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Early life cancer and chemotherapy lead to cognitive deficits related to alterations in microglial-associated gene expression in prefrontal cortex.
Brain Behav Immun
October 2023
University of Cincinnati, College of Medicine, Department of Pharmacology and Systems Physiology, Cincinnati, OH, USA. Electronic address:
Children that survive leukemia are at an increased risk for cognitive difficulties. A better understanding of the neurobiological changes in response to early life chemotherapy will help develop therapeutic strategies to improve quality of life for leukemia survivors. To that end, we used a translationally-relevant mouse model consisting of leukemic cell line (L1210) injection into postnatal day (P)19 mice followed by methotrexate, vincristine, and leucovorin chemotherapy.
View Article and Find Full Text PDFPerinatal Morphine Exposure Leads to Sex-Dependent Executive Function Deficits and Microglial Changes in Mice.
eNeuro
October 2022
Department of Pharmacology & Systems Physiology, University of Cincinnati, Cincinnati, Ohio 45267.
Children exposed prenatally to opioids are at an increased risk for behavioral problems and executive function deficits. The prefrontal cortex (PFC) and amygdala (AMG) regulate executive function and social behavior and are sensitive to opioids prenatally. Opioids can bind to toll-like receptor 4 (TLR4) to activate microglia, which may be developmentally important for synaptic pruning.
View Article and Find Full Text PDFModeling infectious diseases of the central nervous system with human brain organoids.
Transl Res
December 2022
Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin Madison, Madison, Wisconsin. Electronic address:
Bacteria, fungi, viruses, and protozoa are known to infect and induce diseases in the human central nervous system (CNS). Modeling the mechanisms of interaction between pathogens and the CNS microenvironment is essential to understand their pathophysiology and develop new treatments. Recent advancements in stem cell technologies have allowed for the creation of human brain organoids, which more closely resembles the human CNS microenvironment when compared to classical 2-dimensional (2D) cultures.
View Article and Find Full Text PDFCXCL13 expressed on inflamed cerebral blood vessels recruit IL-21 producing T cells to damage neurons following stroke.
J Neuroinflammation
May 2022
Department of Pathology and Laboratory Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
Background: Ischemic stroke is a leading cause of mortality worldwide, largely due to the inflammatory response to brain ischemia during post-stroke reperfusion. Despite ongoing intensive research, there have not been any clinically approved drugs targeting the inflammatory component to stroke. Preclinical studies have identified T cells as pro-inflammatory mediators of ischemic brain damage, yet mechanisms that regulate the infiltration and phenotype of these cells are lacking.
View Article and Find Full Text PDFTranslationally relevant mouse model of early life cancer and chemotherapy exposure results in brain and small intestine cytokine responses: A potential link to cognitive deficits.
Brain Behav Immun
January 2022
University of Cincinnati, College of Medicine, Department of Pharmacology and Systems Physiology, Cincinnati, OH, USA. Electronic address:
Survivors of acute lymphoblastic leukemia (ALL), the most common childhood cancer, are at increased risk for long-term cognitive problems, including executive function deficits. The chemotherapeutic agent methotrexate (MTX) is used to treat most ALL patients and is closely associated with cognitive deficits. To address how early life cancer chemotherapy leads to cognitive deficits, we developed a translationally relevant mouse model of leukemia survival that exposed mice to leukemic cells and chemotherapeutic drugs (vincristine and MTX, with leucovorin rescue) in early life.
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