Patients with liver disease may present hepatic enceph- alopathy (HE), a complex neuropsychiatric syndrome covering a wide range of neurological alterations, including cognitive and motor disturbances. HE reduces the ...Patients with liver disease may present hepatic enceph- alopathy (HE), a complex neuropsychiatric syndrome covering a wide range of neurological alterations, including cognitive and motor disturbances. HE reduces the quality of life of the patients and is associated with poor prognosis. In the worse cases HE may lead to coma or death. The mechanisms leading to HE which are not well known are being studied using animal models. The neurological alterations in HE are a consequence of impaired cerebral function mainly due to alterations in neurotransmission. We review here some studies indicating that alterations in neurotransmission associated to different types of glutamate receptors are responsible for some of the cognitive and motor alterations present in HE. These studies show that the function of the signal transduction pathway glutamate-nitric oxide-cGMP associated to the NMDA type of glutamate receptors is impaired in brain in vivo in HE animal models as well as in brain of patients died of HE. Activation of NMDA receptors in brain activates this pathway and increases cGMP. In animal models of HE this increase in cGMP induced by activation of NMDA receptors is reduced, which is responsible for the impairment in learning ability in these animal models. Increasing cGMP by pharmacological means restores learning ability in rats with HE and may be a new therapeutic approach to improve cognitive function in patients with HE. However, it is necessary to previously assess the possible secondary effects.Patients with HE may present psychomotor slowing, hypokinesia and bradykinesia. Animal models of HE also show hypolocomotion. It has been shown in rats with HE that hypolocomotion is due to excessive activation of metabotropic glutamate receptors (mGluRs) in substantia nigra pars reticulata. Blocking mGluR1 in this brain area normalizes motor activity in the rats, suggesting that a similar treatment for patients with HE could be useful to treat psychomotor slowing and hypokinesia. However, the possible secondary effects of mGluR1 antagonists should be previously evaluated. These studies are setting the basis for designing therapeutic procedures to specifically treat the individual neurological alterations in patients with HE.展开更多
目的观察机械通气联合丹参多酚酸治疗重症颅脑损伤患者临床疗效,及其对患者神经功能及结局的影响。方法选取2016年3月-2019年6月于邯钢医院治疗的重症颅脑损伤患者65例,按照随机数字表法分为对照组(n=33例)和观察组(n=32例)。所有患者...目的观察机械通气联合丹参多酚酸治疗重症颅脑损伤患者临床疗效,及其对患者神经功能及结局的影响。方法选取2016年3月-2019年6月于邯钢医院治疗的重症颅脑损伤患者65例,按照随机数字表法分为对照组(n=33例)和观察组(n=32例)。所有患者均给予常规重型颅脑损伤治疗(例如脱水、激素、防感染及营养支持等)及对应的手术治疗。两组患者均在损伤后及手术后立即给予机械通气。观察组在对照组基础上给予丹参多酚酸盐。比较两组患者临床疗效;比较两组患者治疗前后美国国立卫生研究院卒中量表(National Institute of Health stroke scale,NIHSS)评分、神经功能重建相关因子[脑源性神经营养因子(brain-derived neurotrophic fac⁃tor,BDNF)及神经生长因子(nerve growth factor,NGF)水平]、凝血因子[纤维蛋白原(fibrinogen,FIB)、凝血酶时间(thrombin time,TT)、凝血酶原时间(prothrombin time,PT)、活化部分凝血酶原时间(activated partial prothrombin time,APTT)];比较两组患者预后情况。结果观察组的临床总有效率为93.75%,高于对照组的75.76%(χ^(2)=4.730,P=0.030)。治疗前,两组患者NIHSS评分、NGF、BDNF、PT、APTT、FIB、TT无差异(P≥0.05)。治疗后6个月,观察组NIHSS评分低于对照组(t=2.551,P=0.014)。治疗2周后,观察组NGF、BDNF及FIB水平高于对照组(t=12.048,P=0.000;t=8.389,P=0.000;t=6.574,P=0.000);TT水平低于对照组(t=2.891,P=0.000);两组患者PT、APTT水平无差异(P≥0.05)。两组患者轻度残疾率及死亡率无差异(P≥0.05);观察组的重度残疾率低于对照组(χ^(2)=4.920,P=0.027),恢复良好率高于对照组(χ^(2)=4.480,P=0.034)。结论机械通气联合丹参多酚酸盐治疗重症颅脑损伤具有良好的临床疗效,可以改善患者的神经功能,改善凝血功能,改善患者预后。展开更多
基金Supported by grants from the Ministerio de Ciencia y Tecnología, No. SAF2002-00851 and SAF2005-06089 and from Ministerio de Sanidad, No. Red G03-155 and PI050253 of Spain and by grants from Consellería de Empresa, Universidad y Ciencia, and de Sanidad, Generalitat Valenciana, No. Grupos03/001, GV04B-055, GV04B-012, GVS05/082 and ACOMP06/005 and AP-005/06
文摘Patients with liver disease may present hepatic enceph- alopathy (HE), a complex neuropsychiatric syndrome covering a wide range of neurological alterations, including cognitive and motor disturbances. HE reduces the quality of life of the patients and is associated with poor prognosis. In the worse cases HE may lead to coma or death. The mechanisms leading to HE which are not well known are being studied using animal models. The neurological alterations in HE are a consequence of impaired cerebral function mainly due to alterations in neurotransmission. We review here some studies indicating that alterations in neurotransmission associated to different types of glutamate receptors are responsible for some of the cognitive and motor alterations present in HE. These studies show that the function of the signal transduction pathway glutamate-nitric oxide-cGMP associated to the NMDA type of glutamate receptors is impaired in brain in vivo in HE animal models as well as in brain of patients died of HE. Activation of NMDA receptors in brain activates this pathway and increases cGMP. In animal models of HE this increase in cGMP induced by activation of NMDA receptors is reduced, which is responsible for the impairment in learning ability in these animal models. Increasing cGMP by pharmacological means restores learning ability in rats with HE and may be a new therapeutic approach to improve cognitive function in patients with HE. However, it is necessary to previously assess the possible secondary effects.Patients with HE may present psychomotor slowing, hypokinesia and bradykinesia. Animal models of HE also show hypolocomotion. It has been shown in rats with HE that hypolocomotion is due to excessive activation of metabotropic glutamate receptors (mGluRs) in substantia nigra pars reticulata. Blocking mGluR1 in this brain area normalizes motor activity in the rats, suggesting that a similar treatment for patients with HE could be useful to treat psychomotor slowing and hypokinesia. However, the possible secondary effects of mGluR1 antagonists should be previously evaluated. These studies are setting the basis for designing therapeutic procedures to specifically treat the individual neurological alterations in patients with HE.
文摘目的观察机械通气联合丹参多酚酸治疗重症颅脑损伤患者临床疗效,及其对患者神经功能及结局的影响。方法选取2016年3月-2019年6月于邯钢医院治疗的重症颅脑损伤患者65例,按照随机数字表法分为对照组(n=33例)和观察组(n=32例)。所有患者均给予常规重型颅脑损伤治疗(例如脱水、激素、防感染及营养支持等)及对应的手术治疗。两组患者均在损伤后及手术后立即给予机械通气。观察组在对照组基础上给予丹参多酚酸盐。比较两组患者临床疗效;比较两组患者治疗前后美国国立卫生研究院卒中量表(National Institute of Health stroke scale,NIHSS)评分、神经功能重建相关因子[脑源性神经营养因子(brain-derived neurotrophic fac⁃tor,BDNF)及神经生长因子(nerve growth factor,NGF)水平]、凝血因子[纤维蛋白原(fibrinogen,FIB)、凝血酶时间(thrombin time,TT)、凝血酶原时间(prothrombin time,PT)、活化部分凝血酶原时间(activated partial prothrombin time,APTT)];比较两组患者预后情况。结果观察组的临床总有效率为93.75%,高于对照组的75.76%(χ^(2)=4.730,P=0.030)。治疗前,两组患者NIHSS评分、NGF、BDNF、PT、APTT、FIB、TT无差异(P≥0.05)。治疗后6个月,观察组NIHSS评分低于对照组(t=2.551,P=0.014)。治疗2周后,观察组NGF、BDNF及FIB水平高于对照组(t=12.048,P=0.000;t=8.389,P=0.000;t=6.574,P=0.000);TT水平低于对照组(t=2.891,P=0.000);两组患者PT、APTT水平无差异(P≥0.05)。两组患者轻度残疾率及死亡率无差异(P≥0.05);观察组的重度残疾率低于对照组(χ^(2)=4.920,P=0.027),恢复良好率高于对照组(χ^(2)=4.480,P=0.034)。结论机械通气联合丹参多酚酸盐治疗重症颅脑损伤具有良好的临床疗效,可以改善患者的神经功能,改善凝血功能,改善患者预后。
