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

Year 2023, Volume: 15 Issue: 1, 1122 - 1136, 01.05.2023

Mohsen Safakheil , Mina Ramezani , Azadeh Mohammadgholi

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 (MCAO/R) animal model treated with exosomes combined with recombinant tissue plasminogen activator (rt-PA). MCAO/R was induced in 25 adult male Wistar rats. Rats received rt-PA (10 mg/kg, i.v.) or exosomes (100 µg/kg) derived from bone marrow mesenchymal stem cells (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 (P<0.05). A considerable increase in superoxide dismutase (SOD) enzyme was observed in the combination therapy group compared to the MCAO/R group (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 (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

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