Effect of Sertoli Cell Transplant and Rapamycin Pretreatment on Middle Cerebral Artery Occlusion-Induced Brain Ischemia in a Rat Model.

OBJECTIVES: Stroke exacts a heavy toll on death and disability worldwide. In animal studies, cell transplant has shown a positive effect by inducing neurogenesis, angiogenesis, and modulating inflammation. Cell transplant therapy could provide researchers with new strategies for treating stroke. The mechanistic target of rapamycin is a central signaling pathway for coordination and control; the administration of rapamycin, a key modulator of this pathway, could be a new therapeutic approach in neurological disorders.

MATERIALS AND METHODS: Adult rats were grouped into 5 main groups: control, sham, rapamycin receiving, Sertoli cell receiving, and rapamycin plus Sertoli cell receiving groups. Sertoli cells were taken from another rat tissue and injected into the right striatum region. After 5 days, ischemic induction was performed, and rapamycin injection (300 mg/kg) was performed 1 hour before surgery. After 24 hours, some regions of the brain, including the cortex, striatum, and piriform cortex-amygdala, were isolated for evaluation.

RESULTS: Our results showed that infarct volume, brain edema, and blood-brain barrier permeability assessments were significantly reduced in some areas of the brain in rats that received rapamycin plus Sertoli cells compared with results shown in the control group.

CONCLUSIONS: Pretreatment with Sertoli cell transplant plus rapamycin injection may enhance neural survival during ischemia through increased glial cell-derived neurotrophic factor and vascular endothelial growth factor, inhibiting the mechanistic target of rapamycin pathway and increasing autophagy performance.