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Vol. 9, No. 3, 1999
Issue release date: May–June 1999
Cerebrovasc Dis 1999;9:131–135

Potential Usefulness of Basic Fibroblast Growth Factor as a Treatment for Stroke

Ay H. · Ay I. · Koroshetz W.J. · Finklestein S.P.
Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Boston, Mass., USA

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Within the past few years, a growing body of evidence has accumulated indicating that exogenously administered neurotrophic growth factors may limit the extent of acute ischemic neural injury and enhance functional neurorecovery following stroke. One of the most widely studied growth factor in this regard is basic fibroblast growth factor (bFGF). In preclinical studies, bFGF administered intravenously within hours after the onset of ischemia reduces infarct size, presumably due to direct protection of cells at the borders (penumbra) of cerebral infarction. On the other hand, if bFGF is administered intracisternally starting at one day after ischemia, infarct size is not reduced, but recovery of sensorimotor function of the impaired limbs is increased, presumably due to enhancement of new neuronal sprouting and synapse formation in the intact uninjured brain. Clinical trials of the intravenous administration of bFGF as a cytoprotective agent in acute stroke are in progress. Trials of the delayed administration of bFGF as a recovery-promoting agent in subacute stroke are anticipated.

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  1. Cuevas P, Gimenez-Gallego G, Martinez-Murillo R, Carceller F: Immunohistochemical localization of basic fibroblast growth factor in ependymal cells of the rat lateral and third ventricles. Acta Anat 1991;141:307–310.
  2. Matsuyama A, Iwata H, Okumura N, Yoshida S, Imaizumi K, Lee Y, Shiraishi S, Shiosaka S: Localization of basic fibroblast growth factor-like immunoreactivity in the rat brain. Brain Res 1992;587:49–65.
  3. Gonzalez AM, Berry M, Maher PA, Logan A, Baird A: A comprehensive analysis of the distribution of FGF-2 and FGFR 1 in the rat brain. Brain Res 1995;701:201–226.
  4. Wanaka A, Johnson EM Jr, Milbrandt J: Localization of FGF receptor mRNA in the adult rat central nervous system by in situ hybridization. Neuron 1990;5:267–281.

    External Resources

  5. Mattson MP, Barger SW: Programmed cell life: Neuroprotective signal transduction and ischemic brain injury; in Moskowitz MA and Caplan LR (eds): Cerebrovascular Diseases. 19th Princeton Stroke Conf. Newton, Butterworth-Heinemann 1995, pp 271–290.
  6. Finklestein SP, Fanning PJ, Caday CG, Powell PP, Foster J, Clifford EM, Klagsbrun M: Increased levels of basic fibroblast growth factor (bFGF) following focal brain injury. Restorative Neurol Neurosci 1990;1:387–394.
  7. Speliotes EK, Caday CG, Do T, Weise J, Kowall NW, Finklestein SP: Increased expression of basic fibroblast growth factor (bFGF) following focal cerebral infarction in the rat. Brain Res Mol Brain Res 1996;39:31–42.
  8. Logan A, Frautschy SA, Gonzalez A-M, Baird A: A time course for the focal elevation of synthesis of basic fibroblast growth factor and one of it high-affinity receptors (flg) following a localized cortical brain injury. J Neurosci 1992;12:3828–3837.
  9. Masumura M, Murayama N, Inoue T, Ohno T: Selective induction of fibroblast growth factor receptor-1 mRNA after transient focal ischemia in the cerebral cortex of rats. Neurosci Lett 1996;213:119–122.
  10. Fisher M, Meadows M-E, Do T, Weise J, Trubetskoy V, Charette M, Finklestein SP: Delayed treatment with intravenous basic fibroblast growth factor reduces infarct size following permanent focal cerebral ischemia in rats. J Cereb Blood Flow Metab 1995;15:953–959.
  11. Cuevas P, Fernandes-Ayerdi A, Carceller F, Colin S, Mascarelli F, Muñoz-Willery I, Gimenez-Gallego G: Central nervous system distribution of fibroblast growth factor injected into the blood stream. Neurol Res 1996;18:267–272.
  12. Yamada K, Kinoshita A, Kohmura E, Sakaguchi T, Taguchi J, Kataoka K, Hayakawa T: Basic fibroblast growth factor prevents thalamic degeneration after cortical infarction. J Cereb Blood Flow Metab 1991;11:472–478.
  13. Nakata N, Kato H, Kogure K: Protective effects of basic fibroblast growth factor against hippocampal neuronal damage following cerebral ischemia in the gerbil. Brain Res 1993;605:354–356.
  14. Nozaki K, Finklestein SP, Beal MF: Basic fibroblast growth factor protects against hypoxia-ischemia and NMDA neurotoxicity in neonatal rats. J Cereb Blood Flow Metab 1993;13:221–228.
  15. Koketsu N, Berlove DJ, Moskowitz MA, Kowall NW, Caday CG, Finklestein SP: Pretreatment with intraventricular basic fibroblast growth factor (bFGF) decreases infarct size following focal cerebral ischemia in rats. Ann Neurol 1994;35:451–457.
  16. Tanaka R, Miyasaka Y, Yada K, Ohwada T, Kameya T: Basic fibroblast growth factor increases regional cerebral blood flow and reduces infarct size after experimental ischemia in a rat model. Stroke 1995;26:2154–2158.
  17. Huang Z, Chen K, Huang PL, Finklestein SP, Moskowitz MA: bFGF ameliorates focal ischemic injury by blood flow-independent mechanisms in eNOS mutant mice. Am J Physiol 1996;272:H1401–H1405.
  18. Jiang N, Finklestein SP, Do T, Caday CG, Charette M, Choop M: Delayed intravenous administration of basic fibroblast growth factor (bFGF) reduces infarct volume in a model of focal cerebral ischemia/reperfusion in the rat. J Neurol Sci 1996;139:173–179.

    External Resources

  19. Tatlisumak T, Takano K, Carano RA, Fisher M: Effect of basic fibroblast growth factor on experimental focal ischemia studied by diffusion-weighted and perfusion imaging. Stroke 1996;27:2292–2297.
  20. Bethel A, Kirsch JR, Koehler RC, Finklestein SP: Intravenous basic fibroblast growth factor decreases brain injury resulting from focal ischemia in cats. Stroke 1997;28:609–615.
  21. Ren JM, Finklestein SP: Time window of infarct reduction by intravenous basic fibroblast growth factor in focal cerebral ischemia. Eur J Pharmacol 1997;327:11–16.

    External Resources

  22. Cuevas P, Carceller F, Ortega S, Zazo M, Nieto I, Gimenez-Gallego G: Hypotensive activity of fibroblast growth factor. Science 1991;254:1208–1210.

    External Resources

  23. Rosenblatt S, Irikura K, Caday CG, Finklestein SP, Moskowitz MA: Basic fibroblast growth factor (bFGF) dilates rat pial arterioles. J Cereb Blood Flow Metab 1994;14:70–74.

    External Resources

  24. Jones TA, Schallert T: Use-dependent growth of pyramidal neurons after neocortical damage. J Neurosci 1994;14:2140–2152.
  25. Stroemer RP, Kent TA, Hulsebosch CE: Neocortical neural sprouting, synaptogenesis, and behavioral recovery after neocortical infarction in rats. Stroke 1995;26:2135–2144.
  26. Weiller C, Chollet F, Friston KJ, Wise RJ, Frackowiak RS: Functional reorganization of the brain in recovery from striatocapsular infarction in man. Ann Neurol 1992;31:463–472.
  27. Cao Y, D’Olhaberriague L, Vikingstad EM, Levine SR, Welch KM: Pilot study of functional MRI to assess cerebral activation of motor function after poststroke hemiparesis. Stroke 1998;29:112–122.
  28. Cramer SC, Nelles G, Benson RR, Kaplan JD, Parker RA, Kwong KK, Kennedy DN, Finklestein SP, Rosen BR: A functional MRI study of subjects recovered from hemiparetic stroke. Stroke 1997;28:2518–2527.
  29. Rowntree S, Kolb B: Blockade of basic fibroblast growth factor retards recovery from motor cortex injury in rats. Eur J Neurosci 1997;9:2432–2441.
  30. Patel MN, McNamara JO: Selective enhancement of axonal branching of cultured dentate gyrus neurons by neurotrophic factors. Neuroscience 1995;69:763–770.

    External Resources

  31. Walicke P, Cowan WM, Ueno N, Baird A, Guillemin R: Fibroblast growth factor promotes survival of dissociated hippocampal neurons and enhances neurite extension. Proc Natl Acad Sci USA 1986;83:3012–3016.
  32. Himmelseher S, Pfenninger E, Georgieff M: Effects of basic fibroblast growth factor on hippocampal neurons after axonal injury. J Trauma 1997;42:659–664.
  33. Otto D, Unsicker K: Basic FGF reverses chemical and morphological deficits in the nigrostriatal system of MPTP-treated mice. J Neurosci 1990;10:1912–1921.
  34. Kawamata T, Alexis NE, Dietrich WD, Finklestein SP: Intracisternal basic fibroblast growth factor (bFGF) enhances behavioral recovery following focal cerebral infarction in the rat. J Cereb Blood Flow Metab 1996;16:542–547.
  35. Kawamata T, Dietrich DW, Schallert T, Gotts JE, Cocke RR, Benowitz LI, Finklestein SP: Intracisternal basic fibroblast growth factor enhances functional recovery and up-regulates the expression of a molecular marker of neuronal sprouting following focal cerebral infarction. Proc Natl Acad Sci USA 1997;94:8179–8184.
  36. Mazue G, Bertolero F, Jacob C, Sarmientos P, Roncucci R: Preclinical and clinical studies with recombinant human basic fibroblast growth factor. Ann NY Acad Sci 1991;638:329–340.
  37. Mazue G, Bertolero F, Garofano L, Brughera M, Carminati P: Experience with the preclinical assessment of basic fibroblast growth factor (bFGF). Toxicol Lett 1992;64–65:329–338.
  38. Mazue G, Newman AJ, Scampini G, Della Torre P, Hard GC, Iatropoulos MJ, Williams GM, Bagnasco SM: The histopathology of kidney changes in rats and monkeys following intravenous administration of massive doses of FCE 26184, human basic fibroblast growth factor. Toxicol Pathol 1993;21:490–501.
  39. Gross JL, Herblin WF, Dusak BA, Czerniak P, Diamond MD, Sun T, Eidsvoog K, Dexter DL, Yayon A: Effects of modulation of basic fibroblast growth factor on tumor growth in vivo. J Natl Cancer Inst 1993;85:121–131.
  40. Leith JT, Michelson S: Effects of administration of basic fibroblast growth factor on hypoxic fractions in xenografted DLD-2 human tumors: Time dependence. Br J Cancer 1993;68:727–731.
  41. Fiblast Safety Study Group: Clinical safety trial of intravenous basic fibroblast growth factor (bFGF, Fiblast®) in acute stroke (abstract). 23rd Int Joint Conf Stroke Cereb Circ, Stroke 1998;29:287.

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