Mice Expressing a Bovine Basic Fibroblast Growth Factor Transgene in the Brain Show Increased Resistance to Hypoxemic‐Ischemic Cerebral Damage

Background and Purpose Cerebral intraventricular infusion of acidic or basic fibroblast growth factor has been shown to attenuate ischemic damage to hippocampal CA1 neurons in the gerbil. The purpose of the present study was to determine if the basic fibroblast growth factor transgenic mouse has an enhanced ability to resist the effects of severe cerebral hypoxemia-oligemia. Methods Mice that were transgenic for bovine basic fibroblast growth factor were exposed to right carotid artery ligation, hyperglycemia, and 20 minutes of 1% carbon monoxide. After 5 days' recovery, brains were examined for histological damage. Results Counts of CA1 neurons in the right hippocampus showed a significantly higher number of neurons per millimeter CA1 in hypoxic-ischemic transgenic mice compared with nontransgenic controls (transgenic, 260±33; nontransgenic, 151 ±37 neurons per millimeter CA1; P<.05). Conclusions The results indicate that basic fibroblast growth factor transgenic mice, as judged by CA1 hippocampal neuronal survival, have an enhanced ability to resist the effects of a complex hypoxic-ischemic cerebral insult. (Stroke. 1993;24:1735-1739.)

[1]  S. Finklestein,et al.  Delayed administration of basic fibroblast growth factor protects against N-methyl-D-aspartate neurotoxicity in neonatal rats. , 1993, European journal of pharmacology.

[2]  V. Macmillan,et al.  Acidic Fibroblast Growth Factor Infusion Reduces Ischemic CA1 Hippocampal Damage in the Gerbil , 1993, Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques.

[3]  M. DiFiglia,et al.  Basic fibroblast growth factor protects striatal neurons in vitro from NMDA-receptor mediated excitotoxicity , 1992, Brain Research.

[4]  C. Epstein,et al.  Attenuation of focal cerebral ischemic injury in transgenic mice overexpressing CuZn superoxide dismutase. , 1991, Proceedings of the National Academy of Sciences of the United States of America.

[5]  C. Epstein,et al.  Cold‐induced brain edema and infarction are reduced in transgenic mice overexpressing CuZn‐Superoxide dismutase , 1991, Annals of neurology.

[6]  E. Kohmura,et al.  Basic Fibroblast Growth Factor Prevents Thalamic Degeneration after Cortical Infarction , 1991, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[7]  M. Mattson,et al.  Evidence for calcium-reducing and excitoprotective roles for the calcium-binding protein calbindin-1328k in cultured hippocampal neurons , 1991, Neuron.

[8]  Mark P. Mattson,et al.  Glia protect hippocampal neurons against excitatory amino acid-induced degeneration: Involvement of fibroblast growth factor , 1990, International Journal of Developmental Neuroscience.

[9]  S. Kater,et al.  Fibroblast growth factor and glutamate: opposing roles in the generation and degeneration of hippocampal neuroarchitecture , 1989, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[10]  T. Wieloch,et al.  Impairment of protein ubiquitination may cause delayed neuronal death , 1989, Neuroscience Letters.

[11]  D. Choi,et al.  Glutamate neurotoxicity and diseases of the nervous system , 1988, Neuron.

[12]  S. Finklestein,et al.  Increased basic fibroblast growth factor (bFGF) immunoreactivity at the site of focal brain wounds , 1988, Brain Research.

[13]  D. Gospodarowicz,et al.  Structural characterization and biological functions of fibroblast growth factor. , 1987, Endocrine reviews.

[14]  D. Choi Ionic dependence of glutamate neurotoxicity , 1987, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[15]  J. Fiddes,et al.  Nucleotide sequence of a bovine clone encoding the angiogenic protein, basic fibroblast growth factor. , 1986, Science.

[16]  J. Olney,et al.  Glutamate and the pathophysiology of hypoxic–ischemic brain damage , 1986, Annals of neurology.

[17]  B. Cullen,et al.  Transcriptional activity of avian retroviral long terminal repeats directly correlates with enhancer activity , 1985, Journal of virology.

[18]  D. Melton,et al.  Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmids containing a bacteriophage SP6 promoter. , 1984, Nucleic acids research.

[19]  Takaaki Kirino,et al.  Delayed neuronal death in the gerbil hippocampus following ischemia , 1982, Brain Research.

[20]  S. Rehncrona,et al.  Brain Lactic Acidosis and Ischemic Cell Damage: 2. Histopathology , 1981, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[21]  W. Rutter,et al.  Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. , 1979, Biochemistry.

[22]  J. Brierley,et al.  A New Model of Bilateral Hemispheric Ischemia in the Unanesthetized Rat , 1979, Stroke.

[23]  F. Plum,et al.  Graded hypoxia-oligemia in rat brain. I. Biochemical alterations and their implications. , 1973, Archives of neurology.

[24]  T. Nowak Protein synthesis and the heart shock/stress response after ischemia. , 1990, Cerebrovascular and brain metabolism reviews.