Crocetin Regulates Functions of Neural Stem Cells to Generate New Neurons for Cerebral Ischemia Recovery.

Many neurons undergo apoptosis after ischemic stroke. In adult rodent brains, neurogenesis has the potential for neuronal replacement and can be activated by external conditions to repair the injury. Crocetin (CRO), naturally extracted from the plant Saffron, acts as a neuroprotective agent for ischemic stroke. However, the underlying mechanism remains unknown. In this work, the effect of CRO on neural stem cell behaviors and subventricular zone neurogenesis after CRO-treatment were investigated. Initially, CRO with different concentrations was incubated with neural stem cells (NSCs) to detect proliferation and differentiation in vitro. Second, in vivo ischemic stroke was induced in adult rats by middle cerebral artery occlusion and treated with CRO using the pharmaceutical product nimodipine as a comparison. The behavioral functions, infarcted volume, and apoptosis Nissl bodies of rats were noticeably improved after CRO-treatment, comparable to those of nimodipine. In addition, the regional cerebral blood flow monitored by laser speckle contrast imaging was increased. Neurogenesis and neuronal precursor differentiation in vivo were assessed by 5-Bromo-2' deoxyuridine labeling and immunostaining for neural cell type-specific markers. Brain tissue examined after ischemic stroke showed significantly increased neuronal regeneration in the focal ischemic injury area. Meanwhile, the length of neurites was prolonged, indicating that CRO could potentially promote neurite extension to enhance cell-cell communication. These findings demonstrated that CRO facilitated the neuronal differentiation of NSCs by activating subventricular zone neurogenesis in damaged cortex and striatum sites to repair ischemic stroke. This article is protected by copyright. All rights reserved.