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    The role of PTX3 in brain inflammation and repair.

    Rodriguez Grande, Beatriz

    [Thesis]. Manchester, UK: The University of Manchester; 2014.

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    Abstract

    Pentraxin 3 (PTX3) is an acute phase protein which regulates peripheral inflammationand it has been suggested to have neuroprotective properties. Inflammation iscommonly associated with poor outcome during diverse central nervous system (CNS)disorders, but the role of PTX3 in brain inflammation is completely unknown. Westudied the role of PTX3 in brain inflammation and repair after stroke, a CNS disorderwhich is the third cause of death worldwide. To induce ischaemic stroke, we used themiddle cerebral artery occlusion (MCAo) model and found that the pro-inflammatorycytokine interleukin (IL)-1 was the inducer of PTX3 expression in the brain. Theanalysis of markers of inflammation and repair up to 14 days after MCAo in wild typeand PTX3 knockout (KO) mice revealed that, in general, lack of PTX3 has a negativeeffect on recovery after MCAo. PTX3 KO mice had delayed oedema resolution,defective glial scar, impaired microglial proliferation and reduced angiogenesis andneurogenesis. Therefore, PTX3 emerges as a target for stroke recovery and possiblyother CNS inflammatory diseases. PTX3 was, however, not involved in remoteneurodegeneration in the substantia nigra (SN) (an area of the brain remote butconnected with the area affected by the stroke), but we observed that remoteinflammation preceded remote neuronal death in the SN. Therefore, prevention ofremote inflammation may help prevent remote neurodegeneration in the SN afterstroke. This could have long term implications in SN neurodegeneration, which is akey pathological feature of Parkinson´s disease.

    Bibliographic metadata

    Type of resource:
    Content type:
    Form of thesis:
    Type of submission:
    Degree type:
    Doctor of Philosophy
    Degree programme:
    PhD Neuroscience
    Publication date:
    Location:
    Manchester, UK
    Total pages:
    242
    Abstract:
    Pentraxin 3 (PTX3) is an acute phase protein which regulates peripheral inflammationand it has been suggested to have neuroprotective properties. Inflammation iscommonly associated with poor outcome during diverse central nervous system (CNS)disorders, but the role of PTX3 in brain inflammation is completely unknown. Westudied the role of PTX3 in brain inflammation and repair after stroke, a CNS disorderwhich is the third cause of death worldwide. To induce ischaemic stroke, we used themiddle cerebral artery occlusion (MCAo) model and found that the pro-inflammatorycytokine interleukin (IL)-1 was the inducer of PTX3 expression in the brain. Theanalysis of markers of inflammation and repair up to 14 days after MCAo in wild typeand PTX3 knockout (KO) mice revealed that, in general, lack of PTX3 has a negativeeffect on recovery after MCAo. PTX3 KO mice had delayed oedema resolution,defective glial scar, impaired microglial proliferation and reduced angiogenesis andneurogenesis. Therefore, PTX3 emerges as a target for stroke recovery and possiblyother CNS inflammatory diseases. PTX3 was, however, not involved in remoteneurodegeneration in the substantia nigra (SN) (an area of the brain remote butconnected with the area affected by the stroke), but we observed that remoteinflammation preceded remote neuronal death in the SN. Therefore, prevention ofremote inflammation may help prevent remote neurodegeneration in the SN afterstroke. This could have long term implications in SN neurodegeneration, which is akey pathological feature of Parkinson´s disease.
    Thesis main supervisor(s):
    Thesis co-supervisor(s):
    Thesis advisor(s):
    Language:
    en

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    Manchester eScholar ID:
    uk-ac-man-scw:236761
    Created by:
    Rodriguez Grande, Beatriz
    Created:
    11th October, 2014, 11:13:40
    Last modified by:
    Rodriguez Grande, Beatriz
    Last modified:
    9th January, 2019, 09:48:55

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