RESUMEN
Delayed cerebral infarction (DCI) contributes to the burden of morbidity and mortality acquired by patients with aneurysmal subarachnoid hemorrhage (SAH). Cisternal lavage may prevent DCI. Delivery of lavage therapy to the basal cisterns, however, is challenging. Here, we report a novel method for the delivery of cisternal lavage using a cisterno-ventricular catheter (CVC) inserted via the fenestrated lamina terminalis during aneurysm clipping. In two high-risk aSAH patients a CVC was inserted into the third ventricle through the fenestrated lamina terminalis during aneurysm clipping. Post-operatively, continuous cisternal lavage using Urokinase or Nimodipine was applied using an external ventricular drain (EVD) as inflow tract and the CVC as outflow tract. Neurological outcome at 6â¯months was assessed by modified Rankin scale. Catheter placement into the third ventricle through the fenestrated lamina terminalis was performed without complications. Application of a free-running electrolyte solution containing Urokinase or Nimodipine via the EVD and drainage via the CVC was feasible. Cisternal Nimodipine application normalized sonographic vasospasm in both cases. DCI did not occur. CVC placement for ventriculo-cisternal lavage may represent a useful method for DCI prevention. It can be considered in aSAH patients at risk for DCI if the chiasmatic region is accessed during aneurysm clipping.
Asunto(s)
Infarto Cerebral/prevención & control , Hemorragia Subaracnoidea/complicaciones , Hemorragia Subaracnoidea/cirugía , Irrigación Terapéutica/métodos , Ventriculostomía/métodos , Catéteres , Infarto Cerebral/etiología , Procedimientos Endovasculares/métodos , Femenino , Humanos , Hipotálamo/cirugía , Masculino , Persona de Mediana Edad , Irrigación Terapéutica/instrumentación , Tercer Ventrículo/cirugía , Vasoespasmo Intracraneal/etiología , Vasoespasmo Intracraneal/prevención & controlRESUMEN
Delayed Cerebral Infarction (DCI) due to Cerebral Vasospasm (CVS) is an important contributor to poor outcome after aneurysmal subarachnoid haemorrhage (aSAH). Despite established risk factors CVS and DCI are unpredictable at the individual patient level. Efficient treatments are lacking. We report a novel rescue therapy for DCI: Access to the basal cisterns by stereotactic catheter ventriculocisternostomy (STX-VCS) and direct cisternal application of the spasmolytic agent Nimodipine. On the basis of individual treatment decisions three aSAH patients who developed CVS underwent STX-VCS. Continuous lavage with Nimodipine was performed. CVS was assessed by daily transcranial doppler ultrasonography. Neurological outcome at 3â¯months was assessed by modified Rankin scale. STX-VCS was performed without complications in all patients. CVS rapidly resolved upon cisternal application of Nimodipine. CVS recurred in two patients upon interruption of Nimodpine application and resolved upon restart of Nimodipine. DCI did not occur in all three cases. STX-VCS and cisternal Nimodipine application is a novel rescue therapy for CVS treatment and DCI-prevention in patients with aSAH.
Asunto(s)
Infarto Cerebral/prevención & control , Nimodipina/administración & dosificación , Vasodilatadores/administración & dosificación , Vasoespasmo Intracraneal/tratamiento farmacológico , Ventriculostomía/métodos , Catéteres , Infarto Cerebral/etiología , Femenino , Humanos , Imagenología Tridimensional , Masculino , Persona de Mediana Edad , Técnicas Estereotáxicas , Hemorragia Subaracnoidea/complicaciones , Ultrasonografía Doppler Transcraneal , Vasoespasmo Intracraneal/etiologíaRESUMEN
BACKGROUND: Acupuncture is a traditional method that has been widely used in various fields of medicine with therapeutic effect. However, evidence of effectiveness to support the application of electroacupuncture (EA) during the process of ischaemia is scarce. OBJECTIVES: To investigate dynamic changes in hypoxia-inducible factor (HIF)-1α expression as well as its association with neurological status in rats subjected to acute ischaemic stroke and EA intervention. METHODS: Forty adult male rats were randomly divided into three groups that received sham surgery (Control group, n=10) or underwent middle cerebral artery occlusion and EA (MCAO+EA group, n=15) or minimal acupuncture as a control treatment (MCAO+MA group, n=15). The rats in the MCAO+EA and MCAO+MA groups received EA or acupuncture without any electrical current, respectively, during 90 min of ischaemia. Rats in the Control group received the same surgical procedure but without MCAO. EA involved electrical stimulation of needles inserted into the quadriceps at 50 Hz frequency and 3 mA current intensity. Neurological status was evaluated on postoperative day 1, and cerebral infarction volume (IV) and HIF-1α expression 24 hours later. RESULTS: Neurological scores were improved and cerebral IV was decreased in the MCAO+EA group compared to the MCAO+MA group (both p<0.05). Moreover, HIF-1α expression was higher in the MCAO+EA group versus the MCAO+MA group (p<0.05). CONCLUSIONS: EA enhanced recovery of neurological function, decreased cerebral IV and increased HIF-1α expression in ischaemic rats. Further research is needed to determine whether EA is effective for stroke treatment through the stimulation of muscle contraction.
Asunto(s)
Isquemia Encefálica/terapia , Encéfalo , Electroacupuntura , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Accidente Cerebrovascular/terapia , Puntos de Acupuntura , Terapia por Acupuntura , Animales , Encéfalo/metabolismo , Encéfalo/patología , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Infarto Cerebral/prevención & control , Modelos Animales de Enfermedad , Hipoxia , Masculino , Contracción Muscular , Músculo Esquelético , Examen Neurológico , Fármacos Neuroprotectores , Ratas Sprague-Dawley , Accidente Cerebrovascular/metabolismo , Accidente Cerebrovascular/patología , Resultado del Tratamiento , Regulación hacia ArribaRESUMEN
OBJECTIVE: Occurrence of cerebral vasospasm after onset of aneurysmal subarachnoid hemorrhage (SAH) is a critical factor determining clinical prognosis. Eicosapentaenoic acid and docosahexaenoic acid, both ω-3 fatty acids (ω-3FA), can suppress cerebral vasospasm, and docosahexaenoic acid can relax vessel vasoconstriction and have neuroprotective effects. We investigated whether administration of ω-3FA prevented cerebral vasospasm occurrence and improved clinical outcomes after aneurysmal SAH. METHODS: From 2012 to 2015, 100 consecutive patients with aneurysmal SAH were divided into 2 periods. Between 2012 and 2013 (control period), 45 patients received standard management. Between 2014 and 2015 (ω-3FA period), 55 patients were prospectively treated with additional ω-3FA. Occurrence of cerebral vasospasm, occurrence of cerebral infarction caused by vasospasm, and modified Rankin Scale scores at 30 days and 90 days after onset of SAH for each period were evaluated and compared. RESULTS: The frequency of angiographic cerebral vasospasm in the ω-3FA period was significantly lower than in the control period (12 patients vs. 23 patients, P = 0.004). The frequency of new infarction caused by vasospasm in the ω-3FA period was also significantly lower than in the control period (5 patients vs. 14 patients, P = 0.011). There was a significant difference in modified Rankin Scale scores at 90 days after onset of SAH between the groups (P = 0.031). No adverse events were associated with ω-3FA administration. CONCLUSIONS: Administration of ω-3FA after aneurysmal SAH may reduce the frequency of cerebral vasospasm and may improve clinical outcomes.
Asunto(s)
Infarto Cerebral/prevención & control , Ácidos Docosahexaenoicos/uso terapéutico , Ácido Eicosapentaenoico/uso terapéutico , Ácidos Grasos Omega-3/uso terapéutico , Hemorragia Subaracnoidea/tratamiento farmacológico , Vasoespasmo Intracraneal/prevención & control , Adulto , Anciano , Anciano de 80 o más Años , Angiografía de Substracción Digital , Ácido Araquidónico/sangre , Estudios de Casos y Controles , Angiografía Cerebral , Infarto Cerebral/diagnóstico por imagen , Infarto Cerebral/etiología , Cromatografía de Gases , Ácidos Docosahexaenoicos/sangre , Ácido Eicosapentaenoico/sangre , Ésteres , Femenino , Estudio Históricamente Controlado , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Estudios Prospectivos , Estudios Retrospectivos , Ultrasonografía Doppler Transcraneal , Vasoespasmo Intracraneal/complicaciones , Vasoespasmo Intracraneal/diagnóstico por imagenRESUMEN
BACKGROUND: Salidroside is a biologically active compound derived from Rhodiola rosea L. Studies showed that salidroside after i.v. injection is extensively metabolized to p-tyrosol and only trace amounts of salidroside are found in the brain tissue. OBJECTIVE: The aim of the study was to investigate the neuroprotective effects of p-tyrosol in the global cerebral ischemia-reperfusion (GCI) model. STUDY DESIGN: A total of 103 Wistar rats were assigned to groups of sham-operated (n=10), control (n=42), p-tyrosol-treated (n=36), and pentoxifylline-treated (n=15) animals. The rats of control, p-tyrosol-treated, and pentoxifylline-treated groups received intravenously 0.9% NaCl solution, 2% solution of p-tyrosol in doses of 5mg/kg, 10mg/kg, and 20mg/kg, and pentoxifylline in a dose of 100mg/kg, respectively, daily for 5 days. Rats were examined at days 1, 3, and 5 after GCI. After evaluation of neurological deficit, animals were euthanized for morphological and biochemical characterization. METHODS: Rats of control, p-tyrosol-treated, and pentoxifylline-treated groups were exposed to three-vessel model of GCI. Neurological deficit, numeric density of neurons in hippocampal CA1 region, and percentage of neurons with focal and total chromatolysis were studied. Biochemical study assessed contents of conjugated dienes and fluorescent products in brain homogenate. RESULTS: In control group, only 50.0% of rats survived by day 5 after the GCI; 38.1% of survived animals had severe neurologic deficit. In brain tissue of PTX-treated rats, the levels of diene conjugates and fluorescent products were 79% and 73%, respectivley, at day 5 compared with control. Differences in diene conjugates were statistically significant compared with control. The survival rate of animals treated with 20mg/kg p-tyrosol was 82.3% at day 5 after GCI. In p-tyrosol-treated GCI rats, the numeric density of neurons in the hippocampal CA1 region was higher by 31% compared with control. The percentage of neurons with focal and total chromatolysis decreased by 27% and 43%, respectively. At day 5 after GCI, the levels of conjugated dienes and fluorescent products were significantly lower (by 37% and 45%, respectively) in group of animals treated with 20mg/kg p-tyrosol compared with control. Moderate neuroprotective effects of 5mg/kg p-tyrosol administration were documented only at day 5 after GCI. In case of 10mg/kg p-tyrosol administration, neuroprotection was documented sooner: at day 1 or 3 after GCI. However, administration of 5 and 10mg/kg p-tyrosol did not affect animal survival. CONCLUSION: Course administration of intravenous p-tyrosol in a dose of 20mg/kg increased survival, reduced neurological deficit after GCI, attenuated neuronal damage in the hippocampus, and attenuated lipid peroxidation in brain tissue in animals subject to GCI with reperfusion.
Asunto(s)
Isquemia Encefálica/prevención & control , Fármacos Neuroprotectores/farmacología , Alcohol Feniletílico/análogos & derivados , Daño por Reperfusión/prevención & control , Animales , Antioxidantes/farmacología , Conducta Animal/efectos de los fármacos , Isquemia Encefálica/patología , Isquemia Encefálica/psicología , Región CA1 Hipocampal/efectos de los fármacos , Región CA1 Hipocampal/patología , Infarto Cerebral/patología , Infarto Cerebral/prevención & control , Actividad Motora/efectos de los fármacos , Neuronas/efectos de los fármacos , Pentoxifilina/farmacología , Alcohol Feniletílico/farmacología , Ratas , Ratas Wistar , Daño por Reperfusión/patología , Daño por Reperfusión/psicología , Vasodilatadores/farmacologíaRESUMEN
Tilia americana var. mexicana (T. americana) is a plant widely used in Mexico for its medicinal properties on the central nervous system. In the present study, we designed a protocol to investigate the neuroprotective effects of non-polar and polar extracts of T. americana on damage induced by cerebral ischaemia in mice. Vehicle or extracts were administered immediately after ischaemia. Functional neurological deficit, survival percentage and infarct area were determined in each experimental group. Results showed that groups treated with non-polar or polar extracts of T. americana had increased survival rate, improved neurological deficits and diminished the infarct area in relation to the ischaemic group. In conclusion, this study confirms the neuroprotective activity of T. americana, suggests a possible synergism between non-polar and polar constituents and supports its potential as a useful aid in the clinical management of stroke.
Asunto(s)
Isquemia Encefálica/prevención & control , Fármacos Neuroprotectores/farmacología , Tilia/química , Animales , Isquemia Encefálica/mortalidad , Isquemia Encefálica/patología , Infarto Cerebral/patología , Infarto Cerebral/prevención & control , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Hexanos , Ratones , Enfermedades del Sistema Nervioso/prevención & control , Enfermedades del Sistema Nervioso/psicología , Fármacos Neuroprotectores/química , Extractos Vegetales/farmacología , Solventes , Análisis de Supervivencia , AguaRESUMEN
OBJECTIVE: The aim of this study was to evaluate the possible beneficial effects of Mentat against transient global ischemia and reperfusion-induced brain injury in rats. METHODS: The neuroprotective effects of Mentat were evaluated against transient global ischemia and reperfusion (I/R)-induced brain injury in rats. Various neurobehavioral and biochemical parameters were assessed, followed by morphologic and histopathologic evaluation of brain tissue to conclude the protective effect of Mentat. Additionally, in vitro antioxidant assays were performed to explore the antioxidant capacity of Mentat and detailed liquid chromatography-mass spectrometry (LC-MS/MS) profiling was carried out to identify the active phytoconstituents responsible for the protective effects of Mentat. RESULTS: Sixty minutes of transient global ischemia followed by 24 h reperfusion (I/R) caused significant alterations in the cognitive and neurologic functions in the ischemia control group (P < 0.01) compared with the sham control. Furthermore, 2,3,5-triphenyltetrazolium chloride staining of the ischemia control group showed 20.85% ± 0.39% of cerebral infarct area (P < 0.01), increased brain volume (% edema 17.81% ± 1.576%; P < 0.01), and increased lipid peroxidation (P < 0.01) in the brain homogenate. Additionally, the histopathology of the ischemia control group showed severe brain injury compared with the sham control group. Interestingly, pretreatment with Mentat (250 and 500 mg/kg, p.o.) and quercetin (20 mg/kg, p.o.) for 7 d has alleviated all pathological changes observed due to I/R injury. Mentat also showed very good antioxidant activity in in vitro assays (2,2-diphenyl-l-picrylhydrazyl, ferric-reducing antioxidant power, and oxygen radical absorbance capacity assays). Furthermore, the detailed LC-MS/MS analysis of Mentat was performed and enclosed for identifying the actives responsible for its protective effects. CONCLUSIONS: These findings suggest that Mentat is a neuroprotective agent that may be a useful adjunct in the management of ischemic stroke and its rehabilitation especially with respect to associated memory impairment and other related neurologic conditions.
Asunto(s)
Infarto Cerebral/prevención & control , Ataque Isquémico Transitorio/tratamiento farmacológico , Peroxidación de Lípido/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Extractos Vegetales/farmacología , Daño por Reperfusión/prevención & control , Animales , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Edema Encefálico/tratamiento farmacológico , Edema Encefálico/etiología , Infarto Cerebral/etiología , Infarto Cerebral/patología , Cromatografía Liquida/métodos , Modelos Animales de Enfermedad , Ataque Isquémico Transitorio/complicaciones , Ataque Isquémico Transitorio/patología , Masculino , Espectrometría de Masas/métodos , Fármacos Neuroprotectores/administración & dosificación , Extractos Vegetales/administración & dosificación , Quercetina/administración & dosificación , Quercetina/farmacología , Ratas , Ratas Wistar , Daño por Reperfusión/etiología , Daño por Reperfusión/patología , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: In this study, we investigated the neuroprotective effect of the hairy root extract of Angelica gigas NAKAI (Angelica Gigantis Radix) on transient focal cerebral ischemia in rats through the regulation of angiogenesis molecules. METHODS: Male Sprague-Dawley rats were induced focal cerebral ischemia by a transient middle cerebral artery occlusion (tMCAO) for 90 min, and then orally administrated with the water extract of A. gigas hairy roots (AG). After 24 h reperfusion, infarction volume and the changes of BBB permeability were measured by TTC and Evans Blue (EB) staining. The neuronal cell damage and the activation of glial cells were assessed by immunohistochemistry in the ischemic brain. The expression of angiogenesis-induced proteins such as angiopoietin-1 (Ang-1), and vascular endothelial growth factor (VEGF), inflammatory protein such as intercellular adhesion molecule-1 (CAM-1), tight junction proteins such as ZO-1, and Occludin and the phosphorylation of phosphatidylinositol 3-kinase (PI3K)/AKT were determined in the ischemic brains by Western blot, respectively. RESULTS: The treatment of AG extract significantly decreased the volumes of brain infarction, and edema in MACO-induced ischemic rats. AG extract decreased the increase of BBB permeability, and neuronal death and inhibited the activation of astrocytes and microglia in ischemic brains. AG extract also significantly increased the expression of Ang-1, Tie-2, VEGF, ZO-1 and Occludin through activation of the PI3K/Akt pathway. AG extract significantly increased the expression of ICAM-1 in ischemic brains. CONCLUSIONS: Our results indicate that the hairy root of AG has a neuroprotective effect in ischemic stroke.
Asunto(s)
Angelica , Angiopoyetina 1/metabolismo , Ataque Isquémico Transitorio/tratamiento farmacológico , Neovascularización Fisiológica/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Fitoterapia , Accidente Cerebrovascular/metabolismo , Animales , Astrocitos , Barrera Hematoencefálica/efectos de los fármacos , Encéfalo/metabolismo , Infarto Cerebral/prevención & control , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Molécula 1 de Adhesión Intercelular/metabolismo , Ataque Isquémico Transitorio/metabolismo , Ataque Isquémico Transitorio/patología , Masculino , Fármacos Neuroprotectores/farmacología , Ocludina/metabolismo , Permeabilidad , Fosfatidilinositol 3-Quinasas/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Sprague-Dawley , Accidente Cerebrovascular/tratamiento farmacológico , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
AIMS: Ginsenoside-Rg1 (G-Rg1), a saponin that is a primary component of ginseng, is very useful and important in traditional Chinese medicine for stroke. The objective of this study was to explore the mechanisms underlying the neuroprotective effect of G-Rg1 on focal cerebral ischemia/reperfusion. MAIN METHODS: Focal cerebral ischemia was induced by middle cerebral artery occlusion. Neurological examinations were performed by using Longa's 5-point scale. The brain infarct volume was determined by the 2,3,5-triphenyltetrazolium chloride staining. The permeability of the blood-brain barrier (BBB) was evaluated by Evans blue dye. Western blot and quantitative RT-PCR were used to assess protease-activated receptor-1 (PAR-1) expression. KEY FINDINGS: After G-Rg1 treatment, there was a significant decrease in the neurobehavioral function score compared with normal saline (NS) treatment after ischemia/reperfusion (P<0.05). G-Rg1 significantly reduced the infarct volume compared with NS treatment after ischemia/reperfusion (P<0.001). The permeability of the BBB was significantly decreased in the G-Rg1 group compared with the NS group (P<0.05 or P<0.01). Western blot and quantitative real time RT-PCR indicated that G-Rg1 administration down-regulated the expression of PAR-1 in the ischemic hemisphere compared with NS administration (P<0.01 and P<0.05, respectively). The level of PAR-1 expression strongly correlated with BBB permeability in both the G-Rg1- and NS-treated rats (r=0.856 and r=0.908, respectively, P<0.01). SIGNIFICANCE: G-Rg1 may ameliorate the neurological injury, the brain infarct volume and the BBB permeability induced by focal cerebral ischemia in rats and its neuroprotective mechanism is related to the down-regulation of PAR-1 expression.
Asunto(s)
Ginsenósidos/farmacología , Fármacos Neuroprotectores/farmacología , Receptor PAR-1/antagonistas & inhibidores , Daño por Reperfusión/prevención & control , Animales , Conducta Animal/efectos de los fármacos , Barrera Hematoencefálica/efectos de los fármacos , Infarto Cerebral/patología , Infarto Cerebral/prevención & control , Regulación hacia Abajo/efectos de los fármacos , Masculino , Ratas , Ratas Sprague-Dawley , Receptor PAR-1/biosíntesisRESUMEN
BACKGROUND: To investigate the effects and potential mechanism of electroacupuncture intervention on expressions of Angiotensin II and its receptors-mediated signaling pathway in experimentally induced cerebral ischemia. METHODS: Totally 126 male Wistar rats were randomly divided into control group, model group and EA group. The latter two were further divided into ten subgroups (n = 6) following Middle Cerebral Artery Occlusion (MCAO). Changes in regional cerebral blood flow (rCBF) and expressions of Angiotensin II and its receptors (AT1R, AT2R), as well as effector proteins in phosphatidyl inositol signal pathway were monitored before and at different times after MCAO. RESULTS: MCAO-induced decline of ipsilateral rCBF was partially suppressed by electroacupuncture, and contralateral blood flow was also superior to that of model group. Angiotensin II level was remarkably elevated immediately after MCAO, while electroacupuncture group exhibited significantly lower levels at 1 to 3 h and the value was significantly increased thereafter. The enhanced expression of AT1R was partially inhibited by electroacupuncture, while increased AT2R level was further induced. Electroacupuncture stimulation attenuated and postponed the upregulated-expressions of Gq and CaM these upregulations. ELISA results showed sharply increased expressions of DAG and IP3, which were remarkably neutralized by electroacupuncture. CONCLUSIONS: MCAO induced significant increases in expression of Angiotensin II and its receptor-mediated signal pathway. These enhanced expressions were significantly attenuated by electroacupuncture intervention, followed by reduced vasoconstriction and improved blood supply in ischemic region, and ultimately conferred beneficial effects on cerebral ischemia.
Asunto(s)
Angiotensina II/metabolismo , Isquemia Encefálica/terapia , Cerebro/patología , Electroacupuntura , Receptores de Angiotensina/metabolismo , Flujo Sanguíneo Regional , Animales , Isquemia Encefálica/metabolismo , Infarto Cerebral/prevención & control , Cerebro/metabolismo , Modelos Animales de Enfermedad , Infarto de la Arteria Cerebral Media , Masculino , Ratas , Ratas Wistar , Regulación hacia ArribaRESUMEN
We evaluated the neuroprotective effects of an anti-oxidative nutrient rich enteral diet (AO diet) that contained rich polyphenols (catechins and proanthocyanidins) and many other anti-oxidative ingredients. Wistar rats were treated with either vehicle, normal AO diet (containing 100kcal/100mL, catechin 38.75mg/100mL and proanthocyanidin 19mg/100mL, 1mL/day), or high AO diet (containing 10 times the polyphenols of the normal AO diet) for 14 days, and were subjected to 90min of transient middle cerebral artery occlusion. The AO diet improved motor function, reduced cerebral infarction volume, and decreased both peroxidative markers such as 4-hydroxynonenal, advanced glycation end products, 8-hydroxy-2-deoxyguanosine and inflammatory markers such as monocyte chemotactic protein-1, ionized calcium-binding adapter molecule-1, and tumor necrosis factor-α. Our study has shown that an AO diet has neuroprotective effects through both anti-oxidative and anti-inflammatory mechanisms, indicating that nutritional control with polyphenols could be useful for patients with acute ischemic stroke.
Asunto(s)
Antioxidantes/uso terapéutico , Daño Encefálico Crónico/prevención & control , Isquemia Encefálica/dietoterapia , Dieta , Infarto de la Arteria Cerebral Media/dietoterapia , Inflamación/prevención & control , Proantocianidinas/uso terapéutico , 8-Hidroxi-2'-Desoxicoguanosina , Administración Oral , Aldehídos/análisis , Animales , Biomarcadores , Química Encefálica , Daño Encefálico Crónico/etiología , Isquemia Encefálica/complicaciones , Infarto Cerebral/etiología , Infarto Cerebral/patología , Infarto Cerebral/prevención & control , Desoxiguanosina/análogos & derivados , Desoxiguanosina/análisis , Productos Finales de Glicación Avanzada/análisis , Infarto de la Arteria Cerebral Media/complicaciones , Inflamación/etiología , Masculino , Estrés Oxidativo , Ratas , Ratas WistarRESUMEN
OBJECTIVE: To examine recent trends in the use of secondary stroke prevention medicines by transient ischaemic attack (TIA) and ischaemic stroke survivors. DESIGN, SETTING AND PARTICIPANTS: Retrospective observational study of patients aged ≥ 65 years who were hospitalised with a TIA or ischaemic stroke between January 2000 and December 2009. Use of antihypertensive, antithrombotic and lipid-lowering medicines by patients was determined monthly, using claims data from the Australian Government Department of Veterans' Affairs, commencing in January 2003. MAIN OUTCOME MEASURE: Monthly prevalence of use of secondary stroke prevention medicines. RESULTS: Between 2003 and 2009, small increases in use (less than 2% relative increase annually) were observed for antihypertensive and antithrombotic medicines among 19 019 patients. There was a 9% relative increase in use of lipid-lowering therapy each year. The proportion of patients dispensed all three recommended medicine classes nearly doubled over the 7-year period. By December 2009, about 80% of patients were dispensed an antihypertensive, 75% received an antithrombotic and 60% were dispensed lipid-lowering therapy. Almost half of the population were dispensed all three recommended classes by the end of the study period. CONCLUSIONS: Increased use of secondary stroke prevention medicines was shown in this study, in accordance with national stroke guideline recommendations and initiatives supporting quality use of medicines in Australia. There may be opportunity to further increase use of these medicines among older Australians who have had a TIA or ischaemic stroke.
Asunto(s)
Antihipertensivos/uso terapéutico , Infarto Cerebral/epidemiología , Infarto Cerebral/prevención & control , Utilización de Medicamentos/tendencias , Fibrinolíticos/uso terapéutico , Hipolipemiantes/uso terapéutico , Ataque Isquémico Transitorio/epidemiología , Ataque Isquémico Transitorio/prevención & control , Anciano , Anciano de 80 o más Años , Australia , Estudios Transversales , Femenino , Humanos , Revisión de Utilización de Seguros/estadística & datos numéricos , Masculino , Programas Nacionales de Salud/estadística & datos numéricos , Estudios Retrospectivos , Prevención Secundaria , Veteranos/estadística & datos numéricosRESUMEN
OBJECTIVE: TSI is a new drug derived from Chinese medicine for treatment of ischemic stroke in China. The aim of this study was to verify the therapeutic effect of TSI in a rat model of MCAO, and further explore the mechanism for its effect. METHODS: Male Sprague-Dawley rats were subjected to right MCAO for 60 minutes followed by reperfusion. TSI (1.67 mg/kg) was administrated before reperfusion via femoral vein injection. Twenty-four hours after reperfusion, the fluorescence intensity of DHR 123 in, leukocyte adhesion to and albumin leakage from the cerebral venules were observed. Neurological scores, TTC staining, brain water content, Nissl staining, TUNEL staining, and MDA content were assessed. Bcl-2/Bax, cleaved caspase-3, NADPH oxidase subunits p47(phox)/p67(phox)/gp91(phox), and AMPK/Akt/PKC were analyzed by Western blot. RESULTS: TSI attenuated I/R-induced microcirculatory disturbance and neuron damage, activated AMPK, inhibited NADPH oxidase subunits membrane translocation, suppressed Akt phosphorylation, and PKC translocation. CONCLUSIONS: TSI attenuates I/R-induced brain injury in rats, supporting its clinic use for treatment of acute ischemic stroke. The role of TSI may benefit from its antioxidant activity, which is most likely implemented via inactivation of NADPH oxidase through a signaling pathway implicating AMPK/Akt/PKC.
Asunto(s)
Alquenos/uso terapéutico , Medicamentos Herbarios Chinos/uso terapéutico , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Microcirculación/efectos de los fármacos , NADPH Oxidasas/fisiología , Neuronas/efectos de los fármacos , Polifenoles/uso terapéutico , Daño por Reperfusión/tratamiento farmacológico , Proteínas Quinasas Activadas por AMP/fisiología , Alquenos/farmacología , Animales , Apoptosis/efectos de los fármacos , Permeabilidad Capilar/efectos de los fármacos , Infarto Cerebral/etiología , Infarto Cerebral/patología , Infarto Cerebral/prevención & control , Medicamentos Herbarios Chinos/farmacología , Infarto de la Arteria Cerebral Media/enzimología , Infarto de la Arteria Cerebral Media/fisiopatología , Leucocitos/efectos de los fármacos , Peroxidación de Lípido/efectos de los fármacos , Masculino , Trastornos del Movimiento/etiología , Trastornos del Movimiento/prevención & control , Proteínas del Tejido Nervioso/fisiología , Neuronas/enzimología , Fosforilación/efectos de los fármacos , Polifenoles/farmacología , Proteína Quinasa C/fisiología , Transporte de Proteínas/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/fisiología , Ratas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno/metabolismo , Daño por Reperfusión/enzimología , Daño por Reperfusión/fisiopatología , Transducción de Señal/efectos de los fármacosRESUMEN
Salvianolate has been reported to possess protective properties. However, its specific mechanisms have yet to be identified. Our study aimed to identify the molecular mechanism of antioxidative stress function of salvianolate on rat ischemia and reperfusion brain tissues. Rats were randomly distributed into three experimental groups: sham, model and intervention . All animal neurobehavioral tests were performed at the end of 72-h reperfusion per Longa's method, and rats with a score of 0 (no neurological deficit) or 4 (severe neurological deficit with impaired consciousness) were excluded. Brain slices were obtained after 72 h of reperfusion and stained with triphenyltetrazolium chloride. Western blot analysis and quantitative real-time polymerase chain reaction (qRT-PCR) were used to determine levels of GOLPH3, Akt/p-Akt, and mTOR/p-mTOR expressions in ischemic cortex. Salvianolate (18mg/kg intraperitoneal injection) significantly decreased the neurological deficit scores of rats in groups of 72 h I/R and reduced the number of TUNELpositive cells in the cerebral cortex when given at onset and at 24 and 48 h after reperfusion, leading to decreased cerebral infarction in rats after ischemia/reperfusion injury. Results of Western blot and qRT-PCR showed that salvianolate could significantly upregulate the expression of Golgi phosphoprotein-3 as well as the phosphorylation of Akt and mTOR. Above findings indicate that salvianolate exerts potent and long-term neuroprotective effects in the model of cerebral I/R, and Golgi phosphoprotein-3 and its downstream activation of Akt/mTOR signaling pathway may provide a new insight for the antioxidative effect of salvianolate.
Asunto(s)
Antioxidantes/farmacología , Proteínas Portadoras/metabolismo , Infarto Cerebral/metabolismo , Extractos Vegetales/farmacología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Recombinantes de Fusión/metabolismo , Serina-Treonina Quinasas TOR/metabolismo , Animales , Western Blotting , Isquemia Encefálica/complicaciones , Isquemia Encefálica/metabolismo , Infarto Cerebral/prevención & control , Modelos Animales de Enfermedad , Etiquetado Corte-Fin in Situ , Masculino , Fármacos Neuroprotectores/farmacología , Ratas , Ratas Sprague-Dawley , Reacción en Cadena en Tiempo Real de la Polimerasa , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiologíaRESUMEN
Dragon's blood is a bright red resin obtained from Dracaena cochinchinensis (Lour.) S.C.Chen (Yunnan, China). As a traditional Chinese medicinal herb, it has great traditional medicinal value and is used for wound healing and to stop bleeding. Its main biological activity comes from phenolic compounds. In this study, phenolic compounds were made into dropping pills and their protective effects were examined by establishing focal cerebral ischemia rats model used method of Middle Cerebral Artery Occlusion (MCAO), and by investigating indexes of neurological scores, infarct volume, cerebral index, cerebral water content and oxidation stress. Compared to model group, high, middle and low groups of Dragon's blood dropping pills could improve the neurological function significantly (p<0.01) and reduce cerebral infarct volume of focal cerebral ischemia rats remarkably (p<0.05-0.01). Meanwhile, each group could alleviate cerebral water content and cerebral index (p<0.05-0.01) and regulate oxidative stress of focal cerebral ischemia rats obviously (p<0.05-0.01). Activities of middle group corresponded with that treated with positive control drug. The results obtained here showed that Dragon's blood dropping pills had protective effects on focal cerebral ischemia rats.
Asunto(s)
Antioxidantes/uso terapéutico , Isquemia Encefálica/tratamiento farmacológico , Encéfalo/efectos de los fármacos , Dracaena/química , Estrés Oxidativo/efectos de los fármacos , Fenoles/uso terapéutico , Fitoterapia , Animales , Antioxidantes/metabolismo , Antioxidantes/farmacología , Encéfalo/metabolismo , Encéfalo/fisiopatología , Isquemia Encefálica/complicaciones , Isquemia Encefálica/patología , Infarto Cerebral/etiología , Infarto Cerebral/prevención & control , Modelos Animales de Enfermedad , Malondialdehído/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Fenoles/farmacología , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Ratas , Ratas Sprague-Dawley , Resinas de Plantas/farmacología , Resinas de Plantas/uso terapéutico , Agua/metabolismoRESUMEN
To detect and identify natural antioxidants in Swertia chirayita with protective effect against cerebral infarction, a screening method, using column chromatography and cerebral ischemia-reperfusion injury in rat, was developed. Seventeen compounds were purposefully separated and identified by Nuclear Magnetic Resonance, Fourier Transform Infrared Spectroscopy, Ultraviolet Spectrum, and Mass Spectrometry. The purified compounds were further screened by radical scavenging activity and cerebral ischemia-reperfusion injury in rats. Two compounds showed apparent radical scavenging activity and neuroprotective activity. The two compounds were identified as 1-hydroxy-2,3,4,6-tetramethoxyxanthone and 1,5,8-trihydroxy-3-methoxy xanthone, and were preliminarily considered as primary natural neuroprotective antioxidants in Swertia chirayita. These two compounds (20 mg kg-1) markedly decreased infarct size to below 5%, and also caused a significant improvement of activities of superoxide dismutase (SOD) (92.90 ± 11.19 U ml-1), glutathione peroxidase (GSH-Px) (122.58 ± 12.31 µmol mg-1) and a decrease in the content of malondialdehyde (MDA) (3.98 ± 2.00 nmol ml-1) in serum. The two compounds showed strong capability for protective effects against cerebral damages induced by ischemia-reperfusion, and the protective effect may be related to the inhibition of lipid peroxidation. The use of the screening method based on tracing separation and ischemia reperfusion would provide a new way for detection of radical-scavenging and natural neuroprotective compounds from Swertia chirayita or complex matrices.
Asunto(s)
Infarto Cerebral/prevención & control , Depuradores de Radicales Libres/aislamiento & purificación , Fármacos Neuroprotectores/aislamiento & purificación , Fitoterapia , Swertia/química , Animales , Evaluación Preclínica de Medicamentos , Femenino , Depuradores de Radicales Libres/uso terapéutico , Masculino , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Extractos Vegetales/uso terapéutico , Plantas Medicinales/química , Ratas , Daño por Reperfusión/prevención & controlRESUMEN
Apoptosis is believed to play important roles in neuronal cell death associated with cerebral ischemia. We now provided evidence that imperatorin (IMp), the main composition of the dried root or rhizome of R Radix Angelicae Dahuricae, took advantage on oxygen glucose deprivated/reperfusion (OGD-R) SH-SY5Y cell line through neuronal apoptosis inhibition. Our data had shown that imperatorin reduced the number of apoptosis cells after OGD-R, this effect was associated with the inhibition of the apoptosis factors Bax and caspase-3, and the upregulation of anti-apoptosis factor Bcl-2. In the meantime, the protective factor BDNF was upregulated significantly by imperatorin treatment. In our experiment in vivo, imperatorin decreased the infract volume significantly in dose of 5 mg/kg and 10 mg/kg, and the behavior ability was increased in the 10mg/kg of imperatorin. Our observations show that imperatorin exerted protective effect on cerebral ischemia both in vitro and in vivo, this effect is associated with its anti-apoptosis function.
Asunto(s)
Angelica/química , Apoptosis/efectos de los fármacos , Isquemia Encefálica/tratamiento farmacológico , Cerebro/efectos de los fármacos , Furocumarinas/uso terapéutico , Fitoterapia , Daño por Reperfusión/prevención & control , Animales , Conducta Animal/efectos de los fármacos , Isquemia Encefálica/metabolismo , Isquemia Encefálica/patología , Caspasa 3/metabolismo , Línea Celular , Infarto Cerebral/metabolismo , Infarto Cerebral/prevención & control , Cerebro/citología , Cerebro/metabolismo , Cerebro/patología , Furocumarinas/farmacología , Glucosa/metabolismo , Hipoxia , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Oxígeno/metabolismo , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Ratas Sprague-Dawley , Daño por Reperfusión/metabolismo , Daño por Reperfusión/patología , Rizoma , Regulación hacia Arriba , Proteína X Asociada a bcl-2/metabolismoRESUMEN
ITH12246 (ethyl 5-amino-2-methyl-6,7,8,9-tetrahydrobenzo[b][1,8]naphthyridine-3-carboxylate) is a 1,8-naphthyridine described to feature an interesting neuroprotective profile in in vitro models of Alzheimer's disease. These effects were proposed to be due in part to a regulatory action on protein phosphatase 2A inhibition, as it prevented binding of its inhibitor okadaic acid. We decided to investigate the pharmacological properties of ITH12246, evaluating its ability to counteract the memory impairment evoked by scopolamine, a muscarinic antagonist described to promote memory loss, as well as to reduce the infarct volume in mice suffering phototrombosis. Prior to conducting these experiments, we confirmed its in vitro neuroprotective activity against both oxidative stress and Ca(2+) overload-derived excitotoxicity, using SH-SY5Y neuroblastoma cells and rat hippocampal slices. Using a predictive model of blood-brain barrier crossing, it seems that the passage of ITH12246 is not hindered. Its potential hepatotoxicity was observed only at very high concentrations, from 0.1 mM. ITH12246, at the concentration of 10 mg/kg i.p., was able to improve the memory index of mice treated with scopolamine, from 0.22 to 0.35, in a similar fashion to the well-known Alzheimer's disease drug galantamine 2.5 mg/kg. On the other hand, ITH12246, at the concentration of 2.5 mg/kg, reduced the phototrombosis-triggered infarct volume by 67%. In the same experimental conditions, 15 mg/kg melatonin, used as control standard, reduced the infarct volume by 30%. All of these findings allow us to consider ITH12246 as a new potential drug for the treatment of neurodegenerative diseases, which would act as a multifactorial neuroprotectant.
Asunto(s)
Isquemia Encefálica/prevención & control , Infarto Cerebral/prevención & control , Trastornos de la Memoria/prevención & control , Naftiridinas/uso terapéutico , Proteínas del Tejido Nervioso/efectos de los fármacos , Fármacos Neuroprotectores/uso terapéutico , Proteína Fosfatasa 2/efectos de los fármacos , Animales , Barrera Hematoencefálica , Señalización del Calcio/efectos de los fármacos , Línea Celular , Infarto Cerebral/patología , Enfermedad Hepática Inducida por Sustancias y Drogas/etiología , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Hipocampo/efectos de los fármacos , Ratones , Estructura Molecular , Terapia Molecular Dirigida , Naftiridinas/química , Naftiridinas/farmacología , Proteínas del Tejido Nervioso/fisiología , Fármacos Neuroprotectores/química , Fármacos Neuroprotectores/farmacología , Oligomicinas/toxicidad , Estrés Oxidativo/efectos de los fármacos , Fosforilación/efectos de los fármacos , Proteína Fosfatasa 2/fisiología , Procesamiento Proteico-Postraduccional/efectos de los fármacos , Ratas , Rotenona/toxicidad , Escopolamina/antagonistas & inhibidores , Escopolamina/toxicidad , Proteínas tau/metabolismoRESUMEN
OBJECTIVE: To tentatively establish a diagnosis and treatment mode for effectively controlling the progress of cerebral microlesions (CM) and preventing the incidence of cerebral infarction (CI) by comparing different intervention modes for treating CM. METHODS: Using a prospective, nonrandomized, controlled trial, 408 subjects with multiple CM were assigned to the Chinese medical pharmacy intervention group (Group A, 100 case), the aspirin intervention group (Group B, 104 cases), the negative control group (Group C, 100 cases), and the non-intervention group (Group D, 104 cases). No intervention was given to those in Group D. Patients in the other 3 groups were intervened by life style and routine therapies of vasculogenic risk factors. Those in Group A took Guizhi Fuling Pill (GFP) and earthworm powder additionally. Those in Group B took aspirin additionally. They were routinely followed-up. The CM, the changes of vasculogenic risk factors, and the incidence rate of CI were compared among the 4 groups. RESULTS: The total effective rate of CM was 66.67% in Group A, obviously higher than that of Group B (52.32%), Group C (42.86%), and Group D (37.04%), respectively. It was obviously higher in Group B than in Group D, showing statistical difference (P <0.01, P <0.05). After treatment, the serum levels of LDL-C, TC, and TG were obviously lower in Group A than in Group B (P <0.05); the serum levels of LDL-C and TC were obviously lower in Group A than in Group C (P <0.01); the systolic pressure was obviously lower in Group A than in Group D (P <0.05). The systolic pressure and the serum TC level were obviously lower in Group C than in Group D (P <0.05). The incidence rate of CI was 2.17% (2/92 cases) in Group A, obviously lower than that of Group C (11.36% ,10/88 cases) and Group D (14.44%, 13/90 cases), showing statistical difference (P <0.05). But there was no statistical difference between Group A and Group B (6.74% ,6/89 cases) (P >0.05). CONCLUSIONS: GFP combined earthworm powder could treat CM, control vasculogenic risk factors, and finally prevent the incidence of CI. Standard Chinese medical intervention mode showed the optimal effects in treating CM and preventing the incidence of CI, and perhaps it could be spread clinically.
Asunto(s)
Infarto Cerebral/prevención & control , Medicamentos Herbarios Chinos/uso terapéutico , Fitoterapia , Adulto , Anciano , Anciano de 80 o más Años , Aspirina/uso terapéutico , Encéfalo/patología , Infarto Cerebral/tratamiento farmacológico , Infarto Cerebral/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Factores de Riesgo , Resultado del TratamientoRESUMEN
To examine the preventive and therapeutic effects of ginsenoside Rb1 for neural injury during cerebral infarction, we used a middle cerebral artery occlusion (MCAO) model in rats to investigate the effects of ginsenoside Rb1 with Edaravone as a control. Ginsenoside Rb1 was given to the rats by intragastric administration either before or after the MCAO surgery to study its preventive and therapeutic effects. Ginsenoside Rb1-treated rats had a smaller infarct volume than the positive control. Interleukin-1 (IL-1), brain-derived neurotrophic factor (BDNF), tumor necrosis factor-α (TNF-α), neurofilament (NF) and growth associated protein-43 (GAP-43) were measured to determine brain damage and the recovery of nerves. These findings suggest that ginsenoside Rb1 has neuroprotective effects in rats, and the protection efficiency is higher than Edaravone. The protective mechanism is different from Edaravone. The preventive ability of ginsenoside Rb1 is higher than its repair ability in neuroprotection in vivo.