsciousness / 天津医药

Objective To investigate the role of NMDA receptors in central medial thalamus (CMT) in the unconscious?ness induced by general anesthesia. Methods A total of 60 rat models for microinfusion were assigned into 4 groups (n=15 for each group). After induction with propofol, 10 mmol/L (NMDA10 group), 20 mmol/L (NMDA 20 group) and 40 mmol/L (NMDA40 group) of NMDA and normal saline (group C) with equal volume were microinfused into CMT. The incidence of purposeful movement and recovery time of righting reflex were observed in each group respectively. Infusion sites were local?ized by histological method. Results When the microinfusion site localized within CMT, comparing with group C, the recov?ery time of righting reflex reduced notably in three NMDA groups (P0.05). Conclusion Microinfusion of NMDA agonist into CMT reverses propofol anesthesia, indicating that NMDA receptor in CMT may contribute to the propofol-induced unconsciousness.

Understanding of Structure and Function of Vestibular Cortex / 대한평형의학회지

The vestibular end-organs generate very sophisticated gravity sensory information about head movement by sensing head acceleration in three-dimensional space. Vestibular information is crucial for higher brain functions such as cognition of spatial orientation, spatial memory, and perception of self-motion. The term "vestibular cortex" represents cortical area where vestibular information is processed, converged with other sensory inputs to maintain cortical functions. The vestibular cortex gives rise to commend signals that control the vestibulosomatic reflex through the modulation of vestibular nuclear activity in the brainstem. The vestibular cortex includes such different cortical regions as the premotor region of the frontal cortex, parietal areas, temporal areas, and a central core region called parietoinsular vestibular cortex. This paper summarizes systemically animal and clinical research data concerned with the vestibular cortex in order to understand anatomy and functions of the vestibular cortex and to provide a basic literature for further study.

Expression level of nuclear factor-kappa,substance P and aquaporin 4 gene in the joint synovium and the change of discharge frequency of pain sensitive neuron in the ventral posteriolateral thalamic nuclens of acute gout rats / 中华风湿病学杂志

Objective To investigate the expression level of nuclear factor-kappa(NF-κB),substance P(SP)and aquaporin 4(AQP4)gene and the change of discharge frequency of pain sensitive neurons (PSN)in the ventral posteriolateral thalamic nucleus(VPL)of acute gout(AG)rats.The neuro-genic inflammation of AG was explored.Methods Forty-eight rats were randomly divided into two groups:the control group and the AG group. According to the time interval after injection of monosodiumurate(MSU)into the the unilateral ankle joint,the AG group was subdivided into seven groups,ie.0.5 hours group,2 hours group,6 hours group,12 hours group,24 hours group,48 hours group and 72 hours group.There were 6 rats in each group.After recording of the discharge frequency of PSN in rats VPL nucleus,the expression level of NF-κB,SP and AQP4 gene in the rats joint synovium were evaluated at mRNA level by PCR in above mentioned time.Results In the 0.5 hours group,the discharge frequency of PSN in the rats VPL nueleus and the expression level of SP gene in the rats joint synovium had increased immediately after the injection of MSU(P＜0.05).In the 6 hours group,they reached the peak level(P＜0.05),and in the 12 hours group,they began to decrease gradually(P＜0.05).In the 0.5 hours group,the expression level of NF-κB and AQP4 gene increased after the injection of MSU(P＜0.05).However,their peak level presented at the 12 hours(P＜0.05),and they decreaged after 24 hours(P＜0.05).The statistical analysis of correlation had shown that there were positive correlation among the expression level of NF-κB,substance P.AQP4 gene and the change of discharge frequency of PSN in the rats VPL nucleus.Conclusion The discharge frequency of PSN in the rats VPL and the expression level of SP gene in the rats ioint synovium can be used to evaluate the Severity of pain in the AG rats.The expression level of NF-κB and SP gene can reflect the severity of neurogenic intlammation.We can know the severity of edema of the joint synovium by detecting the expression level of AQP4 gene.Pain and neurogenic inflammation play an important role in the pathogenesis of AG.Combingelectrophysiology and biochemical technique can shade light on the pathogenesis of AG from different aspects.In the meantime,it may provide a new method for developing new drugs and new approaches for clinical treatment.

Thalamic Ataxia in the Elderly

Ataxia is one of the most serious neurological symptoms in elderly The clarification of the related anatomical structures are necessary for the understanding of pathophysiologic mechanisms of ataxia. We have recently experienced a case of thalamic infarct in the territory of thalamogeniculate artery. The localization of lesion was based on CT and MR imaging. At first time, right hemiparesis and ataxia were prominent. Hemiparesis was transient but ataxia had been persistent for several months. It has been suspected that thalamus could be the part of neural circuits in balancing. Our case support this suggestion clinically. Based on clinical observations, a plausible extrapolation can be made to thalamic ataxia. It maybe related with dysfunction of dentatorubrothalamic and corticopontine pathway. Thus our case led us to conclude that thalamus could be engaged in balance control of human body.

Effect of electrical stimulation of the medial thalamus on neuronal activity of the thalamic ventrobasal complex in the anesthetized cat / 全日本鍼灸学会雑誌

The preceding companion paper reported the influence of stimulation of the centre median nucleus (CM) of the thalamus on neuronal activity in the thalamic ventrobasal complex (VB). In the present study, a modification of the medial thalamus (MTh) except for the CM on activity in the somatosensory relay neurons of the thalamus was investigated in the cat. Extracellular multi-unitary discharges were recorded simultaneously from the VB using the multimicroelectrode system. The effects of MTh stimulation with a pulse train on VB neuronal activity were examined. The response of VB neuron to stimulation of other MTh nuclei were classified into the same four classes as that for CM stimulation : inhibited and then excited type; excited type; inhibited type; and non-responsive type. All four types of responses were observed in several nuclei of the MTh, such as the CM, central lateral nucleus (CL), mediodorsal nucleus (MD) and ventral posterior medial nucleus (VPM). MTh stimulation was more effective in nociceptive neurons than in non-nociceptive neurons. However, the effect of MTh stimulation differed among simultaneously recorded nociceptive neurons even when their receptive fields and recording sites were in close proximity. In some VB neurons, the response to stimulation applied to the center of the receptive field was also suppressed by MTh stimulation. Furthermore, an inhibitory effect on the response to stimulation applied to the periphery of the receptive field was observed even when the response to stimulation applied to the center of the receptive field was not inhibited by MTh stimulation. Thus, a large component of the MTh can modify VB neuronal activity and may be involved in the somatosensory system through complex mechanisms.

The antinociceptive effect of fentanyl on the discharges of the neurons in the parafascicular nucleus evoked by coronary artery occlusion / 中华麻醉学杂志

Objective The purpose of this study was to determine if parafascicular nucleus of thalamus is involved in the nociceptive stimulation evoked by coronary artery occlusion-induced acute myocardial ischemia and to investigate the effect of fentanyl on this nociceptive stimulation. Methods Male SD rats weighing 260-300 g were operated upon under general anesthesia with intraperitoneal urethane (1.2 g ? kg -1 ) and local infiltration of the skin incision. The discharges of pain-sensitive neurons (PSN) were recorded for 20 seconds every 5 min using single-barrel glass electrode before and after the coronary artery occlusion ( CAO) . The study was divided into 3 groups: group Ⅰ CAO alone ( n = 9); group Ⅱ CAO + fentanyl ( n = 6) : fentanyl 0.01 mg ?kg-1 was administered iv 15 min after CAO; group Ⅲ CAO + fentanyl + naloxone ( n = 6) : naloxone 0.04 mg? kg-1 was administered iv 15 min after intravenous fentanyl administration. Results The discharge frequency was significantly increased following CAO and peaked within 5-10 min after CAO and maintained for 60 min. The increased frequency of nociceptive discharge was significantly inhibited within 10 min after fentanyl and intravenous naloxone could completely antagonize the inhibitory effect of fentanyl. Conclusion Visceral pain can be evoked by acute myocardial ischemia induced by coronary artery occlusion. Thalamic parafascicular nucleus is involved in the perception of nociception in CNS. Opioid receptors play a critical role in the modulation of the nociception.

Stereotaxic Thalamotomy in the Management of Parkinson's Disease

A retrospective analysis was done on twenty-nine patients with Parkinson's disease who underwent thirty-five stereotaxic thalamotomies during the past 21 years. Eighteen patients received unilateral surgery, and six received two-staged bilateral surgery. Five had second stage operation after contralateral operation at other hospitals. Thirteen patients were followed-up for a period of six months to 12 years but the remainder were lost to follow-up. Parkinsonism scoring scale was designed and used to investigate postsurgical results and progress of patients. Clinical symptoms improved in 94.7% immediately after surgery. Only one patient had permanent neurological deficit resulting from the operation. A long-term follow-up study, with statistical analysis, suggested that progressive worsening after surgery was not ue to recurrence of tremor and rigidity but aggravation of bradykinesia and axial symptoms in the natural course of the disease. After unilateral surgery, 53.3% of patients had progressive aggravation of symptoms in contralateral side. It is believed that surgical treatment should be considered in patients presenting symptoms of tremor and rigidity. Bilateral surgery is indicated in patients who have bilateral symptoms or contralateral aggravation of symptoms after an initial operation.