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Journal of Neuroscience, Vol 15, 8223-8233, Copyright © 1995 by Society for Neuroscience
Inflammatory leukocytic recruitment and diffuse neuronal degeneration are separate pathological processes resulting from traumatic brain injury
HD Soares, RR Hicks, D Smith and TK McIntosh
Department of Developmental Biology, St. Jude Children's Hospital, Memphis, Tennessee 38101-0318, USA.
The present study characterized whether inflammatory leukocytic
infiltration is temporally and regionally correlated with neuronal
degeneration and/or blood brain barrier (BBB) breakdown resulting from
traumatic brain injury. Adult rats were sacrificed at 5 min, 2, 4, 12, 24,
and 72 hr after lateral fluid percussion brain injury. BBB breakdown,
neuronal degeneration and leukocyte infiltration were assessed using
immunocytochemistry, silver impregnation and toluidine blue and eosin
staining. BBB breakdown and neuronal degeneration occurred concomitantly in
injured cortex, hippocampus, and along the dorsolateral quadrant of the
diencephalon. However, neuronal degeneration within deep diencephalic
structures transpired in the absence of IgG extravasation. Neutrophils were
observed only in regions exhibiting BBB damage and were first apparent in
injured cortex and hippocampus between 2-12 hr posttrauma lining the
vasculature and filling subarachnoid/subdural spaces. Neutrophils then
migrated from damaged vasculature into traumatized cortical and hippocampal
parenchyma by 24 hr after lateral fluid percussion injury. Macrophages were
also observed within cortical parenchyma at 24 hr and completely filled the
cortical lesion site by 72 hr after injury. Macrophages were not as
abundant throughout hippocampal parenchyma and were found only in
hippocampal regions exhibiting focal hemorrhage at 72 hr. Finally,
neutrophils did not migrate to deep diencephalic structures that showed no
BBB damage despite extensive neuronal degeneration. Indeed, lateral fluid
percussion elicits inflammatory leukocytic recruitment only in regions
experiencing concomitant BBB damage and neuronal degeneration. In summary,
inflammatory leukocytic recruitment and diffuse neuronal degeneration are
separate pathological processes resulting from traumatic brain injury.
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