Effect of neuregulin-1 on histopathological and functional outcome after controlled cortical impact in mice.
Neuregulin-1 is a pleiotropic endogenous growth factor that is neuroprotective in experimental models of cerebral ischemia. We tested the hypothesis that pretreatment with neuregulin-1 would be similarly protective after traumatic brain injury in mice. Mice were administered neuregulin-1 or equal amounts of vehicle intravenously immediately before controlled cortical impact. Injured mice were subjected to motor and cognitive testing, and brain tissue loss was quantitated at 4 weeks. Compared to vehicle, pretreatment with neuregulin-1 had no effect on brain tissue loss, motor function, or acquisition of a spatial learning task. However, neuregulin-1 treated mice showed improved retention of spatial memory versus vehicle-treated mice in subsequent probe trials (p<0.05). These proof-of-principle data suggest that neuregulin-1 may improve some functional outcomes after brain trauma. Further studies are therefore warranted to more carefully explore molecular mechanisms, dose-responses, and relationships between morphological outcome and long-term recovery.
Lok
Josephine
J
Neuroprotection Research Laboratory, Department of Radiology, Massachusetts General Hospital, and Program in Neuroscience, Harvard Medical School, Boston, Massachusetts, USA. jlok1@partners.org
Wang
Hui
H
Murata
Yoshihiro
Y
Zhu
Hai Hao
HH
Qin
Tao
T
Whalen
Michael J
MJ
Lo
Eng H
EH
D000818:Animals; D001930:Brain Injuries / Q000517:prevention & control*; D002540:Cerebral Cortex / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008568:Memory / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D020890:Neuregulin-1 / Q000627:therapeutic use*; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D020127:Recovery of Function / Q000187:drug effects*
D020890:Neuregulin-1; D018696:Neuroprotective Agents