Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have shown promise in promoting functional recovery in male rodent models of traumatic brain injury (TBI). This study aimed to assess the effects of human MSC-derived sEVs on functional recovery, neuroprotection, and neuroinflammation in female rats subjected to TBI. Young female rats were subjected to TBI induced by controlled cortical impact injury over the left parietal cortex. sEVs or phosphate-buffered saline (PBS) was administered intravenously 1 day post-injury. A battery of sensorimotor and cognitive functions was assessed post-injury. At day 35, brains were collected for histological analyses of lesion volume, neuroprotection, and neuroinflammation. Compared to the PBS treatment, sEVs significantly reduced the frequency of foot-faults, adhesive removal time, and modified Neurological Severity Scores ( p < 0.05 vs. PBS). Moreover, sEVs significantly enhanced cognitive abilities, demonstrated by a shorter time to locate the hidden platform and an increased percentage of time spent in the target quadrant during the Morris water maze test ( p < 0.05). Furthermore, sEV administration significantly decreased the size of brain lesions, reduced hippocampal neuronal cell loss, increased synaptophysin expression, and attenuated neuroinflammation following injury ( p < 0.05). These findings, in conjunction with previous studies of sEV benefits in male TBI rats, indicate that delayed (1 day post-injury) intravenous delivery of human MSC-derived sEVs could be an effective treatment approach for TBI in both sexes.
Zhang et al. (Sun,) studied this question.
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