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Cerebral Tissue (cerebral + tissue)
Terms modified by Cerebral Tissue Selected AbstractsProteomic Identification of the Involvement of the Mitochondrial Rieske Protein in EpilepsyEPILEPSIA, Issue 3 2005Heike Junker Summary:,Purpose: Kindled seizures are widely used to model epileptogenesis, but the molecular mechanisms underlying the attainment of kindling status are largely unknown. Recently we showed that achievement of kindling status in the Sprague,Dawley rat is associated with a critical developmental interval of 25 ± 1 days; the identification of this long, well-defined developmental interval for inducing kindling status makes possible a dissection of the cellular and genetic events underlying this phenomenon and its relation to normal and pathologic brain function. Methods: By using proteomics on cerebral tissue from our new rat kindling model, we undertook a global analysis of protein expression in kindled animals. Some of the identified proteins were further investigated by using immunohistochemistry. Results: We report the identification of a modified variant of the Rieske iron-sulfur protein, a component of the mitochondrial cytochrome bc1 complex, whose isoelectric point is shifted toward more alkaline values in the hippocampus of kindled rats. By immunohistochemistry, the Rieske protein is well expressed in the hippocampus, except in the CA1 subfield, an area of selective vulnerability to seizures in humans and animal models. We also noted an asymmetric, selective expression of the Rieske protein in the subgranular neurons of the dorsal dentate gyrus, a region implicated in neurogenesis. Conclusions: These results indicate that the Rieske protein may play a role in the response of neurons to seizure activity and could give important new insights into the molecular pathogenesis of epilepsy. [source] Cooperation between toll-like receptor,2 and,4 in the brain of mice challenged with cell wall components derived from gram-negative and gram-positive bacteriaEUROPEAN JOURNAL OF IMMUNOLOGY, Issue 4 2003Nathalie Laflamme Abstract In this study we investigated whether induction of toll-like receptor,2 (TLR2) amplifies the effect of a cell wall component derived from gram-positive bacteria, namely peptidoglycan (PGN). Mice received a first systemic lipopolysaccharide (LPS) injection to pre-induce TLR2 in various regions of the brain, and 6,h later, a second administration of either LPS or PGN. The data show a robust transcriptional activation of TLR2, TNF-, and monocyte chemotactic protein-1 (MCP-1) in microglial cells of mice challenged twice with LPS, whereas PGN essentially abolished this response. TLR4 plays a critical role in this process, because C3H/HeJ mice no longer responded to LPS but exhibited a normal reaction to PGN. Conversely, a robust signal for genes encoding innate immune proteinswas found in the brain of TLR2-deficient mice challenged with LPS. However, the second LPS bolus failed to trigger TNF-, and IL-12 in TLR2-deficient mice, while the same treatment caused a strong induction of these genes in the cerebral tissue of wild-type littermates. The present data provide evidence that cooperation exists between TLR4 and TLR2. While TLR4 is absolutely necessary to engage the innate immune response in the brain, TLR2 participates in the regulation of genes encoding TNF-, and IL-12 during severe endotoxemia. Such collaboration between TLR4 and TLR2 may be determinant for the transfer from the innate to the adaptive immunity within the CNS of infected animals. [source] Diabetes hyperglycemia and recovery from strokeGERIATRICS & GERONTOLOGY INTERNATIONAL, Issue 1-2 2001Christopher S Gray Strokeis a major cause of death and severe disability in older people. Despite the burden of disease, there is still no safe, simple and proven medical therapy for the treatment of acute stroke. Advances in acute stroke treatment have been either consistently disappointing (neuroprotective therapy) or fraught with controversy regarding risk/benefit (thrombolysis), and attention is once again being directed towards physiological variables that may influence outcome. Both insulin-dependent and non-insulin-dependent diabetes mellitus are major risk factors for stroke. Diabetes mellitus has also been shown to be associated with increased mortality and reduced functional outcome after stroke. Hyperglycemia is a frequent finding following stroke and may reflect the metabolic stress of the acute event, so-called stress hyperglycemia, and/or underlying impaired glucose metabolism. Several large clinical studies have now demonstrated a positive association between a raised blood glucose and poor outcome from stroke; greater mortality and reduced functional recovery. What is not clear is to what extent hyperglycemia is a ,normal' physiological response to stroke or whether hyperglycemia per se increases cerebral damage in the acute phase. There are many potential mechanisms by which hyperglycemia can exert a harmful effect upon cerebral tissue and it is probable that an important relationship exists, not only between glucose and stroke outcome, but also between insulin and neuroprotection. It remains to be determined whether lowering and maintaining ,normal' glucose levels in the immediate aftermath of stroke, combined with the administration of insulin as an acute treatment, can modify this outcome. [source] Elastin-derived peptides: Matrikines critical for glioblastoma cell aggressiveness in a 3-D systemGLIA, Issue 16 2009Bérénice Coquerel Abstract In the most common primary brain tumors, malignant glioma cells invade the extracellular matrix (ECM) and proliferate rapidly in the cerebral tissue, which is mainly composed of hyaluronan (HA) along with the elastin present in the basement membrane of blood vessels. To determine the role of ECM components in the invasive capacity of glioma cell lines, we developed a 3-D cell-culture system, based on a hydrogel in which HA can be coreticulated with kappa-elastin (HA-,E). Using this system, the invasiveness of cells from four glioma cell lines was dramatically increased by the presence of ,E and a related, specific peptide (VGVAPG)3. In addition, MMP-2 secretion increased and MMP-12 synthesis occurred. Extracellular injections of ,E or (VGVAPG)3 provoked a pronounced and dose-dependent increase in [Ca2+]i. ,E significantly enhanced the expression of the genes encoding elastin-receptor and tropoelastin. We propose the existence of a positive feedback loop in which degradation of elastin generates fragments that stimulate synthesis of tropoelastin followed by further degradation as well as migration and proliferation of the very cells responsible for degradation. All steps in this ECM-based loop could be blocked by the addition of either of the EBP antagonists, lactose, and V-14 peptide, suggesting that the loop itself should be considered as a new therapeutic target. © 2009 Wiley-Liss, Inc. [source] Prion diseases: contribution of high-resolution immunomorphologyJOURNAL OF CELLULAR AND MOLECULAR MEDICINE, Issue 4 2001J-G. Fournier Abstract The transmisible spongiform encephalopathies or prion diseases are fatal neurological diseases that occur in animals and humans. They are characterized by the accumulation in the cerebral tissue of the abnormal form of prion protein (PrPsc) produced by a post-translational event involving conformational change of its normal cellular counterpart (PrPc). In this short review, we present some results on the biology of prion proteins which have benefited from morphological approaches combining the electron microscopy techniques and the immunodetection methods. We discuss data concerning in particular the physiological function of the normal cellular prion prion (PrPc) which have allowed to open up new vistas on prion diseases, the biogenesis of amyloid plaque and the cellular site involved in the prion protein conversion process. [source] Synergistic inhibitory effect of ascorbic acid and acetylsalicylic acid on prostaglandin E2 release in primary rat microgliaJOURNAL OF NEUROCHEMISTRY, Issue 1 2003Bernd L. Fiebich Abstract Ascorbic acid (vitamin C) has been suggested to protect cerebral tissue in a variety of pathophysiological situations such as head trauma, ischemia or Alzheimer's disease. Most of these protective actions have been attributed to the antioxidative capacity of ascorbic acid. Besides the presence of elevated levels of oxygen radicals, prostaglandins produced by neurones and microglial cells seem to play an important role in prolonged tissue damage. We investigated whether ascorbic acid alone inhibits prostaglandin E2 (PGE2) synthesis and may augment the inhibitory effect of acetylsalicylic acid on prostaglandin synthesis. Ascorbic acid dose-dependently inhibited PGE2 synthesis in lipopolysaccharide-treated primary rat microglial cells (IC50 = 3.70 µm). In combination with acetylsalicylic acid (IC50 = 1.85 µm), ascorbic acid augmented the inhibitory effect of acetylsalicylic acid on PGE2 synthesis (IC50 = 0.25 µm in combination with 100 µm ascorbic acid). Ascorbic acid alone or in combination with acetylsalicylic acid did not inhibit cyclooxygenase-2 (COX-2) protein synthesis but inhibited COX-2 enzyme activity. Our results show that ascorbic acid and acetylsalicylic acid act synergistically in inhibiting PGE2 synthesis, which may help to explain a possible protective effect of ascorbic acid in various brain diseases. [source] Circulating cell wall components derived from gram-negative, not gram-positive, bacteria cause a profound induction of the gene-encoding Toll-like receptor 2 in the CNSJOURNAL OF NEUROCHEMISTRY, Issue 3 2001Nathalie Laflamme The recent characterization of human homologs of Toll may be the missing link for the transduction events leading to nuclear factor-,B (NF-,B) activity and proinflammatory gene transcription during innate immune response. Mammalian cells may express as many as 10 distinct Toll-like receptors (TLRs), although TLR2 is a key receptor for recognizing cell wall components of Gram-positive bacteria. The present study investigated the effects of circulating bacterial cell wall components on the expression of the gene-encoding TLR2 across the mouse brain. Surprisingly, while Gram-negative components caused a robust increase in TLR2 transcription within the cerebral tissue, peptidoglycan (PGN) and lipoteichoic acid (LTA), either alone or combined, failed to modulate the receptor transcript. Indeed, the mRNA levels for TLR2 in the choroid plexus and few other regions of the brain remained similar between vehicle-, LTA-, PGN-, and LTA/PGN-administered mice at all the times evaluated (i.e. 30 min to 24 h post-intraperitoneal injection). This contrasts with the profound de novo expression of TLR2 following a single systemic injection of the lipopolysaccharide (LPS). The signal was first detected in regions devoid of blood,brain barrier and few blood vessels and microcapillaries. A second wave of TLR2 expression was also detected from these structures to their surrounding parenchymal cells that stained for a microglial marker iba1. The rapid induction of I,B, (index of NF-,B activity) and up-regulation of the adaptor protein MyD88 suggest that LPS-induced TLR2 transcription may be dependent on the NF-,B pathway. These data provide the evidence that TLR2 is not only present in the brain, but its encoding gene is regulated by cell wall components derived from Gram-negative, not Gram-positive, bacteria. The robust wave of TLR2-expressing microglial cells may have a determinant impact on the innate immune response that occurs in the brain during systemic infection by Gram-negative, not Gram-positive, bacteria. [source] Remyelination can be extensive in multiple sclerosis despite a long disease courseNEUROPATHOLOGY & APPLIED NEUROBIOLOGY, Issue 3 2007R. Patani Experimental studies using models of multiple sclerosis (MS) indicate that rapid and extensive remyelination of inflammatory demyelinated lesions is not only possible, but is the normal situation. The presence of completely remyelinated MS lesions has been noted in numerous studies and routine limited sampling of post mortem MS material suggests that remyelination may be extensive in the early stages but eventually fails. However, visual macroscopic guided sampling tends to be biased towards chronic demyelinated lesions. Here we have extensively sampled cerebral tissue from two MS cases to investigate the true extent of remyelination. Sections were cut from 185 cerebral tissue blocks and stained with haematoxylin and eosin (H&E), luxol fast blue and cresyl fast violet (LFB/CFV) and anti-myelin oligodendrocyte glycoprotein, human leucocyte antigen-DR (HLA-DR) and 200 kDa neurofilament protein antibodies. Demyelinated areas were identified in 141 blocks, comprising both white matter (WMLs) and/or grey matter lesions. In total, 168 WMLs were identified, 22% of which were shadow plaques, 73% were partially remyelinated and only 5% were completely demyelinated. The average extent of lesion remyelination for all WMLs investigated was 47%. Increased density of HLA-DR+ macrophages and microglia at the lesion border correlated significantly with more extensive remyelination. Results from this study of two patients with long standing disease suggest that remyelination in MS may be more extensive than previously thought. [source] Cerebral Mass Due to Neurocutaneous Melanosis: Eight Years LaterPEDIATRIC DERMATOLOGY, Issue 5 2001Julie V. Schaffer M.D. Neurocutaneous melanosis (NCM) is associated most commonly with giant congenital melanocytic nevi (CMN), in particular those on the scalp or in a posterior axial location that are accompanied by satellite congenital nevi. It also can occur in patients with multiple medium-sized CMN. In general, the prognosis of those with symptomatic NCM is poor, even in the absence of malignancy, while the prognosis of those with asymptomatic NCM detected via screening varies and is more difficult to predict. Herein we report an asymptomatic patient with a giant CMN and multiple satellite nevi who had a screening magnetic resonance imaging (MRI) study at age 5 months that showed a rounded area of increased signal in the right temporal lobe on T1-weighted images, suggestive of parenchymal melanosis. This melanotic mass was resected at age 10 months, and histologic examination of the surgical specimen showed prominent perivascular collections of benign, pigment-containing melanocytes within cerebral tissue. The patient remains healthy 8 years later. His excellent long-term outcome and other reports of NCM with localized central nervous system (CNS) involvement apparent on MRI may have implications for management, including early imaging of patients with high-risk CMN and potential surgical intervention for NCM. [source] Protection of Mouse Brain from Aluminum-induced Damage by Caffeic AcidCNS: NEUROSCIENCE AND THERAPEUTICS, Issue 1 2008Jun-Qing Yang The natural product caffeic acid is a specific inhibitor of 5-lipoxygenase (5-LOX); it also possesses antioxidant and antiinflammatory properties. The current study was designed to determine whether the neuroprotective properties of caffeic acid are due to inhibition of 5-LOX. Cerebral damage was induced in mice by intracerebroventricular microinjection of aluminum (5.0 ,g aluminum in 2.0 ,L, once a day, for 5 days). Caffeic acid was administered intragastrically at 30 min prior to aluminum and repeated daily for an additional 10 days. The brain injury was determined by observation of behavioral changes in mice, as well as by measuring biochemical and pathological changes in the cerebral tissue. The levels of 5-LOX proteins and 5-LOX mRNA expression were measured in brain tissue. Aluminum impaired learning and memory in mice produced neuronal death in hippocampi, elevated brain malondialdehyde levels, increased protein expression of amyloid precursor protein (APP), amyloid beta, and 5-LOX. It also increased 5-LOX mRNA expression and decreased choline acetyl transferase (ChAT) protein expression in the brain tissue of mice. Caffeic acid prevented brain damage as well as behavioral and biochemical changes caused by aluminum overload. The results of this study suggest that overexpression of 5-LOX accompanies the cerebral injury induced by aluminum overload in mice, and that selective inhibitors of 5-LOX may have potential value in the treatment of aluminum neurotoxicity and conceivably of diseases associated with neuronal injury. [source] High transcytosis of melanotransferrin (P97) across the blood,brain barrierJOURNAL OF NEUROCHEMISTRY, Issue 4 2002Michel Demeule Abstract The blood,brain barrier (BBB) performs a neuroprotective function by tightly controlling access to the brain; consequently it also impedes access of proteins as well as pharmacological agents to cerebral tissues. We demonstrate here that recombinant human melanotransferrin (P97) is highly accumulated into the mouse brain following intravenous injection and in situ brain perfusion. Moreover, P97 transcytosis across bovine brain capillary endothelial cell (BBCEC) monolayers is at least 14-fold higher than that of holo-transferrin, with no apparent intra-endothelial degradation. This high transcytosis of P97 was not related to changes in the BBCEC monolayer integrity. In addition, the transendothelial transport of P97 was sensitive to temperature and was both concentration- and conformation-dependent, suggesting that the transport of P97 is due to receptor-mediated endocytosis. In spite of the high degree of sequence identity between P97 and transferrin, a different receptor than the one for transferrin is involved in P97 transendothelial transport. A member of the low-density lipoprotein receptor protein family, likely LRP, seems to be involved in P97 transendothelial transport. The brain accumulation, high rate of P97 transcytosis and its very low level in the blood suggest that P97 could be advantageously employed as a new delivery system to target drugs directly to the brain. [source] | |||||||||||||