Elsevier

Neuroscience

Volume 141, Issue 2, 2006, Pages 637-644
Neuroscience

Cellular neuroscience
Early infiltration of CD8+ macrophages/microglia to lesions of rat traumatic brain injury

https://doi.org/10.1016/j.neuroscience.2006.04.027Get rights and content

Abstract

Local inflammatory responses play an important role in mediating secondary tissue damage in traumatic brain injury. Characterization of leukocytic subpopulations contributing to the early infiltration of the damaged tissue might aid in further understanding of lesion development and contribute to definition of cellular targets for selective immunotherapy. In a rat traumatic brain injury model, significant CD8+ cell accumulation was observed 3 days post-injury. The CD8+ cells were strictly distributed to the pannecrotic areas and around the pannecrotic perimeter. The morphology, time course of accumulation and distribution of CD8+ cells were similar to that of reactive ED1+ and endothelial monocyte-activating polypeptide II+ microglia/macrophages, but different from W3/13+ T cells. Further double-labeling experiments confirmed that the major cellular sources of CD8 were reactive macrophages/microglia. Both the location of these CD8+ macrophages/microglia to the border of the pannecrosis and their co-expression of endothelial monocyte-activating polypeptide II and P2X4 receptor suggest they might have a central role in lesion development and might thus be candidates for development of immunotherapeutic, anti-inflammatory strategies.

Section snippets

Animal experiments

Lewis rats (8–9 weeks of age, 350–400 g, Elevage Janvier, Le Genest-St-Isle, France) were housed with equal daily periods of light and dark and free access to food and water. All procedures were performed in accordance with the published International Health Guidelines under a protocol approved by the Administration District Official Committee. The number of rats used and their suffering were minimized.

TBI was induced using a weight-drop contusion model in anesthetized rats according to a

TBI-induced cortical injury

TBI by weight drop is a well-established animal model for brain trauma studies and was reported to generate a reproducible injury in the ipsilateral cortex. Here the development of the lesion following TBI was analyzed using HE staining. Selective neuronal loss and necrotic loci in the impacted somatosensory cortex was seen 12 h post-TBI using microscopy. Coagulation necrosis (pannecrosis), where no neuronal structure can be observed, was seen 2 days post-injury in ipsilateral somatosensory

Discussion

We have analyzed early accumulation of CD8+ macrophages/microglia in rat brains up to 96 h after TBI induced by weight-drop contusion. Significant CD8+ cell accumulation was observed 3 days post-TBI and increased steadily. The CD8+ cells were strictly distributed to areas of pannecrosis and mainly accumulated at the edge of the pannecrosis. The morphology, time course and distribution of CD8+ cells were similar to reactive ED1+ and EMAPII+ macrophages/microglia, but different from few

Conclusion

In conclusion, we report the early recruitment of activated CD8+ macrophages in rat TBI induced by weight-drop contusion. These activated CD8+ phagocytes are mainly distributed to the border of pannecrosis. The abundance of this subpopulation and their strategic location suggest that they might have a role in early lesion formation and probably CD8+ macrophages could be a suitable target for the development of immunotherapeutic, anti-inflammatory agents in TBI.

Acknowledgments

This work has been supported in part by the BMBF.

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