ABSTRACT
Hydroquinone (HQ), a major benzene metabolite, occurs naturally in various plants and is manufactured for commercial use. Although HQ displays various biological effects, its neuroprotective effects following ischemic insults have not been investigated. In this study, we first examined neuroprotective effects of HQ in a rat model of transient focal cerebral ischemia. Animals were subjected to transient middle cerebral artery occlusion for 120 min. HQ (50 or 100 mg/kg) or vehicle was intraperitoneally administered once at 30 min after ischemia-reperfusion. Neuroprotection by treatment with 100 mg/kg of HQ was shown using evaluation of neurological deficits, positron-emission tomography (PET) and 2,3,5-triphenyltetrazoliumchloride (TTC) staining. In addition, HQ treatment significantly attenuated ischemia-induced Evans blue dye extravasation from blood vessels and significantly increased immunoreactivities of SMI-71 (an endothelial BBB marker) and glucose transporter-1 (GLUT-1, an endothelial cell marker) in ischemic cortex compared to the vehicle-treated ischemia-operated group. Confocal microscopy and western blot analysis also showed that HQ treatment maintained expressions of tight junction proteins (zonula occludens-1 and occludin) in the ischemic cortex. Post-treatment with HQ protected neurons from transient focal cerebral ischemic injury and the neuroprotective effect of HQ might be closely associated with prevention of BBB disruption via maintaining SMI-71 and GLUT-1 expressions as well as prevention of the degradation of zonula occludens-1 and occludin proteins.
Subject(s)
Blood-Brain Barrier/drug effects , Capillary Permeability/drug effects , Hydroquinones/pharmacology , Infarction, Middle Cerebral Artery/drug therapy , Neuroprotective Agents/pharmacology , Reperfusion Injury/prevention & control , Animals , Blood-Brain Barrier/metabolism , Blood-Brain Barrier/ultrastructure , Cytoprotection , Disease Models, Animal , Glucose Transporter Type 1/metabolism , Infarction, Middle Cerebral Artery/metabolism , Infarction, Middle Cerebral Artery/pathology , Infarction, Middle Cerebral Artery/physiopathology , Male , Motor Activity/drug effects , Occludin/metabolism , Positron-Emission Tomography , Rats, Sprague-Dawley , Reperfusion Injury/metabolism , Reperfusion Injury/pathology , Reperfusion Injury/physiopathology , Zonula Occludens-1 Protein/metabolismABSTRACT
Nuclear factor-kappa B (NFκB) signal is essential for neuronal survival and its activation may protect neuron against various stimuli. Since purinergic signals activate NFκB through the P2X7 receptor, we investigated the distinct pattern of NF-κB phosphorylation in neurons by P2X7 receptor activation following status epilepticus (SE) in an effort to understand the role of P2X7 receptor in epileptogenic insult. In non-SE animals, 2'(3')-O-(4-benzoyl)benzoyl adenosine 5'-triphosphate (BzATP, a P2X7R agonist) treatment increased only p52-Ser869 NF-κB phosphorylation in neuron. Following SE, p52-Ser865, p52-Ser869, p65-Ser276, p65-Ser311, p65-Ser468, and p65-Ser529 NF-κB phosphorylation was significantly decreased in CA1 and CA3 neurons. However, BzATP treatment prevented reductions in p65-Ser276, p65-Ser311, p65-Ser529, and p52-Ser869 NF-κB phosphorylations in CA1 and/or CA3 neurons induced by SE. Furthermore, BzATP treatment reduced SE-induced p65-Ser311, p65-Ser468, p65-Ser536, and p52-Ser869 NF-κB phosphorylations in astrocytes. These findings indicate that P2X7 functions may be involved in the regulation of SE-induced reactive astrocytes and neuronal degeneration via NF-κB phosphorylations in response to pilocarpine-induced SE in the rat hippocampus.
Subject(s)
Hippocampus/metabolism , NF-kappa B/metabolism , Receptors, Purinergic P2X7/metabolism , Status Epilepticus/metabolism , Animals , Hippocampus/diagnostic imaging , Hippocampus/pathology , Male , Phosphorylation/physiology , Radiography , Rats , Rats, Sprague-Dawley , Status Epilepticus/pathologyABSTRACT
Haemangioblastoma is a slow-growing, highly vascular tumour and typically occurs in the cerebellum but can also occur in the brainstem and spinal cord. Because of their hypervascularity and location, cerebellar haemangioblastomas can be difficult to remove. The purpose of preoperative embolization of haemangioblastomas is to decrease the intraoperative blood loss and to facilitate excision. However, the safety and efficacy of this procedure remain controversial. Here, we report the case of a man with cerebellar haemangioblastoma who underwent preoperative embolization with Onyx. The tumour was completely removed with minimal tumour bleeding. There was no complication related to embolization.
Subject(s)
Brain Neoplasms/surgery , Dimethyl Sulfoxide/therapeutic use , Embolization, Therapeutic , Hemangioblastoma/surgery , Polyvinyls/therapeutic use , Preoperative Care , Adult , Blood Loss, Surgical/prevention & control , Combined Modality Therapy , Humans , Male , Neoadjuvant Therapy , Treatment OutcomeABSTRACT
Bone adapts to its environment. Osteoblasts and osteocytes are subject to mechanical load in vivo. It has been shown that osteoblasts alter cytokine expression in response to mechanical loading. However, signal transduction pathways that mediate bone cell response to mechanical stimuli have not been elucidated. In this study, we report an increase in proinflammatory gene expression in response to fluid shear stress (FSS) in human mesenchymal stem cells (hMSCs) and mouse preosteoblasts. Fluid shear stress (FSS)-induced effect was blocked by the inhibition of the calcineurin-NFATc1 axis, thus implicating a role for nuclear factor of activated T cells (NFAT) signaling in mechanotransduction.
