Psychometric analysis in children with mental retardation due to perinatal hypoxia treated with fibroblast growth factor (FGF) and showing improvement in mental development

Aguilar, Lizeth Camacho; Islas, Antonia Pérez; Rosique, P.; Hernandez, Bruno Agostinho; Portillo, Elizabeth Mendoza; Herrera, José-Luís; Cortés, Rocío; Cruz, S.; Alfaro, Federico Hernández; Martín, Rebeca; Cantu, Juan

doi:10.1111/j.1365-2788.1993.tb00321.x

Cited by 15 publications

(8 citation statements)

References 27 publications

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“…Some of the pathological effects of high bFGF levels may be mediated by astrocytes and microglia, as raising bFGF in ventricular cerebrospinal fluid of neonatal rats led to astroglial and microglial reactivity (Goddard et al, 2002). Despite its properties of neuroprotection (Aguilar et al, 1993; Kirschner et al, 1995), based on its effects on glia, bFGF is considered a stem/progenitor cell activator whose downregulation benefits WM OL recovery.…”

Section: Strategies For Improving Protection and Repairmentioning

confidence: 99%

Pharmacological approaches to intervention in hypomyelinating and demyelinating white matter pathology

Chew

DeBoy

2016

Neuropharmacology

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White matter disease afflicts both developing and mature central nervous systems. Both cell intrinsic and extrinsic dysregulation result in profound changes in cell survival, axonal metabolism and functional performance. Experimental models of developmental white matter (WM) injury and demyelination have not only delineated mechanisms of signaling and inflammation, but have also paved the way for the discovery of pharmacological approaches to intervention. These reagents have been shown to enhance protection of the mature oligodendrocyte cell, accelerate progenitor cell recruitment and/or differentiation, or attenuate pathological stimuli arising from the inflammatory response to injury. Here we highlight reports of studies in the CNS in which compounds, namely peptides, hormones, and small molecule agonists/antagonists, have been used in experimental animal models of demyelination and neonatal brain injury that affect aspects of excitotoxicity, oligodendrocyte development and survival, and progenitor cell function, and which have been demonstrated to attenuate damage and improve WM protection in experimental models of injury. The molecular targets of these agents include growth factor and neurotransmitter receptors, morphogens and their signaling components, nuclear receptors, as well as the processes of iron transport and actin binding. By surveying the current evidence in non-immune targets of both the immature and mature WM, we aim to better understand pharmacological approaches modulating endogenous oligodendroglia that show potential for success in the contexts of developmental and adult WM pathology.

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Section: Strategies For Improving Protection and Repairmentioning

confidence: 99%

Pharmacological approaches to intervention in hypomyelinating and demyelinating white matter pathology

Chew

DeBoy

2016

Neuropharmacology

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“…Concerning a possible relation between FGF‐2 signaling and altered mental capacities, behavioral studies would help to get more insight into this issue. In this context, it is worth mentioning that FGF‐2 administered to children with mental retardation increased significantly their mental development and IQ (Aguilar et al,1993).…”

Section: Discussionmentioning

confidence: 99%

Fibroblast growth factor‐2 deficiency affects hippocampal spine morphology, but not hippocampal catecholaminergic or cholinergic innervation

Zechel

Unsicker

Halbach

2009

Developmental Dynamics

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The availability of fibroblast growth factor-2 (FGF-2) -deficient mice has permitted studying the role of endogenous FGF-2. Several studies have reported that neocortical but not hippocampal neurons are lost in FGF-2-deficient mice. Here, we show that neuronal densities within the basolateral amygdala are unaltered in FGF-2؊/؊ mice. Moreover, we provide evidence that FGF-2 mutant mice display no obvious alterations in the catecholaminergic or cholinergic innervation of the hippocampus. With regard to the formation of dendritic spines, our studies reveal that endogenous FGF-2 is not essential for hippocampal spinogenesis; however, FGF-2 affects the length of individual spines. Such alterations in spine morphology may be related to disturbances in mental capacities or alterations in neuronal plasticity. Of interest, in this context, animal models of mental retardation develop no alterations in hippocampal spine densities, but display higher numbers of long dendritic spines. Thus, FGF-2 may also affect learning and memory by altering spine morphology. Developmental Dynamics 238:343-350, 2009.

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“…FGFR inhibition is trialed for treatment of malignancy, and paracrine FGFs have a potential in angiogenesis, cytoprotection, and tissue repair. Regarding psychiatric disease, there is one study in children with mental retardation caused by perinatal hypoxia (Aguilar and others 1993). A large developmental and cognitive improvement (+10 IQ points) was reported after treatment with intramuscular injections of FGF2, compared with placebo-treated children.…”

Section: Treatmentmentioning

confidence: 99%

Fibroblast Growth Factors in Neurodevelopment and Psychopathology

et al. 2013

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In psychiatric disorders, the effect of genetic and environmental factors may converge on molecular pathways and brain circuits related to growth factor functioning. In this review, we describe how disturbances in fibroblast growth factors (FGFs) and their receptors influence behavior by affecting brain development. Recently, several studies reported associations of members of the FGF family with psychiatric disorders. FGFs are key candidates to modulate the impact of environmental factors, such as stress. Mutant mice for FGF receptor 1 show schizophrenia-like behaviors that are related to general loss of neurons and postnatal glia dysfunction. Mice lacking FGF2, a FGFR1 ligand, show similar reductions in brain volume and hyperactivity, as well as increased anxiety behaviors. FGFR2 and FGF17 are involved in the development of frontal brain regions and impairments in cognitive and social behaviors, respectively. Moreover, treatment with FGF2 was beneficial for depressive and cognitive measures in several animal studies and one human study. These findings indicate the importance of the FGF system with respect to developing novel etiology-directed treatments for psychopathology.

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Psychometric analysis in children with mental retardation due to perinatal hypoxia treated with fibroblast growth factor (FGF) and showing improvement in mental development

Cited by 15 publications

References 27 publications

Pharmacological approaches to intervention in hypomyelinating and demyelinating white matter pathology

Pharmacological approaches to intervention in hypomyelinating and demyelinating white matter pathology

Fibroblast growth factor‐2 deficiency affects hippocampal spine morphology, but not hippocampal catecholaminergic or cholinergic innervation

Fibroblast Growth Factors in Neurodevelopment and Psychopathology

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