Magnetic nanomagnetic nanoparticles combining with Slit2 gene and bone marrow mononuclear cells to improve cognitive dysfunction in rats with chronic cerebral ischemia

TL;DR

This study explores using magnetic nanoparticles and bone marrow cells to improve cognitive function in rats with chronic brain ischemia.

Contribution

A novel approach combining magnetic nanoparticles, Slit2 gene, and bone marrow cells to treat cognitive dysfunction in CCH rats.

Findings

CCH rats showed increased neurological scores and brain injury markers compared to the sham group.

Slit2 and Robo4 expression levels were significantly elevated in CCH rats.

BMP-PEI-Slit2/BMMNC treatment improved neurological function after Robo4 siRNA administration.

Abstract

Purpose: Cognitive dysfunction caused by chronic cerebral hypoperfusion (CCH) is the leading cause of vascular dementia. Therefore, it is necessary to explore the mechanism that causes cerebral injury and find an effective therapy.

Methods: Bone marrow mononuclear cells (BMMNCs) were extracted to detect the activity by CCK-8 kit and verify the transfection efficiency using reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR). A CCH rat model was established. Superparamagnetic iron oxide nanoparticles (BMPs)-PEI-Slit2/BMMNCs were injected into the tail vein and intervened with an external magnetic field. Hematoxylin and eosin staining was used to observe the pathological changes in brain tissue. The Slit/Robo pathway-related proteins Slit2 and Robo4 were detected by RT-qPCR and Western blotting.

Results: The neurological score of the CCH group significantly increased compared with that of the sham group (P<0.05). The levels of brain injury markers S-100β and NSE were significantly higher in the CCH group than in the sham group (P<0.05). Neuronal apoptosis in the frontal cortex and hippocampus of CCH rats significantly increased compared with that of the sham group (P<0.05). The expression levels of Slit2 and Robo4 mRNAs and proteins in brain tissue of CCH rats significantly increased (P<0.05). The neurological function scores of CCH rats treated with BMP-PEI-Slit2/BMMNC significantly increased after Robo4 siRNA administration (P<0.05).

Conclusion: BMP combination with the CCH-related gene Slit2 can effectively improve the efficiency of BMMNC transplantation in treatment.

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