AIM: To study the risks and benefits of intracerebroventricular(ICV) opiate pumps for the management of benign head and face pain.METHODS: SSix patients with refractory trigeminal neuralgia and/or cluster headaches we...AIM: To study the risks and benefits of intracerebroventricular(ICV) opiate pumps for the management of benign head and face pain.METHODS: SSix patients with refractory trigeminal neuralgia and/or cluster headaches were evaluated for implantation of an ICV opiate infusion pump using either ICV injections through an Ommaya reservoir or external ventricular drain. Four patients received morphine ICV pumps and two patient S received a hydromorphone pump. Of the Four patients with morphine ICV pumps, one patient had the medication changed to hydromorphone. Preoperative and post-operative visual analog scores(VAS) were obtained. Patients were evaluated post-operatively for a minimum of 3 mo and the pump dosage was adjusted at each outpatient clinic visit according to the patient's pain level.RESULTS: All 6 patients had an intracerebroventricular opiate injection trial period, using either an Ommaya reservoir or an external ventricular drain. There was an average VAS improvement of 75.8%. During the trial period, no complications were observed. Pump implantation was performed an average of 3.7 wk(range 1-7) after the trial injections. After implantation, an average of 20.7 ± 8.3 dose adjustments were made over 3-56 mo after surgery to achieve maximal pain relief. At the most recent follow-up(26.2 mo, range 3-56), VAS scores significantly improved from an average of 7.8 ± 0.5(range 6-10) to 2.8 ± 0.7(range 0-5) at the final dose(mean improvement 5.0 ± 1.0, P < 0.001). All patients required a stepwise increase in opiate infusion rates to achieve maximal benefit. The most common complications were nausea and drowsiness, both of which resolved with pump adjustments. On average, infusion pumps were replaced every 4-5 years.CONCLUSION: These results suggest that ICV delivery of opiates may potentially be a viable treatment option for patients with intractable pain from trigeminal neuralgia or cluster headache.展开更多
The nuclear factor-kB (NF-kB) is one member of a ubiquitously expressed family of Rel-related transcription factors that serve as critical regulators of proinflammatory genes. The immunomodulatory potential of thymuli...The nuclear factor-kB (NF-kB) is one member of a ubiquitously expressed family of Rel-related transcription factors that serve as critical regulators of proinflammatory genes. The immunomodulatory potential of thymulin and its effect on NF-kB in vivo, particularly in the central nervous system (CNS), is not well characterized. In this study, the role of endotoxin (ET) in regulating NF-kB was unraveled in various compartments of the CNS. Stereotaxic localization reverberated specific intracerebroventricular (ICV) injection of ET into the CNS, with or without pretreatment with ICV thymulin. Treatment with ET upregulated the expression and nuclear trans-localization of NF-kB1 (p50), NF-kB2 (p52), RelA (p65), RelB (p68) and c-Rel (p75) in the hippocampus (HC), an effect abrogated by ICV pretreatment with thymulin. Thymulin modulated the phosphorylation of IkB-a in the HC by upregulating the cytosolic accumulation of IkB-a and downregulating its phosphorylation (pIkB-a). Further analysis of the DNA-binding activity revealed an upregulated activity in the HC relative to saline-constitutive expression of the RelA (p65) subunit. ET did not induce the DNA-binding activity of NF-kB in the diencephalon (DE) or substantia nigra (SN) at various time points, when compared with baseline levels of expression. Intraperitoneal (IP) injections of ET in vivo upregulated the expression of NF-kB subunits in the liver and reduced the cytosolic accumulation of IkB-a by inducing pIkB-a. Furthermore, IP pretreatment with thymulin followed by ICV展开更多
Objective To investigate the pretreatment effects of Rhodiola rosea (R. rosea) extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer’s disease (AD...Objective To investigate the pretreatment effects of Rhodiola rosea (R. rosea) extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer’s disease (AD). Methods Male Sprague-Dawley rats were pretreated with R. rosea extract at doses of 1.5, 3.0, and 6.0 g/kg for 3 weeks, followed by bilateral intracerebroventricular injection with streptozotocin (1.5 mg/kg) on days 1 and 3. Behavioral alterations were monitored after 2 weeks from the lesion using Morris water maze task. Three weeks after the lesion, the rats were sacrificed for measuring the malondialdehyde (MDA), glutathione reductase (GR) and reduced glutathione (GSH) levels in hippocampus and histopathology of hippocampal neurons. Results The MDA level was significantly increased while the GR and GSH levels were significantly decreased with striking impairments in spatial learning and memory and severe damage to hippocampal neurons in the model rat induced by intracerebroventricular injection of streptozotocin. These abnormalities were significantly improved by pretreatment with R. rosea extract (3.0 g/kg). Conclusion R. rosea extract can protect rats against cognitive deficits, neuronal injury and oxidative stress induced by intracerebroventricular injection of streptozotocin, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD.展开更多
Apelin-13 inhibits neuronal apoptosis caused by hydrogen peroxide,yet apoptosis following cerebral ischemia-reperfusion injury has rarely been studied.In this study,Apelin-13(0.1 μg/g) was injected into the lateral v...Apelin-13 inhibits neuronal apoptosis caused by hydrogen peroxide,yet apoptosis following cerebral ischemia-reperfusion injury has rarely been studied.In this study,Apelin-13(0.1 μg/g) was injected into the lateral ventricle of middle cerebral artery occlusion model rats.TTC,TUNEL,and immunohistochemical staining showed that compared with the cerebral ischemia/reperfusion group,infarct volume and apoptotic cell number at the ischemic penumbra region were decreased in the Apelin-13 treatment group.Additionally,Apelin-13 treatment increased Bcl-2 immunoreactivity and decreased caspase-3 immunoreactivity.Our findings suggest that Apelin-13 is neuroprotective against cerebral ischemia/reperfusion injury through inhibition of neuronal apoptosis.展开更多
Parkinson's disease is a progressive neurological disease characterized by the degeneration of dopaminergic neurons in the substantia nigra.A highly similar pattern of neurodegeneration can be induced by 1-methyl-...Parkinson's disease is a progressive neurological disease characterized by the degeneration of dopaminergic neurons in the substantia nigra.A highly similar pattern of neurodegeneration can be induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) or 1-methyl-4-phenylpyridinium ion(MPP+),which cause the death of dopaminergic neurons.Administration of MPTP or MPP+ results in Parkinson's disease-like symptoms in rodents.However,it remains unclear whether intracerebroventricular MPP+ administration affects neurogenesis in the substantia nigra and subgranular zone or whether brain-derived neurotrophic factor alters the effects of MPP+.In this study,MPP+(100 nmol) was intracerebroventricularly injected into mice to model Parkinson's disease.At 7 days after administration,the number of bromodeoxyuridine(Brd U)-positive cells in the subgranular zone of the hippocampal dentate gyrus increased,indicating enhanced neurogenesis.In contrast,a reduction in Brd U-positive cells was detected in the substantia nigra.Administration of brain-derived neurotrophic factor(100 ng) 1 day after MPP+ administration attenuated the effect of MPP+ in the subgranular zone and the substantia nigra.These findings reveal the complex interaction between neurotrophic factors and neurotoxins in the Parkinsonian model that result in distinct effects on the catecholaminergic system and on neurogenesis in different brain regions.展开更多
目的观察中枢与外周β-内啡肽对缺血后心肌的影响及其在侧脑室吗啡预处理减轻大鼠心肌缺血/再灌注损伤中的含量变化,探讨β-内啡肽在中枢吗啡预处理在体大鼠缺血后心肌保护作用中的角色。方法66只♂SD大鼠,分别建立侧脑室微量注射和心...目的观察中枢与外周β-内啡肽对缺血后心肌的影响及其在侧脑室吗啡预处理减轻大鼠心肌缺血/再灌注损伤中的含量变化,探讨β-内啡肽在中枢吗啡预处理在体大鼠缺血后心肌保护作用中的角色。方法66只♂SD大鼠,分别建立侧脑室微量注射和心肌缺血/再灌注损伤动物模型。随机分为假手术(Sham)组、缺血对照(CON)组、缺血预处理(IPC)组、中枢和外周β-内啡肽激动剂(Icv/Iv-EP)组、中枢吗啡预处理(MPC组)、中枢β-内啡肽阻断剂(Icv-MPC-Anti-EP/Icv-Anti-EP-MPC)组、外周β-内啡肽阻断剂(Icv-MPC+Iv-Anti-EP)组、中枢和外周β-内啡肽阻断剂自身对照(Icv/Iv-Anti-EP)组。观察平均动脉压(MAP)、心率(HR)、压力心率乘积(RPP)、缺血危险区(AAR)、梗死区(IS)体积、IS/AAR等的变化;同时以免疫组化观察下丘脑弓状核(arcuate nucleus,ARC),中脑导水管周围灰质(periaque-ductalgray,PAG)及左室心肌(myocardium of left ventricle,MC)β-内啡肽的阳性表达。结果与CON组相比,IPC、MPC、Icv-EP、Iv-EP、Icv-Anti-EP-MPC、Icv-MPC+Iv-Anti-EP组均明显降低IS/AAR(P<0.01);Icv-MPC-Anti-EP组虽然取消MPC的保护效应(P<0.01),但较CON组差异仍有统计学意义(P<0.05);与CON组相比,MPC组减弱了ARC中β-内啡肽的阳性表达(P<0.05),同时明显增强PAG和左室心肌的免疫反应强度(P<0.05;P<0.01)。结论中枢与外周β-内啡肽对缺血后心肌损伤有保护作用;侧脑室吗啡预处理后可能促进下丘脑弓状核释放β-内啡肽,后者作为神经递质部分参与了中枢吗啡预处理介导的心肌保护效应。展开更多
文摘AIM: To study the risks and benefits of intracerebroventricular(ICV) opiate pumps for the management of benign head and face pain.METHODS: SSix patients with refractory trigeminal neuralgia and/or cluster headaches were evaluated for implantation of an ICV opiate infusion pump using either ICV injections through an Ommaya reservoir or external ventricular drain. Four patients received morphine ICV pumps and two patient S received a hydromorphone pump. Of the Four patients with morphine ICV pumps, one patient had the medication changed to hydromorphone. Preoperative and post-operative visual analog scores(VAS) were obtained. Patients were evaluated post-operatively for a minimum of 3 mo and the pump dosage was adjusted at each outpatient clinic visit according to the patient's pain level.RESULTS: All 6 patients had an intracerebroventricular opiate injection trial period, using either an Ommaya reservoir or an external ventricular drain. There was an average VAS improvement of 75.8%. During the trial period, no complications were observed. Pump implantation was performed an average of 3.7 wk(range 1-7) after the trial injections. After implantation, an average of 20.7 ± 8.3 dose adjustments were made over 3-56 mo after surgery to achieve maximal pain relief. At the most recent follow-up(26.2 mo, range 3-56), VAS scores significantly improved from an average of 7.8 ± 0.5(range 6-10) to 2.8 ± 0.7(range 0-5) at the final dose(mean improvement 5.0 ± 1.0, P < 0.001). All patients required a stepwise increase in opiate infusion rates to achieve maximal benefit. The most common complications were nausea and drowsiness, both of which resolved with pump adjustments. On average, infusion pumps were replaced every 4-5 years.CONCLUSION: These results suggest that ICV delivery of opiates may potentially be a viable treatment option for patients with intractable pain from trigeminal neuralgia or cluster headache.
文摘The nuclear factor-kB (NF-kB) is one member of a ubiquitously expressed family of Rel-related transcription factors that serve as critical regulators of proinflammatory genes. The immunomodulatory potential of thymulin and its effect on NF-kB in vivo, particularly in the central nervous system (CNS), is not well characterized. In this study, the role of endotoxin (ET) in regulating NF-kB was unraveled in various compartments of the CNS. Stereotaxic localization reverberated specific intracerebroventricular (ICV) injection of ET into the CNS, with or without pretreatment with ICV thymulin. Treatment with ET upregulated the expression and nuclear trans-localization of NF-kB1 (p50), NF-kB2 (p52), RelA (p65), RelB (p68) and c-Rel (p75) in the hippocampus (HC), an effect abrogated by ICV pretreatment with thymulin. Thymulin modulated the phosphorylation of IkB-a in the HC by upregulating the cytosolic accumulation of IkB-a and downregulating its phosphorylation (pIkB-a). Further analysis of the DNA-binding activity revealed an upregulated activity in the HC relative to saline-constitutive expression of the RelA (p65) subunit. ET did not induce the DNA-binding activity of NF-kB in the diencephalon (DE) or substantia nigra (SN) at various time points, when compared with baseline levels of expression. Intraperitoneal (IP) injections of ET in vivo upregulated the expression of NF-kB subunits in the liver and reduced the cytosolic accumulation of IkB-a by inducing pIkB-a. Furthermore, IP pretreatment with thymulin followed by ICV
文摘Objective To investigate the pretreatment effects of Rhodiola rosea (R. rosea) extract on cognitive dysfunction, oxidative stress in hippocampus and hippocampal neuron injury in a rat model of Alzheimer’s disease (AD). Methods Male Sprague-Dawley rats were pretreated with R. rosea extract at doses of 1.5, 3.0, and 6.0 g/kg for 3 weeks, followed by bilateral intracerebroventricular injection with streptozotocin (1.5 mg/kg) on days 1 and 3. Behavioral alterations were monitored after 2 weeks from the lesion using Morris water maze task. Three weeks after the lesion, the rats were sacrificed for measuring the malondialdehyde (MDA), glutathione reductase (GR) and reduced glutathione (GSH) levels in hippocampus and histopathology of hippocampal neurons. Results The MDA level was significantly increased while the GR and GSH levels were significantly decreased with striking impairments in spatial learning and memory and severe damage to hippocampal neurons in the model rat induced by intracerebroventricular injection of streptozotocin. These abnormalities were significantly improved by pretreatment with R. rosea extract (3.0 g/kg). Conclusion R. rosea extract can protect rats against cognitive deficits, neuronal injury and oxidative stress induced by intracerebroventricular injection of streptozotocin, and may be used as a potential agent in treatment of neurodegenerative diseases such as AD.
基金supported by the National Natural Science Foundation of China,No.30971081,31271243,81070961 and 81241052the Natural Science Foundation of Shandong Province of China,No.ZR2011CM027 and 2012GGA08100
文摘Apelin-13 inhibits neuronal apoptosis caused by hydrogen peroxide,yet apoptosis following cerebral ischemia-reperfusion injury has rarely been studied.In this study,Apelin-13(0.1 μg/g) was injected into the lateral ventricle of middle cerebral artery occlusion model rats.TTC,TUNEL,and immunohistochemical staining showed that compared with the cerebral ischemia/reperfusion group,infarct volume and apoptotic cell number at the ischemic penumbra region were decreased in the Apelin-13 treatment group.Additionally,Apelin-13 treatment increased Bcl-2 immunoreactivity and decreased caspase-3 immunoreactivity.Our findings suggest that Apelin-13 is neuroprotective against cerebral ischemia/reperfusion injury through inhibition of neuronal apoptosis.
基金supported by the National Natural Science Foundation of China,No.31320103906(to TB)
文摘Parkinson's disease is a progressive neurological disease characterized by the degeneration of dopaminergic neurons in the substantia nigra.A highly similar pattern of neurodegeneration can be induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP) or 1-methyl-4-phenylpyridinium ion(MPP+),which cause the death of dopaminergic neurons.Administration of MPTP or MPP+ results in Parkinson's disease-like symptoms in rodents.However,it remains unclear whether intracerebroventricular MPP+ administration affects neurogenesis in the substantia nigra and subgranular zone or whether brain-derived neurotrophic factor alters the effects of MPP+.In this study,MPP+(100 nmol) was intracerebroventricularly injected into mice to model Parkinson's disease.At 7 days after administration,the number of bromodeoxyuridine(Brd U)-positive cells in the subgranular zone of the hippocampal dentate gyrus increased,indicating enhanced neurogenesis.In contrast,a reduction in Brd U-positive cells was detected in the substantia nigra.Administration of brain-derived neurotrophic factor(100 ng) 1 day after MPP+ administration attenuated the effect of MPP+ in the subgranular zone and the substantia nigra.These findings reveal the complex interaction between neurotrophic factors and neurotoxins in the Parkinsonian model that result in distinct effects on the catecholaminergic system and on neurogenesis in different brain regions.
文摘目的观察中枢与外周β-内啡肽对缺血后心肌的影响及其在侧脑室吗啡预处理减轻大鼠心肌缺血/再灌注损伤中的含量变化,探讨β-内啡肽在中枢吗啡预处理在体大鼠缺血后心肌保护作用中的角色。方法66只♂SD大鼠,分别建立侧脑室微量注射和心肌缺血/再灌注损伤动物模型。随机分为假手术(Sham)组、缺血对照(CON)组、缺血预处理(IPC)组、中枢和外周β-内啡肽激动剂(Icv/Iv-EP)组、中枢吗啡预处理(MPC组)、中枢β-内啡肽阻断剂(Icv-MPC-Anti-EP/Icv-Anti-EP-MPC)组、外周β-内啡肽阻断剂(Icv-MPC+Iv-Anti-EP)组、中枢和外周β-内啡肽阻断剂自身对照(Icv/Iv-Anti-EP)组。观察平均动脉压(MAP)、心率(HR)、压力心率乘积(RPP)、缺血危险区(AAR)、梗死区(IS)体积、IS/AAR等的变化;同时以免疫组化观察下丘脑弓状核(arcuate nucleus,ARC),中脑导水管周围灰质(periaque-ductalgray,PAG)及左室心肌(myocardium of left ventricle,MC)β-内啡肽的阳性表达。结果与CON组相比,IPC、MPC、Icv-EP、Iv-EP、Icv-Anti-EP-MPC、Icv-MPC+Iv-Anti-EP组均明显降低IS/AAR(P<0.01);Icv-MPC-Anti-EP组虽然取消MPC的保护效应(P<0.01),但较CON组差异仍有统计学意义(P<0.05);与CON组相比,MPC组减弱了ARC中β-内啡肽的阳性表达(P<0.05),同时明显增强PAG和左室心肌的免疫反应强度(P<0.05;P<0.01)。结论中枢与外周β-内啡肽对缺血后心肌损伤有保护作用;侧脑室吗啡预处理后可能促进下丘脑弓状核释放β-内啡肽,后者作为神经递质部分参与了中枢吗啡预处理介导的心肌保护效应。
