title: Vascular and neuronal protection induced by the ocular administration of nerve growth factor in diabetic-induced rat encephalopathy.
abstract: BACKGROUND
  Based on our previous findings on the efficacy of ocular applied nerve growth factor as eye drops (oNGF) to act in brain and counteract neuronal damage, we hypothesized that oNGF treatment might revert neuronal atrophy occurring in diabetic brain also by controlling neurotrophin system changes. The major NGF brain target areas, such as the septum and the hippocampus, were used as an experimental paradigma to test this hypothesis.
  
  
  METHODS
  Bilateral oNGF treatment was performed twice a day for 2 weeks in full-blown streptozotocin-treated adult male rats. The forebrain distribution of cholinergic and endothelial cell markers and NGF receptors were studied by confocal microscopy. The septo-hippocampal content of NGF mature and precursor form and NGF receptors expression were also analyzed by Elisa and Western blot.
  
  
  RESULTS
  oNGF treatment recovers the morphological alterations and the neuronal atrophy in septum and normalized the expression of mature and pro-NGF, as well as NGF receptors in the septum and hippocampus of diabetic rats. In addition, oNGF stimulated brain vascularization and up-regulated the TRKA receptor in vessel endothelium.
  
  
  CONCLUSIONS
  Our findings confirm that reduced availability of mature NGF and NGF signaling impairment favors vascular and neuronal alterations in diabetic septo-hippocampal areas and corroborate the ability of oNGF to act as a neuroprotective agent in brain.
authors.affiliation: Institute of Cellular Biology and Neurobiology, National Research Council (CNR), Rome, Italy. paola.tirassa@inmm.cnr.it
authors.forename: Paola
authors.initials: P
authors.lastname: Tirassa
authors.forename: Mattia
authors.initials: M
authors.lastname: Maccarone
authors.forename: Fulvio
authors.initials: F
authors.lastname: Florenzano
authors.forename: Sara
authors.initials: S
authors.lastname: Cartolano
authors.forename: Sara
authors.initials: S
authors.lastname: De Nicolò
mesh_terms: D060433:Administration, Ophthalmic; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D003928:Diabetic Nephropathies / Q000188:drug therapy* / Q000473:pathology; D006624:Hippocampus / Q000098:blood supply / Q000473:pathology*; D008297:Male; D020932:Nerve Growth Factor / Q000008:administration & dosage*; D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020800:Receptor, Nerve Growth Factor / Q000032:analysis; D020917:Receptor, trkA / Q000032:analysis; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor / Q000032:analysis; D020665:Septum of Brain / Q000473:pathology*; D013311:Streptozocin
chemical_list: D009419:Nerve Tissue Proteins; D018696:Neuroprotective Agents; D020800:Receptor, Nerve Growth Factor; D017978:Receptors, Growth Factor; D017475:Receptors, Nerve Growth Factor; C068313:Ngfr protein, rat; D013311:Streptozocin; D020932:Nerve Growth Factor; D020917:Receptor, trkA