ABSTRACT
Background@#and Purpose Previous studies have revealed the diverse neuroprotective effects of GV1001. In this study, we investigated the effects of GV1001 on focal cerebral ischemia-reperfusion injury (IRI) in rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in neural stem cells (NSCs) and cortical neurons. @*Methods@#Focal cerebral IRI was induced by transient middle cerebral artery occlusion (MCAO). Brain diffusion-weighted imaging (DWI) was performed 2 hours after occlusion, and a total of 37 rats were treated by reperfusion with GV1001 or saline 2 hours after occlusion. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging, immunohistochemistry, and neurobehavioral function analyses were performed. Additionally, OGD/R-injured NSCs and cortical neurons were treated with different GV1001 concentrations. Cell viability, proliferation, migration, and oxidative stress were determined by diverse molecular analyses. @*Results@#In the stroke model, GV1001 protected neural cells against IRI. The most effective dose of GV1001 was 60 μM/kg. The infarct volume on FLAIR 48 hours after MCAO compared to lesion volume on DWI showed a significantly smaller ratio in the GV1001-treated group. GV1001-treated rats exhibited better behavioral functions than the saline-treated rats. Treatment with GV1001 increased the viability, proliferation, and migration of the OGD/R-injured NSCs. Free radicals were significantly restored by treatment with GV1001. These neuroprotective effects of GV1001 have also been demonstrated in OGD/R-injured cortical neurons. Conclusions The results suggest that GV1001 has neuroprotective effects against IRI in NSCs, cortical neurons, and the rat brain. These effects are mediated through the induction of cellular proliferation, mitochondrial stabilization, and anti-apoptotic, anti-aging, and antioxidant effects.
ABSTRACT
Background@#and Purpose Previous studies have revealed the diverse neuroprotective effects of GV1001. In this study, we investigated the effects of GV1001 on focal cerebral ischemia-reperfusion injury (IRI) in rats and oxygen-glucose deprivation/reoxygenation (OGD/R)-induced injury in neural stem cells (NSCs) and cortical neurons. @*Methods@#Focal cerebral IRI was induced by transient middle cerebral artery occlusion (MCAO). Brain diffusion-weighted imaging (DWI) was performed 2 hours after occlusion, and a total of 37 rats were treated by reperfusion with GV1001 or saline 2 hours after occlusion. Fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging, immunohistochemistry, and neurobehavioral function analyses were performed. Additionally, OGD/R-injured NSCs and cortical neurons were treated with different GV1001 concentrations. Cell viability, proliferation, migration, and oxidative stress were determined by diverse molecular analyses. @*Results@#In the stroke model, GV1001 protected neural cells against IRI. The most effective dose of GV1001 was 60 μM/kg. The infarct volume on FLAIR 48 hours after MCAO compared to lesion volume on DWI showed a significantly smaller ratio in the GV1001-treated group. GV1001-treated rats exhibited better behavioral functions than the saline-treated rats. Treatment with GV1001 increased the viability, proliferation, and migration of the OGD/R-injured NSCs. Free radicals were significantly restored by treatment with GV1001. These neuroprotective effects of GV1001 have also been demonstrated in OGD/R-injured cortical neurons. Conclusions The results suggest that GV1001 has neuroprotective effects against IRI in NSCs, cortical neurons, and the rat brain. These effects are mediated through the induction of cellular proliferation, mitochondrial stabilization, and anti-apoptotic, anti-aging, and antioxidant effects.
ABSTRACT
No abstract available.
Subject(s)
Anti-N-Methyl-D-Aspartate Receptor Encephalitis , Diagnostic Tests, RoutineABSTRACT
No abstract available.
Subject(s)
Asymptomatic Diseases , Carotid Artery, Internal , Carotid Stenosis , FingersABSTRACT
The authors recently found a mistake in their previously published article.
ABSTRACT
Leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5) has been reported to play critical roles in the proliferation of various cancer cells. However, the roles of LGR5 in brain tumors and the specific intracellular signaling proteins directly associated with it remain unknown. Expression of LGR5 was first measured in normal brain tissue, meningioma, and pituitary adenoma of humans. To identify the downstream signaling pathways of LGR5, siRNA-mediated knockdown of LGR5 was performed in SH-SY5Y neuroblastoma cells followed by proteomics analysis with 2-dimensional polyacrylamide gel electrophoresis (2D-PAGE). In addition, the expression of LGR5-associated proteins was evaluated in LGR5-inhibited neuroblastoma cells and in human normal brain, meningioma, and pituitary adenoma tissue. Proteomics analysis showed 12 protein spots were significantly different in expression level (more than two-fold change) and subsequently identified by peptide mass fingerprinting. A protein association network was constructed from the 12 identified proteins altered by LGR5 knockdown. Direct and indirect interactions were identified among the 12 proteins. HSP 90-beta was one of the proteins whose expression was altered by LGR5 knockdown. Likewise, we observed decreased expression of proteins in the hnRNP subfamily following LGR5 knockdown. In addition, we have for the first time identified significantly higher hnRNP family expression in meningioma and pituitary adenoma compared to normal brain tissue. Taken together, LGR5 and its downstream signaling play critical roles in neuroblastoma and brain tumors such as meningioma and pituitary adenoma.
Subject(s)
Humans , Brain , Brain Neoplasms , Cell Proliferation , Dermatoglyphics , Electrophoresis, Polyacrylamide Gel , GTP-Binding Proteins , Heterogeneous-Nuclear Ribonucleoproteins , Intracellular Signaling Peptides and Proteins , Meningioma , Neuroblastoma , Pituitary Neoplasms , ProteomicsABSTRACT
BACKGROUND AND PURPOSE: Neurogenesis in the adult brain is important for memory and learning, and the alterations in neural stem cells (NSCs) may be an important aspect of Alzheimer's disease (AD) pathogenesis. The phosphatidylinositol 3-kinase (PI3K) pathway has been suggested to have an important role in neuronal cell survival and is highly involved in adult neurogenesis. Candesartan is an angiotensin II receptor antagonist used for the treatment of hypertension and several studies have reported that it also has some neuroprotective effects. We investigated whether candesartan could restore the amyloid-β(25–35) (Aβ₂₅₋₃₅) oligomer-inhibited proliferation of NSCs by focusing on the PI3K pathway. METHODS: To evaluate the effects of candesartan on the Aβ₂₅₋₃₅ oligomer-inhibited proliferation of NSCs, the NSCs were treated with several concentrations of candesartan and/or Aβ₂₅₋₃₅ oligomers, and MTT assay and trypan blue staining were performed. To evaluate the effect of candesartan on the Aβ-inhibited proliferation of NSCs, we performed a bromodeoxyuridine (BrdU) labeling assay. The levels of p85α PI3K, phosphorylated Akt (pAkt) (Ser473), phosphorylated glycogen sinthase kinase-3β (pGSK-3β) (Ser9), and heat shock transcription factor-1 (HSTF-1) were analyzed by Western blotting. RESULTS: The BrdU assays demonstrated that NSC proliferation decreased with Aβ25-35 oligomer treatment; however, a combined treatment with candesartan restored it. Western blotting displayed that candesartan treatment increased the expression levels of p85α PI3K, pAkt (Ser473), pGSK-3β (Ser9), and HSTF. The NSCs were pretreated with a PI3K inhibitor, LY294002; the effects of candesartan on the proliferation of NSCs inhibited by Aβ₂₅₋₃₅ oligomers were almost completely blocked. CONCLUSIONS: Together, these results suggest that candesartan restores the Aβ₂₅₋₃₅ oligomer-inhibited proliferation of NSCs by activating the PI3K pathway.
Subject(s)
Adult , Humans , Alzheimer Disease , Amyloid , Blotting, Western , Brain , Bromodeoxyuridine , Cell Survival , Glycogen , Hot Temperature , Hypertension , Learning , Memory , Neural Stem Cells , Neurogenesis , Neurons , Neuroprotective Agents , Phosphatidylinositol 3-Kinase , Phosphatidylinositols , Receptors, Angiotensin , Shock , Trypan BlueABSTRACT
BACKGROUND AND PURPOSE: Alzheimer's disease (AD) is the most common form of dementia which typically manifests as loss of memory and cognitive functions. Currently, available treatments for AD provide only symptomatic improvement and the benefit is minimal. Stem cell therapy (SCT) has been considered a promising treatment option for AD. We investigated the caregiver's perception about implementation of SCT in their AD patients, and determined the factors related to SCT. METHODS: A total of 100 caregivers, who cared for their AD patients, were interviewed at two hospitals. Structured open and closed questions about SCT for AD were asked by trained interviewers using the conventional in-person method. In addition, 60 dementia-related physicians were randomly interviewed via an e-mail questionnaire. RESULTS: Of the 100 subjects, 61 caregivers replied that they wanted their AD patients to receive SCT. Approximately 50% of the caregivers expected high improvement in cognitive function, behavioral and psychological symptoms, and activities of daily living, and physical improvements among their AD patients. However, physicians had much lower expectations of improvements in the above parameters. Multi-variate analysis revealed that female gender [odds ratio (OR): 3.747, 95% confidence interval (CI): 1.425–9.851] and familiarity with stem cells (OR: 3.873, 95% CI: 1.290–11.622) were independently associated with caregivers' desire that their AD patients should undergo SCT. The major source of information on SCT was television (76.7%), and the most reliable source of information on SCT was physicians (83.6%). CONCLUSIONS: In this study, many caregivers of AD patients fantasized and overestimated the need for SCT in comparison with physicians' expectation. Therefore, it is necessary for physicians to develop strategies for educating caregivers about the appropriate risks and benefits of SCT.
Subject(s)
Female , Humans , Activities of Daily Living , Alzheimer Disease , Caregivers , Cognition , Dementia , Electronic Mail , Memory , Methods , Recognition, Psychology , Risk Assessment , Stem Cells , TelevisionABSTRACT
No abstract available.
Subject(s)
Cranial Irradiation , Leukoencephalopathies , Parkinsonian DisordersABSTRACT
No abstract available.
Subject(s)
Humans , Antibodies , Cerebellar Ataxia , Guillain-Barre SyndromeABSTRACT
Progressive multifocal leukoencephalopathy (PML) is a very rare and often fatal demyelinating disease of central nervous system (CNS), which mostly occurs in patients with immunosuppression such as acquired immunodeficiency syndrome (AIDS) patients, transplant patients and patients receiving chemotherapy. PML usually manifests with acute or subacute neurologic deficit. and its late diagnosis may lead death or significant permanent disability. We report a 33-year old man diagnosed with PML in AIDS, who initially presented with gradual onset of dementia. Most symptoms of PML were progressed rapidly for several months, and characterized by focal neurological symptoms. On the other hand, we were experienced in patients without focal neurological symptoms and ongoing overall cognitive decline slowly. Patients with immunosuppression can be presented in a variety of neurological symptoms, detailed examinations for cognitive functions were needed in early stage of the disease.
Subject(s)
Adult , Humans , Acquired Immunodeficiency Syndrome , Central Nervous System , Delayed Diagnosis , Dementia , Demyelinating Diseases , Drug Therapy , Hand , Immunosuppression Therapy , Leukoencephalopathy, Progressive Multifocal , Neurologic ManifestationsABSTRACT
BACKGROUND: Multiple sclerosis (MS) is a demyelinating disease of the central nervous system. Secondary amyloidosis can occur as a complication of chronic systemic inflammatory and infectious diseases. Until now there has been no report of secondary amyloidosis associated with MS. We report herein a case of renal biopsy-proven secondary amyloidosis in a patient with MS. CASE REPORT: A 41-year-old woman with MS was hospitalized due to aggravated quadriparesis and edema in both lower extremities. Laboratory findings showed nephrotic-range proteinuria and hypoalbuminemia. A percutaneous renal biopsy procedure was performed, the results of which revealed secondary amyloid-A-type amyloidosis associated with MS. CONCLUSIONS: This is the first report of secondary amyloidosis associated with MS.