The effect of epidermal growth factor in the injured brain after trauma in rats

Dong Sun, Ross Bullock, Nabil Altememi, Zhengwen Zhou, Sarah Hagood, Andrew Rolfe, Melissa J. McGinn, Robert Hamm, Raymond J. Colello

Research output: Contribution to journalArticle

64 Citations (Scopus)

Abstract

Epidermal growth factor (EGF) is a known mitogen for neural stem and progenitor cells (NS/NPCs) in the central nervous system (CNS). In vitro, EGF maintains NS/NPCs in the proliferative state, whereas in the normal rodent brain it promotes their proliferation and migration in the subventricular zone (SVZ). Additionally, EGF administration can augment neuronal replacement in the ischemic-injured adult striatum. Recently we found that the SVZ and the hippocampus display an injury-induced proliferative response following traumatic brain injury (TBI) that is linked to increased EGF expression. As adult neurogenesis is associated with cognitive function, we hypothesized that post-TBI administration of EGF could affect neurogenesis and cognitive recovery. Adult rats were intraventricularly infused with EGF or vehicle for 7 days following TBI. 5-Bromo-2-deoxyuridine (BrdU) was administered to label proliferating cells and the animals were sacrificed at 1 or 4 weeks post-injury. Using immunohistochemistry and stereology, we found that at 1 week post-injury, compared to vehicle-infused animals EGF-infused animals had significantly more BrdU-positive cells in the SVZ and hippocampus concomitant with enhanced EGF receptor expression. At 4 weeks post-injury, the number of BrdU-positive cells in the hippocampus was similar in both groups, suggesting that EGF does not support long-term survival of newly generated cells. Furthermore, we found that the EGF-induced proliferative population differentiated preferentially toward astroglial phenotype. Nevertheless, animals treated with EGF showed significant improvement in cognitive function, which was accompanied by reduced hippocampal neuronal cell loss. Collectively, the data from this study demonstrate that EGF exerts a neuroprotective rather than neurogenic effect in protecting the brain from injury.

Original languageEnglish
Pages (from-to)923-938
Number of pages16
JournalJournal of Neurotrauma
Volume27
Issue number5
DOIs
StatePublished - May 1 2010
Externally publishedYes

Fingerprint

Epidermal Growth Factor
Lateral Ventricles
Bromodeoxyuridine
Hippocampus
Neural Stem Cells
Neurogenesis
Wounds and Injuries
Cognition
Traumatic Brain Injury
Stem Cells
Mitogens
Epidermal Growth Factor Receptor
Brain Injuries
Rodentia
Central Nervous System
Immunohistochemistry
Phenotype
Brain

Keywords

  • Epidermal growth factor
  • Hippocampus
  • Morris water maze
  • Neurogenesis
  • Subventricular zone
  • Traumatic brain injury

ASJC Scopus subject areas

  • Clinical Neurology

Cite this

Sun, D., Bullock, R., Altememi, N., Zhou, Z., Hagood, S., Rolfe, A., ... Colello, R. J. (2010). The effect of epidermal growth factor in the injured brain after trauma in rats. Journal of Neurotrauma, 27(5), 923-938. https://doi.org/10.1089/neu.2009.1209

The effect of epidermal growth factor in the injured brain after trauma in rats. / Sun, Dong; Bullock, Ross; Altememi, Nabil; Zhou, Zhengwen; Hagood, Sarah; Rolfe, Andrew; McGinn, Melissa J.; Hamm, Robert; Colello, Raymond J.

In: Journal of Neurotrauma, Vol. 27, No. 5, 01.05.2010, p. 923-938.

Research output: Contribution to journalArticle

Sun, D, Bullock, R, Altememi, N, Zhou, Z, Hagood, S, Rolfe, A, McGinn, MJ, Hamm, R & Colello, RJ 2010, 'The effect of epidermal growth factor in the injured brain after trauma in rats', Journal of Neurotrauma, vol. 27, no. 5, pp. 923-938. https://doi.org/10.1089/neu.2009.1209
Sun D, Bullock R, Altememi N, Zhou Z, Hagood S, Rolfe A et al. The effect of epidermal growth factor in the injured brain after trauma in rats. Journal of Neurotrauma. 2010 May 1;27(5):923-938. https://doi.org/10.1089/neu.2009.1209
Sun, Dong ; Bullock, Ross ; Altememi, Nabil ; Zhou, Zhengwen ; Hagood, Sarah ; Rolfe, Andrew ; McGinn, Melissa J. ; Hamm, Robert ; Colello, Raymond J. / The effect of epidermal growth factor in the injured brain after trauma in rats. In: Journal of Neurotrauma. 2010 ; Vol. 27, No. 5. pp. 923-938.
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