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Chronic upregulation of activated microglia immunoreactive for galectin-3/Mac-2 and nerve growth factor following
Charu Venkatesan1, MaryAnn Chrzaszcz, Nicole Choi
1Division of Neurology, Department of Pediatrics, Northwestern University Feinberg School of Medicine, Chicago, IL 60614, USA. cvenkatesan@childrensmemorial.org
Background:
Diffuse axonal injury in patients with traumatic brain injury (TBI) can be associated with morbidity ranging from cognitive difficulties to coma. Magnetic resonance imaging scans now allow early detection of axonal injury following TBI, and have linked cognitive disability in these patients to white matter signal changes. However, little is known about the pathophysiology of this white matter injury, and the role of microglial activation in this process. It is increasingly recognized that microglia constitute a heterogeneous population with diverse roles following injury. In the present studies, we tested the hypothesis that following diffuse axonal injury involving the corpus callosum, there is upregulation of a subpopulation of microglia that express the lectin galectin-3/Mac-2 and are involved in myelin phagocytosis.
Methods:
Adult mice were subject to midline closed skull injury or sham operation and were sacrificed 1, 8, 14 or 28 days later. Immunohistochemistry and immunofluorescence techniques were used to analyze patterns of labelling within the corpus callosum qualitatively and quantitatively.
Results:
Activated microglia immunoreactive for galectin-3/Mac-2 were most abundant 1 day following injury. Their levels were attenuated at later time points after TBI but still were significantly elevated compared to sham animals. Furthermore, the majority of galectin-3/Mac-2+ microglia were immunoreactive for nerve growth factor in both sham and injured animals.
Conclusions:
Our results suggest that galectin-3/Mac-2+ microglia play an important role in the pathogenesis of diffuse axonal injury both acutely and chronically and that they mediate their effects, at least in part by releasing nerve growth factor.
Insights
Activated microglia expressing galectin-3/Mac-2 are crucial in diffuse axonal injury following traumatic brain injury. These cells are involved in myelin phagocytosis and release nerve growth factor, impacting brain recovery.
Area of Science:
- Neuroscience
- Immunology
- Pathology
Background:
- Traumatic brain injury (TBI) can cause diffuse axonal injury (DAI), leading to significant cognitive deficits.
- Microglial activation is implicated in DAI, but its specific role and the heterogeneity of microglial responses remain unclear.
- This study investigates the role of galectin-3/Mac-2 expressing microglia in DAI pathogenesis.
Purpose of the Study:
- To test the hypothesis that microglia expressing galectin-3/Mac-2 are upregulated following diffuse axonal injury.
- To determine if these specific microglia are involved in myelin phagocytosis.
- To explore the role of galectin-3/Mac-2+ microglia in the chronic and acute phases of DAI.
Main Methods:
- Adult mice underwent midline closed skull injury or sham procedures.
- Immunohistochemistry and immunofluorescence were used to analyze microglial activation and lectin expression in the corpus callosum.
- Samples were collected at 1, 8, 14, and 28 days post-injury.
Main Results:
- Galectin-3/Mac-2 positive microglia were most abundant one day after injury.
- Elevated levels of these microglia persisted compared to sham controls throughout the study period.
- Most galectin-3/Mac-2+ microglia also expressed nerve growth factor.
Conclusions:
- Galectin-3/Mac-2 expressing microglia are integral to the pathogenesis of DAI.
- These microglia contribute to both acute and chronic injury processes.
- Nerve growth factor release by galectin-3/Mac-2+ microglia is a key mechanism in DAI.
