Project description:Many extracellular matrix (ECM) changes occur in the brain after traumatic brain injury. This work sought to understand the dynamics of ECM modifications after TBI by comparing RNA transcription between ipsilateral and contralateral brain regions. Mice underwent controlled cortical impact (with a 2mm depth) using a pneumatic impactor. Seven days later, brain tissue was harvested from the site of injury and from the corresponding contralateral cortex. Microarrays were used to measure gene expression to compare these tissues.
Project description:Here we investigated the topographical relationship of early transcriptional responses to a single, focal TBI in mice by controlled cortical impact (CCI). Guided by the presence of the anterior commissure (AC) in coronal sections at the rostro-caudal point of impact, we compared gene expression changes in the neocortex (CTX) and corpus callosum-external capsule (CC-EC), striatum (STR) and AC. Injury-induced gene expression changes were detected in the CTX, CC-EC and STR but not AC and were principally segregated based on cytoarchitecture, and secondarily by proximity to the site of impact. Additionally, unbiased spatial clustering revealed a positive relationship between proximity to the impact and the number of acutely differentially expressed genes within the laminar CTX. Next, we examined the effects of systemic depletion of neutrophils and monocytes on spatial gene expression changes in the injured brain.
Project description:We report the miRNAs differentially expressed in the orbitofrontal cortex of adult male rats 5 weeks after a controlled cortical injury model of traumatic brain injury (TBI). Animals underwent 3 repeated mild injuries on days 1, 4 and 7. Tissue was collected on day 42.
Project description:Traumatic brain injury (TBI) initiates cellular and molecular cascades that impair neurogenesis and promote chronic neuroinflammation, ultimately contributing to cognitive and functional decline. We previously demonstrated that L-myc–expressing human neural stem (LMNSC01) cells migrate to sites of injury and modulate biomarkers associated with neuroprotection and repair after repeated intranasal (IN) administration. Here, we tested whether a single bulk IN dose of LMNSC01 is sufficient to induce neuroprotective changes in gene and protein expression following injury. Immunocompetent male rats underwent controlled cortical impact (CCI) or sham surgery, followed by a single bulk IN dose of LMNSC01 or vehicle on postoperative day 7. Transcriptomic profiling of brain tissue from injured and LMNSC01-treated rats revealed upregulation of immune modulation and tissue repair genes (Il22ra1, Il1rn, Gfi1, Ddx60) and downregulation of genes involved in microglial activation and cytokine signaling (Xcr1, Ccl21a, Ccl9) compared to controls. Proteomic analysis confirmed reduced levels of inflammatory cytokines and endothelial activation markers (ICAM-1, PDGF-AA, TCK-1). Multiplex immunohistochemistry showed LMNSC01-mediated changes in microglial activation, macrophage infiltration, and vascular remodeling. These findings highlight the potential of single IN LMNSC01 dose to reprogram neuroinflammatory and tissue remodeling networks and offer a clinically translatable strategy to improve long-term outcomes after TBI.
Project description:To elucidate the epigenomic features of hippocampal cells following mTBI, approximately 50,000 nuclei were profiled from matched hippocampal tissues of three mice subjected to controlled cortical impact (CCI) and three sham-operated controls. Cell type-specific chromatin accessibility changes in response to mTBI were identified.
Project description:Neuroprotective potential of intranasally delivered L-myc immortalized human neural stem cells in female rats after a controlled cortical impact injury