Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0917798 (cerebral ischemia)
 17,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Contrast material enhancement for cross-sectional imaging has been used since the mid 1970s for computed tomography and the mid 1980s for magnetic resonance imaging. Knowledge of the patterns and mechanisms of contrast enhancement facilitate radiologic differential diagnosis. Brain and spinal cord enhancement is related to both intravascular and extravascular contrast material. Extraaxial enhancing lesions include primary neoplasms (meningioma), granulomatous disease (sarcoid), and metastases (which often manifest as mass lesions). Linear pachymeningeal (dura-arachnoid) enhancement occurs after surgery and with spontaneous intracranial hypotension. Leptomeningeal (pia-arachnoid) enhancement is present in meningitis and meningoencephalitis. Superficial gyral enhancement is seen after reperfusion in cerebral ischemia, during the healing phase of cerebral infarction, and with encephalitis. Nodular subcortical lesions are typical for hematogenous dissemination and may be neoplastic (metastases) or infectious (septic emboli). Deeper lesions may form rings or affect the ventricular margins. Ring enhancement that is smooth and thin is typical of an organizing abscess, whereas thick irregular rings suggest a necrotic neoplasm. Some low-grade neoplasms are "fluid-secreting," and they may form heterogeneously enhancing lesions with an incomplete ring sign as well as the classic "cyst-with-nodule" morphology. Demyelinating lesions, including both classic multiple sclerosis and tumefactive demyelination, may also create an open ring or incomplete ring sign. Thick and irregular periventricular enhancement is typical for primary central nervous system lymphoma. Thin enhancement of the ventricular margin occurs with infectious ependymitis. Understanding the classic patterns of lesion enhancement--and the radiologic-pathologic mechanisms that produce them--can improve image assessment and differential diagnosis.
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PMID:Patterns of contrast enhancement in the brain and meninges. 1737 67

The tumor necrosis factor superfamily (TNFSF) of cytokines comprises 19 ligands and 28 receptors (1). Ligand-mediated activation of TNFSF receptors plays a role in the pathogenesis of multiple central nervous system (CNS) diseases such as multiple sclerosis (2) and cerebral ischemia (3). Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the TNFSF (4) that binds a small cell surface receptor known as fibroblast growth factor-inducible 14 (Fn14) (5-7). There is a growing body of evidence indicating that the interaction between TWEAK and Fn14 plays a role on cell death, regulation of the permeability of the neurovascular unit (NVU) and development of an inflammatory response in the CNS under physiological and pathological conditions (8, 9). Accordingly, here we will review the information available to this date on the role of this cytokine and its receptor in the CNS.
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PMID:Tweak and FN14 in central nervous system health and disease. 1748 58

Tumor necrosis factor-like weak inducer of apoptosis (TWEAK) is a member of the tumor necrosis factor superfamily that acts on responsive cells via binding to a cell surface receptor named fibroblast growth factor-inducible 14 (Fn14). TWEAK can regulate numerous cellular responses in vitro and in vivo. Recent studies have indicated that TWEAK and Fn14 are expressed in the central nervous system (CNS), and that in response to a variety of stimuli, including cerebral ischemia, there is an increase in TWEAK and Fn14 expression in perivascular astrocytes, microglia, endothelial cells, and neurons with subsequent increase in the permeability of the blood-brain barrier (BBB) and cell death. Furthermore, there is a growing body of evidence indicating that TWEAK induces the activation of the NF-kappaB in the CNS with release of proinflammatory cytokines and matrix metalloproteinases. In addition, inhibition of TWEAK activity by either treatment with a Fn14-Fc fusion protein or neutralizing anti-TWEAK antibodies has shown therapeutic efficacy in animal models of ischemic stroke, cerebral edema, and multiple sclerosis.
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PMID:TWEAK and the central nervous system. 1791 14

Specialized glia, termed reactive astrocytes, accompany numerous pathologic conditions affecting the central nervous system, including stroke, multiple sclerosis, and neoplasia. To better define this important cell type, we employed high-density microarray gene expression profiling using two in vitro models of reactive gliosis (stimulation with dbcAMP or IL-1beta/IFNgamma). We identified 44 differentially expressed transcripts common to both in vitro models and demonstrated that a subset of these genes are also differentially expressed in response to experimental autoimmune encephalomyelitis and focal cerebral ischemia in vivo. Moreover, this pattern of differential gene expression is not observed in hyperproliferating or neoplastic glia.
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PMID:Expression profiling identifies a molecular signature of reactive astrocytes stimulated by cyclic AMP or proinflammatory cytokines. 1805 18

Bone marrow stromal cells are multipotential cells that can be induced to differentiate into osteoblasts, chondrocytes, myocytes and adipocytes in different microenvironments. Recent studies revealed that bone marrow stromal cells could improve neurological deficits of various damages or diseases of the central nervous system such as Parkinson's disease, brain trauma, spinal cord injury and multiple sclerosis, and promote glia-axonal remodeling in animal brain subjected to an experimentally induced stroke. In the present study, bone marrow stromal cells were intracerebrally transplanted into the cerebrum following a transient middle cerebral artery occlusion. Our aim was to find out whether the bone marrow stromal cells could survive and express neural phenotypic proteins and, in addition, whether they could restore the behavioral and functional deficits of the cerebral ischemic rats. Our results demonstrated that transplanted bone marrow stromal cells survived and migrated to areas around the lesion site. Some of them exhibited marker proteins of astrocytes and oligodendrocytes. Bone marrow stromal cell implantation significantly reduced the transient middle cerebral artery occlusion-induced cortical loss and thinning of the white matter and enhanced cortical beta-III-tubulin immunoreactivity. Rats implanted with bone marrow stromal cells showed significant improvement in their performance of elevated body swing test and forelimb footprint analysis and only transient recovery of the adhesive-removal test. Our data support bone marrow stromal cells as a valuable source of autologous or allogenic donor cells for transplantation to improve the outcome following cerebral ischemia.
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PMID:Transplanted bone marrow stromal cells migrate, differentiate and improve motor function in rats with experimentally induced cerebral stroke. 1864 94

Calpain is a ubiquitous calcium-sensitive protease that is essential for normal physiologic neuronal function. However, alterations in calcium homeostasis lead to persistent, pathologic activation of calpain in a number of neurodegenerative diseases. Pathologic activation of calpain results in the cleavage of a number of neuronal substrates that negatively affect neuronal structure and function, leading to inhibition of essential neuronal survival mechanisms. In this review, we examine the mechanistic underpinnings of calcium dysregulation resulting in calpain activation in the acute neurodegenerative diseases such as cerebral ischemia and in the chronic neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, Huntington's disease, multiple sclerosis, prion-related encephalopathy, and amylotrophic lateral sclerosis. The premise of this paper is that analysis of the signaling and transcriptional consequences of calpain-mediated cleavage of its various substrates for any neurodegenerative disease can be extrapolated to all of the neurodegenerative diseases vulnerable to calcium dysregulation.
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PMID:Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration. 1868 46

Minocycline is a semi-synthetic, second-generation tetracycline analog which is effectively crossing the blood-brain barrier, effective against gram-positive and -negative infections. In addition to its own antimicrobacterial properties, minocycline has been reported to exert neuroprotective effects over various experimental models such as cerebral ischemia, traumatic brain injury, amyotrophic lateral sclerosis, Parkinson's disease, kainic acid treatment, Huntington' disease and multiple sclerosis. Minocycline has been focused as a neuroprotective agent over neurodegenerative disease since it has been first reported that minocycline has neuroprotective effects in animal models of ischemic injury [Yrjanheikki J, Keinanen R, Pellikka M, Hokfelt T, Koisinaho J. Tetracyclines inhibit microglial activation and are neuroprotective in global brain ischemia. Proc Natl Acad Sci USA 1998;95:15769-74; Yrjanheikki J, Tikka T, Keinanen R, Goldsteins G, Chan PH, Koistinaho J. A tetracycline derivative, minocycline, reduces inflammation and protects against focal cerebral ischemia with a wide therapeutic window. Proc Natl Acad Sci USA 1999;96:13496-500]. Recently, the effect of minocycline on Alzheimer's disease has been also reported. Although its precise primary target is not clear, the action mechanisms of minocycline for neuroprotection reported so far are; via; the inhibition of mitochondrial permeability-transition mediated cytochrome c release from mitochondria, the inhibition of caspase-1 and -3 expressions, and the suppression of microglial activation, involvement in some signaling pathways, metalloprotease activity inhibition. Because of the high tolerance and the excellent penetration into the brain, minocycline has been clinically tried for some neurodegenerative diseases such as stroke, multiple sclerosis, spinal cord injury, amyotropic lateral sclerosis, Hungtington's disease and Parkinson's disease. This review will briefly summarize the effects and action mechanisms of minocycline on neurodegenerative diseases.
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PMID:Minocycline and neurodegenerative diseases. 1897 95

Recognition of the importance of the endocannabinoid system in both homeostasis and pathologic responses raised interest recently in the development of therapeutic agents based on this system. The CB(2) receptor, a component of the endocannabinoid system, has significant influence on immune function and inflammatory responses. Inflammatory responses are major contributors to central nervous system (CNS) injury in a variety of diseases. In this report, we present evidence that activation of CB(2) receptors, by selective CB(2) agonists, reduces inflammatory responses that contribute to CNS injury. The studies demonstrate neuroprotective effects in experimental autoimmune encephalomyelitis, a model of multiple sclerosis, and in a murine model of cerebral ischemia/reperfusion injury. In both cases, CB(2) receptor activation results in reduced white cell rolling and adhesion to cerebral microvessels, a reduction in immune cell invasion, and improved neurologic function after insult. In addition, administration of the CB(1) antagonist SR141716A reduces infarct size following ischemia/reperfusion injury. Administration of both a selective CB(2) agonist and a CB(1) antagonist has the unique property of increasing blood flow to the brain during the occlusion period, suggesting an effect on collateral blood flow. In summary, selective CB(2) receptor agonists and CB(1) receptor antagonists have significant potential for neuroprotection in animal models of two devastating diseases that currently lack effective treatment options.
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PMID:Modulation of cannabinoid receptor activation as a neuroprotective strategy for EAE and stroke. 1925 56

We performed a study on levels of the total prion protein (PrP) in humans affected by different neurological diseases and assessed the influence of several factors such as age, gender, and disease severity on the cerebrospinal fluid PrP levels. PrP-ELISA technique was used to analyze cerebrospinal fluid (CSF) samples. 293 CSF samples of patients with Creutzfeldt-Jakob-disease (CJD), Alzheimer's disease, dementia with Lewy-bodies, Parkinson's disease, multiple sclerosis, cerebral ischemia, generalized epileptic seizures, and meningitis and encephalitis in comparison to controls were analyzed. We found a significant reduction of CSF PrP levels in patients suffering from all neurodegenerative disorders analyzed. This group exhibited mean PrP values of 164 ng/ml while non-neurodegenerative disorder patients and healthy controls showed PrP levels of 208 ng/ml and 226 ng/ml, respectively. CSF levels correlated with disease severity in CJD, Alzheimer's disease, and dementia with Lewy-bodies. The finding of decreased PrP levels in the CSF of patients not only with CJD but also in other neurodegenerative disorders is intriguing. Age-, gender-, and genetic-specific factors might be involved in the PrP c regulation.
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PMID:Total prion protein levels in the cerebrospinal fluid are reduced in patients with various neurological disorders. 1954 14

Superparamagnetic iron oxide nanoparticles have diverse diagnostic and potential therapeutic applications in the central nervous system (CNS). They are useful as magnetic resonance imaging (MRI) contrast agents to evaluate: areas of blood-brain barrier (BBB) dysfunction related to tumors and other neuroinflammatory pathologies, the cerebrovasculature using perfusion-weighted MRI sequences, and in vivo cellular tracking in CNS disease or injury. Novel, targeted, nanoparticle synthesis strategies will allow for a rapidly expanding range of applications in patients with brain tumors, cerebral ischemia or stroke, carotid atherosclerosis, multiple sclerosis, traumatic brain injury, and epilepsy. These strategies may ultimately improve disease detection, therapeutic monitoring, and treatment efficacy especially in the context of antiangiogenic chemotherapy and antiinflammatory medications. The purpose of this review is to outline the current status of superparamagnetic iron oxide nanoparticles in the context of biomedical nanotechnology as they apply to diagnostic MRI and potential therapeutic applications in neurooncology and other CNS inflammatory conditions.
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PMID:Superparamagnetic iron oxide nanoparticles: diagnostic magnetic resonance imaging and potential therapeutic applications in neurooncology and central nervous system inflammatory pathologies, a review. 1975 21


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