Investigators will use two-photon microscopy in laboratory animals undergoing surgical removal of a part of the skull, to determine how the surgery activates an immune inflammatory response that may result in damage to synaptic connections between brain cells.
Brain surgery in laboratory animals provides a model for studying the effects of surgery in humans and is also a model of brain injury. The investigators will remove a part of the skull in laboratory animals, replace it with a glass plate, and image the response of immune cells. These include innate immune cells called “microglia” that reside in the brain, These cells activate glial cells, which support the synaptic connections between the brain’s neurons. This activation is thought to be an important response to brain injury, which produces inflammation. Immune overreaction to inflammation, however, may lead to damaging changes in the brain’s structure and function. The researchers hypothesize that this damage occurs not by the microglial cells, but by the circulating immune cells that they recruit into the brain to serve as reinforcements.
Using cellular imaging through the glass plate, investigators will determine how activation of microglia, and their subsequent recruitment of circulating immune cells, occurs and subsequently regulates changes in synapses. They also will determine whether the resultant loss and gain (“remodeling”) of synapses requires primarily the resident microglial cells or also the recruited immune cells. Since the months required for stabilizing synaptic changes in the laboratory animal is similar to the time required by patients undergoing surgery or injured by trauma or stroke, the research may lead to new insights into therapies for stabilizing brain connections that could be tested in humans.
Significance: The research may lead to development of new anti-inflammatory treatment strategies to accelerate synapse stabilization following stroke, brain injury, or brain surgery.