Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population.

Abstract:

INTRODUCTION:We have demonstrated previously that the intravenous delivery of multipotent adult progenitor cells (MAPC) after traumatic brain injury affords neuroprotection via interaction with splenocytes, leading to an increase in systemic anti-inflammatory cytokines. We hypothesize that the observed modulation of the systemic inflammatory milieu is related to T regulatory cells and a subsequent increase in the locoregional neuroprotective M2 macrophage population. METHODS:C57B6 mice were injected with intravenous MAPC 2 and 24 hours after controlled cortical impact injury. Animals were euthanized 24, 48, 72, and 120 hours after injury. In vivo, the proportion of CD4(+)/CD25(+)/FOXP3(+) T-regulatory cells were measured in the splenocyte population and plasma. In addition, the brain CD86(+) M1 and CD206(+) M2 macrophage populations were quantified. A series of in vitro co-cultures were completed to investigate the need for direct MAPC:splenocyte contact as well as the effect of MAPC therapy on M1 and M2 macrophage subtype apoptosis and proliferation. RESULTS:Significant increases in the splenocyte and plasma T regulatory cell populations were observed with MAPC therapy at 24 and 48 hours, respectively. In addition, MAPC therapy was associated with an increase in the brain M2/M1 macrophage ratio at 24, 48 and 120 hours after cortical injury. In vitro cultures of activated microglia with supernatant derived from MAPC:splenocyte co-cultures also demonstrated an increase in the M2/M1 ratio. The observed changes were secondary to an increase in M1 macrophage apoptosis. CONCLUSIONS:The data show that the intravenous delivery of MAPC after cortical injury results in increases in T regulatory cells in splenocytes and plasma with a concordant increase in the locoregional M2/M1 macrophage ratio. Direct contact between the MAPC and splenocytes is required to modulate activated microglia, adding further evidence to the central role of the spleen in MAPC-mediated neuroprotection.

journal_name

J Neuroinflammation

authors

Walker PA,Bedi SS,Shah SK,Jimenez F,Xue H,Hamilton JA,Smith P,Thomas CP,Mays RW,Pati S,Cox CS Jr

doi

10.1186/1742-2094-9-228

subject

Has Abstract

pub_date

2012-09-28 00:00:00

pages

228

issn

1742-2094

pii

1742-2094-9-228

journal_volume

9

pub_type

杂志文章
  • Distinct cytokine patterns may regulate the severity of neonatal asphyxia-an observational study.

    abstract:BACKGROUND:Neuroinflammation and a systemic inflammatory reaction are important features of perinatal asphyxia. Neuroinflammation may have dual aspects being a hindrance, but also a significant help in the recovery of the CNS. We aimed to assess intracellular cytokine levels of T-lymphocytes and plasma cytokine levels ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-017-1023-2

    authors: Bajnok A,Berta L,Orbán C,Veres G,Zádori D,Barta H,Méder Ü,Vécsei L,Tulassay T,Szabó M,Toldi G

    更新日期:2017-12-12 00:00:00

  • Lack of neuroinflammation in the HIV-1 transgenic rat: an [(18)F]-DPA714 PET imaging study.

    abstract:BACKGROUND:HIV-associated neuroinflammation is believed to be a major contributing factor in the development of HIV-associated neurocognitive disorders (HAND). In this study, we used micropositron emission tomography (PET) imaging to quantify neuroinflammation in HIV-1 transgenic rat (Tg), a small animal model of HIV, ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-015-0390-9

    authors: Lee DE,Yue X,Ibrahim WG,Lentz MR,Peterson KL,Jagoda EM,Kassiou M,Maric D,Reid WC,Hammoud DA

    更新日期:2015-09-17 00:00:00

  • Microglial-derived microparticles mediate neuroinflammation after traumatic brain injury.

    abstract:BACKGROUND:Local and systemic inflammatory responses are initiated early after traumatic brain injury (TBI), and may play a key role in the secondary injury processes resulting in neuronal loss and neurological deficits. However, the mechanisms responsible for the rapid expansion of neuroinflammation and its long-term ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-017-0819-4

    authors: Kumar A,Stoica BA,Loane DJ,Yang M,Abulwerdi G,Khan N,Kumar A,Thom SR,Faden AI

    更新日期:2017-03-15 00:00:00

  • The contribution of activated astrocytes to Aβ production: implications for Alzheimer's disease pathogenesis.

    abstract:BACKGROUND:β-Amyloid (Aβ) plays a central role in Alzheimer's disease (AD) pathogenesis. Neurons are major sources of Aβ in the brain. However, astrocytes outnumber neurons by at least five-fold. Thus, even a small level of astrocytic Aβ production could make a significant contribution to Aβ burden in AD. Moreover, act...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-8-150

    authors: Zhao J,O'Connor T,Vassar R

    更新日期:2011-11-02 00:00:00

  • LPS and TNF alpha modulate AMPA/NMDA receptor subunit expression and induce PGE2 and glutamate release in preterm fetal ovine mixed glial cultures.

    abstract:BACKGROUND:White matter injury (WMI) is the major antecedent of cerebral palsy in premature infants, and is often associated with maternal infection and the fetal inflammatory response. The current study explores the therapeutic potential of glutamate receptor blockade or cyclooxygenase-2 (COX-2) inhibition for inflamm...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-10-153

    authors: Weaver-Mikaere L,Gunn AJ,Mitchell MD,Bennet L,Fraser M

    更新日期:2013-12-17 00:00:00

  • Omega-3 polyunsaturated fatty acid supplementation attenuates microglial-induced inflammation by inhibiting the HMGB1/TLR4/NF-κB pathway following experimental traumatic brain injury.

    abstract:BACKGROUND:Microglial activation and the subsequent inflammatory response in the central nervous system play important roles in secondary damage after traumatic brain injury (TBI). High-mobility group box 1 (HMGB1) protein, an important mediator in late inflammatory responses, interacts with transmembrane receptor for ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-017-0917-3

    authors: Chen X,Wu S,Chen C,Xie B,Fang Z,Hu W,Chen J,Fu H,He H

    更新日期:2017-07-24 00:00:00

  • Human oligodendroglial cells express low levels of C1 inhibitor and membrane cofactor protein mRNAs.

    abstract::BACKGROUND: Oligodendrocytes, neurons, astrocytes, microglia, and endothelial cells are capable of synthesizing complement inhibitor proteins. Oligodendrocytes are vulnerable to complement attack, which is particularly observed in multiple sclerosis. This vulnerability may be related to a deficiency in their ability t...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-1-17

    authors: Hosokawa M,Klegeris A,McGeer PL

    更新日期:2004-08-24 00:00:00

  • Therapeutic hypercapnia reduces blood-brain barrier damage possibly via protein kinase Cε in rats with lateral fluid percussion injury.

    abstract:BACKGROUND:This study investigated whether therapeutic hypercapnia (TH) ameliorated blood-brain barrier (BBB) damage and improved the neurologic outcome in a rat model of lateral fluid percussion injury (FPI), and explored the possible underlying mechanism. METHODS:Rats underwent lateral FPI and received inhalation of...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-019-1427-2

    authors: Yang WC,Wang Q,Chi LT,Wang YZ,Cao HL,Li WZ

    更新日期:2019-02-13 00:00:00

  • Amyloid β peptide-induced inhibition of endothelial nitric oxide production involves oxidative stress-mediated constitutive eNOS/HSP90 interaction and disruption of agonist-mediated Akt activation.

    abstract:BACKGROUND:Amyloid β (Aβ)-induced vascular dysfunction significantly contributes to the pathogenesis of Alzheimer's disease (AD). Aβ is known to impair endothelial nitric oxide synthase (eNOS) activity, thus inhibiting endothelial nitric oxide production (NO). METHOD:In this study, we investigated Aβ-effects on heat s...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-015-0304-x

    authors: Lamoke F,Mazzone V,Persichini T,Maraschi A,Harris MB,Venema RC,Colasanti M,Gliozzi M,Muscoli C,Bartoli M,Mollace V

    更新日期:2015-05-03 00:00:00

  • Alleviation of secondary brain injury, posttraumatic inflammation, and brain edema formation by inhibition of factor XIIa.

    abstract:BACKGROUND:Traumatic brain injury (TBI) is a devastating neurological condition and a frequent cause of permanent disability. Posttraumatic inflammation and brain edema formation, two pathological key events contributing to secondary brain injury, are mediated by the contact-kinin system. Activation of this pathway in ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-017-0815-8

    authors: Hopp S,Nolte MW,Stetter C,Kleinschnitz C,Sirén AL,Albert-Weissenberger C

    更新日期:2017-02-20 00:00:00

  • Integrin CD11b mediates locus coeruleus noradrenergic neurodegeneration in a mouse Parkinson's disease model.

    abstract:BACKGROUND:The loss of locus coeruleus noradrenergic (LC/NE) neurons in the brainstem is reported in multiple neurodegenerative disorders, including Parkinson's disease (PD). However, the mechanisms remain unclear. Strong evidence suggested that microglia-mediated neuroinflammation contributes to neurodegeneration in P...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-020-01823-3

    authors: Hou L,Qu X,Qiu X,Huang R,Zhao X,Wang Q

    更新日期:2020-05-06 00:00:00

  • Dual roles of the adenosine A2a receptor in autoimmune neuroinflammation.

    abstract:BACKGROUND:Conditions of inflammatory tissue distress are associated with high extracellular levels of adenosine, due to increased adenosine triphosphate (ATP) degradation upon cellular stress or the release of extracellular ATP upon cell death, which can be degraded to adenosine by membrane-bound ecto-enzymes like CD3...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-016-0512-z

    authors: Ingwersen J,Wingerath B,Graf J,Lepka K,Hofrichter M,Schröter F,Wedekind F,Bauer A,Schrader J,Hartung HP,Prozorovski T,Aktas O

    更新日期:2016-02-26 00:00:00

  • Role of the indoleamine-2,3-dioxygenase/kynurenine pathway of tryptophan metabolism in behavioral alterations in a hepatic encephalopathy rat model.

    abstract:BACKGROUND:This study aims to explore the role of indoleamine-2,3-dioxygenase (IDO)/kynurenine (KYN) pathway of tryptophan (TRY) metabolism in behavioral alterations observed in hepatic encephalopathy (HE) rats. METHODS:Expression levels of proinflammatory cytokines were tested by QT-PCR and ELISA, levels of IDOs were...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-017-1037-9

    authors: Jiang X,Xu L,Tang L,Liu F,Chen Z,Zhang J,Chen L,Pang C,Yu X

    更新日期:2018-01-04 00:00:00

  • High serum levels of transforming growth factor β1 are associated with increased cortical thickness in cingulate and right frontal areas in healthy subjects.

    abstract:BACKGROUND:Transforming growth factor β (TGF-β) is a cytokine having multiple functions in the central nervous system such as promoting repair mechanisms in degenerative diseases and stroke. To date, however, its neuroprotective effects in non-disease conditions have not been studied METHODS:With the aim of exploring ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-9-42

    authors: Piras F,Salani F,Bossù P,Caltagirone C,Spalletta G

    更新日期:2012-02-28 00:00:00

  • Antibodies to myelin oligodendrocyte glycoprotein in HIV-1 associated neurocognitive disorder: a cross-sectional cohort study.

    abstract:BACKGROUND:Neuroinflammation and demyelination have been suggested as mechanisms causing HIV-1 associated neurocognitive disorder (HAND). This cross-sectional cohort study explores the potential role of antibodies to myelin oligodendrocyte glycoprotein (MOG), a putative autoantigen in multiple sclerosis, in the pathoge...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-7-79

    authors: Lackner P,Kuenz B,Reindl M,Morandell M,Berger T,Schmutzhard E,Eggers C

    更新日期:2010-11-17 00:00:00

  • Interactions between inflammatory mediators and corticosteroids regulate transcription of genes within the Kynurenine Pathway in the mouse hippocampus.

    abstract:BACKGROUND:Increased tryptophan metabolism towards the production of kynurenine via indoleamine/tryptophan-2,3-dioxygenases (DOs: Ido1, Ido2, and Tdo2) is strongly associated with the prevalence of major depressive disorder in patients and the induction of depression-like behaviors in animal models. Several studies hav...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-016-0563-1

    authors: Brooks AK,Lawson MA,Smith RA,Janda TM,Kelley KW,McCusker RH

    更新日期:2016-05-03 00:00:00

  • The link between chronic pain and Alzheimer's disease.

    abstract::Chronic pain often occurs in the elderly, particularly in the patients with neurodegenerative disorders such as Alzheimer's disease (AD). Although studies indicate that chronic pain correlates with cognitive decline, it is unclear whether chronic pain accelerates AD pathogenesis. In this review, we provide evidence th...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章,评审

    doi:10.1186/s12974-019-1608-z

    authors: Cao S,Fisher DW,Yu T,Dong H

    更新日期:2019-11-06 00:00:00

  • Pro-inflammatory pattern of IgG1 Fc glycosylation in multiple sclerosis cerebrospinal fluid.

    abstract:BACKGROUND:Immunoglobulin G (IgG) effector functions are regulated by the composition of glycans attached to a conserved N-glycosylation site in the Fc part. Intrathecal production of IgG, especially IgG1, is a hallmark of multiple sclerosis (MS), but nothing is known about IgG Fc glycosylation in MS and in cerebrospin...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-015-0450-1

    authors: Wuhrer M,Selman MH,McDonnell LA,Kümpfel T,Derfuss T,Khademi M,Olsson T,Hohlfeld R,Meinl E,Krumbholz M

    更新日期:2015-12-18 00:00:00

  • Urate inhibits microglia activation to protect neurons in an LPS-induced model of Parkinson's disease.

    abstract:BACKGROUND:Multiple risk factors contribute to the progression of Parkinson's disease, including oxidative stress and neuroinflammation. Epidemiological studies have revealed a link between higher urate level and a lower risk of developing PD. However, the mechanistic basis for this association remains unclear. Urate p...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-018-1175-8

    authors: Bao LH,Zhang YN,Zhang JN,Gu L,Yang HM,Huang YY,Xia N,Zhang H

    更新日期:2018-05-02 00:00:00

  • Suppression of MAPK attenuates neuronal cell death induced by activated glia-conditioned medium in alpha-synuclein overexpressing SH-SY5Y cells.

    abstract:BACKGROUND:Parkinson's disease (PD) is a neurodegenerative disease with characteristics and symptoms that are well defined. Nevertheless, its aetiology remains unknown. PD is characterized by the presence of Lewy bodies inside neurons. α-Synuclein (α-syn) is a soluble protein present in the pre-synaptic terminal of neu...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-015-0412-7

    authors: Yshii LM,Denadai-Souza A,Vasconcelos AR,Avellar MC,Scavone C

    更新日期:2015-10-26 00:00:00

  • Sphingosine-1-phosphate receptor subtype 1 activation in the central nervous system contributes to morphine withdrawal in rodents.

    abstract::Opioid therapies for chronic pain are undermined by many adverse side effects that reduce their efficacy and lead to dependence, abuse, reduced quality of life, and even death. We have recently reported that sphingosine-1-phosphate (S1P) 1 receptor (S1PR1) antagonists block the development of morphine-induced hyperalg...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-020-01975-2

    authors: Doyle TM,Hutchinson MR,Braden K,Janes K,Staikopoulos V,Chen Z,Neumann WL,Spiegel S,Salvemini D

    更新日期:2020-10-22 00:00:00

  • Leukemia inhibitory factor modulates the peripheral immune response in a rat model of emergent large vessel occlusion.

    abstract:BACKGROUND:The migration of peripheral immune cells and splenocytes to the ischemic brain is one of the major causes of delayed neuroinflammation after permanent large vessel stroke. Other groups have demonstrated that leukemia inhibitory factor (LIF), a cytokine that promotes neural cell survival through upregulation ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-018-1326-y

    authors: Davis SM,Collier LA,Winford ED,Leonardo CC,Ajmo CT Jr,Foran EA,Kopper TJ,Gensel JC,Pennypacker KR

    更新日期:2018-10-15 00:00:00

  • Ecto-5'-nucleotidase (CD73) attenuates inflammation after spinal cord injury by promoting macrophages/microglia M2 polarization in mice.

    abstract:BACKGROUND:Immune activation, specifically activation of macrophages and resident microglia, leading to inflammation is a key component in the progression of spinal cord injury (SCI). Macrophages/microglia exist in two states-the classically activated M1 phenotype that confers pro-inflammatory effects or the alternativ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-018-1183-8

    authors: Xu S,Zhu W,Shao M,Zhang F,Guo J,Xu H,Jiang J,Ma X,Xia X,Zhi X,Zhou P,Lu F

    更新日期:2018-05-22 00:00:00

  • Human mesenchymal stem/stromal cells suppress spinal inflammation in mice with contribution of pituitary adenylate cyclase-activating polypeptide (PACAP).

    abstract:BACKGROUND:Adult human mesenchymal stem/stromal cells (hMSCs) from bone marrow have been reported to exhibit beneficial effects on spinal cord injury (SCI). A neuropeptide, pituitary adenylate cyclase-activating polypeptide (PACAP) is known to decrease neuronal cell death and inflammatory response after ischemia, SCI, ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-015-0252-5

    authors: Tsumuraya T,Ohtaki H,Song D,Sato A,Watanabe J,Hiraizumi Y,Nakamachi T,Xu Z,Dohi K,Hashimoto H,Atsumi T,Shioda S

    更新日期:2015-02-22 00:00:00

  • Active immunization against complement factor C5a: a new therapeutic approach for Alzheimer's disease.

    abstract:BACKGROUND:Alzheimer's disease (AD) is the most common neurodegenerative disease characterized by neuronal loss due to amyloid beta aggregations, neurofibrillary tangles, and prominent neuroinflammation. Recently, interference with neuroinflammation as a new therapeutic approach for AD treatment gained great interest. ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-015-0369-6

    authors: Landlinger C,Oberleitner L,Gruber P,Noiges B,Yatsyk K,Santic R,Mandler M,Staffler G

    更新日期:2015-08-16 00:00:00

  • Evidence for the involvement of gamma delta T cells in the immune response in Rasmussen encephalitis.

    abstract:BACKGROUND:Rasmussen encephalitis (RE) is a rare neuroinflammatory disease characterized by intractable seizures and progressive atrophy on one side of the cerebrum. Perivascular cuffing and clusters of T cells in the affected cortical hemisphere are indicative of an active cellular immune response. METHODS:Peripheral...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-015-0352-2

    authors: Owens GC,Erickson KL,Malone CC,Pan C,Huynh MN,Chang JW,Chirwa T,Vinters HV,Mathern GW,Kruse CA

    更新日期:2015-07-19 00:00:00

  • Endothelial α6β4 integrin protects during experimental autoimmune encephalomyelitis-induced neuroinflammation by maintaining vascular integrity and tight junction protein expression.

    abstract:BACKGROUND:Extracellular matrix (ECM) proteins play critical functions regulating vascular formation and function. Laminin is a major component of the vascular basal lamina, and transgenic mice deficient in astrocyte or pericyte laminin show defective blood-brain barrier (BBB) integrity, indicating an important instruc...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-017-0987-2

    authors: Welser JV,Halder SK,Kant R,Boroujerdi A,Milner R

    更新日期:2017-11-09 00:00:00

  • Ultrastructural evidence of microglial heterogeneity in Alzheimer's disease amyloid pathology.

    abstract:BACKGROUND:Alzheimer's disease (AD) is the most common neurodegenerative disease, characterized by the deposition of extracellular fibrillar amyloid β (fΑβ) and the intracellular accumulation of neurofibrillary tangles. As AD progresses, Aβ drives a robust and prolonged inflammatory response via its recognition by micr...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-019-1473-9

    authors: El Hajj H,Savage JC,Bisht K,Parent M,Vallières L,Rivest S,Tremblay MÈ

    更新日期:2019-04-16 00:00:00

  • Anti-inflammatory therapy by ibudilast, a phosphodiesterase inhibitor, in demyelination of twitcher, a genetic demyelination model.

    abstract::BACKGROUND: Twitcher mouse (twi/twi) is an authentic murine model of Krabbe's disease. Accumulation of psychosine, resulting in apoptosis of oligodendrocytes and subsequent demyelination, is a cardinal event to the pathogenesis of this disease. Moreover, recruitment of inflammatory cells plays a significant role in th...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/1742-2094-2-10

    authors: Kagitani-Shimono K,Mohri I,Fujitani Y,Suzuki K,Ozono K,Urade Y,Taniike M

    更新日期:2005-04-06 00:00:00

  • Functional characteristics of Th1, Th17, and ex-Th17 cells in EAE revealed by intravital two-photon microscopy.

    abstract:BACKGROUND:T helper (Th) 17 cells are a highly plastic subset of T cells, which in the context of neuroinflammation, are able to acquire pathogenic features originally attributed to Th1 cells (resulting in so called ex-Th17 cells). Thus, a strict separation between the two T cell subsets in the context of experimental ...

    journal_title:Journal of neuroinflammation

    pub_type: 杂志文章

    doi:10.1186/s12974-020-02021-x

    authors: Loos J,Schmaul S,Noll TM,Paterka M,Schillner M,Löffel JT,Zipp F,Bittner S

    更新日期:2020-11-26 00:00:00