Long-Term Intranasal Nerve Growth Factor Treatment Favors Neuron Formation in de novo Brain Tissue
Objective To date, no safe and effective pharmacological treatment has been clinically validated for improving post-stroke neurogenesis. Growth factors are good candidates but low safety has limited their application in the clinic. An additional restraint is the delivery route. Intranasal delivery p...
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Published in | Frontiers in cellular neuroscience Vol. 16; p. 871532 |
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Main Authors | , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Lausanne
Frontiers Research Foundation
19.07.2022
Frontiers Frontiers Media S.A |
Subjects | |
Online Access | Get full text |
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Summary: | Objective
To date, no safe and effective pharmacological treatment has been clinically validated for improving post-stroke neurogenesis. Growth factors are good candidates but low safety has limited their application in the clinic. An additional restraint is the delivery route. Intranasal delivery presents many advantages.
Materials and Methods
A brain lesion was induced in twenty-four rats. Nerve growth factor (NGF) 5 μg/kg/day or vehicle was given intranasally from day 10 post-lesion for two periods of five weeks, separated by a two-week wash out period with no treatment. Lesion volume and atrophy were identified by magnetic resonance imaging (MRI). Anxiety and sensorimotor recovery were measured by behavior tests. Neurogenesis, angiogenesis and inflammation were evaluated by histology at 12 weeks.
Results
Remarkable neurogenesis occurred and was visible at the second and third months after the insult. Tissue reconstruction was clearly detected by T2 weighted MRI at 8 and 12 weeks post-lesion and confirmed by histology. In the new tissue (8.1% of the lesion in the NGF group
vs.
2.4%, in the control group at 12 weeks), NGF significantly increased the percentage of mature neurons (19%
vs.
7%). Angiogenesis and inflammation were not different in the two groups. Sensorimotor recovery was neither improved nor hampered by NGF during the first period of treatment, but NGF treatment limited motor recovery in the second period.
Interpretation
The first five-week period of treatment was very well tolerated. This study is the first presenting the effects of a long treatment with NGF and has shown an important tissue regeneration rate at 8 and 12 weeks post-injury. NGF may have increased neuronal differentiation and survival and favored neurogenesis and neuron survival through subventricular zone (SVZ) neurogenesis or reprogramming of reactive astrocytes. For the first time, we evidenced a MRI biomarker of neurogenesis and tissue reconstruction with T2 and diffusion weighted imaging. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 Reviewed by: Anna Stokowska, University of Gothenburg, Sweden; Claudia Alia, Institute of Neuroscience (CNR), Italy These authors have contributed equally to this work This article was submitted to Cellular Neuropathology, a section of the journal Frontiers in Cellular Neuroscience Edited by: Marta Perez-Rando, University of Valencia, Spain Present address: Alice Le Friec, Department of Biological and Chemical Engineering – Medical Biotechnology, Aarhus C, Denmark |
ISSN: | 1662-5102 1662-5102 |
DOI: | 10.3389/fncel.2022.871532 |