scholarly journals CX3CL1 Recruits NK Cells Into the Central Nervous System and Aggravates Brain Injury of Mice Caused by Angiostrongylus cantonensis Infection

2021 ◽  
Vol 11 ◽  
Author(s):  
Rong Zhang ◽  
Tingting Miao ◽  
Min Qin ◽  
Chengsi Zhao ◽  
Wei Wang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Nervous System ◽  
Brain Injury ◽  
Nk Cells ◽  
Brain Tissue ◽  
Brain Damage ◽  
Adoptive Transfer ◽  
Angiostrongylus Cantonensis ◽  
The Brain

BackgroundAngiostrongylus cantonensis (A. cantonensis), is a food-borne zoonotic parasite that can cause central nervous system (CNS) injury characterized by eosinophilic meningitis. However, the pathogenesis of angiostrongylosis remains elusive. Natural killer cells (NK cells) are unique innate lymphocytes important in early defense against pathogens. The aim of this study was to investigate the role of NK cells in A. cantonensis infection and to elucidate the key factors that recruit NK cells into the CNS.MethodsMouse model of A. cantonensis infection was established by intragastric administration of third-stage larvae. The expression of cytokines and chemokines at gene and protein levels was analyzed by qRT-PCR and ELISA. Distribution of NK cells was observed by immunohistochemistry and flow cytometry. NK cell-mediated cytotoxicity against YAC-1 cells was detected by LDH release assay. The ability of NK cells to secrete cytokines was determined by intracellular flow cytometry and ELISA. Depletion and adoptive transfer of NK cells in vivo was induced by tail vein injection of anti-asialo GM1 rabbit serum and purified splenic NK cells, respectively. CX3CL1 neutralization experiment was performed by intraperitoneal injection of anti-CX3CL1 rat IgG.ResultsThe infiltration of NK cells in the CNS of A. cantonensis-infected mice was observed from 14 dpi and reached the peak on 18 and 22 dpi. Compared with uninfected splenic NK cells, the CNS-infiltrated NK cells of infected mice showed enhanced cytotoxicity and increased IFN-γ and TNF-α production ability. Depletion of NK cells alleviated brain injury, whereas adoptive transfer of NK cells exacerbated brain damage in A. cantonensis-infected mice. The expression of CX3CL1 in the brain tissue and its receptor CX3CR1 on the CNS-infiltrated NK cells were both elevated after A. cantonensis infection. CX3CL1 neutralization reduced the percentage and absolute number of the CNS-infiltrated NK cells and relieved brain damage caused by A. cantonensis infection.ConclusionsOur results demonstrate that the up-regulated CX3CL1 in the brain tissue recruits NK cells into the CNS and aggravates brain damage caused by A. cantonensis infection. The findings improve the understanding of the pathogenesis of angiostrongyliasis and expand the therapeutic intervention in CNS disease.

scholarly journals NK cells infiltrating in the central nervous system aggravate brain injury of mice caused by Angiostrongylus cantonensis infection

2020 ◽  
Author(s):  
Rong Zhang ◽  
Tingting Miao ◽  
Min Qin ◽  
Chengsi Zhao ◽  
Wei Wang ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Flow Cytometry ◽  
Nervous System ◽  
Brain Injury ◽  
Nk Cells ◽  
Brain Damage ◽  
Adoptive Transfer ◽  
Angiostrongylus Cantonensis ◽  
Tail Vein ◽  
Tail Vein Injection

Abstract Background Angiostrongylus cantonensis (A. cantonensis), is a food-borne zoonotic parasite that can cause central nervous system (CNS) injury characterized by eosinophilic meningitis. However, the pathogenesis of the neurological impairments caused by A. cantonensis infection has not been well elucidated. Natural killer cells (NK cells) are unique innate lymphocytes important in early defense against pathogens. It was reported that NK cells could migrate to the CNS after brain injury. The aim of the present study was to investigate the role of NK cells in brain injury caused by A. cantonensis infection.Methods Mouse model of A. cantonensis infection was established by intragastric administration of third-stage larvae. Neurological impairments were evaluated by Longa’s score, Clark’s general score and Clark’s focal score. Histopathological changes were observed by hematoxylin and eosin staining. The expression of cytokines at gene and protein levels was analyzed by PCR and ELISA, respectively. Infiltration of NK cells in the CNS was detected by immunohistochemistry and flow cytometry. Depletion of NK cells in infected mice was caused by tail vein injection of anti-asialo GM1 rabbit serum, and adoptive transfer of NK cells was performed by tail vein injection of purified splenic NK cells. NK cell-mediated cytotoxicity against YAC-1 cells was detected by LDH release assay. The cytokine production ability was determined by intracellular flow cytometry and ELISA.Results Mice developed brain inflammation and neurological impairment after A. cantonensis infection. The infiltration of NK cells in the CNS of A. cantonensis-infected mice was observed on 14 dpi and reached the peak on 22 dpi. Compared with the normal splenic NK cells, the CNS-infiltrated NK cells of infected mice expressed lower levels of CD69, NKp46 and NKG2D, but higher levels of NKG2A, and showed enhanced cytotoxicity and increased IFN-γ and TNF-α production ability. Depletion of NK cells alleviated brain injury, whereas adoptive transfer of NK cells exacerbated brain damage in A. cantonensis-infected mice.Conclusions Our results demonstrate that NK cells infiltrate into the CNS and aggravate the brain damage after A. cantonensis infection. The findings improve the understanding the pathogenesis of angiostrongyliasis and expand the therapeutic intervention in CNS disease.

scholarly journals NEUROSONOGRAPHIC STUDY OF CHILDREN WITH HYPOXIC-ISCHEMIC BRAIN IJURY

2020 ◽  
pp. 7-11
Author(s):  
Volotko L. O.
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Injury ◽  
Brain Tissue ◽  
Ischemic Injury ◽  
Ischemic Brain ◽  
Destructive Processes ◽  
The Brain ◽  
Hypoxic Ischemic Injury

The study is aimed at neurosonographic characteristics of brain injury in newborn patients with perinatal hypoxic-ischemic injury of central nervous system, complicated with inflectional process (meningitis, ventriculitis). It is settled that brain immaturity, hydrocephalic syndrome, ischemia of the brain tissue and intraventricular hemorrhages are found 2 times more often in infants with perinatal hypoxic-ischemic injury of central nervous system, complicated with inflectional process. This fact generally characterizes disorders of the hemato-encephalic barrier and the development of destructive processes in the tissue of the brain.

scholarly journals Mycobacterium of tuberculosis with defective cell wall, determined in the brain of the biological model with spongional changes

2019 ◽  
Vol 23 (1) ◽  
pp. 12-19
Author(s):  
O.P. Lysenko ◽  
V.V. Vlasenko ◽  
H.K. Palii ◽  
I.H. Vlasenko ◽  
O.A. Nazarchuk
Keyword(s):  
Central Nervous System ◽  
Cell Wall ◽  
Nervous System ◽  
Mycobacterium Tuberculosis ◽  
Brain Damage ◽  
Molecular Genetic Study ◽  
Central Nervous System Damage ◽  
Infectious Dose ◽  
Microbiological Methods ◽  
The Brain

Mycobacterium tuberculosis is endowed with resistance to adverse factors and rapidly forms drug resistance. The aim is to study of the connection of tuberculosis infection and the development of brain damage with signs of spongymorphic changes. There were investigated canned 10% formalin fragments of the brain of 2 goats with signs of central nervous system damage by histological, microbiological methods. For microbiological examination, 3–5 years brain samples after were sowed on the MycСel DW nutrient medium with a growth stimulator. The molecular genetic study was performed using a polymerase chain reaction on a Molecular Imager GelDoc TM XR + (BioRad) device. The polypeptide profile was studied electrophoretically. In the goats, who died with symptoms of central nervous system damage, spongiform changes were detected in the brain. In the brain samples, DNA and mycobacterium tuberculosis with a defective cell wall have been detected, accumulation of mycobacterial antigens has been observed in the cells of the brain and in the intercellular space. Despite the fact that brain samples were in 10% formalin for 1 month, 3 years and 5 years, in all cases mycobacterium tuberculosis with a defective cell wall was isolated. Their viability was comparable to the infectiousness of prions. The isolation of mycobacterium tuberculosis with a defective cell wall from the brain did not differ in morphology and polypeptide composition from isolates from tuberculin, FLK-BLV, lymph nodes of cows, patients with tuberculosis. This indicates a high probability that mycobacterial infection, depending on the infectious dose, the characteristics of the strain and host genome, as well as the state of the immune system, can cause oncogenic action, cause active tuberculosis, brain damage, and the cardiovascular system.

Brain Injury Associated With Chronic Alcoholism

CNS Spectrums ◽  
1999 ◽  
Vol 4 (1) ◽  
pp. 66-68,81-87 ◽  
Author(s):  
Paul W. Ragan ◽  
Charles K. Singleton ◽  
Peter R. Martin
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Injury ◽  
Alcohol Abuse ◽  
Brain Damage ◽  
Thiamine Deficiency ◽  
Chronic Alcoholism ◽  
Cerebellar Degeneration ◽  
Wernicke's Encephalopathy ◽  
The Central Nervous System

AbstractAlcoholism can result in a number of severe consequences to the central nervous system, including Korsakoff's psychosis, delusions, delirium, Wernicke's encephalopathy, and cerebellar degeneration. Many of these disorders have a substantially higher prevalence than had been previously believed. Neuropathologic and neuroimaging studies have been instrumental in identifying the changes undergone by the alcoholic brain and the factors that may contribute to alcohol-induced brain damage. Biologic differences appear to make women especially susceptible to central nervous system insult from alcohol abuse. The damage caused by alcohol may be associated, in part, with thiamine deficiency, neuronal excitotoxicity, and magnesium wasting.

Consequences of Anoxia and Ischemia to the Brain

2019 ◽  
pp. 86-91
Author(s):  
Jennifer E. Fugate
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Injury ◽  
Cerebral Edema ◽  
Secondary Injury ◽  
Neurologic Manifestations ◽  
Ischemic Brain ◽  
Electrolyte Disturbances ◽  
The Central Nervous System ◽  
The Brain

Systemic illness can have an abrupt and sometimes profound effect on the central nervous system. Organ failure and acute electrolyte disturbances may cause neurologic manifestations that are often accompanied by a decline in consciousness. Secondary injury is characterized by demyelination, cerebral edema, and anoxic-ischemic brain injury.

scholarly journals Effect of Soluble Complement Receptor-1 on Neutrophil Accumulation after Traumatic Brain Injury in Rats

1995 ◽  
Vol 15 (5) ◽  
pp. 860-864 ◽  
Author(s):  
Susan L. Kaczorowski ◽  
Joanne K. Schiding ◽  
Carol A. Toth ◽  
Patrick M. Kochanek
Keyword(s):  
Traumatic Brain Injury ◽  
Central Nervous System ◽  
Nervous System ◽  
Brain Injury ◽  
Inflammatory Response ◽  
Acute Inflammatory Response ◽  
Complement Receptor ◽  
Neutrophil Accumulation ◽  
The Central Nervous System ◽  
The Brain

As part of the acute inflammatory response, neutrophils accumulate in the central nervous system after injury. Recently, a soluble human recombinant complement receptor (sCR1; BRL 55730; T Cell Sciences, Inc., Cambridge, MA, U.S.A.) has been developed that inhibits the activation of both the classical and the alternative pathways of complement. sCR1 attenuates the effects of the acute inflammatory response in several models of injury outside the central nervous system. The role of complement in traumatic brain injury, however, remains undefined. We hypothesized that treatment with sCR1 would attenuate neutrophil accumulation in the brain after cerebral trauma. Using a randomized, blinded protocol, 18 anesthetized Sprague–Dawley rats were pretreated with sCR1 or saline (control) at both 2 h and 2 min before trauma (weight drop) to the exposed right parietal cortex. A third dose of sCR1 (or saline) was given 6 h after trauma. Coronal brain sections centered on the site of trauma were obtained at 24 h after trauma and analyzed for myeloperoxidase (MPO) activity as a marker of neutrophil accumulation. Complete blood counts with differential were obtained before treatment with sCR1 and at 24 h after trauma. At 24 h after trauma, brain MPO activity was reduced by 41% in sCR1-treated rats compared with control rats [0.1599 ± 0.102 versus 0.27(2 ± 0.178 U/g (mean ± SD); p = 0.02]. The neutrophil count in peripheral blood increased approximately twofold in both groups. Neutrophil accumulation occurring in the brain after trauma is inhibited by sCR1 treatment. This suggests that complement activation is involved in the local inflammatory response to traumatic brain injury and plays an important role in neutrophil accumulation in the injured brain.

scholarly journals Developmental Dysfunction of the Central Nervous System Lymphatics Modulates the Adaptive Neuro-Immune Response in the Perilesional Cortex in a Mouse Model of Traumatic Brain Injury

2021 ◽  
Vol 11 ◽  
Author(s):  
Sara Wojciechowski ◽  
Anaïs Virenque ◽  
Maria Vihma ◽  
Barbara Galbardi ◽  
Erin Jane Rooney ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Central Nervous System ◽  
Immune Response ◽  
T Cells ◽  
Nervous System ◽  
Brain Injury ◽  
T Cell ◽  
Lesion Volume ◽  
The Central Nervous System ◽  
The Brain

RationaleThe recently discovered meningeal lymphatic vessels (mLVs) have been proposed to be the missing link between the immune and the central nervous system. The role of mLVs in modulating the neuro-immune response following a traumatic brain injury (TBI), however, has not been analyzed. Parenchymal T lymphocyte infiltration has been previously reported as part of secondary events after TBI, suggestive of an adaptive neuro-immune response. The phenotype of these cells has remained mostly uncharacterized. In this study, we identified subpopulations of T cells infiltrating the perilesional areas 30 days post-injury (an early-chronic time point). Furthermore, we analyzed how the lack of mLVs affects the magnitude and the type of T cell response in the brain after TBI.MethodsTBI was induced in K14-VEGFR3-Ig transgenic (TG) mice or in their littermate controls (WT; wild type), applying a controlled cortical impact (CCI). One month after TBI, T cells were isolated from cortical areas ipsilateral or contralateral to the trauma and from the spleen, then characterized by flow cytometry. Lesion size in each animal was evaluated by MRI.ResultsIn both WT and TG-CCI mice, we found a prominent T cell infiltration in the brain confined to the perilesional cortex and hippocampus. The majority of infiltrating T cells were cytotoxic CD8+ expressing a CD44hiCD69+ phenotype, suggesting that these are effector resident memory T cells. K14-VEGFR3-Ig mice showed a significant reduction of infiltrating CD4+ T lymphocytes, suggesting that mLVs could be involved in establishing a proper neuro-immune response. Extension of the lesion (measured as lesion volume from MRI) did not differ between the genotypes. Finally, TBI did not relate to alterations in peripheral circulating T cells, as assessed one month after injury.ConclusionsOur results are consistent with the hypothesis that mLVs are involved in the neuro-immune response after TBI. We also defined the resident memory CD8+ T cells as one of the main population activated within the brain after a traumatic injury.

scholarly journals Dynamics of Viral and Proviral Loads of FelineImmunodeficiency Virus within the Feline Central Nervous System duringthe Acute Phase following IntravenousInfection

2003 ◽  
Vol 77 (13) ◽  
pp. 7477-7485 ◽  
Author(s):  
G. Ryan ◽  
D. Klein ◽  
E. Knapp ◽  
M. J. Hosie ◽  
T. Grimes ◽  
...  
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Brain Tissue ◽  
Acute Phase ◽  
Mononuclear Cells ◽  
Ocular Tissue ◽  
Peripheral Blood Mononuclear ◽  
Viral Loads ◽  
Immunodeficiency Virus ◽  
The Brain

ABSTRACT Animal models of human immunodeficiency virus 1, such as feline immunodeficiency virus (FIV), provide the opportunities to dissect the mechanisms of early interactions of the virus with the central nervous system (CNS). The aims of the present study were to evaluate viral loads within CNS, cerebrospinal fluid (CSF), ocular fluid, and the plasma of cats in the first 23 weeks after intravenous inoculation with FIVGL8. Proviral loads were also determined within peripheral blood mononuclear cells (PBMCs) and brain tissue. In this acute phase of infection, virus entered the brain in the majority of animals. Virus distribution was initially in a random fashion, with more diffuse brain involvement as infection progressed. Virus in the CSF was predictive of brain parenchymal infection. While the peak of virus production in blood coincided with proliferation within brain, more sustained production appeared to continue in brain tissue. In contrast, proviral loads in the brain decreased to undetectable levels in the presence of a strengthening PBMC load. A final observation in this study was that there was no direct correlation between viral loads in regions of brain or ocular tissue and the presence of histopathology.

Glucuronyl 3-sulfate occurs exclusively on distal unmyelinated terminals of selected sensory neurons in the peripheral nervous system

1995 ◽  
Vol 53 ◽  
pp. 958-959
Author(s):  
S.S. Spicer ◽  
B.A. Schulte
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Cerebral Cortex ◽  
Peripheral Nervous System ◽  
Sensory Neurons ◽  
Sensory Nerves ◽  
Tissue Antigens ◽  
The Central Nervous System ◽  
The Brain ◽  
Leu 7

Generation of monoclonal antibodies (MAbs) against tissue antigens has yielded several (VC1.1, HNK- 1, L2, 4F4 and anti-leu 7) which recognize the unique sugar epitope, glucuronyl 3-sulfate (Glc A3- SO4). In the central nervous system, these MAbs have demonstrated Glc A3-SO4 at the surface of neurons in the cerebral cortex, the cerebellum, the retina and other widespread regions of the brain.Here we describe the distribution of Glc A3-SO4 in the peripheral nervous system as determined by immunostaining with a MAb (VC 1.1) developed against antigen in the cat visual cortex. Outside the central nervous system, immunoreactivity was observed only in peripheral terminals of selected sensory nerves conducting transduction signals for touch, hearing, balance and taste. On the glassy membrane of the sinus hair in murine nasal skin, just deep to the ringwurt, VC 1.1 delineated an intensely stained, plaque-like area (Fig. 1). This previously unrecognized structure of the nasal vibrissae presumably serves as a tactile end organ and to our knowledge is not demonstrable by means other than its selective immunopositivity with VC1.1 and its appearance as a densely fibrillar area in H&E stained sections.

Complex Trauma and Prenatal Alcohol Exposure: Clinical Implications

2012 ◽  
Vol 13 (2) ◽  
pp. 32-42 ◽  
Author(s):  
Yvette D. Hyter
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Child Development ◽  
Academic Outcomes ◽  
Complex Trauma ◽  
Prenatal Alcohol Exposure ◽  
Alcohol Exposure ◽  
Clinical Implications ◽  
Prenatal Alcohol ◽  
The Brain

Abstract Complex trauma resulting from chronic maltreatment and prenatal alcohol exposure can significantly affect child development and academic outcomes. Children with histories of maltreatment and those with prenatal alcohol exposure exhibit remarkably similar central nervous system impairments. In this article, I will review the effects of each on the brain and discuss clinical implications for these populations of children.

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