Neuregulin-1 reduces ischemia-induced brain damage in rats.
Neuregulin-1 (NRG-1) is expressed throughout the immature and adult central nervous system and it has been demonstrated to influence the migration of a variety of cell types in developing brain. Elevated levels of NRG-1 transcript are found in the adult brain after injury, leading to the suggestion that NRG-1 is involved in the physiological response to neuronal injury. Here, we report our findings that rats pre-treated with NRG-1 protein, undergoing cerebral ischemia 30 min later, had increased motor performance and less cerebral infarction than untreated rats. In the cortex of NRG-1 treated rats, ischemia induced a decrease in caspase-3 immunoreactivity and a reduction in the density of cells positive for terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end-labeling. Improvement in behavioral assays was also found in animals treated with NRG-1. Pre-treatment with NRG-1 did not alter cerebral blood flow or other physiological parameters. NRG-1 reduced ischemia/reperfusion injury, indicating that it may act as an endogenous neuroprotective factor against stroke. Therefore, NRG-1 may represent a target for the development of new treatments for stroke.
Shyu
Woei-Cherng
WC
Neuro-Medical Scientific Center, Tzu-Chi Buddhist General Hospital, Tzu-Chi University, Hualien, Taiwan, ROC.
Lin
Shinn-Zong
SZ
Chiang
Ming-Fu
MF
Yang
Hui-I
HI
Thajeb
Peterus
P
Li
Hung
H
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001921:Brain / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology*; D020170:Caspase 1 / Q000378:metabolism; D002470:Cell Survival; D002544:Cerebral Infarction / Q000209:etiology / Q000473:pathology; D053938:DNA Fragmentation / Q000502:physiology; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D007276:Injections, Intraventricular; D008297:Male; D009043:Motor Activity / Q000502:physiology; D020890:Neuregulin-1 / Q000008:administration & dosage* / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D018696:Neuroprotective Agents / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*
D020890:Neuregulin-1; D018696:Neuroprotective Agents; D004253:DNA Nucleotidylexotransferase; D020170:Caspase 1