The treatment of exosome and recombinant tissue plasminogen activator reduces neuronal cell death in the middle cerebral artery occlusion stroke model of rats

Authors : Mohsen SAFAKHEİL, Mina RAMEZANİ, Azadeh MOHAMMADGHOLİ

Pages : 1122-1136

View : 10 | Download : 21

Publication Date : 2023-05-01

Article Type : Research Paper

Abstract :As brain stroke is one of the leading causes of death worldwide, in the current research neuroprotection and performance improvement have been investigated in the Middle cerebral artery occlusion/reperfusion insert ignore into journalissuearticles values(MCAO/R); animal model treated with exosomes combined with recombinant tissue plasminogen activator insert ignore into journalissuearticles values(rt-PA);. MCAO/R was induced in 25 adult male Wistar rats. Rats received rt-PA insert ignore into journalissuearticles values(10 mg/kg, i.v.); or exosomes insert ignore into journalissuearticles values(100 µg/kg); derived from bone marrow mesenchymal stem cells insert ignore into journalissuearticles values(MSCs);. Following the administration of rt-PA alone or in combination with exosomes, a significant increased score of the EBST test was recorded. Also, a decrease in error level of beam test was observed in the treated groups. Cresyl violet staining revealed that the population of dark cells was significantly reduced in all treated groups. The amount of catalase enzyme was significantly increased in all treated groups, especially in the combination therapy group insert ignore into journalissuearticles values(P<0.05);. A considerable increase in superoxide dismutase insert ignore into journalissuearticles values(SOD); enzyme was observed in the combination therapy group compared to the MCAO/R group insert ignore into journalissuearticles values(P≤0.001);. Our conclusion was approved by the Nlrp1 and Nlrp3 downregulation during combination therapy in the MCAO/R model by a reduction in cell death rate. The density of GFAP-positive cells showed a significant decrease in the exosome with or without rt-PA- treated groups compared to the MCAO/R group insert ignore into journalissuearticles values(P<0.05);. Our observation indicated that exosomes, in combination with rt-PA resulted in a noticeable functional recovery, neuronal regeneration, and reduction of neuronal cell death after a 7-day period of the MCAO/R induction. This novel therapeutic strategy probably can provide a promising treatment for patients who suffered from a stroke.
Keywords : MCAO R, , Exosome, , rt PA, , rat, Neural regeneration