Dr. Maxim Cheeran PhD

These researchers study central nervous system (CNS) responses to injury and infection. Their experiments elucidate mechanisms by which innate and adaptive immune responses alter the neurological outcomes of brain disease. Using well-characterized in vitro and animal models of viral  brain infection and traumatic brain injury, the laboratory investigates how macrophages and T lymphocytes alter disease processes in the brain that impact neurological outcomes. There are three projects that use MSI resources:

• Neuroimmune Responses to Traumatic Brain Injury: This project studies the cumulative effect of repeated brain injury on inflammation, particularly related to the microglial/macrophage population. Chronic neuroinflammation 30 days after second injury will be studied by varying the duration between the two impacts by 3, 7, or 30 d, and varying the severity of two impacts the first one being mild and the second mild or moderate injury. A closed head injury model will also be characterized to understand the changes in inflammation is a clinically relevant model. Finally, umbilical cord blood derived non-hematopoietic stem cells (nhUCBSC) will be evaluated for its therapeutic benefit in bridging the time gaps between two sequential hits that induces an exaggerated immune response.
• Neuroinflammation Leads to Addiction Behavior: Experimental and clinical evidence suggests a direct association between inflammation resulting from TBI and increased risk of drug abuse. These researhcers have shown that there is a persistent inflammatory response to TBI in the murine brain. These experiments will test the hypothesis that the persistent proinflammatory macrophage response to mild TBI accelerates remodeling of neuronal synapses in the mesolimbic pathway leading to increased sensitivity and consumption of opiates. In doing so the researchers will characterize the structural and inflammatory responses to TBI by studying the functional characteristics of activated macrophages in the nucleus accumbens and ventral tegmental regions of the brain. They will then investigate if modulating the inflammatory response will alter the addiction behavior outcomes observed in the murine model of TBI.  
• Neuroinflammation Following SARS-CoV2 Infection in a Murine Model: Compelling evidence indicates that SARS-CoV-2 infection not only harms the lung but also causes damage to multiple organ systems including the brain. One third of COVID-19 survivors suffer from persistent neurological symptoms, while the long-term impact of SARS-CoV-2 infection is currently unknown. This project uses multiple animal models and innovative cellular, molecular, and neurobehavioral approaches to define the acute and long-term impact of SARS-CoV-2 infection on cognitive function and pathogenic processes in aging and Alzheimer’s disease. The aims are to assess the acute and long term impact of SARS-CoV2 infection on neuroinflammation, and trafficking of immune cells into the brain using standard virology and immunology methods and advanced molecular approaches (including spatial genomics, single cell transcriptomics, and whole brain imaging). The researchers will investigate the mechanisms that enhance inflammation due to age, apolipoprotein E and cerebral β-amyloidosis following SARS-CoV2 infection.

The ultimate goal of all these projects is to identify novel points of intervention that can be manipulated to mitigate or inhibit the adverse outcomes ensuing brain infection or injury.