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Title: Loss of function associated with breakdown of the blood-brain barrier in the central nervous system : an in vivo study
Author: Delattre, G. R. R.
ISNI:       0000 0004 5362 575X
Awarding Body: University College London (University of London)
Current Institution: University College London (University of London)
Date of Award: 2014
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Blood-brain barrier breakdown is a common feature of neuroinflammatory diseases, such as multiple sclerosis (MS). Indeed, blood proteins may play a role in the pathology of the disease. Here we investigate the link between the presence of blood-borne components in the CNS parenchyma and the expression of neurological deficits. Male Sprague-Dawley rats were injected intraspinally with vascular endothelial growth factor (VEGF), which causes breakdown of the blood-brain barrier, or saline as control. The injection was made unilaterally at the T13 – L1 junction, namely the spinal level that controls hind limb movement. In VEGF-injected animals alone, hind limb motor and sensory deficits consistently appeared at day two after surgery, but not at days 1 or 3 (onwards), as assessed by behavioural and locomotor tests (horizontal ladder test, walking treadmill, von Frey hair test, inclined plane, burrowing). Histological examination revealed the presence of a blood-brain barrier leakage within the spinal cord as assessed by the presence of extravascular IgG and fibrinogen. Activated microglia/macrophages (ED1 + , MHC class II + and OX-42 + cells) were present at the injection site, peaking at day two, along with activated astrocytes. The mechanism responsible for the neurological deficit was investigated by attempting to antagonize specific VEGF signalling pathways, assessing a potential hypoxic state using immunohistochemical techniques, and characterizing neuronal excitability by electrophysiological methods. VEGF injection provokes opening of the blood-brain barrier which is temporally and spatially associated with neuroinflammation and loss of function. The findings indicate a potential mechanism underlying loss of function in inflammatory neurological diseases such as MS.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available