Article
Fibroblast growth factor-2 - A novel mediator of cerebral blood flow autoregulation
Fibroblast growth factor-2 - ein neuer Mediator der zerebralen Blutfluss-Autoregulation
Search Medline for
Authors
Published: | April 23, 2004 |
---|
Outline
Text
Objective
The ability of cerebral arterioles to dilate under hypotensive stress and maintain cerebral blood flow (CBF) represents an integral component of the CBF autoregulation. Although disturbances of CBF autoregulation represent a common clinical problem following brain injury, the mechanisms underlying its regulation are only incompletely understood. Recently, FGF-2 has been demonstrated to play an important role in the regulation of extracerebral microvascular reactivity and in particular the arteriolar dilatory capacity. The aim of the study was to analyse whether FGF-2 is also of relevance for CBF autoregulation.
Methods
Cranial window preparations were peformed in FGF-2 wild type (FGF-2 +/+) and FGF-2 deficient (FGF-2 -/-) mice. Macrohemodynamic monitoring was performed via a catheter implanted into the right common carotid artery. Mean arterial blood pressure was decreased from 100 to 20 mmHg by venous pooling in a hypobaric chamber while the diameter of pial arterioles (PA) was visualized by intravital microscopy. Expression of NOS isoforms was assessed by immunohistochemistry.
Results
FGF-2 -/- mice were characterized by an impaired autoregulatory response with a reduced PA dilation during hypotension (max. dilatation 20±10% versus 45±7% of baseline values). An intra-arterial substitution of FGF-2 failed to reconstitute the disturbed CBF autoregulation in FGF-2 -/- mice (PA dilation by 25±15%) suggesting more complex disturbances within the FGF-2 -/- microcirculation. Histomorphological analyses of PAs as well as immunohistochemistry for NOS isoforms failed to show significnat differences between FGF-2 -/- and FGF-2 +/+ mice.
Conclusions
Our study suggests a novel function for FGF-2, i.e. the involvement of CBF autoregulation. Future studies will have to focus on the underlying mechansims and the clinical relevance of these results.