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Updated: Apr 6, 2026
Electromagnetic Controlled Closed-Head Model of Mild Traumatic Brain Injury in Mice
Published on: September 28, 2022
Shape descriptors of the "never resting" microglia in three different acute brain injury models in mice
Elisa R Zanier1, Stefano Fumagalli, Carlo Perego
1IRCCS - Istituto di Ricerche Farmacologiche Mario Negri, Department of Neuroscience, Via La Masa 19, 20156, Milan, Italy, elisa.zanier@marionegri.it.
Background:
The study of microglia and macrophage (M/M) morphology represents a key tool to understand the functional activation state and the pattern of distribution of these cells in acute brain injury. The identification of reliable quantitative morphological parameters is urgently needed to understand these cell roles in brain injury and to explore strategies aimed at therapeutically manipulating the inflammatory response.
Methods:
We used three different clinically relevant murine models of focal injury, namely, controlled cortical impact brain injury (traumatic brain injury (TBI)) and transient and permanent occlusion of middle cerebral artery (tMCAo and pMCAo, respectively). Twenty-four hours after injury, M/M cells were labeled by CD11b, and ×40 photomicrographs were acquired by unbiased sampling of the lesion core using a motorized stage microscope. Images were processed with Fiji software to obtain shape descriptors.
Results:
We validated several parameters, including area, perimeter, Feret's diameter (caliper), circularity, aspect ratio, and solidity, providing quantitative information on M/M morphology over wide tissue portions. We showed that the shape descriptors that best represent M/M ramification/elongation are area and perimeter, while circularity and solidity provide information on the ameboid shape. We also provide evidence of the involvement of different populations in local inflammatory events, with macrophages replacing microglia into the lesion core when reperfusion does not occur. Analysis of CD45(high)+ cell morphology, whose shape does not change, did not yield any difference, thus confirming the reliability of the approach.
Conclusions:
We have defined specific morphological features that M/M acquire in response to different acute insults by applying a sensitive and readily applicable approach to cell morphological analysis in the brain tissue. Potential application of this method can be extended to all cell types able to change shape following activation, e.g., astrocytes, or to different disease states, including chronic pathologies.
Insights
Quantitative analysis of microglia and macrophage morphology reveals distinct shape changes in acute brain injury. This method accurately quantifies cell activation and distribution, aiding therapeutic strategy development.
Area of Science:
- Neuroscience
- Immunology
- Cell Biology
Background:
- Microglia and macrophage (M/M) morphology is crucial for understanding brain injury responses.
- Quantitative morphological parameters are needed to elucidate M/M roles and guide therapeutic interventions.
Purpose of the Study:
- To define reliable quantitative morphological parameters for microglia and macrophages in acute brain injury.
- To establish a sensitive and applicable method for cell morphological analysis in brain tissue.
Main Methods:
- Utilized murine models of traumatic brain injury (TBI) and middle cerebral artery occlusion (MCAo).
- Acquired ×40 photomicrographs of CD11b-labeled M/M cells from lesion cores.
- Processed images using Fiji software to extract shape descriptors like area, perimeter, and circularity.
Main Results:
- Validated parameters including area, perimeter, circularity, and solidity for M/M morphology.
- Area and perimeter reflect M/M ramification/elongation, while circularity and solidity indicate ameboid shape.
- Demonstrated macrophage infiltration into the lesion core in non-reperfusion scenarios, distinct from microglia.
Conclusions:
- Defined specific M/M morphological features in response to acute brain insults.
- Developed a sensitive and applicable approach for cell morphological analysis in brain tissue.
- The method is extendable to other cell types (e.g., astrocytes) and chronic pathologies.
