title: Combination of growth factor treatment and scaffold deposition following traumatic brain injury has only a temporary effect on regeneration.
abstract: The recovery after traumatic brain injury (TBI) is hampered by the poor regenerative capacity of the brain. Today there is no treatment available that effectively restores lost brain tissue, but much research is focused on the stimulation of endogenous neural stem cells to viably and functionally repopulate the injured parenchyma. It is crucial that the therapies have a proven long-term effect on both regeneration and functional recovery to be clinically interesting. Here we have studied the induction of stem cell activation in rats at three weeks and six weeks after inducing TBI using controlled cortical impact model at a severe setting. We combined intracerebroventricular growth factor and scaffold treatment in order to accomplish an optimal effect on the stem cell regeneration. Immediately after TBI epidermal growth factor infusion with osmotic minipumps was started and continued for seven days. The pumps were removed and an extracellular matrix scaffold containing vascular endothelial growth factor was deposited into the cortical cavity. Three weeks after injury there was a positive effect of the treatment with a significant increase in neuronal and astrocytic regeneration. However, after six weeks there was no difference in the number of newly generated neurons and astrocytes in treated or untreated rats. Evaluation of tissue loss and spatial learning in the Morris water maze corroborated that the treatment had no effect at the later time point. Our results highlight the importance of long-term studies to ensure that a promising effect on tissue regeneration and functional outcome is not only temporary.
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Clausen
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Tone
authors.initials: T
authors.lastname: Lindh
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden.
authors.forename: Shabnam
authors.initials: S
authors.lastname: Salimi
authors.affiliation: Department of Neuroscience, Uppsala University, Uppsala, Sweden. Electronic address: anna.erlandsson@pubcare.uu.se.
authors.forename: Anna
authors.initials: A
authors.lastname: Erlandsson
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D001930:Brain Injuries / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology / Q000601:surgery; D004195:Disease Models, Animal; D004343:Drug Implants / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D004815:Epidermal Growth Factor / Q000008:administration & dosage*; D005109:Extracellular Matrix; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D009416:Nerve Regeneration / Q000187:drug effects* / Q000502:physiology; D058953:Neural Stem Cells / Q000187:drug effects / Q000502:physiology; D055495:Neurogenesis / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000008:administration & dosage*; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D016896:Treatment Outcome; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage*
chemical_list: D004343:Drug Implants; D018696:Neuroprotective Agents; D042461:Vascular Endothelial Growth Factor A; D004815:Epidermal Growth Factor
keywords: Epidermal growth factor; Neural stem cells; Regeneration; Scaffold; Traumatic brain injury; Vascular endothelial factor