Dysfunction of the microRNA (miR) network has been emerging as a major regulator in neurological diseases. However, little is known about the functional significance of unique miRs in ischemic brain damage. Here, we found that miR-497 is induced in mouse brain after transient middle cerebral artery occlusion (MCAO) and mouse N2A neuroblastoma (N2A) cells after Oxygen-Glucose-Deprivation (OGD). Loss-of-miR-497 function significantly suppresses OGD-induced N2A cell death, whereas gain-of-miR-497 function aggravates OGD-induced neuronal loss. Moreover, miR-497 directly binds to the predicted 3'-UTR target sites of bcl-2/-w genes. Furthermore, knockdown of cerebral miR-497 effectively enhances bcl-2/-w protein levels in the ischemic region, attenuates ischemic brain infarction, and improves neurological outcomes in mice after focal cerebral ischemia. Taken together, our data suggest that miR-497 promotes ischemic neuronal death by negatively regulating anti-apoptotic proteins, bcl-2 and bcl-w. We raise the possibility that this pathway may contribute to the pathogenesis of the ischemic brain injury in stroke.

Cerebral vascular endothelial cell (CEC) degeneration significantly contributes to blood-brain barrier (BBB) breakdown and neuronal loss after cerebral ischemia. Recently, emerging data suggest that peroxisome proliferator-activated receptor ␦ (PPAR␦) activation has a potential neuroprotective role in ischemic stroke. Here we report for the first time that PPAR␦ is significantly reduced in oxygen-glucose deprivation (

Zika virus (ZIKV) infection causees neurologic complications, includingGuillain-Barré syndrome in adults and central nervous system (CNS) abnormalities in fetuses. We investigated the immune response, especially the CD8 ϩ T cell response in C57BL/6 (B6) wild-type (WT) mice, during ZIKV infection. We found that a robust CD8 ϩ T cell response was elicited, major histocompatibility complex class I-restricted CD8 ϩ T cell epitopes were identified, a tetramer that recognizes ZIKV-specific CD8 ϩ T cells was developed, and virus-specific memory CD8 ϩ T cells were generated in these mice. The CD8 ϩ T cells from these infected mice were functional, as evidenced by the fact that the adoptive transfer of ZIKV-specific CD8 ϩ T cells could prevent ZIKV infection in the CNS and was cross protective against dengue virus infection. Our findings provide comprehensive insight into immune responses against ZIKV and further demonstrate that WT mice could be a natural and easy-access model for evaluating immune responses to ZIKV infection.IMPORTANCE ZIKV infection has severe clinical consequences, including GuillainBarré syndrome in adults, microcephaly, and congenital malformations in fetuses and newborn infants. Therefore, study of the immune response, especially the adaptive immune response to ZIKV infection, is important for understanding diseases caused by ZIKV infection. Here, we characterized the CD8 ϩ T cell immune response to ZIKV in a comprehensive manner and identified ZIKV epitopes. Using the identified immunodominant epitopes, we developed a tetramer that recognizes ZIKVspecific CD8 ϩ T cells in vivo, which simplified the detection and evaluation of ZIKVspecific immune responses. In addition, the finding that tetramer-positive memory CD8 ϩ T cell responses were generated and that CD8 ϩ T cells can traffic to a ZIKVinfected brain greatly enhances our understanding of ZIKV infection and provides important insights for ZIKV vaccine design.KEYWORDS CD8 ϩ T cell, ZIKV, central nervous system, cross protection, immunocompetent mouse model Z ika virus (ZIKV) is a mosquito-transmitted flavivirus and a member of the Flaviviridae family of positive-stranded RNA enveloped viruses; the virus has also been found to be sexually and vertically transmitted (1). It was identified in 1947 in sentinel monkeys in Uganda (2). After its introduction into Brazil in 2015, ZIKV spread rapidly, both (i) causing a mild syndrome characterized by self-limiting fever, headache, myalgia, rash, and conjunctivitis and (ii) resulting in severe clinical consequences, including Guillain-