Buckwalter Lab Research
Astrocytes and Neuroinflammation
Many cell types participate in the response to brain damage, including neurons, microglia, astrocytes, and peripheral leukocytes circulating in the blood. Astrocytes have emerged as key regulators of inflammation in the injured or diseased nervous system. We are therefore interested in understanding the capacity of astrocytes to limit the brain’s inflammatory response and neural damage in rodent models of stroke.
To investigate this question, we use transgenic mouse models that allow us to manipulate specific signaling pathways in astrocytes and subsequently study gene and protein expression, and outcomes, after injury.
Previous projects in the lab have found that the transforming growth factor beta (TGFb) signaling pathway is important for limiting immune responses in stroke and CNS Toxoplasma gondii infection. We seek to further understand the anti-inflammatory mechanism of TGFb and its downstream signaling molecules by using mouse models to manipulate and image TGFb signaling after stroke and viral vectors to influence TGFb signaling.
We measure the effects on functional recovery from brain injury, the cellular and molecular immune response, and cell-specific signaling pathways.
Peripheral Glia and the Neuroinflammatory Reflex
Pneumonia is a common complication in stroke and traumatic brain injury patients and it is a result of profound immune suppression. The mechanisms behind this brain injury-induced immune suppression are not well known, however, increased sympathetic tone has been implicated.
We seek to accomplish this by characterizing the basic biology of glial cells in the lung and elsewhere in the periphery, and by studying their role in the inflammatory response by using models of lung infection and acute stroke.
Chronic inflammation and post-stroke dementia
Stroke survivors are twice as likely to develop dementia in the decade after their stroke as those that didn’t have a stroke. Additionally, stroke patients are at increased risk for developing clinical depression. These delayed cognitive changes following stroke remain poorly understood, but we have found evidence in mice of late, adaptive immune responses in the brain after stroke that cause cognitive impairment.
We are now investigating the effects of the adaptive immune response on cognitive outcome in human stroke patients and seeking to understand its mechanisms in rodent models of stroke.