Biomedical subjects

I Muñoz-Willery

Publications and source records attributed to I Muñoz-Willery.

7 recordsLinked to original sources

PubMed1998

Intravenous fibroblast growth factor penetrates the blood-brain barrier and protects hippocampal neurons against ischemia-reperfusion injury.

BACKGROUND: Fibroblast growth factors (FGFs) play a role in neuronal survival after brain ischemia when administered intrace-rebrally. However, the clinical problems that chronic intracerebral infusion of FGFs involves may restrict its use. The purpose of this study was to analyze if FGFs administered intravenously might afford neuroprotection against transient brain ischemia in the light of new published data that suggest that these polypeptides cross the blood brain-barrier (BBB). METHODS: The efficacy of acidic fibroblast growth factor (aFGF) treatment was analyzed in a gerbil model of 5 min forebrain ischemia followed by 7 days of reperfusion. Native and nonmitogenic aFGF was injected in gerbils as a bolus through a jugular vein at the onset of reperfusion. Control animals received in the same manner vehicle solution alone. Seven days later, neuroprotection was evaluated histologically. Penetration of the FGF across the BBB was assessed by autoradiographic studies in rats. For that purpose, we injected through the jugular vein 0.1 microgram of uniformly labeled native 14C-basic fibroblast growth factor (bFGF), 0.1 microgram of heat-denatured 14C-bFGF, or a coinjection of 14C-bFGF with a 900-fold excess of unlabeled bFGF. Two hours later, animals were killed for morphological studies. RESULTS: We report that a venous injection of either native or nonmitogenic form of aFGF after 5 min forebrain ischemia in the gerbil significantly reduced the occurrence of delayed neuronal death (DND) in the CA1 sector of the hippocampus. We also confirmed that blood-borne 14C-bFGF accumulates in CA1 pyramidal neurons.

Animals↗

PubMed1996

Correction of hypertension by normalization of endothelial levels of fibroblast growth factor and nitric oxide synthase in spontaneously hypertensive rats.

Acidic and basic fibroblast growth factors (FGFs) share a wide range of diverse biological activities. To date, low levels of FGF have not been correlated with a pathophysiologic state. We report that blood vessels of spontaneously hypertensive rats are shown to be associated with a marked decrement in endothelial basic FGF content. This decrement correlates both with hypertension and with a decrease in the endothelial content of nitric oxide synthase. Restoration of FGF to physiological levels in the vascular wall, either by systemic administration or by in vivo gene transfer, significantly augmented the number of endothelial cells with positive immunostaining for nitric oxide synthase, corrected hypertension, and ameliorated endothelial-dependent responses to vasoconstrictors. These results suggest an important role for FGFs in blood pressure homeostasis and open new avenues for the understanding of the etiology and treatment of hypertension.

Animals↗

PubMed1996

Fibroblast growth factor decreases locomotor activity in rats.

The spontaneous locomotor behavior of rats receiving subcutaneous administration of either acidic or basic fibroblast growth factors was recorded in an activity cage. We report that doses between 1 and 100 micrograms/kg significantly decreased the horizontal and vertical activity, as well as the exploratory and stereotypy behavior of the rats. These effects of fibroblast growth factors seem to be specific since (i) they were cancelled by protein hydrolysis and anti-fibroblast growth factor antibodies, (ii) they were unrelated to their hypotensive activity and (iii) they were not attributable to their high structural similarity with the cytokine interleukin-1. Thus fibroblast growth factors did not show any thermogenic activity, did not affect the hypothalamic output of corticotropin-releasing factor and did not change the plasma levels of corticosterone. Pretreatment of the rats with a specific inhibitor of brain nitric oxide synthase prevented the effects of fibroblast growth factors, suggesting the involvement of nitric oxide in these behavioral modifications. Our results contribute to the accumulating evidence describing non-mitogenic activities of fibroblast growth factors.

Animals↗

PubMed1996

Central nervous system distribution of fibroblast growth factor injected into the blood stream.

It has been shown that fibroblast growth factors (FGFs) protect hypocampal CAI cells from the effects of transient ischemia when injected either intraventrically or intravenously. The effectiveness of the systemic treatment seems to suggest that FGFs cross the blood-brain barrier to some extent. The appearance of basic fibroblast growth factor (bFGF) in the rat central nervous system after systemic administration have been autoradiographically examined using a 14C uniformly labeled preparation. Our results show that, two hours after a systemic bolus administration, bFGF spots in several populations of neuronal and in non-neural cells except in glial cells. Label accumulation was imperceptible when either 14C-bFGF was heated previously to the systemic injection or was co-administered with an excess of unlabeled bFGF. Our results indicate the existence of a saturable transport system of FGFs across the blood-brain barrier.

Animals↗

PubMed1994

Effect of low pH and heparin on the structure of acidic fibroblast growth factor.

Changes in the fluorescence of the single tryptophan of acidic fibroblast growth factor have been used to monitor the effect of low pH on the conformation of the molecule, and the consequences of heparin binding and high ionic strength under such conditions. These studies demonstrate that the conformation of the protein changes reversibly below pH 5, and that heparin, depending on the conditions, may either prevent that change or induce a new irreversible modification of the structure, which runs parallel to the partial inactivation of the protein. It is also demonstrated that secondary heparin-binding sites appear at low pH, which favor the formation of precipitates at some protein/heparin ratios. Precipitation and inactivation of fibroblast growth factor at low pH may hinder its wound-healing activity, since acidification seems frequent in wounds.

3T3 Cells↗

PubMed1992

Single-step purification on DEAE-sephacel of recombinant polypeptides produced in Escherichia coli.

We describe a method for the purification of recombinant proteins based upon the selective interaction of the choline-binding domain of the pneumococcal murein hydrolase and tertiary amines. Proteins of interest, fused to the binding domain by a peptide linker, containing the cleaving sequence recognized by blood coagulation factor Xa, can either be assayed for biological activities in vitro and in vivo or have the binding moiety removed to yield a totally unmodified form, suitable for clinical and functional studies. The method can also be applied to the production of low molecular mass peptides. The principle of the technique is illustrated with acidic fibroblast growth factor and with a neuropeptide-like fragment of ten amino acids contained within its sequence.

3T3 Cells↗

PubMed1992

Fibroblast growth factor injected in cerebral ventricles does not decrease mean arterial blood pressure.

Intracerebroventricular injections of acidic fibroblast growth factor (aFGF) in rats did not elicit any change in the mean arterial blood pressure, and also did not appreciably affect the hypotensive effect of intravenous injections of aFGF. These observations are of general clinical interest, since such effects could constitute important drawbacks for the therapeutic applications of FGF.

Animals↗