下丘脑外侧区胃泌素神经元对大鼠胃缺血-再灌注损伤的作用

目的:观察下丘脑外侧区(1ateral hypothalamic alrea,LHA)对胃缺血-再灌注损伤(gastric ischemia-reperfu-sion injury,GI-RI)的影响,并对LHA的调控通路进行了初步分析.方法:采用夹闭大鼠腹腔动脉30 min,松开动脉夹血流复灌60 min的GI-RI模型,用电和化学刺激、电损毁和核团微量注射等方法.结果:(1)电或化学刺激LHA均显著加重GI-RI;(2)背侧迷走复合体(dorsal vagal complex,DVC)内微量注射五肽胃泌素后,对GI-RI的效应与电刺激一致;(3)电解损毁双侧DVC或DVC内微量注射胃泌素受体阻断剂丙谷胺均可取消电刺激LHA加重GI-RI的作用;(4)切断膈下迷走神经后电刺激LHA,GI-RI则减轻.结论:LHA具有加重大鼠GI-RI的作用;LHA的这种作用可能是因电或化学刺激后,激活了其中的胃泌素能神经元,经其下行投射纤维释放胃泌素作用于DVC神经元上的胃泌素受体,并通过迷走神经介导,从而影响GI-RI.     

红核在大脑皮质下行调控脊髓伤害感受性传递中的作用

以电刺激外周感受野诱发的大鼠脊髓背角WDR和NS神经元的晚串放电（C-反应）为指标，以串脉中刺激对侧大脑脚（CP）作为条件刺激，在C-反应受到明显抑制的神经元。分别观察了电解损毁红核（RN）和RN内注射兴奋性氨基酸的受体拮抗剂对刺激CP的下行抑制作用的影响。结果发现：损毁同侧RN后，刺激CP对C反应的抑制作用明显减弱，而损毁同侧RN背侧结构，对侧RN及假损毁RN均无此效应；RN内微量注射兴奋性氨基酸受体拮抗剂AP5和DNQX均可减弱刺激CP对C-反应的抑制。提示RN至少部分参与大脑皮质对脊髓伤害感受性传递的下行抑制作用。且以同侧RN为主；在与痛觉调制有关的皮质-RN通路中既有NMDA受体又有非NMDA受体的参与。     

下丘脑室旁核对大鼠胃缺血——再灌注损伤调控的神经机制

采用夹闭大鼠腹腔动脉30min,松开动脉夹血流复灌1h的胃缺血-再灌注损伤模型,观察了电和化学刺激以及电损毁下丘脑室旁核（paraventricular nucleus,PVN）对大鼠胃缺血-再灌注损伤(gastric ischemia-reperfu-sion injury,GI-RI）的影响,并对其调控的神经机制进行了初步研究。结果表明：①电刺激PVN或PVN内注射L-谷氨酸后,GI-RI均显著减轻;②电解损毁双侧PVN则能加重GI-RI;③损毁双侧孤束核（nucleus tractus solitarius,NTS）后,能取消电刺激PVN对GI-RI的减轻作用;④去除脑垂体后不影响电刺激PVN对GI-RI的作用;⑤分别切断膈下迷走神经和切除腹腔交感神经节后,电刺激PVN使GI-RI较单纯电刺激PVN组明显减轻。提示：PVN是对GI-RI具有保护作用的特异性中枢部位,孤束核以及外周迷走神经、交感神经均参与了PVN对GI-RI的调控,而与室旁核-垂体通路似无关系。     

谷氨酸对丘脑束旁核痛兴奋神经元放电的影响

目的：观察脑室注射谷氨酸（Glu)对大鼠丘脑束旁核（PF）痛兴奋神经元（PEN）电变化的影响。方法：以电脉冲刺激右侧坐骨神经作为伤害性痛刺激，用玻璃微电极细胞外记录神经元放电的变化。结果：（1）伤害性刺激使大鼠丘脑PF的PEN诱发放电频率增加；（2）脑室注射Glu(1.5μg/10μl）加强PEN的电活动，使PEN放电频率的净增值增加，潜伏期缩短；（3）这种作用可被Glu的NMDA受体拮抗剂MK－801（0．17μg/0.5μl)所阻断。结论：Glu在中枢痛沉调制中可能起兴奋作用，而NMDA受体参与介导中枢伤害性信息的传递过程。     

弥漫性颅脑外伤对DVC及内脏活动的作用

目的观察弥漫性脑损伤（DBI）大鼠延髓内脏带（MVZ）中背侧迷走神经复合体（DVC）的神经元放电频率的变化以及观察内脏活动的变化，为临床防治DBI引起的并发症提供理论依据。方法在成功建立DBI大鼠模型基础上，应用电生理学方法，观察DBI发生后1h、2h、6h、12h、24h，大鼠MVZ中DVC神经元放电频率的变化以及DBI大鼠心率、呼吸频率和胃电活动的变化。结果DBI1h，DVC神经元放电频率、胃电、心率和呼吸频率开始出现变化；DBI2h，上述指标出现较为显著的变化，呈现第一次变化高峰。DBI6h时其变化与DBI2h时相类似；而在DBI12h时，上述指标呈现第二次更为显著的变化高峰，直至DBI24h时仍然呈现相对高水平的改变，但较DBI12h时为低。结论DBI发生后，MVZ的DVC中神经元的激活是导致内脏活动发生改变的原动力。     

新生期注射谷氨酸单钠对刺激下丘脑弓状核镇痛作用的影响

下丘脑弓状核（ＡＲＣ）是脑内β－内啡肽（β－ＥＮＤ）能神经元胞体集中的一个主要核团。新生期注射谷氨酸单钠（ＭＳＧ）能选择性地损毁ＡＲＣ中的神经元胞体而不累及路过纤维，是研究ＡＲＣ中神经元生理功能的一个良好模型。本实验利用这个实验模型研究刺激ＡＲＣ的镇痛效应。结果发现在这种ＭＳＧ处理的大鼠，刺激ＡＲＣ不再出现明显的镇痛效应（用电刺激鼠尾－嘶叫法测定）。这时脑室内注射β－ＥＮＤ（５μｇ／１０μｌ）能使刺激ＡＲＣ的镇痛效应恢复；若脑室注射多巴胺（ＤＡ，５μｇ／１０μｌ）不仅没有恢复作用，反而能削弱正常大鼠刺激ＡＲＣ的镇痛效应。实验结果提示，经ＭＳＧ处理的大鼠之所以不出现明显的镇痛效应，可能是由于ＡＲＣ中丧失了β－ＥＮＤ能神经元的结果，ＤＡ能神经元在其中不起重要作用。     

迷走神经刺激对红藻氨酸致痫大鼠海马及齿状回NMDAR1的影响

目的：利用红藻氨酸（ＫＡ）致大鼠复杂部分性发作模型，观察海马及齿状回等易损脑区Ｎ－甲基－Ｄ－门冬氨酸受体１亚单位（ＮＭＤＡＲ１）的变化，以期进一步探明迷走神经刺激治疗癫痫的作用机制。方法：免疫细胞化学法。结果：正常大鼠ＮＭＤＡＲ１阳性结构可见于海马各区及齿状回；ＫＡ给药后１ｈ海马ＣＡ１、ＣＡ３齿状回ＮＭＤＡＲ１的密度开始增高；３１ｈ达高峰，以后逐渐下降，２４ｈ后基本恢复正常；预先给予左侧迷走神经电     

刺激蓝斑对外伤性脑水肿发生发展的影响

本文采用大鼠脑损伤模型，通过刺激或损毁蓝斑，研究中枢去甲肾上腺素（ＮＥ）能神经元兴奋或抑制对外伤性脑水肿的影响。结果表明，脑损伤后刺激蓝斑强化中枢ＮＥ能神经元兴奋，可明显加重脑水肿；相反，预先损毁蓝斑，消除中枢ＮＥ能神经元兴奋，则脑损伤后继发性脑损害和脑水肿明显减轻。提示脑损伤后中枢ＮＥ能神经元兴奋性增高可能是外伤性脑水肿发生和发展的重要因素之一。     

α2—肾上腺素能受体影响糖尿病通过敏尾神经中C和Aδ单位的传入活动

目的：观察静脉注射α－肾上腺素能受体激动剂和拮抗剂以刺激交感神经（sympathetic stimulation,SS)对糖尿病痛过敏大鼠神经中C和Aδ单位的影响。方法：测定糖尿病过敏大鼠尾神经C和Aδ单位放电情况及相关因素对其影响。结果：在注射α2－受体激动剂可乐定后，糖尿病过大鼠无自发放电的部分C（3／16）和Aδ（14／35）单位由静息状态转入活动状态；在具有自发放电的C（8／41）和Aδ（22／79）单位中，α2－受体拮抗育亨宾能阻断这些单位的自发电活动，而可乐定则使这些单位的放电频率增加；α1－受体激动剂苯肾上腺素和拮抗剂哌唑嗪不影响C和Aδ单位的电活动。SS可引起糖尿病痛过敏大鼠无自发放电的部分C（10／33）和Aδ（26／57）单位产生新的传入活动，而注射育亨宾后SS不再对这些单位产生兴奋作用；哌唑嗪和β－受体拮抗剂心安不影响SS对C和Aδ单位的作用；SS能引起糖尿病通过敏大鼠有自发放电的C（8／41）和Aδ（22／79）单位的放电频率增加，注射育亨宾后这些单位的自发电活动消失，重复SSS不再使这些单位产生传放电，而哌唑嗪则无此作用。结论：去甲肾上腺素（NA）通过α2－肾上腺素能受体兴奋糖尿病痛过敏大鼠的C和Aδ单位。     

丘脑中央下核和顶盖前区前核分别参与介导强电针和弱电针的 …

在大鼠以强电刺激外周感受野诱发的脊髓背角ＷＤＲ和ＮＳ神经元的晚串放电（Ｃ－反应）作为伤害感受性反应，观察了双侧丘脑中央下核（Ｓｍ）或顶盖前区前核（ＡＰｔＮ）内微量注射局麻药利多卡因对不同强度电针引起的镇痛效应的影响。结果表明：双侧Ｓｍ局麻可明显减弱强电针对Ｃ－反应的抑制效应，但对弱电针的抑制效应无明显影响，双侧ＡＰｔＮ局麻可明显减弱弱电针对Ｃ－反应的抑制效应，但以强电针的抑制效应无明显影响，结果提     

Ghrelin projection from the lateral hypothalamus area to the dorsal vagal complex and its regulation of gastric motility in cisplatin-treated rats

ObjectiveTo investigate ghrelin projection from the lateral hypothalamus area (LHA) to the dorsal vagal complex (DVC) and its regulation of gastric motility in cisplatin-treated rats.Materials and methodsIn the present study, the protein and mRNA expression of ghrelin and its receptor GHSR-1a were measured by Western blot and PCR, respectively. The ghrelin fiber projections arising from the LHA and projecting to the DVC were investigated by retrograde tracing combined with fluoro-immunohistochemical staining. The effects of ghrelin in the DVC, electrical stimulation of the LHA, and electrical lesion of the DVC on gastric motility were measured in cisplatin-treated rats.ResultsGhrelin fibers originating in the LHA projected to the DVC. The protein and mRNA expression of GHSR-1a was greater in cisplatin-treated rats than in saline-treated rats. Conversely, the expression of ghrelin in the LHA and DVC was reduced in cisplatin-treated rats. Cisplatin treatment also reduced gastric contractions. Ghrelin administrated into the DVC significantly promoted gastric motility, an effect completely blocked by treatment with the ghrelin receptor antagonist [D-Lys-3]-GHRP-6. In addition, electrical stimulation of the LHA promoted gastric motility, though this effect was much weaker in cisplatin-treated rats than in control rats. The excitatory effect of electrical stimulation of the LHA on gastric motility was partially blocked by pretreatment of the DVC with [D-Lys-3]-GHRP-6. Electrical lesion of the DVC diminished the excitatory effect that was induced by electrical stimulation of the LHA.ConclusionsDVC, especially AP, may have a role for gastric contraction induced by the stimulation of the LHA. This regulation on gastric motility was weaker in cisplatin-treated rats than in saline-treated rats, possibly due to reduced ghrelin expression in the LHA and ghrelin projection from the LHA to the DVC.     

The orexinergic neural pathway from the lateral hypothalamus to the nucleus accumbens and its regulation of palatable food intake

ObjectiveTo explore the orexinergic pathway from the lateral hypothalamus (LHA) to the nucleus accumbens (NAc) and its regulation on the palatable food intake.MethodsFluorescent gold retrograde tracing combined with fluoro-immunohistochemical staining were used to observe the projection of orexinergic neurons from LHA to NAc. The orexin-A expression in LHA and c-Fos in NAc were studied after electrical stimulation of LHA. The firing rates of neurons were monitored by single-unit extracellular electric discharge recording and the palatable food intake were measured after orexin microinjection in NAc or electrical stimulation of LHA.Results(1) Fluorescent gold retrograde tracing combined with fluoro-immunohistochemical staining showed some orexinergic neural projection from the LHA to the NAc shell. (2) Electrical stimulation of LHA significantly enhanced the expression of orexin-A in LHA and the expression of c-Fos in NAc (P < .05). (3) The results of single-unit extracellular discharge recording showed that the microinjection of orexin in NAc or electrical stimulation of LHA significantly increased the discharge activity of gastric distension responsive neurons in NAc, and the effect could be partly blocked by pretreatment of orexin-A receptor inhibitor SB334867 in NAc (P < .05). (4) Microinjection orexin-A in NAc or electrical stimulation of LHA significantly increased the palatable food intake in rats, and the effect also was partly inhibited by pretreatment of SB334867 in NAc (P < .05).ConclusionThere is an orexinergic pathway from LHA to NAc, which may have potential regulatory effects on food reward and obesity.     

Central control of gastric acid secretion by extralateralhypothalamic nuclei

Whether secretion of gastric acid (GAS) is in response to peripheral and/or central administration of chemical or electrical stimuli can be differentiated by vagotomy. GAS has been shown to be controlled by specific lateral hypothalamic (LHA) neurons. Application of 2-deoxy-D-glucose (2-DG) or insulin to the LHA by microinjection or iontophoresis has experimentally induced GAS. The paraventricular nucleus (PVN) has now been found to also affect GAS. GAS was produced more copiously and more quickly by rostral PVN lesion than by lesion of the ventromedial (VMH) or dorsomedial (DMH) nucleus, and nearly as much by caudal PVN lesion. Microinjection of 2-DG into the LHA induced GAS more potently in animals with rostral PVN lesions than in those with caudal PVN, VMH or DMH lesions, or in intact animals. Results indicate that the PVN may be an additional central site from which GAS is affected.     

Effects of lesion and stimulation of rat hypothalamic arcuate nucleus on the pain system

Electrolytic lesion and stimulation of the arcuate nucleus of the hypothalamus (ARH) were investigated in Wistar albino rats. 1) Discrete lesion of the ARH is followed by hyperalgesia as manifested by significantly high values of pain rating in the formalin test and by depressed analgesic effect of electroacupuncture stimulation on digastric electromyogram (dEMG) activity. 2) ARH stimulation appreciably suppressed both the responses of neurons in the lateral hypothalamus (LHA) and dEMG activity induced by tooth pulp stimulation. The suppressive influence of ARH stimulation on the responses of LHA neurons was antagonized by intraperitoneally injected and electrophoretically applied naloxone. It is thus suggested that the ARH is involved in induction or modulation of opioid-mediated analgesia.     

Competence of nerve tissue as distal insert promoting nerve regeneration in a silicone chamber

In some medial forebrain bundle (MFB) sites, self-stimulation is often modulated by hunger or satiety. With electrodes in the nucleus accumbens (NAC) such modulation rarely occurs. The influence of food deprivation on MFB self-stimulation is the main basis for the hypothesis that electrical stimulation of the MFB can mimic the rewarding effect of food for hungry animals. To investigate this hypothesis, unit activity was recorded from the lateral hypothalamic area (LHA) of freely moving rats during rewarding stimulation at loci in both MFB and NAC, and during food ingestion. Of 63 neurons tested during MFB stimulation, 41 were inhibited, 19 were activated, and 3 were not influenced. NAC stimulation suppressed 8 of the 31 neurons tested, excited 16, and elicited no response in the remaining 7. During ingestion, 29 of the 63 neurons tested were inhibited and one was facilitated. Of 29 neurons suppressed by food, 20 were also inhibited by rewarding MFB stimulation, but 10 of 13 neurons inhibited by food were excited by rewarding NAC stimulation. Thus, most LHA neurons inhibited during feeding were also inhibited by rewarding MFB stimulation. Rewarding NAC stimulation, however, does not inhibit most LHA neurons that are inhibited by food. This result suggests that LHA neurons which are inhibited by food might be involved in mediation of the rewarding effect of electrical stimulation at some sites in the MFB. Nevertheless, self-stimulation may occur by activating reward processes other than those related to food, because rewarding NAC stimulation does not inhibit LHA neurons which are suppressed by food.     

Lateral hypothalamus modulates gut-sensitive neurons in the dorsal vagal complex

The lateral hypothalamus (LH) regulates metabolic, behavioral and autonomic functions. The influence of the LH on gastrointestinal function and feeding behavior may be mediated by the dorsal vagal complex (DVC). In the present experiment, we used tract tracing and neurophysiologic techniques to evaluate the interrelationship between the LH and DVC. Using the tracer DiI, we demonstrated that the LH projects to both the nucleus of the solitary tract (NST) and the dorsal motor nucleus of the vagus (DMNV). We determined the effects of electrical stimulation of the LH and/or distention of the gastrointestinal tract on the firing rates of 107 DMNV neurons and 68 NST neurons. As previously reported, the majority of the DMNV neurons were inhibited and the majority of the NST neurons were excited by gastrointestinal distention. Electrical stimulation of the LH significantly changed the spontaneous activities of 71% of the DMNV neurons (46 excited and 30 inhibited). Of the 68 NST neurons characterized, 25 neurons were inhibited and 8 were excited by LH stimulation. In a separate experiment, we characterized the effects of both electrical and chemical stimulation of the LH on 36 DMNV and 14 NST neurons. Glutamate (0.8 nM) induced similar responses in the DVC neurons as electrical stimulation of the LH. The results indicate that the LH influences the electrical activity of DVC neurons. This effect may be the mechanism by which the LH modulates gastrointestinal function and feeding behavior.     

Lateral hypothalamic area orexin-A influence the firing activity of gastric distension-sensitive neurons and gastric motility in rats

The orexins system consists of two G-protein coupled receptors (the orexin-1 and the orexin-2 receptor) and two neuropeptides, orexin-A and orexin-B. Orexin-A is an excitatory neuropeptide that regulates arousal, wakefulness and appetite. Recent studies have shown that orexin-A may promote gastric motility. We aim to explore the effects of orexin-A on the gastric -distension (GD) sensitive neurons and gastric motility in the lateral hypothalamic area (LHA), and the possible regulation by the paraventricular nucleus (PVN). Extracellular single unit discharges were recorded and the gastric motility was monitored by administration of orexin-A into the LHA and electrical stimulation of the PVN. There were GD neurons in the LHA, and administration of orexin-A to the LHA could increase the firing rate of both GD-excitatory (GD-E) and GD-inhibited (GD-I) neurons. The gastric motility was significantly enhanced by injection of orexin-A into the LHA with a dose dependent manner, which could be completely abolished by pre-treatment with orexin-A receptor antagonist SB334867. Electrical stimulation of the PVN could significantly increase the firing rate of GD neurons responsive to orexin-A in the LHA as well as promote gastric motility of rats. However, those effects could be partly blocked by pre-treatment with SB334867 in the LHA. It is suggested that orexin-A plays an important role in promoting gastric motility via LHA. The PVN may be involved in regulation of LHA on gastric motility.     

CRF microinjected into the dorsal vagal complex inhibits TRH analog- and kainic acid-stimulated gastric contractility in rats

The effect of CRF microinjected into the dorsal vagal complex (DVC) on centrally-stimulated gastric contractility was investigated in fasted, urethane-anesthetized rats. Miniature strain gauge force transducers were acutely implanted on the corpus of the stomach and contractility was analyzed by computer. Microinjection of the stable thyrotropin-releasing hormone (TRH) analog, RX 77368, (26 pmol) into the DVC induced a 12.2-fold stimulation of gastric contractility within 30 min. Corticotropin-releasing factor (CRF) (63-210 pmol) microinjected into the DVC concomitantly with RX 77368 (26 pmol) induced a dose-related inhibition of stimulated gastric contractility. Neither CRF alone (210 pmol) nor vehicle modified basal gastric contractility. Microinjection of kainic acid (141 pmol) into the raphe pallidus nucleus induced a 3.6-fold stimulation of gastric contractility after 45 min. This stimulation was suppressed by bilateral microinjection of CRF (105 pmol/site) into the DVC. These results demonstrate that CRF acts in the DVC to inhibit centrally-stimulated gastric contractility and suggest that TRH and CRF may interact in the DVC to regulate gastric motor function.     

Functional heterogeneity of the monkey lateral hypothalamus in the control of feeding

Regional differences in the effects of electrical (ES) and chemical stimulation on execution of a bar-press feeding task, and in neuronal activity related to feeding, glucose sensitivity, and odor responsiveness were examined in the lateral hypothalamic area (LHA) of monkeys. In satiated animals, ES of the far lateral and ventral LHA induced bar-press feeding. In hungry animals, ES of the dorsal LHA suppressed the feeding task only during the stimulation period, but prolonged feeding suppression that occurred after ES of the ventromedial LHA. Microinjection of Na-glutamate into LHA sites where ES was effective in suppressing feeding had no effect, but it was effective in the medial hypothalamus. Glucose-sensitive (GS) neurons decreased in activity during bar pressing and/or during the ingestion period. Glucose-insensitive (GIS) neurons showed a cue-related excitation more often than GS neurons. Odor-responding GS and GIS cells were localized in ventromedial and lateral LHA sites, respectively. The present study suggests the regional heterogeneity of the LHA in feeding regulation, depending on both hunger and satiety states.