ACTIVATION PEPTIDE OF COAGULATION FACTOR IX REDUCES INFARCT AREA IN A RAT MODEL OF ISCHEMIC STROKE

Coagulation factor IX (F9) is a plasma protein comprising 471 amino acids. During coagulation, F9 is activated by cleavages that release an activating peptide (F9-AP) between the light and heavy chains. We previously reported that F9-AP reduced cerebral edema via vascular permeability, exerting neuroprotective effects in traumatic brain injury. However, the effects of F9-AP remain unclear. In this study, we investigated the in vivo effects of F9-AP in a rat model of ischemic stroke.
An ischemic stroke rat model was established using photochemically induced thrombosis (PIT). F9-AP was then administered to PIT rats. The surrounding ischemic stroke tissue was stained with 2,3,5-triphenyltetrazolium chloride (TTC). Immunohistochemistry was performed using anti-BDNF, anti-Iba1, anti-glial fibrillary acidic protein (GFAP), anti-CD31, and anti-NeuN antibodies. BDNF expression was analyzed using western blotting.
TTC staining revealed that the infarct area was reduced in the F9-AP group. Additionally, BDNF expression in the peri-infarct region was higher in the F9-AP group, as confirmed by immunohistochemistry and western blotting. Furthermore, immunofluorescence staining revealed a reduction in the number of microglia in the peri-infarct region in the F9-AP group. In contrast, no differences were observed in vascular endothelial cells, mature neurons, or astrocytes between the F9-AP and control groups.
Administration of F9-AP in the PIT model reduced the cerebral infarct area. These findings suggest that F9-AP exerts protective effects against ischemic brain injury.