Synthetic peptide derived from the Bordetella pertussis bacterium reduces infarct volume after transient middle cerebral artery occlusion in the rat.
We explored the therapeutic potential of a peptide (F20) derived from the filamentous hemagglutinin of Bordetella pertussis in a model of ischemic cell injury after transient (2 hours) middle cerebral artery (MCA) occlusion in the rat. Animals were divided into two groups-(1) F20 peptide group: rats (n = 11) were subjected to 2 hours of transient MCA occlusion, and F20 peptide was administered intravenously (50 nmol) at 0 hours of reperfusion and intraperitoneally (150 nmol/dose) at 2, 4, 6, 8, 22, and 30 hours of reperfusion; (2) control group: rats (n = 10) were administered peptide F23 (a scrambled version of peptide F20) with the same experimental protocol as the F20 peptide group. Forty-six hours after reperfusion, animals were sacrificed, and brain tissue was stained with triphenyltetrazolium chloride for evaluation of tissue damage. To measure neutrophil numbers in ischemic tissue, myeloperoxidase (MPO) immunostaining was performed on a coronal cerebral section in each animal. There was a significant reduction of ischemic infarct volume (36%, p < 0.05) in the F20 group of animals compared with the F23 group. The area of the ischemic lesion was highly correlated with the numbers of the immunoreactive MPO cells (r = 0.78, p < 0.001). The data demonstrate that the F20 peptide significantly reduces infarct volume and intraparenchymal neutrophil numbers after transient MCA occlusion.
Zhang
R L
RL
Department of Neurology, Henry Ford Health Sciences Center, Detroit, MI, USA.
Chopp
M
M
Tang
W X
WX
Zhang
Z G
ZG
Putney
S D
SD
Starzyk
R M
RM
D018829:Adhesins, Bacterial / Q000737:chemistry / Q000627:therapeutic use*; D000595:Amino Acid Sequence; D000818:Animals; D001479:Basal Ganglia / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D015415:Biomarkers; D001886:Bordetella pertussis; D002536:Cerebral Arteries / Q000502:physiology; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D002544:Cerebral Infarction / Q000473:pathology / Q000517:prevention & control*; D004334:Drug Administration Schedule; D006388:Hemagglutinins / Q000737:chemistry / Q000627:therapeutic use*; D002546:Ischemic Attack, Transient / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D016018:Least-Squares Analysis; D008297:Male; D008969:Molecular Sequence Data; D010455:Peptides / Q000008:administration & dosage / Q000138:chemical synthesis / Q000627:therapeutic use*; D009195:Peroxidase / Q000032:analysis; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D015424:Reperfusion; D013997:Time Factors; D010566:Virulence Factors, Bordetella
D018829:Adhesins, Bacterial; D015415:Biomarkers; D006388:Hemagglutinins; D010455:Peptides; D010566:Virulence Factors, Bordetella; C065273:filamentous hemagglutinin adhesin, Bordetella pertussis; D009195:Peroxidase