Differential regulation of blood-brain barrier permeability in brain trauma and pneumococcal meningitis-role of Src kinases.

Abstract:

:Increased vascular permeability causing vasogenic brain edema is characteristic for many acute neurological diseases such as stroke, brain trauma, and meningitis. Src family kinases, especially c-Src, play an important role in regulating blood-brain barrier permeability in response to VEGF, but also mediate leukocyte function and cytokine signalling. Here we demonstrate that pharmacological inhibition of Src or c-Src deficiency does not influence cerebrospinal fluid (CSF) pleocytosis, brain edema formation, and bacterial outgrowth during experimental pneumococcal meningitis despite the increased cerebral expression of inflammatory chemokines, such as IL-6, CCL-9, CXCL-1, CXCL-2 and G-CSF as determined by protein array analysis. In contrast, inhibition of Src significantly reduced brain edema formation, lesion volume, and clinical worsening in cold-induced brain injury without decreasing cytokine/chemokine expression. While brain trauma was associated with increased cerebral VEGF formation, VEGF levels significantly declined during pneumococcal meningitis. Therefore, we conclude that in brain trauma blood-brain barrier tightness is regulated by the VEGF/Src pathway whereas c-Src does not influence brain edema formation and leukocyte function during bacterial meningitis.

journal_name

Exp Neurol

journal_title

Experimental neurology

authors

Paul R,Angele B,Popp B,Klein M,Riedel E,Pfister HW,Koedel U

doi

10.1016/j.expneurol.2006.08.003

subject

Has Abstract

pub_date

2007-01-01 00:00:00

pages

158-67

issue

1

eissn

0014-4886

issn

1090-2430

pii

S0014-4886(06)00470-5

journal_volume

203

pub_type

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