scholarly journals Neuronal MCP-1 Expression in Response to Remote Nerve Injury

2001 ◽  
Vol 21 (1) ◽  
pp. 69-76 ◽  
Author(s):  
Alexander Flügel ◽  
Gerhard Hager ◽  
Andrea Horvat ◽  
Christoph Spitzer ◽  
Gamal M. A. Singer ◽  
...  
Keyword(s):  
T Cell ◽  
Inflammatory Responses ◽  
Nerve Lesion ◽  
Monocyte Chemoattractant ◽  
Direct Injury ◽  
Inflammatory Activation ◽  
The Central Nervous System ◽  
Inducible Protein ◽  
The Brain

Direct injury of the brain is followed by inflammatory responses regulated by cytokines and chemoattractants secreted from resident glia and invading cells of the peripheral immune system. In contrast, after remote lesion of the central nervous system, exemplified here by peripheral transection or crush of the facial and hypoglossal nerve, the locally observed inflammatory activation is most likely triggered by the damaged cells themselves, that is, the injured neurons. The authors investigated the expression of the chemoattractants monocyte chemoattractant protein MCP-1, regulation on activation normal T-cell expressed and secreted (RANTES), and interferon-gamma inducible protein IP10 after peripheral nerve lesion of the facial and hypoglossal nuclei. In situ hybridization and immunohistochemistry revealed an induction of neuronal MCP-1 expression within 6 hours postoperation, reaching a peak at 3 days and remaining up-regulated for up to 6 weeks. MCP-1 expression was almost exclusively confined to neurons but was also present on a few scattered glial cells. The authors found no alterations in the level of expression and cellular distribution of RANTES or IP10, which were both confined to neurons. Protein expression of the MCP-1 receptor CCR2 did not change. MCP-1, expressed by astrocytes and activated microglia, has been shown to be crucial for monocytic, or T-cell chemoattraction, or both. Accordingly, expression of MCP-1 by neurons and its corresponding receptor in microglia suggests that this chemokine is involved in neuron and microglia interaction.

Mouse Wnt genes exhibit discrete domains of expression in the early embryonic CNS and limb buds

Development ◽  
1993 ◽  
Vol 119 (1) ◽  
pp. 247-261 ◽  
Author(s):  
B.A. Parr ◽  
M.J. Shea ◽  
G. Vassileva ◽  
A.P. McMahon
Keyword(s):  
Limb Development ◽  
Expression Patterns ◽  
Limb Buds ◽  
Expression Studies ◽  
The Family ◽  
The Central Nervous System ◽  
Discrete Domains ◽  
Early Developmental ◽  
The Brain

Mutation and expression studies have implicated the Wnt gene family in early developmental decision making in vertebrates and flies. In a detailed comparative analysis, we have used in situ hybridization of 8.0- to 9.5-day mouse embryos to characterize expression of all ten published Wnt genes in the central nervous system (CNS) and limb buds. Seven of the family members show restricted expression patterns in the brain. At least three genes (Wnt-3, Wnt-3a, and Wnt-7b) exhibit sharp boundaries of expression in the forebrain that may predict subdivisions of the region later in development. In the spinal cord, Wnt-1, Wnt-3, and Wnt-3a are expressed dorsally, Wnt-5a, Wnt-7a, and Wnt-7b more ventrally, and Wnt-4 both dorsally and in the floor plate. In the forelimb primordia, Wnt-3, Wnt-4, Wnt-6 and Wnt-7b are expressed fairly uniformly throughout the limb ectoderm. Wnt-5a RNA is distributed in a proximal to distal gradient through the limb mesenchyme and ectoderm. Along the limb's dorsal-ventral axis, Wnt-5a is expressed in the ventral ectoderm and Wnt-7a in the dorsal ectoderm. We discuss the significance of these patterns of restricted and partially overlapping domains of expression with respect to the putative function of Wnt signalling in early CNS and limb development.

Rapid chemokine secretion from endothelial cells originates from 2 distinct compartments

Blood ◽  
2004 ◽  
Vol 104 (2) ◽  
pp. 314-320 ◽  
Author(s):  
Inger Øynebråten ◽  
Oddmund Bakke ◽  
Per Brandtzaeg ◽  
Finn-Eirik Johansen ◽  
Guttorm Haraldsen
Keyword(s):  
Endothelial Cells ◽  
T Cell ◽  
Innate Immune System ◽  
Intracellular Localization ◽  
Interferon Γ ◽  
Innate Immune ◽  
Monocyte Chemoattractant Protein 1 ◽  
Monocyte Chemoattractant ◽  
Rapid Release ◽  
Inducible Protein

Abstract The neutrophil-attracting chemokine interleukin 8 (IL-8) is stored in the Weibel-Palade body (WPB) of endothelial cells (ECs) from which it can be rapidly released after exposure to the secretagogues histamine or thrombin. In this manner, IL-8 may enable rapid recruitment of leukocytes to inflammatory sites. To explore the possible storage of EC-derived chemokines that may attract other subsets of leukocytes, we examined the intracellular localization and secretagogue responsiveness of growth-related oncogene α (GROα), monocyte chemoattractant protein-1 (MCP-1), eotaxin-3, interferon-γ-inducible protein 10 (IP-10), and regulated on activation, normal T-cell expressed and secreted (RANTES). While eotaxin-3, GROα, and MCP-1 were rapidly released from ECs, the release of the T-cell attractors RANTES and IP-10 was not sensitive to the secretagogues. Moreover, of the 3 former chemokines, only eotaxin-3 was stored in WPBs. GROα and MCP-1 resided mainly in smaller vesicles compatible with sorting to a different, histamine-responsive compartment, which has been described in ECs although not reported to contain chemokines. In conclusion, we propose that rapid release of chemokines is restricted to those primarily recruiting leukocytes of the innate immune system, and that their storage in ECs is not restricted to the WPB compartment. (Blood. 2004;104:314-320)

Cytosolic phospholipase A2α regulates induction of brain cyclooxygenase-2 in a mouse model of inflammation

2005 ◽  
Vol 288 (6) ◽  
pp. R1774-R1782 ◽  
Author(s):  
Adam Sapirstein ◽  
Hideyuki Saito ◽  
Sarah J. Texel ◽  
Tarek A. Samad ◽  
Eileen O’Leary ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Inflammatory Responses ◽  
Arachidonic Acid Metabolism ◽  
Cyclooxygenase 2 ◽  
Phospholipase A ◽  
Wild Type ◽  
Cytosolic Phospholipase ◽  
The Central Nervous System ◽  
Cox 2 ◽  
The Brain

The products of arachidonic acid metabolism are key mediators of inflammatory responses in the central nervous system, and yet we do not know the mechanisms of their regulation. The phospholipase A2 enzymes are sources of cellular arachidonic acid, and the enzymes cyclooxygenase-2 (COX-2) and microsomal PGE synthase-1 (mPGES-1) are essential for the synthesis of inflammatory PGE2 in the brain. These studies seek to determine the function of cytosolic phospholipase A2α (cPLA2α) in inflammatory PGE2 production in the brain. We wondered whether cPLA2α functions in inflammation to produce arachidonic acid or to modulate levels of COX-2 or mPGES-1. We investigated these questions in the brains of wild-type mice and mice deficient in cPLA2α (cPLA2α−/−) after systemic administration of LPS. cPLA2α−/− mice had significantly less brain COX-2 mRNA and protein expression in response to LPS than wild-type mice. The reduction in COX-2 was most apparent in the cells of the cerebral blood vessels and the leptomeninges. The brain PGE2 concentration of untreated cPLA2α−/− mice was equal to their wild-type littermates. After LPS treatment, however, the brain concentration of PGE2 was significantly less in cPLA2α−/− than in cPLA2α+/+ mice (24.4 ± 3.8 vs. 49.3 ± 11.6 ng/g). In contrast to COX-2, mPGES-1 RNA levels increased equally in both mouse genotypes, and mPGES-1 protein was unaltered 6 h after LPS. We conclude that cPLA2α regulates COX-2 levels and modulates inflammatory PGE2 levels. These results indicate that cPLA2α inhibition is a novel anti-inflammatory strategy that modulates, but does not completely prevent, eicosanoid responses.

scholarly journals Expression and distribution of synaptotagmin isoforms in the zebrafish retina

2020 ◽  
Author(s):  
Diane Henry ◽  
Christina Joselevitch ◽  
Gary G. Matthews ◽  
Lonnie P. Wollmuth
Keyword(s):  
Amino Acid ◽  
Large Family ◽  
Amino Acid Residues ◽  
Ribbon Synapses ◽  
The Family ◽  
Class 1 ◽  
The Central Nervous System ◽  
Asynchronous Release ◽  
The Brain

ABSTRACTSynaptotagmins belong to a large family of proteins. While various synaptotagmins have been implicated as Ca2+ sensors for vesicle replenishment and release at conventional synapses, their roles at retinal ribbon synapses remain incompletely understood. Zebrafish is a widely used experimental model for retinal research. We therefore investigated the homology between human, rat, mouse, and zebrafish synaptotagmins 1 to 10 using a bioinformatics approach. We also characterized the expression and distribution of various synaptotagmin (syt) genes in the zebrafish retina using RT-PCR and in situ hybridization, focusing on the family members whose products likely underlie Ca2+-dependent exocytosis in the central nervous system (synaptotagmins 1, 2, 5 and 7). We find that most zebrafish synaptotagmins are well conserved and can be grouped in the same classes as mammalian synaptotagmins, based on crucial amino acid residues needed for coordinating Ca2+ binding and determining phospholipid binding affinity. The only exception is synaptotagmin 1b, which lacks 34 amino acid residues in the C2B domain and is therefore unlikely to bind Ca2+ there. Additionally, the products of zebrafish syt5a and syt5b genes share identity with mammalian class 1 and 5 synaptotagmins. Zebrafish syt1, syt2, syt5 and syt7 paralogues are found in the zebrafish brain, eye, and retina, excepting syt1b, which is only present in the brain. The complementary expression pattern of the remaining paralogues in the retina suggests that syt1a and syt5a may underlie synchronous release and syt7a and syt7b may mediate asynchronous release or other Ca2+ dependent processes in different types of retinal neurons.

Nose to Brain Drug Delivery System: A Comprehensive Review

2020 ◽  
Vol 10 (4) ◽  
pp. 288-299
Author(s):  
Pankaj Kumar ◽  
Varun Garg ◽  
Neeraj Mittal
Keyword(s):  
Drug Delivery ◽  
Drug Delivery System ◽  
Delivery System ◽  
Anatomy And Physiology ◽  
Brain Drug Delivery ◽  
System A ◽  
Interesting Approach ◽  
The Central Nervous System ◽  
The Brain

Nose to brain drug delivery system is an interesting approach to deliver a drug directly in the brain through the nose. Intranasal drug delivery is very beneficial because it avoids first-pass metabolism and achieves a greater concentration of drugs in the central nervous system (CNS) at a low dose. This delivery system is used for the treatment of various neurological disorders such as Parkinson's disease, Alzheimer's disease, schizophrenia, dementia, brain cancer, etc. To treat such types of diseases, different formulations like nanoparticles (NPs), microemulsions, in situ gel, etc. can be used depending on the physiochemical properties of the drug. In this review, some essential characteristics related to the delivery of nose to the brain and their possible obstacles are underlined, which include anatomy and physiology of nose to brain delivery. This review also summarizes innovations from the past three to five years.

Arachidonic Acid Derivatives and Neuroinflammation

2021 ◽  
Vol 20 ◽  
Author(s):  
Era Gorica ◽  
Vincenzo Calderone
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Arachidonic Acid ◽  
Prostaglandin E2 ◽  
Phospholipase A2 ◽  
Inflammatory Responses ◽  
The Central Nervous System ◽  
The Brain ◽  
Arachidonic Acid Derivatives

: Neuroinflammation is characterized by dysregulated inflammatory responses localized within the brain and spinal cord. Neuroinflammation plays a pivotal role in the onset of several neurodegenerative disorders and is considered a typical feature of these disorders. Microglia perform primary immune surveillance and macrophage-like activities within the central nervous system. Activated microglia are predominant players in the central nervous system response to damage related to stroke, trauma, and infection. Moreover, microglial activation per se leads to a proinflammatory response and oxidative stress. During the release of cytokines and chemokines, cyclooxygenases and phospholipase A2 are stimulated. Elevated levels of these compounds play a significant role in immune cell recruitment into the brain. Cyclic phospholipase A2 plays a fundamental role in the production of prostaglandins by releasing arachidonic acid. In turn, arachidonic acid is biotransformed through different routes into several mediators that are endowed with pivotal roles in the regulation of inflammatory processes. Some experimental models of neuroinflammation exhibit an increase in cyclic phospholipase A2, leukotrienes, and prostaglandins such as prostaglandin E2, prostaglandin D2, or prostacyclin. However, findings on the role of the prostacyclin receptors have revealed that their signalling suppresses Th2-mediated inflammatory responses. In addition, other in vitro evidence suggests that prostaglandin E2 may inhibit the production of some inflammatory cytokines, attenuating inflammatory events such as mast cell degranulation or inflammatory leukotriene production. Based on these conflicting experimental data, the role of arachidonic acid derivatives in neuroinflammation remains a challenging issue.

scholarly journals Effect of olfactory bulb ablation on spread of a neurotropic coronavirus into the mouse brain.

1990 ◽  
Vol 172 (4) ◽  
pp. 1127-1132 ◽  
Author(s):  
S Perlman ◽  
G Evans ◽  
A Afifi
Keyword(s):  
Olfactory Bulb ◽  
Hepatitis Virus ◽  
Anterior Commissure ◽  
Olfactory Pathway ◽  
Surgical Ablation ◽  
Viral Transport ◽  
The Central Nervous System ◽  
Trigeminal Nerves ◽  
The Brain

Previous results suggested that, after intranasal inoculation, mouse hepatitis virus (MHV), a neurotropic coronavirus, entered the central nervous system (CNS) via the olfactory and trigeminal nerves. To prove this hypothesis, the effect of interruption of the olfactory pathway on spread of the virus was studied using in situ hybridization. Unilateral surgical ablation of this pathway prevented spread of the virus via the olfactory tract on the side of the lesion. MHV RNA could be detected, however, at distal sites on the operated side, indicating that the virus spread via well-described circuits involving the anterior commissure from the control (intact) side of the brain. Viral transport via the trigeminal nerve was not affected by removal of the olfactory bulb, showing that the surgical procedure was specific for the olfactory pathway. These results prove conclusively that MHV gains entry to the CNS via a transneuronal route, and spreads to additional sites in the brain via known neuroanatomic pathways.

scholarly journals High Frequency of Virus-Specific CD8+ T Cells in the Central Nervous System of Macaques Chronically Infected with Simian Immunodeficiency Virus SIVmac251

2003 ◽  
Vol 77 (22) ◽  
pp. 12346-12351 ◽  
Author(s):  
Marcin Moniuszko ◽  
Charlie Brown ◽  
Ranajit Pal ◽  
Elzbieta Tryniszewska ◽  
Wen-Po Tsai ◽  
...  
Keyword(s):  
Central Nervous System ◽  
T Cells ◽  
Nervous System ◽  
Simian Immunodeficiency Virus ◽  
Rhesus Macaques ◽  
Specific Response ◽  
Immunodeficiency Virus ◽  
The Central Nervous System ◽  
The Brain

ABSTRACT Infection with human immunodeficiency virus or simian immunodeficiency virus (SIV) induces virus-specific CD8+ T cells that traffic to lymphoid and nonlymphoid tissues. In this study, we used Gag-specific tetramer staining to investigate the frequency of CD8+ T cells in peripheral blood and the central nervous system of Mamu-A*01-positive SIV-infected rhesus macaques. Most of these infected macaques were vaccinated prior to SIVmac251 exposure. The frequency of Gag181-189 CM9 tetramer-positive cells was consistently higher in the cerebrospinal fluid and the brain than in the blood of all animals studied and did not correlate with either plasma viremia or CD4+-T-cell level. Little or no infection in the brain was documented for most animals by nucleic acid sequence-based amplification or in situ hybridization. These data suggest that this Gag-specific response may contribute to the containment of viral replication in this locale.

scholarly journals Overexpression of human IGF-II mRNA in the brain of transgenic mice modulates IGFBP-2 gene expression in the medulla oblongata

2004 ◽  
Vol 182 (3) ◽  
pp. 445-455 ◽  
Author(s):  
CM Reijnders ◽  
JG Koster ◽  
SC van Buul-Offers
Keyword(s):  
Transgenic Mice ◽  
Choroid Plexus ◽  
Expression Pattern ◽  
Medulla Oblongata ◽  
Granular Layer ◽  
Piriform Cortex ◽  
Igf I ◽  
The Central Nervous System ◽  
The Brain

The insulin-like growth factors, IGF-I and IGF-II, and their binding proteins play an important role in the growth and development of the central nervous system. In the brain, colocalization of IGFs and IGFBPs often occurs, suggesting that IGFBPs can modulate IGF action. In one strain of our human (h)IGF-II transgenic mice, which carry an hIGF-II transgene driven by the H-2Kb promoter, we found overexpression of hIGF-II in the brain, as measured by Northern blot analysis. To clarify the localization and influence of the hIGF-II transgene on different components of the GH-IGF axis in the brain, we studied the expression pattern of the hIGF-II transgene, endogenous IGF-I and IGF-II, and IGFBP-2, -3 and -5 in the brain of prepubertal 4-week-old mice, using nonradioactive in situ hybridization. We found that the hIGF-II transgene is exclusively expressed in neurons of the piriform cortex, the cerebral cortex, the medulla oblongata and the granular layer of the cerebellum. In general, this pattern is comparable to the expression pattern of endogenous IGF-I, with a few exceptions: there is no expression of IGF-I in the granular layer of the cerebellum, whereas the Purkinje cells of the cerebellum and thalamus both express IGF-I but no hIGF-II transgene. This hIGF-II transgene expression pattern contrasts markedly with endogenous IGF-II expression, which is mainly located in nonneuronal cells such as the meninges and choroid plexus, and in some nuclei of the medulla oblongata. The hIGF-II transgene affects neither endogenous IGF-I and IGF-II expression, nor the expression of IGFBP-3, which is located in the choroid plexus. Although the hIGF-II transgene is expressed in neuronal structures similar to IGF-I and IGFBP-5, it is not able to regulate IGFBP-5 expression, as has previously been reported for IGF-I. In the medulla oblongata, the IGFBP-2 expression level showed 10-fold upregulation by the transgene, suggesting a modulating role for IGFBP-2 at the hIGF-II transgene action in this region.

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