1: Brain Res 1993 Oct 29;626(1-2):335-8
Department of Neurology, Harvard Medical School, Children’s Hospital, Boston, MA.
Basic fibroblast growth factor (bFGF) has been shown to have neuroprotective effects in animal models of ischemia. To determine whether bFGF is protective against seizure-induced brain damage, we administered bFGF through osmotic pumps prior to, and after treatment with kainic acid (KA). Recombinant bFGF, CS23, a modified human bFGF, was infused into the lateral ventricles in rats for 2 days before and 5 days after the injection of KA. Control rats received equal volumes of phosphated saline over the same period of time. Infusion of 5 micrograms/ml of bFGF (0.5 microliter/h) did not modify the latency and duration of seizures induced by intraperitoneal injections of KA. However, bFGF prevented cell loss in the hippocampus in 80% of the rats. In control rats, cell loss in the hippocampus was found in all rats. These results indicate that bFGF has a substantial neuroprotective effect.
Neuroprotective effect of chronic infusion of basic fibroblast growth factor on seizure-associated hippocampal damage.
Liu Z, D’Amore PA, Mikati M, Gatt A, Holmes GL
2: Neuroscience 1997 Feb;76(4):1129-38
Basic fibroblast growth factor is highly neuroprotective against seizure-induced long-term behavioural deficits.Liu Z, Holmes GLDepartment of Neurology, Harvard Medical School, Children’s Hospital, Boston, Massachusetts, USA.Basic fibroblast growth factor has been reported to protect neurons of various structures from excitotoxic damage. To study the effects of basic fibroblast growth factor on seizure-induced brain damage we infused the growth factor into the lateral ventricles of 35-day-old rats receiving convulsant dosages of kainic acid. Artificial cerebrospinal fluid or basic fibroblast growth factor at dosages of 0.5 ng/h or 2.5 ng/h was infused into the lateral ventricle continuously for seven days starting two days before and continuing for five days after the animals had kainic acid-induced status epilepticus. At age 80 days the animals underwent behavioural testing using the water maze, open field, and handling tests and at age 95 days were tested for seizure threshold using flurothyl inhalation. Neither artificial cerebrospinal fluid or basic fibroblast growth factor modified the latency or duration of the acute seizures following kainic acid. However, rats infused with 2.5 ng/h, but not 0.5 ng/h of basic fibroblast growth factor, had fewer spontaneous recurrent seizures, a higher seizure threshold, better performance in the handling, open field and water maze test, and less cell loss in the hippocampus when compared to rats receiving artificial cerebrospinal fluid or 0.5 ng/h of basic fibroblast growth factor. These results show that basic fibroblast growth factor has a dose-related neuroprotective effect against seizure-induced long-term behavioural deficits when administered by osmotic pump prior to seizure onset. This neuroprotective effect is not related to an anticonvulsant effect.PMID: 9027873
4: Neurol Res 1994 Oct;16(5):365-9
Neuroprotective effect of acidic fibroblast growth factor on seizure-associated brain damage.Cuevas P, Revilla C, Herreras O, Largo C, Gimenez-Gallego GServicio de Histologia, Hospital Ramon y Cajal, Madrid, Spain.The neuroprotective effect of acidic fibroblast growth factor (aFGF) has been analysed in a rat model of seizures-associated brain damage. We report that after treatment with a convulsivant dose of Kainic acid, systemically administered aFGF prevents neuronal degeneration in specific brain areas, mainly in the hippocampal formation. Our findings extend the potential pharmacological use of fibroblast growth factors and afford new data to understand the neurophysiology of these proteins.PMID: 7532808
5: J Neurosci 1999 Jul15;19(14):6006-16
Stimulation of neonatal and adult brain neurogenesis by subcutaneous injection of basic fibroblast growth factor.Wagner JP, Black IB, DiCicco-Bloom EDepartment of Neuroscience and Cell Biology, University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Piscataway, New Jersey 08854, USA.Mounting evidence indicates that extracellular factors exert proliferative effects on neurogenetic precursors in vivo. Recently we found that systemic levels of basic fibroblast growth factor (bFGF) regulate neurogenesis in the brain of newborn rats, with factors apparently crossing the blood-brain barrier (BBB) to stimulate mitosis. To determine whether peripheral bFGF affects proliferation during adulthood, we focused on regions in which neurogenesis persists into maturity, the hippocampus and the forebrain subventricular zone (SVZ). In postnatal day 1 (P1) rats, 8 hr after subcutaneous injection (5 ng/gm body weight), bFGF increased [(3)H]thymidine incorporation 70% in hippocampal and SVZ homogenates and elicited twofold increases in mitotic nuclei in the dentate gyrus and the dorsolateral SVZ, detected by bromodeoxyuridine immunohistochemistry. Because approximately 25% of proliferating hippocampal cells stimulated in vivo expressed neuronal traits in culture, bFGF-induced mitosis may reflect increased neurogenesis. bFGF effects were not restricted to the perinatal period; hippocampal DNA synthesis was stimulated by peripheral factor in older animals (P7-P21), indicating the persistence of bFGF-responsive cells and activity of peripheral bFGF into late development. To begin defining underlying mechanisms, pharmacokinetic studies were performed in P28 rats; bFGF transferred from plasma to CSF rapidly, levels rising in both compartments in parallel, indicating that peripheral factor crosses the BBB during maturity. Consequently, we tested bFGF in adults; peripheral bFGF increased the number of mitotic nuclei threefold in the SVZ and olfactory tract, regions exhibiting persistent neurogenesis. Our observations suggest that bFGF regulates ongoing neurogenesis via a unique, endocrine-like pathway, potentially coordinating neuron number and body growth, and potentially providing new approaches for treating damaged brain during development and adulthood. PMID: 10407038
Fibroblast growth factor and its implications for developing and regenerating neurons.
Grothe C; Wewetzer K
Institute of Anatomy, University of Freiburg, Germany.
Int J Dev Biol, 40(1):403-10 1996 Feb
FGF is a multifunctional heparin-binding protein which was characterized by its mitogenic and angiogenic action outside the nervous system. Recent data confirm this multifunctionality also with regard to the nervous system. The distribution of FGF and its receptors seems not to be in agreement with the idea of a single function for one population but argues for a more complex action, which might be dependent on the development stage and cell type. FGF and its receptors are widely distributed in the nervous system. In brainstem and spinal cord motoneurons and in sensory ganglia the FGF-2 staining pattern is developmentally regulated suggesting a functional change during embryonic and postnatal development. In addition, after nerve lesion the FGF-2 expression is altered in sensory and motoneurons. Administration of FGF-2 reveals trophic effects on survival and transmitter metabolism in vivo and in vitro. According to a more general neurotrophic factor concept, a physiological role of FGF for distinct neuron populations during development is likely. In the motor system, for example, FGF could act synergistically with certain neurotrophins, CNTF, or other non-identified co-factors. In the sensory system, a possible non-neurotrophic role for at least postnatal and adult sensory neurons has to be further addressed in the future. In order to further define and characterize the actions of the FGFs a mapping of the different family members and their respective receptor molecules during development and in the adult has to be done.
Animal ; Fibroblast Growth Factor GE/*ME/PD ; In Vitro ; Models, Neurological ; Nerve Regeneration GE/*PH ; Nervous System GD/ME ; Neurons DE/*ME ; Rats ; Receptors, Fibroblast Growth Factor ME ; RNA, Messenger GE/ME ; Support, Non-U.S. Gov’t
JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
Country of Publication : SPAIN