Understanding cell chirality and cell-cell interactions at neurovascular unit after brain injury

This federal Project Grant award from the National Institute of Neurological Disorders and Stroke (NINDS), under the Extramural Research Programs in the Neurosciences and Neurological Disorders (CFDA 93.853) program, provides $465,752 to the Regents of the University of Michigan - Dearborn to conduct research on understanding changes in cell chirality and cell-cell interactions within the neurovascular unit (NVU) after traumatic brain injury (TBI). The project aims to evaluate TBI-induced changes in the chirality, polarization, and organelle positioning of microglia, neurons, and brain microvascular endothelial cells, as well as their physical interactions, in order to reveal the relationship between cell chirality and NVU function. The results from this 3-year project, running from September 1, 2024 to August 31, 2027, are expected to provide novel insights into cell chirality regulation and NVU mechanisms, laying the foundation for developing cell-specific therapeutic approaches for various neurological disorders.

Abstract

The neurovascular unit (NVU) is responsible for the maintenance of blood-brain barrier (BBB) integrity, cerebral homeostasis, and control of cerebral blood flow. Evidence indicates that traumatic brain injury (TBI) alters the NVU functions and impairs the integrity of BBB; however, the mechanism is still poorly understood. Cells have been discovered to possess phenotype-dependent intrinsic chirality, which not only reflects cellular behaviors but also influences tissue/organ morphogenesis and physiological functions. The goal of this proposal is to evaluate the TBI-induced changes in cell chirality and cell-cell interactions of microglia, neurons, and brain microvascular endothelial cells (bmecs) within the NVU. We use a pre-established TBI animal model, combined with novel biological and engineering techniques, to complete the aims of the proposed project. Aim 1 determines the chirality, polarization, and organelles positioning of microglia and neurons, as well as the physical interactions between microglia and neurons after TBI. Aim 2 examines the TBI-induced changes in the chirality of bmecs and the interaction between microglia and bmecs. Results obtained from this project will reveal the relationship between cell chirality and cell-cell interactions of microglia, neurons, and bmecs within the NVU. Thus, the accomplishment of this project will provide novel knowledge on cell chirality regulation and mechanisms of NVU function, which will further set the foundation for developing cell-specific therapeutics that can be translated to various neurological disorders.