小脑参与内脏活动调节的研究进展

近年来神经解剖学、神经生理学以及行为学的研究正逐步揭示小脑这一传统意义上的皮层下运动调节中枢在非躯体性活动(主要是内脏活动)的调节中也发挥重要的作用.本文对小脑参与胃肠活动、心血管活动和呼吸活动调节的研究进展做简要综述.     

小脑靶向神经刺激促进吞咽恢复机制的研究进展

大脑的经颅磁刺激和电刺激是目前具有一定应用前景的技术,逐渐在基础研究和临床实 践中得到应用。这种无创的、非侵入性的靶向神经刺激,通过调节神经兴奋性和可塑性来改善或恢复 大脑功能。由于小脑在运动协调、联想和情感等方面与大脑存在神经解剖和功能联系,因此以小脑为 靶点的神经刺激可以更好地了解生理及病理状态下,小脑与大脑吞咽运动区之间的联系,更好地研究 小脑对吞咽皮质区域兴奋性的调节作用,以及对吞咽功能的影响,为神经源性吞咽障碍提供一种潜在 的治疗方法。     

小脑桥脑角区神经与周围血管关系

小脑脑桥角区的神经血管关系密切，结构相对复杂，主要神经有第Ⅴ、Ⅵ、Ⅶ、Ⅷ颅神经及后组颅神经，主要血管有小脑上动脉、小脑前下动脉、小脑后下动脉、基底动脉、椎动脉。回顾近年来的相关研究，将其相互关系综述如下。     

小脑非运动功能异常的影像研究进展

现代神经成像技术已经能在活体上获得近似于真实的小脑与大脑结构功能连接特征。近年来的研究已发现小脑在认知、注意、情感和语言等非运动功能方面起到了重要作用。在神经精神疾病中,小脑异常也参与了神经认知损害。本文针对包括老化、癫痫和精神分裂症在内的典型小脑非运动功能异常,从结构、功能和脑连接角度综述了小脑的影像研究进展。对于探索小脑的非运动功能及其在老化和神经精神疾病中的病理生理机制具有重要的科学意义。     

内镜辅助显微手术治疗桥脑小脑角胆脂瘤

目的 探索神经内镜辅助显微神经手术治疗桥脑小脑角胆脂瘤的实用性及效果。方法 对22例桥脑小脑角胆指瘤进行了神经内镜辅助显微手术切除．术中用0。和30。神经内镜观察各个死角。如果发现有肿瘤残留，在神经内镜辅助下行残留肿瘤切除。结果 术后临床症状、体征均明显改善或消失，均未发生无菌性脑膜炎和迟发性颅内出血等并发症。结论 神经内镜辅助显微手术治疗桥脑小脑角胆脂瘤，有利于提高手术疗效．降低手术并发症。     

神经内镜下桥小脑角区手术入路的解剖学研究

目的 探讨神经内镜下桥小脑角区3种手术入路的应用价值.方法 在神经内镜下分别模拟枕下乙状窦后小脑外侧锁孔入路、枕下乙状窦后幕下小脑上锁孔入路、枕下乙状窦后绒球下锁孔入路,确定到三叉神经出入脑干区(REZ)、面神经REZ及舌咽神经REZ的手术路径及解剖定位标志.结果 枕下乙状窦后小脑外侧锁孔入路可探查三叉神经REZ、面神经REZ、舌咽神经REZ,解剖定位标志为Meckel囊、内耳门、颈静脉孔、三叉神经、面神经、前庭蜗神经和舌咽神经.枕下乙状窦后幕下小脑上锁孔入路可探查三叉神经REZ至Meckel囊,解剖定位标志为岩静脉、三叉神经和Meckel囊.枕下乙状窦后绒球下锁孔入路可探查舌咽神经REZ、面神经REZ,解剖定位标志为第四脑室脉络丛和小脑绒球.结论 对三叉神经显微血管减压术,幕下小脑上锁孔入路优于小脑外侧锁孔人路.对面神经、舌咽神经显微血管减压术,绒球下锁孔入路优于小脑外侧锁孔人路.     

经后颞下人路暴露岩斜区及小脑桥脑角的神经内镜解剖学研究

目的研究经后颞下入路一经天幕暴露岩斜区及小脑桥脑角的神经内镜下血管神经解剖结构，探索岩斜区及小脑桥脑角可利用的间隙。方法成年新鲜尸头9例（18侧），交替使用0°、30°角神经内镜经后颞下入路一经小脑幕探查岩斜区及小脑桥脑角，并用摄像系统对相关的解剖结构及解剖标志纪录。结果小脑桥脑角在神经内镜下分为结构清晰的上、中、下三个间隙，三个间隙均有充分的操作空间，分别经三个间隙推进神经内镜后岩斜区得以暴露。结论神经内镜下经后颞下入路-经天幕能充分的暴露岩斜区、小脑桥脑角及周边解剖结构。     

桥小脑角区上血管神经复合体的显微解剖学研究

目的 研究桥小脑角区上血管神经复合体显微解剖。方法 应用15例经10％甲醛充分固定并灌有乳胶的国人成人头颅湿标本，模拟临床枕下乙状窦后手术入路，在4～25倍手术显微镜下逐层解剖，观察，测量及照相。结果 桥小脑角区上血管神经复合体主要包括三又神经和相关的小脑上动脉、岩静脉及中脑、中脑小脑沟、小脑上脚、小脑幕面。小脑上动脉的行程一般比较恒定，向尾侧凸起的46．88％的尾袢对三叉神经造成压迫。结论 桥小脑角区上血管神经复合体位置深在，结构复杂且周围毗邻脑干、小脑动脉及颅神经等重要的结构，详尽的解剖研究可提高显微血管减压手术成功率并且．尽可能保存神经功能的完整。     

精神病与小脑病变

长期以来,临床医生一直认为小脑病变只会引起运动功能障碍,即平衡和共济运动损害。近来,通过神经生理学研究,对于小脑机能的传统看法,已引起怀疑。新的研究日益表明,小脑与其他神经机能有着广泛的联系和调节作用,而不仅是调节运动机能。如:植物神经系统、边缘系统和较高级皮层机能均受小脑调节。以及与视觉、听觉及触觉也有联系。同时小脑与网状结构、脑干感觉神经核、运动神经核、边缘系统、丘脑和大脑皮层各区均有广泛的联系。小脑通过这些     

扩大翼点入路显微手术切除小脑幕跨幕巨大脑膜瘤(附15例报告)

近年来随着显微外科和神经麻醉学技术的发展，小脑幕脑膜瘤的死亡率和致残率均明显下降。Hamit认为，小脑幕巨大跨幕脑膜瘤是指瘤基底附着于小脑幕或小脑幕切迹处，瘤体横跨小脑幕、瘤径≥3cm的颅底肿瘤，由于该位置毗邻重要的血管神经结构，全切肿瘤一直是神经外科的手术难点。近年来我科采用改良经翼点入路显微手术切除15例该部位脑膜瘤，总结当小脑幕脑膜瘤包裹重要神经血管时的临床表现、诊断、显微外科技术技巧和并发症。统计结果显示提示该入路可以提供安全的解剖暴露，手术效果较好，现报告如下。     

Exaggeration of epileptic-like patterns by nicotine receptor activation during the GABA withdrawal syndrome

To understand how nicotinic cholinergic receptors may participate in epileptic seizures, we tested the effects of nicotine and of the competitive nicotinic antagonists dihydro-beta-erythroidine and alpha-bungarotoxin on synaptic paroxysmal depolarization shifts (PDSs) and intrinsic bursts of action potentials recorded in slices from rats presenting a cortical status epilepticus. This model named GABA-withdrawal syndrome (GWS) appears consecutive to the interruption of a prolonged intracortical GABA infusion. Effects of both nicotinic antagonists suggest a distinct involvement of alpha4-beta2 and alpha7 subunits in shaping individual PDSs and patterning repetitive bursts. On one hand, in GWS rats, an increase of PDS latency and prolongation of PDS and bursts were induced by nicotine and reduced by dihydro-beta-erythroidine, but not by alpha-bungarotoxin. The K+ blocker tetraethylammonium also increased duration without changing latency. Thus, dihydro-beta-erythroidine-sensitive receptors exert distinct controls on the presynaptic generation of PDS and on the process which terminates PDSs and bursts. On the other hand, alpha-bungarotoxin depolarized neurons and generated rhythmic discharges of clustered bursts. Clustered bursts were also observed in slices obtained from GWS rats treated with the acetylcholinesterase inhibitor eserine. We suggest that both dihydro-beta-erythroidine and alpha-bungarotoxin-sensitive sites control paroxysmic activities in GWS and could be involved in some human and animal epilepsies presenting mutations of nicotinic cholinergic receptors.     

Neuroendocrine regulation of seasonal reproductive activity in the male golden hamster

Golden (Syrian) hamsters are seasonal breeders. Under natural photoperiodic conditions, their reproductive systems are functional during spring and summer and atrophic during the fall and winter. This reproductive cycle can be duplicated in the laboratory by exposing the animals to artificially-created photoperiods. The endocrine correlates of photoperiod-induced changes in reproductive activity of the male hamster are fairly well characterized, but the neural control of seasonal reproductive activity has not been as extensively studied. Recent studies indicate that short day (less than 12.5 hr light/day) exposure leads to complex changes in central neurotransmitter metabolism, as well as neurotransmitter and hormonal receptor content, which, in turn, are reversed by exposure to long days or during the period of spontaneous testicular recrudescence. Many of these endocrine and neuroendocrine changes are dependent on the presence of the pineal gland, but photoperiod-induced changes in neurotransmitter metabolism have also been described in pinealectomized hamsters. Further studies of the neuroendocrine transduction of photoperiodic signals will not only provide a better understanding of seasonal reproductive and metabolic activities, but will increase our basic understanding of the neural control of the endocrine system.     

Reticulospinal neurons inactivated by warming of the preoptic area and anterior hypothalamus of rabbits

To identify the premotor neurons for vasoconstrictors of the skin, activities of reticulospinal neurons in the rostroventral medulla, the ear sympathetic nerve (ESNA) and the renal sympathetic nerve (RSNA) were recorded in anesthetized and immobilized Japanese White or New Zealand White rabbits. Two groups of neurons were identified according to their responses to thermal stimulation of the preoptic area and the anterior hypothalamus (POAH) and to electrical stimulation of baroreceptor afferents, the aortic nerve (AN). Neurons (Type I neurons, n = 21) whose activity was inhibited by warm stimulation of the POAH but not inhibited by the AN stimulation were located in sites medial to the rostral ventrolateral medulla (RVLM). The other neurons (Type II neurons, n = 20) whose activity was not inhibited by warm stimulation of the POAH but inhibited by the AN stimulation were located in the RVLM. Because the time course of the inhibitory response of Type I neurons to warm stimulation of the POAH was very similar to that of the inhibitory response of the ESNA and activities of these neurons and the ESNA were not inhibited by the stimulation of the AN, it was suggested the Type I neurons might participate in regulation of activity of the vasoconstrictors of the ear skin. The Type II neurons are considered to be the barosensitive RVLM neurons that regulate systemic arterial pressure by controlling the activity of visceral or muscular sympathetic vasoconstrictors or cardiac sympathetic fibers.     

Uptake blockade of endocannabinoids in the NTS modulates baroreflex-evoked sympathoinhibition

Previous studies supporting a possible physiological role for an endogenous cannabinoid, arachidonylethanolamide (AEA, anandamide), showed a significant increase in AEA content in the nucleus tractus solitarius (NTS) after an increase in blood pressure (BP) and prolonged baroreflex inhibition of renal sympathetic nerve activity (RSNA) after exogenous AEA microinjections into the NTS. These results, along with other studies, support the hypothesis that endogenous AEA can modulate the baroreflex through cannabinoid CB(1) receptor activation within the NTS. This study was performed to characterize the physiological role of endogenously released cannabinoids (endocannabinoids) in regulating baroreflex control of RSNA through actions in the NTS. Endocannabinoid effects were assessed by measuring the RSNA baroreflex response to increased pressure after bilateral microinjections of AM404, an endocannabinoid transport inhibitor, into the NTS of adult male Sprague Dawley rats. AM404 blocks uptake of endocannabinoids and enhances the effects of any endocannabinoids released [M. Beltramo, et al., Functional role of high-affinity anandamide transport, as revealed by selective inhibition, Science 277 (5329) (1997) 1094-1097.] into the NTS. Therefore, it was hypothesized that microinjections of AM404 should exhibit effects similar to microinjections of exogenous AEA. In this study, AM404 microinjections into the NTS were found to significantly prolong baroreflex inhibition of RSNA compared to control, similar to effects of exogenous AEA. This effect is thought to result from an increased endocannabinoid presence in the NTS, leading to prolonged CB(1) receptor activation. These results indicate that endocannabinoids released in the NTS have the potential to modulate baroreflex control at this site in the central baroreflex pathway.     

The medial amygdaloid area is involved in activation of angiotensin II-sensitive neurons in the anterior hypothalamic area

We have previously reported that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that the activities of these AHA angiotensin II-sensitive neurons are enhanced in spontaneously hypertensive rats. It is suggested that there exist neural projections from the medial amygdala to the AHA in rats. In this study, we examined whether neurons in the medial amygdaloid area (MeA) are involved in the activation of AHA angiotensin II-sensitive neurons. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjection of glutamate into the MeA caused an increase in the firing rate of AHA angiotensin II-sensitive neurons. The glutamate-induced increase of firing rate was inhibited by pressure application of the AT1 receptor antagonist losartan onto AHA angiotensin II-sensitive neurons. The microinjection of glutamate into the central amygdaloid area also increased the firing rate of AHA angiotensin II-sensitive neurons, but the glutamate-induced increase of firing rate was not affected by pressure application of losartan onto AHA angiotensin II-sensitive neurons. The microinjection of corticotropin-releasing factor (CRF) into the MeA also increased the firing rate of AHA angiotensin II-sensitive neurons, but the CRF-induced increase of firing rate was not inhibited by pressure application of losartan onto AHA angiotensin II-sensitive neurons. Repeated microinjection of glutamate into the MeA caused an increase in the release of angiotensins in the AHA. These findings indicate that neurons in the MeA are involved in the activation of AHA angiotensin II-sensitive neurons. It seems likely that the activation of AHA angiotensin II-sensitive neurons induced by glutamate but not CRF is partly mediated via the release of angiotensins at AHA angiotensin II-sensitive neuron levels.     

Role of central 5-HT3 receptors in the control of blood pressure in stressed and non-stressed rats

The aim of the present study was to investigate the participation of central 5-HT(3) receptors in the control of blood pressure and heart rate (HR) of non-stressed and stressed rats. The pharmacological stimulation of brain 5-HT(3) receptors by third ventricle injections of the selective 5-HT(3) receptor agonist m-CPBG induced a significant decrease in blood pressure in non-stressed rats and impaired the hypertensive response induced by restraint stress. The blockade of brain 5-HT(3) receptors by the central administration of the selective 5-HT(3) antagonist ondansetron elicited a significant increase in blood pressure in non-stressed rats. Conversely, the hypertensive response induced by restraint stress was not affected by central administration of ondansetron. Additionally, baroreflex-mediated bradycardia during phenylephrine-induced hypertensive response was preserved in non-stressed animals receiving third ventricle injections of m-CPBG, while the baroreflex-mediated tachycardia that occurs during the hypotensive response induced by the administration of sodium nitroprusside was impaired. It is concluded that the serotoninergic component represented by the brain 5-HT(3) receptors exerts a tonic inhibitory influence on the central control of blood pressure in non-stressed rats, probably by a sympathoinhibitory-related mechanism. On the other hand, during stress, this central 5-HT(3)-dependent inhibitory drive is overwhelmed by the different neurochemical systems that harmonically trigger and sustain the hypertensive response.     

Altered Cholinergic Mechanisms and Blood Pressure Regulation in the Rostral Ventrolateral Medulla of DOCA-Salt Hypertensive Rats

We examined whether cholinergic transmission in the rostral ventrolateral medulla (RVLM) of deoxycorticosterone acetate-salt hypertensive rats (DHR) is enhanced and the enhancement is involved in the maintenance of hypertension in DHR, and whether cholineacetyltransferase (ChAT) activities and ChAT mRNA expression are enhanced in neurons intrinsic to the RVLM of DHR. Rats were anesthetized, paralyzed, and artificially ventilated. Unilateral microinjection of cholinergic agents into the RVLM produced a pressor response. The pressor response to physostigmine was greater in DHR than in control rats, whereas the response to carbachol was the same in both sets of rats. Bilateral microinjection of scopolamine into the RVLM produced a decrease in blood pressure. The depressor response was greater in DHR than in control rats. The number of ChAT-activity-detected neurons in the RVLM was greater in DHR than in control rats. The number of ChAT mRNA-expressing neurons in the RVLM was also clearly greater in DHR than in control rats. These results demonstrate that cholinergic transmission in the RVLM is enhanced in DHR, and this enhancement may play a role in the maintenance of hypertension in DHR. It is probable that enhanced activity of cholinergic neurons intrinsic to the RVLM is at least in part, responsible for the enhanced cholinergic transmission in the RVLM of DHR.     

Cholinergic stimulation in the lateral septal area activates anterior hypothalamic area neurons via excitatory amino acid receptors in rats

We have previously reported that some neurons in the anterior hypothalamic area (AHA) are tonically activated by endogenous angiotensins in rats and that activities of these AHA angiotensin II-sensitive neurons are enhanced in spontaneously hypertensive rats. It is suggested that there exist neuronal projections from the lateral septal area (LSV) to the AHA in rats. In this study, we examined whether neurons in the LSV are involved in activation of AHA angiotensin II-sensitive neurons. Male Wistar rats were anesthetized and artificially ventilated. Extracellular potentials were recorded from single neurons in the AHA. Microinjection of carbachol into the LSV caused an increase in firing rate of AHA angiotensin II-sensitive neurons. The carbachol-induced increase of firing rate of AHA angiotensin II-sensitive neurons was inhibited by pressure application of the excitatory amino acid receptor antagonist kynurenate but not by the AT1 receptor antagonist losartan onto the same neurons. Microinjection of carbachol into the LSV also increased the firing rate of AHA ACh-sensitive neurons, and the carbachol-induced increase of firing rate of ACh-sensitive neurons was again abolished by pressure application of kynurenate but not by the muscarinic receptor antagonist scopolamine onto the same neurons. Microinjection of the muscarinic receptor antagonist 4-DAMP into the LSV did not affect the firing rate of AHA angiotensin II-sensitive neurons. These findings indicate that neurons in the LSV are involved in activation of AHA angiotensin II-sensitive neurons. It seems likely that the carbachol-induced activation of AHA angiotensin II-sensitive neurons is mainly mediated via excitatory amino acid receptors at AHA neurons.     

The developmental and neural determinants of the effects of estrogen on feeding behavior in the rat: A theoretical perspective

Conceptually, the neural regulation of feeding behavior is proposed to be a function of the activities of a long-term (day to day) and a short-term (meal to meal) control system. Although these two control systems are presumably involved in a continuous and dynamic interaction, they can be behaviorally and anatomically separated by specific regulatory challenges and brain lesions. Utilizing this general regulatory model for the hypothalamic control of feeding behavior, the effects of estrogen on a variety of behavioral indices of energy regulation are reviewed and discussed. The effects of ovarian hormones on the feeding behavior of both prepubertal and adult female rats when faced with a series of regulatory tests shown to provide specific information about the long- and short-term control of feeding behavior leads to the following conclusions. Modulation of feeding behavior by ovarian hormones is detectable well before the time of puberty in the female rat and is expressed in terms of a 4-day periodicity that is very similar to adult animals. Estrogen appears to modulate feeding behavior primarily by modifying the long-term control of feeding behavior or else the manner in which nutrients are integrated into this long-term system. It is further proposed that estrogen acts upon metabolically specific and unique neural elements in the hypothalamus whose function is to translate error signals derived from the long-term integration of body nutrients into appropriate readjustments in feeding behavior. Although this dual-regulatory model for the hypothalamic control of feeding behavior can account for the majority of the effects of estrogen on feeding behavior, further studies suggest that an “extrahypothalamic” mechanism must mediate certain aspects of the neural control of feeding behavior as well as the behavioral effects of estrogen. Specifically, the present model system can account for the role of carbohydrates in the neural control of feeding behavior, but fats and possibly proteins can modify feeding behavior independent of the hypothalamus. Likewise, estrogen can influence the efficiency with which nutrient loads of fats and proteins can modify subsequent feeding behavior and therefore this proposed “extrahypothalamic” mechanism may mediate those effects of estrogen on feeding behavior that cannot be accounted for by the present dual-regulatory model.     

Involvement of nuclei in the hypothalamus in cardiac sympathoexcitatory reflexes in cats

The hypothalamus is considered to be an important area in the central regulation of cardiovascular function. However, its role in processing excitatory cardiovascular reflexes induced by stimulation of cardiac afferents has not been established. In the present study, using c-Fos immunoreactivity, we located neurons in the hypothalamus activated by inputs from cardiac sympathetic afferents. Following bilateral barodenervation and cervical vagotomy in anesthetized cats, bradykinin (BK, 1-10 microg, in 0.1 ml; n=7) was applied repetitively (6x, every 20 min) to the anterior epicardial surface of the left ventricle. This chemical stimulation caused consistent excitatory cardiovascular reflexes characterized by increases in blood pressure (BP) and heart rate (HR), while the vehicle for BK (0.9% saline, n=6) produced no such responses. Compared to control cats, c-Fos immunoreactive cells were significantly increased (P<0.05) in the arcuate nucleus (ARC), dorsal hypothalamic area (HDA), dorsomedial nucleus, paraventricular hypothalamic nucleus (PVN) and periventricular nucleus in the BK-treated animals. More neurons double-labeled with c-Fos and nitric oxide synthase (NOS) were observed in the PVN following epicardial application of BK (P<0.05). There was no significant increase in co-localization of these two labelings in the other nuclei. These results suggest that several nuclei in the hypothalamus respond to activation of cardiac sympathetic afferents, leading to sympathoexcitatory reflexes. Nitric oxide (NO) may function as a neurotransmitter or as a neuromodulator in the PVN during these cardiac-cardiovascular responses.