局灶性脑缺血再灌注损伤大鼠外周血内皮祖细胞数量的变化及其意义

目的 探讨局灶性脑缺血再灌注损伤(CIR)大鼠外周血内皮祖细胞(EPCs)数量的变化及其意义.方法 50只健康雄性SD大鼠随机分为正常对照组(5只)、假手术组(5只)、CIR模型组(15只)、糖尿病模型组(5只)、糖尿病假手术组(5只)和糖尿病合并CIR组(15只).由链脲佐菌素(STZ)诱导制作糖尿病大鼠模型;采用线栓法制作CIR大鼠模型.各模型大鼠采用Longa评分标准进行神经功能评分.CIR模型组与糖尿病合并CIR组各取5只大鼠采用2,3,5-三苯基氯化四氮唑(TTC)染色,计算其脑梗死体积.用流式细胞仪计数各组大鼠外周血EPCs的数量.结果 糖尿病合并CIR组大鼠神经功能评分[(2.8±1.0)分]明显高于CIR模型组[(1.5±0.3)分],且脑梗死体积[(464.1±169.3)mm3]明显大于CIR模型组[(101.3±57.4)mm3](均P＜0.05).各组中,CIR模型组大鼠外周血EPCs数量最多,糖尿病合并CIR组最少,正常对照组与假手术组多于糖尿病模型组与糖尿病假手术组(均P＜0.01).结论 CIR大鼠外周血EPCs数量增加,有助于修复血管及保护受损脑组织;糖尿病大鼠外周血EPCs数量明显减少,且合并CIR后减少更甚.外周血EPCs数量的检测有助于CIR病情及预后的评估.     

糖尿病大鼠海马内PAI-1的变化及米诺环素对其的影响

目的 探讨纤溶酶原激活物抑制剂-1(PAI-1)在2型糖尿病大鼠海马中的表达情况以及米诺环素对PAl.1表达的影响.方法 高糖高脂饮食加小剂量链脲佐菌素造2型糖尿病模型,将SD大鼠随机分为正常组、糖尿病模型组、米诺环素治疗组,造模成功1周后,米诺环素组每天腹腔注射米诺环素45mg/kg,糖尿病模型组和正常组腹腔注射等量的牛理盐水,连续给药2周,然后取大鼠海马组织,免疫组化检测各组大鼠海马中PAI-1的表达.结果 免疫组化结果分析示正常组、糖尿病组、米诺环素组阳性神经元的平均光密度值(MOD值)分别为0.109±0.007、0.195±0.009、0.161±0.012,与正常组比较,糖尿病组和米诺环素组PAI-1表达的差异均有统计学意义(P＜0.01),糖尿病组和米诺环素组比较差异也有统计学意义(P＜0.01).结论 2型糖尿病大鼠海马神经元内PAI-1的表达异常增高,米诺环素可减少大鼠海马神经元内PAI-1的表达,这可能是米诺环素保护糖尿病认知功能障碍的机制之一.     

糖尿病大鼠颅脑损伤早期CRP的动态变化及意义

目的 探讨糖尿病大鼠颅脑损伤早期血清CRP的变化及意义. 方法 42只SD大鼠根据是否脑损伤和糖尿病分5组,健康对照组6只,假损伤无糖尿病组6只,糖尿病无脑损伤组10只,单纯脑损伤组10只,脑损伤合并糖尿病组10只.用ELISA法测定各组大鼠血清1h、12h、24h、36h、48h、72h CRP的浓度.结果 糖尿病合并脑损伤组及单纯脑损伤组随时间不同血清中CRP含量持续增高,各时间段差异均有统计学意义(P＜0.01),糖尿病合并脑损伤组血清中CRP高于单纯脑损伤组及糖尿病组(P＜0.01).结论 CRP含量变化与颅脑损伤和糖尿病密切相关.糖尿病颅脑损伤后动态测定CRP对监测治疗效果、预后有重要意义.     

中枢类大麻受体拮抗剂利莫那班对2型糖尿病周围神经病变疗效的实验分析

目的 观察利莫那班对大鼠糖尿病周围神经痛变的疗效,探讨其作用机制.方法 采用链尿佐菌素(STZ)腹腔注射诱导形成糖尿病周围神经病变(DPN)模型,随机分为模型对照组、利莫那班小剂量组、利莫那班大剂量组、正常对照组.糖尿病大鼠造模成功后予利莫那班干预,开始给药24周后将模型组和正常组比较痛阈、坐骨神经传导速度.用酶联免疫吸附测定法(ELISA法)分别洲定各组大鼠血清、脊髓及坐骨神经内IL-Iβ、TNF-α的浓度.结果 利莫邢班对DNP大鼠痛阈、坐骨神经传导速度(NCV)有明显改善(P＜0.05).与对照组比较.DPN模型组大鼠的lL-Iβ、TNF-α的含量显著增高(P＜0.05),利莫那班治疗24周后.与DPN模型组比较IL-lβ、TNF-α的含量显著降低(P＜0.05).结论 利莫那班对糖尿病周围神经病变有良好的疗效,可能是通过调节自身免疫功能机制发挥作用.     

神经生长因子对糖尿病神经病变大鼠神经肽和神经传导速度的影响

目的 探讨神经生长因子对糖尿病周围神经病变大鼠神经肽和神经传导速度的影响. 方法 雄性Wistar大鼠35只按随机数字表法分为健康对照组(n=10)、糖尿病模型组(n=13)和神经生长因子治疗组(n=12),后两组用链脲佐菌素制成糖尿病周围神经病变大鼠模型,并给予神经生长因子治疗组神经生长因子治疗(40μg/kg).显微镜下观察并计算背根神经节中P物质、降钙素基因相关肽(CGRP)免疫阳性细胞率,检测运动神经传导速度(MNCV)和感觉神经传导速度(SNCV). 结果 糖尿病模型组大鼠背根神经节中P物质、CGRP免疫阳性细胞率(27.710％±3.471％；36.360％±12.027％)以及神经生长因子治疗组治疗前MNCV [(35.80±6.19) m/s]、SNCV[(39.62±6.69) m/s]与健康对照组[P物质:44.225％±8.213％；CGRP:47.400％±13.723％；MNCV:(55.83±10.30) m/s; SNCV:(47.02±7.52) m/s]相比显著下降,差异有统计学意义(P＜0.05).经神经生长因子治疗后,P物质、CGRP免疫阳性细胞率(49.417％±6.753％;53.811％±7.125％)较糖尿病模型组显著增高,MNCV[(41.80±3.45) m/s]、SNCV[(42.92±6.69) m/s]均治疗前显著增高,差异有统计学意义(P＜0.05). 结论 糖尿病周围神经病变大鼠可出现神经传导速度下降和神经生长因子相关神经肽P物质、CGRP缺乏,而神经生长因子可促进神经肽的表达并提高神经传导速度.     

氯胺酮对糖尿病周围神经病变大鼠脊髓TNF-α表达的影响

目的探讨氯胺酮对糖尿病周围神经病变大鼠的脊髓保护作用。方法成年雌性W istar大鼠70只,随机留取10只为正常对照组(A组),腹腔注射生理盐水(3 m.lkg-1.d-1);其余大鼠用链脲菌素(STZ)制造糖尿病模型,得到48只糖尿病大鼠。将其随机等分为2组:B组为糖尿病对照组(n=24):腹腔注射与A组等体积的生理盐水;C组为氯胺酮治疗组(n=24):腹腔注射氯胺酮10 m.gkg-1(1 m.gm l-1);于治疗后第1、3、5及8周分别进行行为学测定,记录机械痛觉;于第8周测定并记录神经传导速度;取脊髓切片,应用免疫组化方法和图象分析系统检测TNFα-在脊髓背角的表达情况,同时用尼氏染色法观察脊髓的病理形态学改变。结果与A组比较,B组、C组大鼠脊髓背角组织中TNF-a的表达显著升高(P<0.01);与B组比较,C组的TNFα-表达显著降低(P<0.01),并且减轻了糖尿病慢性神经触诱发痛(P<0.01)。结论糖尿病大鼠周围神经病变引起的神经痛与脊髓背角促炎性细胞因子TNFα-有关。而氯胺酮可明显抑制脊髓背角TNFα-的表达,减轻糖尿病神经痛。     

吡格列酮对糖尿病大鼠中枢神经系统11β-羟类固醇脱氢酶1 型表达的影响

目的 研究吡格列酮对糖尿病大鼠海马、下丘脑处11β-羟类固醇脱氢酶1型(11β-HSD1)表达的影响及与认知功能的关系.方法 雄性SD大鼠随机分为对照组(C组)、糖尿病组(D组)、糖尿病+吡格列酮治疗组(DP组),每组10只.8周后行Morris水迷宫评价大鼠的认知功能,Western Blot方法检测大鼠海马、下丘脑处11β-HSD1表达水平.结果 Morris水迷宫中,D组大鼠穿越原平台区次数较C组减少,DP组大鼠较D组增多,差异有统计学意义(P<0.01).在海马和下丘脑处,11β-HSD1表达D组较C组增加,DP组较D组减少,较C组增加,差异有统计学意义(P<0.01).结论 吡格列酮能够降低糖尿病大鼠海马、下丘脑组织局部11β-HSD1表达水平,并且可能是吡格列酮改善糖尿病大鼠空间学习记忆能力的机制之一.     

生长因子在糖尿病大鼠脑缺血再灌注中的表达

目的观察糖尿病大鼠脑缺血再灌注后血管内皮生长因子(VEGF)、转化生长因子-β1(TGF-β1)表达的情况。方法以链脲佐菌素诱导产生实验性糖尿病大鼠,线栓法制作大鼠脑缺血再灌注模型,2%的四氮唑红(TTC)染色法测量梗死体积。采用免疫组化方法观察大鼠脑缺血再灌注6、12、24和48h时程VEGF、TGF-β1表达情况,比较糖尿病对大鼠脑缺血再灌注后脑内VEGF、TGF-β1表达的影响。结果(1)相同时间点糖尿病组梗死体积明显大于正常血糖组(P<0.01)。(2)正常血糖组大鼠及糖尿病组大鼠脑缺血后VEGF、TGF-β1表达均增加,糖尿病组脑缺血后各时间点VEGF、TGF-β1表达均低于正常血糖组(P<0.01)。结论脑缺血再灌注损伤后VEGF、TGF-β1表达增强,提示VEGF、TGF-β1对缺血性脑损伤有保护作用,可能与神经细胞和内皮细胞的自身保护作用有关。糖尿病加重了大鼠脑缺血再灌注损伤,造成VEGF、TGF-β1表达不足。     

糖尿病大鼠脑组织紧密连接蛋白Occludin 表达的变化

目的:研究糖尿病大鼠脑组织紧密连接蛋白Occludin表达的变化.方法:30只雄性SD大鼠随机分为糖尿病1个月组、糖尿病3个月组及正常对照组.腹腔注射链脲佐菌素制作糖尿病大鼠模型,采用逆转录PCR和Western blot法检测大鼠脑组织Occludin mRNA和蛋白的水平.结果:糖尿病1个月组和3个月组大鼠脑组织Occludin mRNA水平[(0.20±0.21),(0.06±0.02)]均较正常对照组(1.00±0.00)显著降低(均P<0.05),且糖尿病3个月组Occludin mRNA水平明显低于糖尿病1个月组(P<0.05).糖尿病1个月组和3个月组大鼠脑组织Occludin蛋白水平[(0.58±0.01),(0.29±0.01)]比正常对照组(1.02±0.06)显著降低(P<0.05-0.01),且糖尿病3个月组Occludin蛋白水平明显低于糖尿病1个月组(P<0.05).结论:糖尿病大鼠脑组织Occludin表达明显降低,并随着病程延长其降低更明显;提示糖尿病使血-脑屏障受到损害.     

糖尿病大鼠脑小血管内皮P-选择素表达研究

目的探讨糖尿病鼠脑小血管病变机制。方法利用1%链脲佐菌素(STZ)诱导的糖尿病动物模型,将SD大鼠随机分为正常组、糖尿病病程8周组(DM8组)、糖尿病病程24周组(DM24组)观察糖尿病对鼠脑血管内皮P-选择素(Ps)表达的影响和炎性标志物血浆C-反应蛋白(CRP)的动态变化。结果正常大鼠脑内无Ps表达;糖尿病大鼠脑内Ps主要表达在直径为7.5~30μm的微血管上。糖尿病大鼠Ps表达较正常大鼠显著增高(P<0.01);随病程延长DM24组的Ps表达较DM8组也有显著增加(P<0.05)。造模前各组大鼠的血浆CRP含量无差异,造模后DM8组、DM24组CRP分别为64.7±8.12mg/L和126.3±12.3mg/L,较正常大鼠均有显著增高(P<0.01),DM24组的较DM8组的也有显著性增高(P<0.05)。结论糖尿病鼠脑微血管内皮P-选择素表达上调与慢性低度炎症反应有关,可能是糖尿病大鼠脑微血管内皮功能紊乱的机制之一。     

Stimulation of functional recovery via the mechanisms of neurorepair by S-nitrosoglutathione and motor exercise in a rat model of transient cerebral ischemia and reperfusion

Purpose: Stroke disability stems from insufficient neurorepair mechanisms. Improvement of functions has been achieved through rehabilitation or therapeutic agents. Therefore, we combined exercise with a neurovascular protective agent, S-nitrosoglutathione (GSNO), to accelerate functional recovery. Methods: Stroke was induced by middle cerebral artery occlusion for 60 min followed by reperfusion in adult male rats. Animals were treated with vehicle (IR group), GSNO (0.25 mg/kg, GSNO group), rotarod exercise (EX group) and GSNO plus exercise (GSNO+EX group). The groups were studied for 14 days to determine neurorepair mechanisms and functional recovery. Results: Treated groups showed reduced infarction, decreased neuronal cell death, enhanced neurotrophic factors, and improved neurobehavioral functions. However, the GSNO+EX showed greater functional recovery (p < 0.05) than the GSNO or the EX group. A GSNO sub group, treated 24 hours after IR, still showed motor function recovery (p < 0.001). The protective effect of GSNO or exercise was blocked by the inhibition of Akt activity. Conclusions: GSNO and exercise aid functional recovery by stimulating neurorepair mechanisms. The improvements by GSNO and exercise depend mechanistically on the Akt pathway. A combination of exercise and GSNO shows greater functional recovery. Improved recovery with GSNO, even administered 24 hours post-IR, demonstrates its clinical relevance.     

Daily voluntary exercise alters the cardiovascular response to hemorrhage in conscious male rats

The present study tested the hypothesis that voluntary wheel-exercised rats would better tolerate severe hemorrhage (HEM) compared to age matched sedentary (SED) controls. Conscious rats housed with (EX, n = 8) or without (SED, n = 8) a running wheel for 6 weeks underwent a 30% total blood volume HEM over 15 min and were euthanized 90 min later and brain tissue was processed for Fos-like immunoreactivity (FLI). Both EX and SED groups displayed typical responses to HEM (initial tachycardia followed by decreased HR and MAP) but at the end of HEM, mean arterial pressure (93 ± 6 vs 58 ± 3 mm Hg) and heart rate (316 ± 17 vs. 247 ± 22 bpm,) were higher in the EX vs. SED animals and 60 min following the end of HEM, HR remained significantly elevated in the EX vs SED animals. The altered HR response to HEM in the EX animals was linked to a significant difference in sympatho-vagal drive identified by heart rate variability analysis and an augmented baroreflex response to hypotension tested in a separate group of animals (n = 4-5/group). In many of the brain regions analyzed, EX rats displayed lower levels of FLI compared to SED rats. Significantly lower levels of FLI in the EX vs SED rats were identified in the middle and caudal external lateral subnucleus of the lateral parabrachial nucleus and the dorsal cap of the hypothalamic paraventricular nucleus. These results suggest that enhanced tolerance to HEM following daily exercise may result from an EX-induced reduction in excitation or exaggerated inhibition in central circuits involved in autonomic control.     

丹参多酚酸通过SIRT1/HMGB1路径改善大鼠脑缺血/再灌注损伤的机制研究

目的 研究丹参多酚酸通过沉默信息调节因子1(silent information regulator protein,SIRT1)/高迁移率蛋白1 (high-mobility group box 1,HMGB1)路径改善大鼠脑缺血再灌注损伤的机制.方法 选择雄性普通级健康132只SD大鼠,随机分为四组:假手术(Sha...     

High dose erythropoietin promotes functional recovery of rats following facial nerve crush

Erythropoietin (Epo) has neuroprotective activity in a variety of settings. Thus, we investigated whether Epo has a role in the functional recovery of rats after facial nerve injury. The right facial nerve of 24 Wistar rats (6 wks old) was crushed twice at the level of the stylomastoid foramen, for 30 s each time, using jeweler’s forceps held perpendicular to the nerve. The left facial nerve did not undergo the surgical lesion. The rats were randomly divided into 4 groups: (group 1) the control group (placebo, treated with saline); and groups treated with Epo at a dose of 1,000 U/kg body weight (group 2), 5,000 U/kg body weight (group 3), and 10,000 U/kg body weight (group 4). The Epo and saline were administered subcutaneously pre-operatively and treatment was repeated every 24 h for the first 2 weeks after the operation. Behavioral recovery from facial paralysis was measured daily, beginning 1 day after surgery, until full recovery of the eye blink reflex and whisker movements were observed. The average recovery times for the full blink reflex and whisker movements were significantly shorter (about 2–3 days) in rats treated with a high dose Epo (5,000, 10,000 U/kg body weight) compared to the placebo-treated rats (p < 0.05). There was no significant difference between low dose Epo-treated rats (1,000 U/kg body weight) and the placebo-treated rats. These results suggest that high dose Epo can promote the functional recovery of rats following facial nerve injury. Further studies are warranted to probe alternative treatment schedules (dose, mode of administration), underlying histological mechanisms and combination treatment with additional neuroprotective factors.     

Behaviorally-induced ultrastructural plasticity in the hippocampal region after cerebral ischemia

Behavioral training has been shown to induce synaptic plasticity in both intact and injured animals. Because of the possibility that the adaptive changes after ischemic damage may make the brain more malleable to behavioral training, we examined the effects of complex environment (EC) housing and exercise (EX) after global cerebral ischemia on synaptic structural alterations. Forty-two adult male Wistar rats were included in the study and assigned to either ischemia or sham group. Following ischemic or sham surgery, rats were randomized to either EC, EX, or social condition (SC, paired housing) group. CA1 was processed for electron microscopy and unbiased stereological techniques were used to evaluate plasticity. Significantly decreased neuron density was seen in anterior and medial CA1 in ischemic animals regardless of behavioral training. Neuron density in anterior CA1 was 31% less than the medial area. Synaptogenesis was influenced by cerebral ischemia and behavioral training in that all ischemic groups and sham EC animals showed greater number of synapses per neuron compared to the sham EX and SC groups. Analysis of synapse configuration showed that the synaptogenesis in ischemia EX and SC rats was formed mainly by synapses with single synaptic boutons, whereas in the ischemia EC and sham EC rats synaptogenesis was formed mainly by synapses with multiple synaptic boutons. Furthermore, housing of sham and ischemia rats in EC resulted in increased number of synapses with perforated postsynaptic density. Together, these data suggest that behavioral experience in EC after insult may be able to enhance synaptic plasticity.     

黄芪甲苷对脑缺血再灌注后血脑屏障的保护作用及IL-1β含量、MMP-9蛋白表达的影响

目的 探讨黄芪甲苷对大鼠脑缺血再灌注后血脑屏障的保护作用及其机制。方法 将SD大鼠72只随机等分为4组:假手术组、生理盐水对照组、小剂量黄芪甲苷治疗组(10 mg/kg)和大剂量黄芪甲苷治疗组(20 mg/kg),采用分光光度计法、酶联免疫吸附法及免疫组化法分别检测各组大鼠脑组织伊文氏蓝、IL-1β含量及MMP-9蛋白的表达水平。结果 与假手术组相比,生理盐水对照组脑组织伊文氏蓝含量明显增多、IL-1β含量显著增高、MMP-9蛋白的表达明显增强(P<0.01); 与生理盐水对照组相比,小剂量黄芪甲苷治疗组及大剂量黄芪甲苷治疗组脑组织伊文氏蓝含量均显著减少、IL-1β含量明显降低、MMP-9蛋白表达明显减弱(P<0.05); 小剂量黄芪甲苷治疗组与大剂量黄芪甲苷治疗组相比,伊文氏蓝、IL-1β含量及MMP-9蛋白表达无显著差异(P>0.05)。结论 黄芪甲苷对脑缺血再灌注后血脑屏障具有保护作用,这可能与其下调IL-1β含量、抑制MMP-9蛋白的表达有关。     

The glucagon-like peptide 1 (GLP-1) analogue, exendin-4, decreases the rewarding value of food: a new role for mesolimbic GLP-1 receptors

The glucagon-like peptide 1 (GLP-1) system is a recently established target for type 2 diabetes treatment. In addition to regulating glucose homeostasis, GLP-1 also reduces food intake. Previous studies demonstrate that the anorexigenic effects of GLP-1 can be mediated through hypothalamic and brainstem circuits which regulate homeostatic feeding. Here, we demonstrate an entirely novel neurobiological mechanism for GLP-1-induced anorexia in rats, involving direct effects of a GLP-1 agonist, Exendin-4 (EX4) on food reward that are exerted at the level of the mesolimbic reward system. We assessed the impact of peripheral, central, and intramesolimbic EX4 on two models of food reward: conditioned place preference (CPP) and progressive ratio operant-conditioning. Food-reward behavior was reduced in the CPP test by EX4, as rats no longer preferred an environment previously paired to chocolate pellets. EX4 also decreased motivated behavior for sucrose in a progressive ratio operant-conditioning paradigm when administered peripherally. We show that this effect is mediated centrally, via GLP-1 receptors (GLP-1Rs). GLP-1Rs are expressed in several key nodes of the mesolimbic reward system; however, their function remains unexplored. Thus we sought to determine the neurobiological substrates underlying the food-reward effect. We found that the EX4-mediated inhibition of food reward could be driven from two key mesolimbic structures-ventral tegmental area and nucleus accumbens-without inducing concurrent malaise or locomotor impairment. The current findings, that activation of central GLP-1Rs strikingly suppresses food reward/motivation by interacting with the mesolimbic system, indicate an entirely novel mechanism by which the GLP-1R stimulation affects feeding-oriented behavior.     

神经调节素1β通过激活Sirt1信号通路抑制自噬改善大鼠脑缺血再灌注损伤研究

目的 探讨神经调节素1β(neuregulin1β,NRG1β)是否通过抑制自噬减轻大鼠大脑中动脉缺血再灌注（middle cerebral artery occlusion reperfusion,MCAO/R）损伤,以及对沉默信息调节因子1(silent information regulator protein 1,Sirt1)信号通路的影响。方法 将210只健康雄性SD大鼠随机分为假手术组（Sham组）、模型组（MCAO/R组）、治疗组（NRG1β组）、激动剂组（SRT501组）、激动剂+治疗组（SRT501+NRG1β组）、抑制剂组（EX527组）和抑制剂+治疗组（EX527+NRG1β组）,每组30只。采用改良线栓法建立MCAO/R模型,线栓由颈外动脉插入颈内动脉18～22 mm,堵塞左侧大脑中动脉起始部。缺血2 h后,缓慢拔出线栓,恢复脑血流22 h。EX527(5 mg/kg)、SRT501(100 mg/kg)于术前30 min腹腔注射,NRG1β(2μg/kg)于拔出线栓后由微量注射器注入颈内动脉。脑缺血2 h、再灌注22 h后采用改良神经损伤严重程度评分（modi...     

普洛迪对局灶性脑缺血大鼠的神经保护作用研究

目的研究普洛迪对局灶性脑缺血大鼠的神经修复作用。方法采用Longa法制备SD大鼠大脑中动脉缺血模型(MCAO),分为:假手术组;持续缺血组;药物干预(普洛迪、金纳多、施普善)组。应用免疫组化法观察巢蛋白(Nestin)和神经元特异性烯醇化酶(NSE)的表达变化,并使用多媒体彩色病理图像分析系统进行定量分析;利用草酸-焦锑酸钾电镜细胞化学技术观察缺血脑组织的超微结构改变。结果药物干预组的病变明显轻于持续缺血组;其中,普洛迪(高剂量)组优于金纳多、施普善组。普洛迪(高剂量)组Nestin的表达升高最显著,NSE的表达下降程度最轻,且呈显著的普洛迪剂量依赖性。结论普洛迪可使缺血后Nestin表达上调,并减轻NSE表达下降程度,从而起到减轻缺血性脑损伤的作用。     

Role of lateral parabrachial opioid receptors in exercise-induced modulation of the hypotensive hemorrhage response in conscious male rats

Some of the benefits of exercise appear to be mediated through modulation of neuronal excitability in central autonomic control circuits. Previously, we identified that six weeks of voluntary wheel running had a protective effect during hemorrhage (HEM), limiting both the hypotensive phase of HEM and enhancing recovery. The present study was undertaken to evaluate the role of opioid release in the lateral parabrachial nucleus (LPBN) on the response to severe HEM in chronically exercised (EX, voluntary) versus sedentary (SED) controls. Male Sprague Dawley rats were allowed either free access to running wheels (EX) or normal cage conditions (SED). After 6 weeks of “training” animals were instrumented with a bilateral cannula directed toward the dorsolateral pons and arterial catheters. After a recovery period, animals underwent central microinjection of either vehicle (VEH; n = 3/group) or the opioid receptor antagonist naloxone (NAL; n = 6/group) followed by withdrawal of 30% of their total estimated blood volume. Following VEH injection, the drop in MAP during and following HEM was significantly attenuated in the EX vs SED animals. Alternatively, NAL microinjection in the dorsolateral pons (20 μM, 200-500 nl) reversed the beneficial effect of EX on the HEM response. NAL microinjection in SED rats did not significantly alter the response to HEM. These data suggest chronic voluntary EX has a beneficial effect on the autonomic response to severe HEM which is mediated, in part, via EX-induced plasticity of the opioid system within the dorsolateral pons.