title: Acidic FGF promotes neurite outgrowth of cortical neurons and improves neuroprotective effect in a cerebral ischemic rat model.
abstract: Acidic fibroblast growth factor (aFGF) is a neurotrophic factor which is a powerful neuroprotective and neuroregenerative factor of the nervous system. Prior study had shown that levels of FGFs significantly increase following ischemic injury, reflecting a physiological protection mechanism. However, few reports demonstrated the efficacy of applying aFGF in cerebral ischemia. A recent report showed that the intranasal aFGF treatment improved neurological functional recovery; however, it did not significantly reduce the lesion size in ischemic rats. The present study examines the neuroprotective effect of aFGF on cortical neuron-glial cultures under oxygen glucose deprivation (OGD)-induced cell damage and investigates whether epidural application of slow-released aFGF could improve benefit on ischemic stroke injury in conscious rats. We used a topical application of aFGF mixed in fibrin glue, a slow-release carrier, over the peri-ischemic cortex and examined such treatment on cerebral infarction and behavioral impairments of rats subjected to focal cerebral ischemia (FCI). Results demonstrate that aFGF effectively protected cortical neuron-glial cultures from OGD-induced neuronal damage. Neurite extension from cortical neurons was significantly enhanced by aFGF, mediated through activation of AKT and ERK. In addition, topical application of fibrin glue-mixed aFGF dose-dependently reduced ischemia-induced brain infarction and improved functional restoration in ischemic stroke rats. Slow-released aFGF not only protected hippocampal and cortical cell loss but reduced microglial infiltration in FCI rats. Our results suggest that aFGF mixed in fibrin glue could prolong the protective/regenerative efficacy of aFGF to the damaged brain tissue and thus improve the functional restorative effect of aFGF.
authors.affiliation: Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan; Center for Neural Regeneration, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan. Electronic address: mjtsai2@vghtpe.gov.tw.
authors.forename: M J
authors.initials: MJ
authors.lastname: Tsai
authors.affiliation: Cheng Hsin General Hospital, Taipei, Taiwan. Electronic address: ch9198@chgh.org.tw.
authors.forename: S K
authors.initials: SK
authors.lastname: Tsai
authors.affiliation: Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan; Center for Neural Regeneration, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan. Electronic address: mchuang@vghtpe.gov.tw.
authors.forename: M C
authors.initials: MC
authors.lastname: Huang
authors.affiliation: Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan. Electronic address: dragonspruce@gmail.com.
authors.forename: D Y
authors.initials: DY
authors.lastname: Liou
authors.affiliation: Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan. Electronic address: cute.shiaoyeh@gmail.com.
authors.forename: S L
authors.initials: SL
authors.lastname: Huang
authors.affiliation: Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan; Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan. Electronic address: smallhsing@gmail.com.
authors.forename: W H
authors.initials: WH
authors.lastname: Hsieh
authors.affiliation: Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan; Center for Neural Regeneration, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: wchuang@vghtpe.gov.tw.
authors.forename: W C
authors.initials: WC
authors.lastname: Huang
authors.affiliation: Department of Pharmacology and Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; Department of Pharmacy, Chung Shan Medical University Hospital, Taichung, Taiwan. Electronic address: sshuang@csmu.edu.tw.
authors.forename: S S
authors.initials: SS
authors.lastname: Huang
authors.affiliation: Neural Regeneration Laboratory, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan; Center for Neural Regeneration, Department of Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, Taiwan; Department and Institute of Pharmacology, National Yang-Ming University, Taipei, Taiwan; School of Medicine, National Yang-Ming University, Taipei, Taiwan. Electronic address: hc_cheng@vghtpe.gov.tw.
authors.forename: H
authors.initials: H
authors.lastname: Cheng
mesh_terms: D000818:Animals; D020520:Brain Infarction / Q000139:chemically induced / Q000188:drug therapy; D015687:Cell Hypoxia / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D016220:Fibroblast Growth Factor 1 / Q000494:pharmacology / Q000627:therapeutic use*; D007839:Functional Laterality; D005947:Glucose / Q000172:deficiency; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000188:drug therapy / Q000473:pathology*; D048748:MAP Kinase Kinase Kinase 3 / Q000378:metabolism; D008297:Male; D009069:Movement Disorders / Q000188:drug therapy / Q000209:etiology; D016501:Neurites / Q000187:drug effects*; D009457:Neuroglia / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D018696:Neuroprotective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D018696:Neuroprotective Agents; D016220:Fibroblast Growth Factor 1; D051057:Proto-Oncogene Proteins c-akt; D048748:MAP Kinase Kinase Kinase 3; D005947:Glucose
keywords: Akt; ERK; aFGF; cortical neuronal cultures; ischemic stroke; neuroprotection