Epidermal growth factor and basic fibroblast growth factor: effects on an overlapping population of neocortical neurons in vitro

Epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) have trophic effects on rat neocortical neurons in vitro. Concentration-response studies reveal that EGF maximally stimulates neuronal survival and process outgrowth at approximately 10 ng/ml, while the maximal effect of bFGF is seen at 10-30 ng/ml. Treatment with maximal concentrations of bFGF results in cultures containing a greater number of neurons with long processes, as well as greater branching of processes, than does treatment with EGF. When EGF and bFGF are added together to cultures the effects are not additive. In addition, bFGF is capable of supporting the survival of neurons previously treated with EGF. These findings indicate that EGF and bFGF affect a largely overlapping population of neocortical neurons, but that bFGF may be a more effective trophic agent for these cells.     

Epidermal growth factor exerts neuronotrophic effects on dopaminergic and GABAergic CNS neurons: comparison with basic fibroblast growth factor.

Basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) have been described to exert neuronotrophic effects on central nervous system neurons in culture. To study the selectivity of trophic actions of these growth factors, neurotransmitter-identified populations of embryonic rat mesencephalon were used. At 20 days in vitro, EGF (3 ng/ml) promoted survival and neurite outgrowth from these neurons. The neuritogenic effect of bFGF (3 ng/ml) was, however, more robust. Quantitative analysis with the neurofilament monoclonal antibody RR97 and ELISA confirmed the differential response, bFGF being 2-2.5 times more effective at all concentrations tested (ED100: 3-10 ng/ml for both EGF and bFGF). At 10 days in vitro, EGF displayed no trophic activity--even at 30 ng/ml. Treatment of mesencephalic cultures with EGF (3 ng/ml) for 20 days stimulated [3H]dopamine and [14C]GABA uptakes about 4-fold. While bFGF (3 ng/ml) also stimulated GABA uptake some 4-fold, dopamine uptake was increased almost 20-fold. Thus, EGF is also capable of enhancing the transmitter traits of selected central neuronal populations; however, the actions of bFGF appear to preferentially address dopaminergic cells.     

Effect of growth factors on proliferation and phenotypic differentiation of human fetal neural stem cells

Human fetal neural stem cells (hNSCs) can be expanded in vitro by mitogens or growth factors, such as basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), and/or leukemia inhibitory factor (LIF). Their effects on proliferation rate and differentiation pattern of hNSCs, however, have not been fully characterized. In this study, we cultured hNSCs in seven regimens, including bFGF, EGF, and LIF, either alone or in combinations. Cells were maintained as neurospheres in treatment media for various periods, up to six passages. A combination of bFGF, EGF, and LIF expanded hNSCs more efficiently than any other treatment as determined by counting total cell numbers using a trypan blue exclusion assay, a WST-1 cell viability assay, and a bromodeoxyuridine incorporation flow cytometric analysis. Differentiation patterns of hNSCs expanded under different conditions were also analyzed. We reported previously that hNSCs primed in vitro with a combination of bFGF, heparin, and laminin (FHL) induced neuronal differentiation toward a cholinergic phenotype. In this study, we show that the FHL priming increases neuronal differentiation while decreasing astroglial generation in all treatment groups as determined by immunostaining. However, cells proliferated under different growth factor conditions do vary in their phenotypic differentiation patterns. Particularly, significant generation of cholinergic cells was observed only in hNSCs expanded with EGF/bFGF or EGF/bFGF/LIF, but not with other treatment regimens, even when they are exposed to the same priming procedure. Our results indicate that hNSCs are highly plastic, with their proliferation and differentiation potential dependent on different growth factor treatments.     

Heterogeneity of human neuroblastoma cell lines in their proliferative responses to basic FGF,NGF, and EGF: Correlation with expression of growth factors and growth factor receptors

Growth factors can induce both proliferation or differentiation of neuroblastoma (NB) cells through interaction with specific receptors. Using two automated colorimetric assays for determinations of cell numbers, the present study demonstrates that (a) different NB and neuroepithelioma cell lines show distinct responses, both qualitatively and quantitatively, to basic FGF (bFGF), NGF, and EGF(b) even closely related NB cell lines (e.g., SK-N-SH, SH-SY5Y, and SHEP) do not respond uniformly to these factors; c) responses of the two neuroepithelioma cell lines employed (SK-N-MC and CHP-100) differ, but match those of certain NB cell lines; and d) two growth factors, bFGF and EGF, may both stimulate or inhibit proliferation, depending on the cell line studied. Specifically, IMR-32, SK-N-SH, and SH-SY5Y showed a mitogenic response to each growth factor. Maximal proliferative responses ranged from 204–355% as compared to controls (100%). GICAN was stimulated by NGF (199%), and SK-N-MC and NMB by EGF (282 and 140%, respectively), but other factors were ineffective. CHP-100 and GIMEN were inhibited by bFGF. NGF and EGF were not effective on CHP-100 cells, while EGF caused an arrest of mitogenic activity in GIMEN cells, and NGF stimulated their proliferation. Cell lines SHEP and LAN1 did not respond to any factor. To begin to analyze putative relationships of growth factor responsiveness and growth factor/growth factor receptor expressions, IMR-32, GIMEN, and LAN1 cell lines were studied for the presence of bFGF, NGF, FGF receptors (R)-1 (flg) and FGFR-4, trk, and low-affinity NGF receptor (p75) mRNAs. All three cell lines expressed bFGF and NGF mRNA, but not the FGFR-1, FGFR-4, trk, and p75 mRNAs. These results suggest extremely diverse patterns of NB/neuroepithelioma cell responsiveness to “mitogenic” growth factors and no overt correlation between such responses and growth factor/growth factor receptor expression. © 1995 Wiley-Liss, Inc.     

Developmental effects of basic fibroblast growth factor and platelet-derived growth factor on glial cells in a three-dimensional cell culture system

In order to study peptide growth factor action in a three-dimensional cellular environment, aggregating cell cultures prepared from 15-day fetal rat telecephalon were grown in a chemically defined medium and treated during an early developmental stage with either bovine fibroblast growth factor (bFGF) or platelet-derived growth factor (PDGF homodimers AA and BB). A single dose (5–50 ng/ml) of either growth factor given to the cultures on day 3 greatly enhanced the developmental increase of the two glia-specific enzyme activities, 2′,3′-cyclic nucleotide 3′-phosphohydrolase (CNP) and glutamine synthetase (GS), whereas it had relatively little effect on total protein and DNA content. Distinct patterns of dose-dependency were found for CNP and GS stimulation. At low concentrations of bFGF (0.5–5 ng/ml) and at all PDGF concentrations applied, the oligodendroglial marker enzyme CNP was the most affected. A relatively small but significant mitogenic effect was observed after treatment with PDGF, particularly at higher concentrations or after repetitive stimulation. The PDGF homodimers AA and BB were similar in their biological effects and potency. The present results show that under histotypic conditions both growth factors, bFGF and PDGF, promote the maturation rather than the proliferation of immature oligodendrocytes and astrocytes.     

Effects of acidic fibroblast growth factor on hippocampal long-term potentiation in fasted rats.

Effects of human recombinant acidic fibroblast growth factor (haFGF) on long-term potentiation (LTP) and the increase of the spike amplitude induced by weak tetanic stimulation were investigated and compared with those of CS23 (modified human basic FGF) in the dentate gyrus of fasted and nonfasted rats. haFGF didn't influence the LTP induced by the tetanus of 100 pulses at 100 Hz in both 24 hr fasted and non-fasted rats. On the other hand, the tetanus of 20 pulses at 60 Hz significantly enhanced the amplitude of population spike and facilitated the generation of LTP by the i.c.v. injection of 10 microliters of 20-40 micrograms/ml haFGF in 24 hr fasted rats but not in non-fasted rats. However, 40 micrograms/ml CS23 induced LTP when the tetanus of 20 pulses at 60 Hz was applied in both fasted and non-fasted states. These results suggest that haFGF might be one of the regulating factors of feeding and memory.     

Basic fibroblast growth factor and epidermal growth factor exert differential trophic effects on CNS neurons

Epidermal growth factor (EGF) and basic fibroblast growth factor (bFGF) are potent mitogenic proteins capable of inducing cell division in a wide variety of cell types. In addition to their mitogenic properties, both proteins have recently been shown to enhance survival and process outgrowth from neurons of central nervous system origin. The full spectrum of neuronal subtypes responding to these factors has not been elucidated. In the present study, EGF was found to enhance survival and process outgrowth of primary cultures of cerebellar neurons of neonatal rat brain. This effect was dose-dependent and was observed with EGF concentrations as low as 100 pg/ml. In marked contrast, bFGF was ineffective in enhancing survival or neurite elongation from cerebellar neurons when tested in the range of 0.1 to 10.0 ng/ml. However, within this concentration range, bFGF did prove effective in stimulating an increase in [3H]thymidine incorporation into primary cultures of cerebellar astrocytes, demonstrating that bFGF was active and that cells in the cerebellum do respond to bFGF. These results suggest that EGF or an EGF-like peptide may act as a neurite elongation and maintenance factor for cerebellar neurons. EGF has now been shown to support striatal, cortical, and cerebellar neurons, suggesting that this factor may have trophic activity throughout the central nervous system. bFGF, in contrast, appears to exert its effects on limited populations of neurons.     

生骨注射液对骨折愈合过程中碱性成纤维细胞生长因子和血管内皮生长因子表达的影响

背景：在促进骨折修复研究中,应用外源性生长因子极不稳定,且造价高不适宜广泛推广,如何有效地促进内源性生长因子的表达将是值得深入研究的课题。 目的：观察生骨注射液对骨折愈合过程中内源性碱性成纤维细胞生长因子和血管内皮生长因子表达的影响。 设计、时间及地点：完全随机分组设计,对照实验,于2007-07/2008-08在华中科技大学同济医学院附属同济医院骨科实验室完成。 材料：清洁级3月龄雄性SD大鼠60只。生骨注射液由当归、土鳖虫、淫羊藿等药物组成,由湖北省中医院提供,质量浓度为1 g/L。 方法：建立SD大鼠胫骨干骨折愈合模型,分成实验组和对照组各30只,分别在骨折断端等量注射生骨注射液和生理盐水,每两日1次,0.2 mL/次。两组分别于术后第1,2,3,4,5,6周时各处死5只大鼠,取材。 主要观察指标：采用免疫组织化学方法,检测两组大鼠骨折愈合过程中不同阶段骨痂组织中碱性成纤维细胞生长因子、血管内皮生长因子蛋白的表达及差异情况。 结果：免疫组织化学染色显示,各时间点实验组骨痂组织中碱性成纤维细胞生长因子、血管内皮生长因子表达量及阳性定位均明显强于对照组。 结论：生骨注射液能够增加骨折愈合过程中碱性成纤维细胞生长因子、血管内皮生长因子在骨痂组织中的表达,这可能是生骨注射液促进骨折愈合的机制之一。     

Effect of basic fibroblast growth factor on neurons cultured from various regions of postnatal rat brain

Neurons from various brain regions of postnatal (15 days after birth) and fetal (16 days gestation) rats were cultured in the presence of basic fibroblast growth factor (bFGF). bFGF increased the survival of neurons from postnatal septum, striatum, midbrain, and hippocampus. Fetal neurons derived from cerebral cortex, septum, striatum, midbrain, thalamus, and colliculus were far more dependent on bFGF for survival in comparison with postnatal neurons. In contrast, cerebellum neurons of postnatal and fetal rat brain did not respond to bFGF. The increase of postnatal and fetal neuronal survival with bFGF treatment (0.01–10 ng/ml) was dose-dependent and reached 2–4-fold and 5–10-fold more than the control, respectively. Fetal cortical neurons showed almost complete dependence on bFGF since almost all neurons died in control cultures. Nerve growth factor was slightly effective only on postnatal septal and striatal neurons, being ineffective on the other neurons tested. These results indicate that bFGF can function as a neurotrophic factor not only on fetal but also on postnatal neurons of the central nervous system, and that bFGF has great potential for application in vivo.     

Basic fibroblast growth factor modulates synaptic transmission in cultured rat hippocampal neurons

Basic fibroblast growth factor (bFGF) is one of the effective growth factors that protect neurons against excitotoxic/ischemic injury and promote neuronal survival. In the present study, we examined the acute modulative effect of bFGF on synaptic transmission by monitoring spontaneous intracellular Ca²⁺ ([Ca²⁺]i]) oscillation, the amplitudes of which reflect excitatory and inhibitory inputs. The hippocampal cells from embryonic day 18 rats were cultured for 11–14 days, and changes in [Ca²⁺]i of single neurons were measured by a microfluometrical technique with fura-2. The amplitude of spontaneous oscillation was decreased by 10 ng/ml bFGF, but not by nerve growth factor (10–1000 ng/ml). Acidic FGF (1000 ng/ml) had a weaker depressant effect. The effect of bFGF was counteracted by suramin. bFGF did not affect the increase in [Ca²⁺]i evoked by glutamate agonists, NMDA or kainate, indicating that glutamate receptors are not involved in the mechanism. This is supported by similar results that kainate-evoked current was not affected by bFGF. On the other hand, bicuculline masked the effect of bFGF on the Ca²⁺ oscillation. But GABA-evoked current was slightly decreased by bFGF. These results suggest the possible role of bFGF in modulating GABAergic rather than glutamatergic neurotransmission.     

Basic fibroblast growth factor rescues CNS neurons from cell death caused by high oxygen atmosphere in culture

In the present study, we cultured rat CNS neurons and tested the neurotrophic support provided by basic fibroblast growth factor (bFGF) to prevent the oxygen-induced neuronal cell death. When rat basal forebrain (septum and vertical limb of diagonal band of Broca) cells of embryonic day 20 were cultured in a serum-free medium containing 5 microM cytosine arabinoside in a 50% oxygen atmosphere, the neuronal cells, which were immunostained by an anti-microtubule-associated protein 2 (MAP2) antibody, gradually died after 1 day in culture. After 3.5 days in culture, only 2-5% of neuronal cells survived. This oxygen-induced cell death of cultured basal forebrain neurons was reversed by the addition of bFGF at a concentration of 100 ng/ml. This cell-saving effect was dose-dependent, and the ED50 value was 12 ng/ml. Nerve growth factor (NGF) and insulin-like growth factor II could not prevent cell death. The activity of choline acetyltransferase was also maintained when bFGF was present in the basal forebrain culture. Viable astroglial cells, which were immunostained by an anti-glial fibrillary acidic protein, accounted for a few percent of the total number of cells after 3 days in culture both with and without 100 ng/ml of bFGF. The survival-enhancing effect of bFGF was observed not only in basal forebrain neurons but also in neocortical and hippocampal neurons. However, the sensitivity to oxygen toxicity of cultured neurons from the 3 CNS regions varied greatly. The neocortical neurons were the most sensitive to oxidative stress, while the hippocampal neurons were the most resistant. These results suggest that bFGF plays an important role in saving neuronal cells from oxidative stress during their long life without division.     

碱性成纤维生长因子和表皮生长因子对脊髓神经干细胞增殖与分化的影响

目的观察碱性成纤维生长因子(bFGF)和表皮生长因子(EGF)对胚胎脊髓神经干细胞(NSC)增殖与分化的影响。方法从14 d胚胎大鼠的脊髓组织中分离培养脊髓NSC,并随机分为3组:EGF组、bFGF组和bFGF+EGF组。通过光镜观察不同时间点各组脊髓NSC克隆细胞团数量及直径大小,并采用免疫荧光染色检测各组脊髓NSC向神经元和星形胶质细胞分化的情况。结果①EGF组培养1、3、7 d后NSC克隆细胞团数量和直径均少于bFGF和bFGF+EGF组,差异有统计学意义(P0.05)。而bFGF+EGF组仅在培养1 d时克隆细胞团数量多于bFGF组,在培养3、7 d时差异无统计学意义。②EGF组分化细胞中神经元比例显著少于bFGF和bFGF+EGF组,星形胶质细胞数量明显大于bFGF和bFGF+EGF组,差异有统计学意义(P0.05)。而bFGF和bFGF+EGF组组间差异无统计学意义。结论 EGF对脊髓NSC克隆形成有一定作用,而bFGF能较好地促进克隆细胞团的形成及生长,两者联合应用在培养早期可显著促进克隆细胞团形成。EGF可诱导脊髓NSC更多分化为星形胶质细胞,而bFGF则可促进脊髓NSC向神经元分化。     

Basic fibroblast growth factor priming increases the responsiveness of immortalized hypothalamic luteinizing hormone releasing hormone neurones to neurotrophic factors

The participation of growth factors (GFs) in the regulation of luteinizing hormone releasing hormone (LHRH) neuronal function has recently been proposed, but little is known about the role played by GFs during early LHRH neurone differentiation. In the present study, we have used combined biochemical and morphological approaches to study the ability of a number of GFs normally expressed during brain development, including basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin and insulin-like growth factor I (IGF-I) to induce survival, differentiation, proliferation, and phenotypic expression of immortalized (GT1-1) LHRH neurones in vitro, at early (3-days in vitro, 3-DIV) and late (8-DIV) stages of neuronal differentiation. Comparison of GF-treated vs untreated neurones grown in serum-deprived (SD) medium demonstrated bFGF to be the most potent, and insulin the least active in promoting neuronal differentiation. Thus, at both 3-DIV and 8-DIV, but especially at 8-DIV, bFGF induced the greatest increase in the total length and number of LHRH processes/cell and in growth cone surface area. bFGF was also the most active at 3-DIV, and IGF-I at 8-DIV, in counteracting SD-induced cell death, whereas EGF was the most potent in increasing [3H]thymidine incorporation. All GFs studied decreased the spontaneous release of LHRH from GT1-1 cells when applied at 3-DIV or 8-DIV, except for insulin which was inactive at both time-points and bFGF which was inactive at 8-DIV. Pre-treatment of GT1-1 cells with a suboptimal ('priming') dose of bFGF for 12 h followed by application of the different GFs induced a sharp potentiation of the neurotrophic and proliferative effects of the latter and particularly of those of IGF-I. Moreover, bFGF priming counteracted EGF-induced decrease in LHRH release and significantly stimulated LHRH secretion following IGF-I or insulin application, suggesting that bFGF may sensitize LHRH neurones to differentiating effects of specific GFs during development.     

bFGF和PDGF-B蛋白在脑缺血再灌注大鼠模型中的表达和血管形成的研究

目的 探讨脑缺血再灌注大鼠不同时间碱性成纤维细胞生长因子(bFGF)和血小板源性生长因子-B(PDGF-B)的表达水平及其与血管形成的关系。方法 采用线栓法制备大鼠大脑中动脉局灶性脑缺血再灌注(MCAO/R)模型,分为假手术组和MCAO/R组,MCAO/R组缺血2 h后根据再灌注时间窗的不同分为0、6、24 h、3、7、14、21 d共7组,应用HE染色观察病理变化并测定脑梗死体积,用免疫组化法检测CD34蛋白的表达水平并计数微血管密度(MVD),用免疫组化法检测bFGF和PDGF-B蛋白的表达水平。结果 bFGF蛋白表达水平在MCAO/R 6 h后即开始升高,3 d到达高峰,7 d开始降低。PDGF-B蛋白表达水平在MCAO/R 24 h后明显升高,3 d到达高峰,7 d有所下降,持续到14 d左右。MVD表达在MCAO/R 3 d开始升高,7 d到达高峰。bFGF和PDGF-B蛋白表达水平与MVD变化呈正相关(P<0.01)。结论 局灶性脑缺血再灌注损伤可诱导bFGF、PDGF-B和新生血管表达增加,激活内源性脑保护机制。     

FGF和EGF对神经干细胞增殖及分化的影响

胚胎和成年哺乳动物脑内均存在的神经干细胞，成纤维细胞生长因子和表皮生长因子对神经干细胞的增殖及分化有一定的影响，ＦＧＦ和ＥＧＦ及其受体在胚胎期和成年期表达各异。ＦＧＦ和ＥＧＦ能促进神经干细胞增殖，在不同的条件下对分化和作用不同。     

Contrasting effects of basic fibroblast growth factor and epidermal growth factor on mouse neonatal olfactory mucosa cells

Basic fibroblast growth factor (bFGF) and epidermal growth factor (EGF) affect proliferation and survival of many cell types, but their role in the maintenance of olfactory mucosa cells remains unclear. In the neonatal mouse olfactory mucosa, cell proliferation mainly occurs in the neuroepithelium and, to a lesser extent, in the lamina propria. To establish whether bFGF and EGF affect proliferation and/or survival of these cells, we isolated olfactory mucosa cells from the neonatal mouse and cultured them as free-floating spheres under bFGF or EGF stimulation. Our data demonstrate that bFGF is a mitogen for the rapidly dividing cells (olfactory neuronal precursors and olfactory ensheathing cells), and also a survival factor for both slowly and rapidly dividing cells of the olfactory mucosa. In contrast, EGF appears to be primarily a survival factor for both the olfactory stem and precursor cells.     

大鼠骨髓间充质干细胞体外诱导向神经元样细胞分化的实验研究

目的研究大鼠骨髓间充质干细胞（BMSCs）离体分离和培养方法,探讨碱性成纤维细胞生长因子（bFGF）、表皮生长因子（EGF）、全反式维甲酸（RA）、神经营养因子（BDNF）在体外诱导BM—SCs向神经元样细胞分化的作用。方法采用出生3周SD大鼠的全骨髓细胞进行培养,传至第3代时,分为三组：A组,bFGF＋EGF＋RA进行诱导分化;B组,BDNF＋RA进行诱导分化;C组,RA诱导分化。在倒置显微镜下每日观察、记录BMSCs的诱导分化情况,并应用免疫细胞化学技术对细胞进行兔抗神经元特异性烯醇化酶（NSE）单抗鉴定。结果A组诱导5d后有大部分细胞具备神经元样细胞形态,胞体呈锥形或圆形,有较长单极或多极的突起,有NSE阳性细胞表达。而B组可有部分NSE阳性细胞、C组细胞有少量NSE阳性细胞。结论bFGF＋EGF＋RA、BDNF＋RA和RA均可在诱导BMSCs向神经样元细胞分化,bFGF＋EGF＋RA组更优于和BDNF＋RA组及RA组。     

Basic fibroblast growth factor (bFGF) increases the survival of embryonic and postnatal basal forebrain cholinergic neurons in primary culture

Basic fibroblast growth factor (bFGF) is found in high concentrations in the mammalian central nervous system. It is a mitogen for glia and it influences the development and survival of specific populations of neurons. In this study, we investigated the effect of various concentrations of bFGF on the survival of embryonic and postnatal cholinergic basal forebrain neurons plated at low and high density in the presence and absence of glia. We observed that 50 and 100 ng/ml of bFGF increased the survival of embryonic cholinergic neurons plated at high density. This effect was observed only in the presence of glia. Lower concentrations of 10 and 20 ng/ml had no effect on cholinergic neuronal survival. The number of GFAP (glial fibrillary acidic protein)-positive cells in high-density embryonic cultures was increased by all concentrations of bFGF. In low-density embryonic cultures, an increase in cholinergic neuron survival was observed at concentrations ranging from 20 to 100 ng/ml. The number of GFAP-positive cells in low-density cultures was also increased by all concentrations of bFGF. Similar to low-density embryonic cultures, the survival of cholinergic neurons from postnatal day 2 cultures was significantly increased in the presence of glia at concentrations of 20, 50 and 100 ng/ml of bFGF. Postnatal glia was affected by all concentrations of bFGF, as was observed in embryonic cultures. This study indicates that high concentrations of bFGF can influence cholinergic neuronal survival by stimulating and increasing glia, which may produce factor(s) that are necessary for cholinergic neuron survival.     

Basic fibroblast growth factor: a potential autocrine regulator of human glioma cell growth

Basic fibroblast growth factor (bFGF) is a potent mitogen and angiogenic factor. bFGF is expressed by a variety of solid human tumors and has been implicated as an autocrine regulator of tumor growth. Different solid tumor lines including glioma, colon carcinoma and melanoma were examined for intracellular immunoreactive bFGF, high- and low-affinity bFGF receptors and mitogenic response to bFGF when grown in chemically defined medium. All tumor lines contained significant levels of bFGF. In addition, all tumor lines contained subsets of five forms of immunoreactive bFGF, as well as 0.68-20 x 10(6) low affinity bFGF binding sites (Kd = 15-300 nM). Most, but not all lines exhibited high affinity bFGF receptors (Kd = 25-40 pM). Glioma cell lines were distinguished by expressing the highest levels of bFGF protein as well as the most high-affinity receptors for bFGF. Furthermore, glioma cell lines were the only tumor type mitogenically responsive to bFGF. These results indicate that glioma cells express high levels of this potent mitogen and angiogenic factor relative to human colon carcinoma and melanoma cells. The expression of bFGF and bFGF receptors by glioma cells may be related to abnormal growth and neoplastic progression in these tumors.     

Heparan sulfate modifies the effects of basic fibroblast growth factor on glial reactivity

Our previous studies have shown that injection of basic fibroblast growth factor (bFGF) into a brain wound enhances astrocyte hypertrophy and macrophage-microglia proliferation in areas adjacent to the lesion. In the present study, designed to test the effects of co-administration of bFGF and heparan sulfate (HS), rats received injections of 200 ng bFGF, 200 ng bFGF with 50 μg HS, or 50 μg HS into a brain wound. Glial proliferation and astrocyte hypertrophy were evaluated in seven non-overlapping subfields in the mid-cortex including the wound edge. Our results show that bFGF-HS, compared to bFGF or HS alone, enhanced the total area of GFAP staining in all subfields except the one nearest to the wound edge. The combination of bFGF and HS did not increase total glial or astrocyte proliferation. We propose that the observed effects resulted from a greater diffusion of bFGF-HS complex into the brain parenchyma, where it bypassed low-affinity binding sites that would otherwise sequester free bFGF. Our results suggest that bFGF-HS complex, compared to bFGF alone, may gain entry into the brain more readily, reach higher concentrations and be more effective as a neurotrophic agent.