The effect of epidermal growth factor in the injured brain after trauma in rats.
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.
Department of Neurosurgery, Virginia Commonwealth University, Richmond, Virginia 23298-0631, USA. dsun@vcu.edu
Dong
D
Sun
M Ross
MR
Bullock
Nabil
N
Altememi
Zhengwen
Z
Zhou
Sarah
S
Hagood
Andrew
A
Rolfe
Melissa J
MJ
McGinn
Robert
R
Hamm
Raymond J
RJ
Colello
D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology / Q000628:therapy*; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004815:Epidermal Growth Factor / Q000008:administration & dosage / Q000627:therapeutic use*; D006801:Humans; D007276:Injections, Intraventricular; D008297:Male; D055495:Neurogenesis / Q000502:physiology; D009473:Neuronal Plasticity / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000008:administration & dosage / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D013234:Stem Cells / Q000187:drug effects / Q000502:physiology; D016896:Treatment Outcome
D018696:Neuroprotective Agents; D011994:Recombinant Proteins; D004815:Epidermal Growth Factor