Acidic FGF promotes neurite outgrowth of cortical neurons and improves neuroprotective effect in a cerebral ischemic rat model. (1st October 2015)

• Record Type: Journal Article
• Authors: Tsai, M.J.; Tsai, S.K.; Huang, M.C.; Liou, D.Y.; Huang, S.L.; Hsieh, W.H.; Huang, W.C.; Huang, S.S.; Cheng, H.
• Is Part Of: Neuroscience. Volume 305(2015)
• Page Start: 238
• Page End: 247
• Publication Date: 2015-10-01
• Subjects: aFGF acidic fibroblast growth factor -- ANOVA analysis of variance -- DMEM Dulbecco's modified Eagle's medium -- FCI focal cerebral ischemia -- GDNF Glial cell line-derived neurotrophic factor -- IR immunoreactive -- LDH lactate dehydrogenase -- MCAo middle cerebral arterial occlusion -- OGD oxygen glucose deprivation -- PI propidium iodide -- rt-PA recombinant tissue plasminogen activator -- TTC 2, 3, 5-triphenyltetrazolium chloride; aFGF -- cortical neuronal cultures -- ischemic stroke -- neuroprotection -- Akt -- ERK; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2015.07.074
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: In culture, aFGF protected OGD-induced neuronal damage. In culture, aFGF increased neuronal connection through activation of AKT and ERK. Fibrin glue-mixed aFGF reduced ischemic brain damage and microglial infiltration. Fibrin glue-mixed aFGF improved functional restoration in MCAo rats. aFGF mixed in fibrin glue prolongs the protective/regenerative efficacy of aFGF in vivo . 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.