RESUMEN
OBJECTIVE: To investigate the application effect of comprehensive intervention combined with cognitive psychological care based on the quality chain in patients with BPH. METHODS: We prospectively selected 110 cases of BPH treated in our hospital from January 2022 to March 2023 and equally randomized them into groups A and B, the former given routine intervention, while the latter comprehensive intervention combined with cognitive psychological care based on the quality chain in addition. We analyzed the results of intervention, the patients' scores on Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS), improvement of clinical indicators, self-efficacy, disease awareness and treatment compliance, and compared the data obtained between the two groups of patients. RESULTS: The effectiveness of intervention was significantly better in group B than in A (96.36% vs 65.45%, χ2 = 17.009, P<0.05). Compared with the baseline, the SAS and SDS scores were remarkably improved in the two groups after intervention (P<0.05), even more significantly in group B than in A (P<0.05). Group B also showed a markedly shorter duration of bladder spasm, lower frequency of bladder spasm per day, shorter urethral catheterization time and postoperative hospital stay, better emotion control and health management, more regular schedule, higher disease knowledge awareness, and better treatment compliance than group A (all P<0.05). CONCLUSION: Comprehensive intervention combined with cognitive psychological care based on the quality chain is significantly effective in improving BPH patients' clinical indicators, disease awareness and treatment compliance, reducing their depression and anxiety, and enhancing their self-efficacy management.
Asunto(s)
Terapia Cognitivo-Conductual , Hiperplasia Prostática , Humanos , Masculino , Hiperplasia Prostática/terapia , Hiperplasia Prostática/psicología , Terapia Cognitivo-Conductual/métodos , Estudios Prospectivos , Ansiedad/terapia , Depresión/terapia , Resultado del Tratamiento , AutoeficaciaRESUMEN
Oxidative stress has been proven to play a critical role in the pathogenesis of neuronal injury. As a novel adipocytokine, omentin is produced by visceral adipose with insulin sensitizing effects and has been revealed to possess anti-inflammatory effects. However, the possible effect of omentin on oxidative stress remains unknown. The present study aimed to detect the potential protective effect of omentin against hydrogen peroxide (H2O2)-induced cytotoxicity of PC12 cells. The results showed that no cytotoxic effect was shown in PC12 cells co-cultured with omentin alone at a concentration of 50-1000 ng/mL. The CCK8 and TUNEL assays suggested that omentin could remarkably attenuate apoptosis induced by 100 µM H2O2. The PCR and western blotting showed that the expression levels of Bax was significantly inhibited by omentin via the upregulation of miR-128-3p at its 3'-UTR. Taken together, these results indicated that omentin protects PC12 cells against H2O2-induced apoptosis, and further studies need to be conducted before utilization in the clinic for the treatment of neurodegenerative diseases.
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Peróxido de Hidrógeno , Animales , Antioxidantes , Apoptosis/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Células PC12 , RatasRESUMEN
Ischemic stroke is one of the leading causes of morbidity and mortality among human worldwide. Unfortunately, cerebral I/R still lacks effective therapeutic targets and strategies. In the study, we found that general control nonderepressible 2 (GCN2) expression was increased following ischemia in the ischemic penumbra in vivo and in vitro. GCN2 suppression using its significant inhibitor, GCN2iB, exhibited a protective role in cerebral I/R injury in mice, as evidenced by the improved neurological deficits and function. GCN2 inhibition with either GCN2iB or genetic knockdown led to significant reduction of pro-apoptotic protein expression, endoplasmic reticulum stress (ERS)-related protein and oxidative stress both in I/R-induced cerebral injury and oxygen-glucose deprivation and reoxygenation (OGD/R) stimulation in N2aâ¯cells. OGD/R-triggered apoptosis and ERS were significantly depended on oxidative stress in vitro. In addition, Forkhead box O 3a (FoxO3a), involved in the reactive oxygen species (ROS) production, was increased during OGD/R stimulation-regulated apoptosis and ERS, which could be abrogated by GCN2 suppression. Consistently, FoxO3a-regulated generation of ROS was markedly ameliorated upon GCN2 suppression with GCN2iB. Thereby, our findings indicated that GCN2 suppression alleviated apoptosis and ERS in cerebral ischemia through reducing FoxO3a-dependent ROS production, illustrating that GCN2 could be a promising target for the therapeutic interventions in cerebral ischemic stroke.
Asunto(s)
Apoptosis , Isquemia Encefálica/metabolismo , Estrés del Retículo Endoplásmico , Proteína Forkhead Box O3/metabolismo , Proteínas Serina-Treonina Quinasas/metabolismo , Animales , Apoptosis/efectos de los fármacos , Isquemia Encefálica/genética , Isquemia Encefálica/terapia , Estrés del Retículo Endoplásmico/efectos de los fármacos , Técnicas de Silenciamiento del Gen , Terapia Genética , Masculino , Ratones , Ratones Endogámicos C57BL , Inhibidores de Proteínas Quinasas/uso terapéutico , Proteínas Serina-Treonina Quinasas/antagonistas & inhibidores , Proteínas Serina-Treonina Quinasas/genética , Especies Reactivas de Oxígeno/metabolismo , Regulación hacia Arriba/efectos de los fármacosRESUMEN
Intracellular calcium homeostasis disorder and mitochondrial dysfunction are involved in many acute and chronic brain diseases, including ischemic brain injury. An imbalance in mitochondrial fission and fusion is one of the most important structural abnormalities found in a large number of mitochondrial dysfunction related diseases. Here, we investigated the effects of mitochondrial division inhibitor A (mdivi A) and mdivi B, two small molecule inhibitors of mitochondrial fission protein dunamin-related protein 1 (Drp-1), in neuronal injury induced by oxygen-glucose deprivation (OGD) in PC12 cells. We found that mdivi A and mdivi B inhibited OGD-induced neuronal injury through attenuating apoptotic cell death. These two inhibitors also preserved mitochondrial function, as evidenced by reduced reactive oxygen species (ROS) generation and cytochrome c release, as well as prevented loss of mitochondrial membrane potential (MMP). Moreover, mdivi A and mdivi B significantly suppressed mitochondrial Ca(2+) uptake, but had no effect on cytoplasmic Ca(2+) after OGD injury. The results of calcium imaging and immunofluorescence staining showed that Drp-1 inhibitors attenuated endoplasmic reticulum (ER) Ca(2+) release and prevented ER morphological changes induced by OGD. These results demonstrate that Drp-1 inhibitors protect against ischemic neuronal injury through inhibiting mitochondrial Ca(2+) uptake from the ER store and attenuating mitochondrial dysfunction.
Asunto(s)
Calcio/metabolismo , Dinaminas/antagonistas & inhibidores , Retículo Endoplásmico/metabolismo , Inhibidores Enzimáticos/farmacología , Mitocondrias/efectos de los fármacos , Animales , Hipoxia de la Célula , Supervivencia Celular/efectos de los fármacos , Citocromos c/metabolismo , Dinaminas/metabolismo , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Mitocondrias/metabolismo , Células PC12 , Ratas , Especies Reactivas de Oxígeno/metabolismoRESUMEN
OBJECTIVE: Aquaporin-4 (AQP4), the main water channel protein in the brain, plays a critical role in water homeostasis and brain edema. Here, we investigated its role in the inflammatory responses after focal cerebral ischemia. METHODS: In AQP4-knockout (KO) and wild-type mice, focal cerebral ischemia was induced by 30 min of middle cerebral arterial occlusion (MCAO). Ischemic neuronal injury and cellular inflammatory responses, as well as the expression and localization of cysteinyl leukotriene CysLT(2) and CysLT(1) receptors, were determined at 24 and 72 h after MCAO. RESULTS: AQP4-KO mice showed more neuronal loss, more severe microglial activation and neutrophil infiltration, but less astrocyte proliferation in the brain after MCAO than wild-type mice. In addition, the protein levels of both CysLT(1) and CysLT(2) receptors were up-regulated in the ischemic brain, and the up-regulation was more pronounced in AQP4-KO mice. The CysLT(1) and CysLT(2) receptors were primarily localized in neurons, microglia and neutrophils; those localized in microglia and neutrophils were enhanced in AQP4-KO mice. CONCLUSION: AQP4 may play an inhibitory role in postischemic inflammation.
Asunto(s)
Acuaporina 4/deficiencia , Isquemia Encefálica/metabolismo , Inflamación/metabolismo , Receptores de Leucotrienos/biosíntesis , Animales , Acuaporina 4/genética , Astrocitos/metabolismo , Western Blotting , Isquemia Encefálica/patología , Recuento de Células , Inmunohistoquímica , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/patología , Inflamación/patología , Leucocitos/metabolismo , Ratones , Ratones Noqueados , Microglía/fisiología , Neutrófilos/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia Arriba , Intoxicación por Agua/metabolismoRESUMEN
The water channel aquaporin-4 (AQP4) is important in brain water homeostasis, and is also involved in astrocyte growth and glial scar formation. It has been reported that AQP4 deficiency attenuates acute ischemic brain injury as a result of reducing cytotoxic edema. Here, we determined whether AQP4 deficiency influences chronic brain injury after focal cerebral ischemia induced by 30 min of middle cerebral artery occlusion (MCAO). AQP4(-/-) mice exhibited a lower survival rate and less body weight gain than wild-type mice, but their neurological deficits were similar to wild-type mice during 35 days after MCAO. At 35 days after MCAO, AQP4(-/-) mice showed more severe brain atrophy and cavity formation in the ischemic hemisphere as well as more neuronal loss in the hippocampus. Furthermore, astrocyte proliferation and glial scar formation were impaired in AQP4(-/-) mice. Therefore, AQP4 deficiency complicated by astrocyte dysfunction aggravates chronic brain injury after focal cerebral ischemia, suggesting that AQP4 may be important in the chronic phase of the post-ischemic recovery process.
Asunto(s)
Acuaporina 4/genética , Ataque Isquémico Transitorio/patología , Ataque Isquémico Transitorio/fisiopatología , Animales , Acuaporina 4/metabolismo , Recuento de Células , Proliferación Celular , Supervivencia Celular , Enfermedad Crónica , Ataque Isquémico Transitorio/metabolismo , Masculino , Ratones , Ratones Noqueados , Neuroglía/patología , Neuronas/patologíaRESUMEN
OBJECTIVE: To determine whether aquaporin-4 (AQP4) regulates acute lesions, delayed lesions, and the associated microglial activation after cryoinjury to the brain. METHODS: Brain cryoinjury was applied to AQP4 knockout (KO) and wild-type mice. At 24 h and on days 7 and 14 after cryoinjury, lesion volume, neuronal loss, and densities of microglia and astrocytes were determined, and their changes were compared between AQP4 KO and wild-type mice. RESULTS: Lesion volume and neuronal loss in AQP4 KO mice were milder at 24 h following cryoinjury, but worsened on days 7 and 14, compared to those in wild-type mice. Besides, microglial density increased more, and astrocyte proliferation and glial scar formation were attenuated on days 7 and 14 in AQP4 KO mice. CONCLUSION: AQP4 deficiency ameliorates acute lesions, but worsens delayed lesions, perhaps due to the microgliosis in the late phase.
Asunto(s)
Acuaporina 4/fisiología , Lesiones Encefálicas/patología , Gliosis/patología , Microglía/patología , Animales , Acuaporina 4/deficiencia , Acuaporina 4/genética , Astrocitos/metabolismo , Encéfalo/metabolismo , Modelos Animales de Enfermedad , Congelación , Ratones , Ratones Noqueados , Microglía/metabolismoRESUMEN
OBJECTIVE: To evaluate the role of water channel AQP4 in NMDA-induced brain injury in mice. METHODS: In AQP4 gene knockout (AQP4(-/-)) mice, brain injury was induced by microinjection of NMDA into the cortex. The injured area was determined by toluidine blue staining, degenerated neurons were detected by Fluro-Jade B staining, and increased blood-brain barrier (BBB) permeability was evaluated by IgG immunostaining. RESULT: Compared with wild-type mice, AQP4(-/-) mice exhibited increased cortical lesion area, aggravated neuron degeneration, and increased BBB disruption after NMDA microinjection. CONCLUSION: AQP4 may play a protective role in NMDA-induced brain injury in mice.
Asunto(s)
Acuaporina 4/genética , Encéfalo/patología , N-Metilaspartato/toxicidad , Animales , Acuaporina 4/fisiología , Barrera Hematoencefálica/patología , Encéfalo/efectos de los fármacos , Ratones , Ratones NoqueadosRESUMEN
OBJECTIVES: Previously we demonstrated the neuroprotective effect of montelukast, a cysteinyl leukotriene receptor-1 (CysLT(1) ) antagonist, on acute brain injury after focal cerebral ischaemia in mice. In this study, we have determined its effect on chronic brain injury after focal cerebral ischaemia in mice and rats. METHODS: After transient focal cerebral ischaemia was induced by middle cerebral artery occlusion, montelukast was intraperitoneally injected in mice or orally administered to rats for five days. Behavioural dysfunction, brain infarct volume, brain atrophy and neuron loss were determined to evaluate brain lesions. KEY FINDINGS: Montelukast (0.1 mg/kg) attenuated behavioural dysfunction, brain infarct volume, brain atrophy and neuron loss in mice, which was similar to pranlukast, another CysLT(1) receptor antagonist. Oral montelukast (0.5 mg/kg) was effective in rats and was more effective than edaravone, a free radical scavenger. CONCLUSION: Montelukast protected mice and rats against chronic brain injury after focal cerebral ischaemia, supporting the therapeutic potential of CysLT(1) receptor antagonists.
Asunto(s)
Acetatos/uso terapéutico , Antipirina/análogos & derivados , Lesión Encefálica Crónica/patología , Lesión Encefálica Crónica/prevención & control , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Infarto de la Arteria Cerebral Media/patología , Degeneración Nerviosa/tratamiento farmacológico , Quinolinas/uso terapéutico , Acetatos/administración & dosificación , Acetatos/farmacología , Administración Oral , Animales , Antipirina/uso terapéutico , Atrofia/prevención & control , Conducta Animal/efectos de los fármacos , Lesión Encefálica Crónica/complicaciones , Cromonas/uso terapéutico , Ciclopropanos , Modelos Animales de Enfermedad , Evaluación Preclínica de Medicamentos , Edaravona , Depuradores de Radicales Libres/uso terapéutico , Inyecciones Intraperitoneales , Antagonistas de Leucotrieno/farmacología , Antagonistas de Leucotrieno/uso terapéutico , Masculino , Ratones , Ratones Endogámicos ICR , Quinolinas/administración & dosificación , Quinolinas/farmacología , Ratas , Ratas Sprague-Dawley , SulfurosRESUMEN
AIMS: We previously reported that cysteinyl leukotriene receptor 2 (CysLT(2)) mediates ischemic astrocyte injury, and leukotriene D(4)-activated CysLT(2) receptor up-regulates the water channel aquaporin 4 (AQP4). Here we investigated the mechanism underlying CysLT(2) receptor-mediated ischemic astrocyte injury induced by 4-h oxygen-glucose deprivation and 24-h recovery (OGD/R). MAIN METHODS: Primary cultures of rat astrocytes were treated by OGD/R to construct the cell injury model. AQP4 expression was inhibited by small interfering RNA (siRNA). The expressions of AQP4 and CysLTs receptors, and the MAPK signaling pathway were determined. KEY FINDINGS: OGD/R induced astrocyte injury, and increased expression of the CysLT(2) (but not CysLT(1)) receptor and AQP4. OGD/R-induced cell injury and AQP4 up-regulation were inhibited by a CysLT(2) receptor antagonist (Bay cysLT2) and a non-selective CysLT receptor antagonist (Bay u9773), but not by a CysLT(1) receptor antagonist (montelukast). Knockdown of AQP4 by siRNA attenuated OGD/R injury. Furthermore, OGD/R increased phosphorylation of ERK1/2 and p38, whose inhibitors relieved the cell injury and AQP4 up-regulation. SIGNIFICANCE: The CysLT(2) receptor mediates AQP4 up-regulation in astrocytes, and up-regulated AQP4 leads to OGD/R-induced injury, which results from activation of the ERK1/2 and p38 MAPK pathways.
Asunto(s)
Acuaporina 4/fisiología , Astrocitos/enzimología , Isquemia Encefálica/metabolismo , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Receptores de Leucotrienos/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo , Animales , Acuaporina 4/biosíntesis , Astrocitos/metabolismo , Astrocitos/fisiología , Western Blotting , Isquemia Encefálica/enzimología , Isquemia Encefálica/fisiopatología , Células Cultivadas , Activación Enzimática/efectos de los fármacos , Fosforilación , Ratas , Ratas Sprague-Dawley , Receptores de Leucotrienos/efectos de los fármacos , Receptores de Leucotrienos/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , SRS-A/análogos & derivados , SRS-A/farmacología , Transducción de Señal/efectos de los fármacos , Transducción de Señal/fisiología , Regulación hacia Arriba/efectos de los fármacosRESUMEN
OBJECTIVE: To prepare and identify a polyclonal antibody against cysteinyl leukotriene receptor (CysLT(2)receptor). METHODS: Rabbits were immunized with KLH-coupled CysLT(2) receptor peptide to prepare the polyclonal antibody (pAb). The titer of the pAb in rabbit plasma was detected by indirect ELISA, and the specificity of the pAb was tested by antigen blockade. The tissue distribution of CysLT(2) receptor was detected by Western blot and immunohistochemistry with the prepared pAb. RESULT: The pAb showed a titer higher than 1/1047296, and was specific to CysLT(2) receptor, without cross-reaction with the antigens of CysLT(1) receptor and GPR17. A higher expression of CysLT(2) receptor in kidney, brain and lung of rats and mice was detected by Western blot analysis using the prepared pAb. The molecular weight of CysLT(2) receptor protein was about 40 kD. Immunohistochemical examination showed that CysLT(2) receptor was expressed mainly in the neuron, and partly in astrocytes in rat brain. CONCLUSION: The prepared CysLT(2) receptor pAb has high sensitivity and specificity, and can be used in Western blot and immunohistochemistry.
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Anticuerpos Monoclonales/biosíntesis , Encéfalo/metabolismo , Receptores de Leucotrienos/inmunología , Receptores de Leucotrienos/metabolismo , Animales , Anticuerpos Monoclonales/inmunología , Riñón/metabolismo , Pulmón/metabolismo , Ratones , Conejos , Ratas , Ratas Sprague-DawleyRESUMEN
OBJECTIVE: To prepare and identify a polyclonal antibody (pAb) against GPR17, a novel cysteinyl leukotriene receptor. METHODS: Rabbits were immunized with KLH-coupled GPR17 peptide to prepare the pAb. The titer of the pAb in rabbit plasma was detected by indirect ELISA, and the specificity of the pAb was tested by antigen blockade. GPR17 tissue distribution was detected by Western blot with the pAb. RESULTS: The pAb showed a titer as high as 1:16 364,and was not cross-reacted with the antigens of CysLT(1) and CysLT(2) receptors. A higher expression of GPR17 in the rat brain and heart was detected using the newly prepared pAb. The molecular weigh of GPR17 protein was about 43 kD. CONCLUSION: The prepared GPR17 pAb has high sensitivity and specificity,and can be used in Western blot for detecting GPR17.
Asunto(s)
Anticuerpos Monoclonales/biosíntesis , Anticuerpos Monoclonales/inmunología , Receptores Acoplados a Proteínas G/inmunología , Receptores de Leucotrienos/inmunología , Animales , Ensayo de Inmunoadsorción Enzimática , Humanos , Conejos , RatasRESUMEN
The actions of cysteinyl leukotrienes (CysLTs) are mediated by activating CysLT receptors, CysLT(1), and CysLT(2). The CysLT(1) receptor mediates vascular responses to CysLTs; however, its effect on the proliferation and migration of endothelial cells is not clarified. To determine this effect, we observed proliferation and migration in EA.hy926 cells, a human endothelial cell line, and the involvement of activation of mitogen-activated protein kinases (MAPKs). We found that LTD(4) did not affect the proliferation, but significantly stimulated the migration of endothelial cells. LTD(4) also induced the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, but not those of p38 or JNK. The LTD(4)-induced migration and ERK1/2 phosphorylation were blocked by the CysLT(1)-receptor antagonist montelukast and the dual antagonist Bay u9773, but not by the CysLT(2)-receptor antagonist Bay cysLT2; the migration was also inhibited by the ERK1/2 inhibitor U0126. Our findings indicate that LTD(4) stimulates the CysLT(1) receptor-mediated migration of endothelial cells; this may be regulated by the ERK1/2 pathway.
Asunto(s)
Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Leucotrieno D4/farmacología , Receptores de Leucotrienos/efectos de los fármacos , Acetatos/farmacología , Butadienos/farmacología , Línea Celular , Ciclopropanos , Células Endoteliales/metabolismo , Inhibidores Enzimáticos/farmacología , Humanos , Antagonistas de Leucotrieno/farmacología , Nitrilos/farmacología , Quinolinas/farmacología , SRS-A/análogos & derivados , SRS-A/farmacología , SulfurosRESUMEN
We recently found that 5-lipoxygenase (5-LOX) is activated to produce cysteinyl leukotrienes (CysLTs), and CysLTs may cause neuronal injury and astrocytosis through activation of CysLT(1) and CysLT(2) receptors in the brain after focal cerebral ischemia. However, the property of astrocyte responses to in vitro ischemic injury is not clear; whether 5-LOX, CysLTs, and their receptors are also involved in the responses of ischemic astrocytes remains unknown. In the present study, we performed oxygen-glucose deprivation (OGD) followed by recovery to induce ischemic-like injury in the cultured rat astrocytes. We found that 1-h OGD did not injure astrocytes (sub-lethal OGD) but induced astrocyte proliferation 48 and 72 h after recovery; whereas 4-h OGD moderately injured the cells (moderate OGD) and led to death 24-72 h after recovery. Inhibition of phospholipase A(2) and 5-LOX attenuated both the proliferation and death. Sub-lethal and moderate OGD enhanced the production of CysLTs that was inhibited by 5-LOX inhibitors. Sub-lethal OGD increased the expressions of CysLT(1) receptor mRNA and protein, while moderate OGD induced the expression of CysLT(2) receptor mRNA. Exogenously applied leukotriene D(4) (LTD(4)) induced astrocyte proliferation at 1-10 nM and astrocyte death at 100-1,000 nM. The CysLT(1) receptor antagonist montelukast attenuated astrocyte proliferation, the CysLT(2) receptor antagonist BAY cysLT2 reversed astrocyte death, and the dual CysLT receptor antagonist BAY u9773 exhibited both effects. In addition, LTD(4) (100 nM) increased the expression of CysLT(2) receptor mRNA. Thus, in vitro ischemia activates astrocyte 5-LOX to produce CysLTs, and CysLTs result in CysLT(1) receptor-mediated proliferation and CysLT(2) receptor-mediated death.
Asunto(s)
Astrocitos/efectos de los fármacos , Hipoxia de la Célula/fisiología , Glucosa/deficiencia , Receptores de Leucotrienos/agonistas , Animales , Animales Recién Nacidos , Araquidonato 5-Lipooxigenasa/metabolismo , Astrocitos/enzimología , Western Blotting , Recuento de Células , Muerte Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Activación Enzimática/efectos de los fármacos , Activación Enzimática/fisiología , Espacio Extracelular/efectos de los fármacos , Espacio Extracelular/metabolismo , Inmunohistoquímica , Leucotrieno D4/farmacología , Proteínas de la Membrana/efectos de los fármacos , Proteínas de la Membrana/fisiología , Ratas , Receptores de Leucotrienos/efectos de los fármacos , Receptores de Leucotrienos/fisiología , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
OBJECTIVE: To determine whether the skilled reaching test is an objective method for evaluating long-term neurological deficits after focal cerebral ischemia in mice. METHODS: In a reaching box, mice were trained to reach food pellets with their left forelimb through a 0.5 cm slit for 3 weeks. Then focal cerebral ischemia was induced by occluding the right middle cerebral artery, and the percentage of success in obtaining food was observed for 4 weeks. In comparison, the neurological deficit score, the holding angle in an inclined board test, and right turns in a corner test were simultaneously performed. At the end of the experiments, brain infarcts and neuron densities were determined. RESULT: After focal cerebral ischemia, the percentage of success in the reaching test was reduced, the right turns in the corner test were increased, the neurological deficit score was increased, and the holding angle in the inclined board test was reduced as well. The holding angle recovered 5 d after ischemia, whereas other 3 indicators remained abnormal until 4 weeks. At the end of the experiments, the brain infarct volumes were increased, and the neuron densities in the cortex, hippocampal CA1 region and striatum were reduced in ischemic mice. CONCLUSION: The skill reaching test is an objective and stable method for evaluating long-term neurological deficits after focal cerebral ischemia in mice.
Asunto(s)
Isquemia Encefálica/fisiopatología , Trastornos del Movimiento/fisiopatología , Desempeño Psicomotor/fisiología , Animales , Conducta Animal/fisiología , Encéfalo/patología , Encéfalo/fisiopatología , Isquemia Encefálica/complicaciones , Recuento de Células , Masculino , Ratones , Ratones Endogámicos ICR , Trastornos del Movimiento/etiología , Examen Neurológico/métodos , Neuronas/patologíaRESUMEN
Cilostazol, a selective inhibitor of phosphodiesterase 3, exerts neuroprotective effects on acute brain injury after cerebral ischemia in rats. However, it is unknown whether cilostazol affects the subacute or chronic ischemic injury. In the present study, we evaluated the dose- and time-dependent effects of cilostazol on acute ischemic brain injury and the long-lasting effect on the late (subacute/chronic) injury in mice with focal cerebral ischemia induced by transient middle cerebral artery occlusion. We found that pre-treatment of cilostazol (injected i.p. at 30 min before ischemia) significantly ameliorated the acute injury 24 h after ischemia, and the effective doses were 3-10 mg/kg. The post-treatment of cilostazol (10 mg/kg) was effective on the acute injury when it was injected 1 and 2 h after ischemia. In addition, for the late injury, post-treatment of cilostazol (10 mg/kg, i.p., for 7 consecutive days after ischemia) attenuated neurological dysfunctions, brain atrophy and infarct volume. It also inhibited astrocyte proliferation/glial scar formation and accelerated the angiogenesis in the ischemic boundary zone 7 and 28 days after ischemia. Thus, we conclude that cilostazol protects against not only the acute injury, but also the late injury in mice with focal cerebral ischemia; especially it can modify brain remodeling, astrogliosis and angiogenesis.