Acute, regional inflammatory response after traumatic brain injury: Implications for cellular therapy.
BACKGROUND
Although cellular therapy has shown promise in the management of traumatic brain injury (TBI), microenvironment interactions between the intracerebral milieu and therapeutic stem cells are poorly understood. We sought to characterize the acute, regional inflammatory response after TBI.


METHODS
Rats underwent a controlled cortical impact (CCI) injury or sham injury, were killed at 6, 12, 24, 48, and 72 hours, and intracerebral fluid (IF) was isolated from the direct injury, penumbral, ipsilateral frontal, and contralateral regions. Cortical and hippocampal areas were also isolated. Regional cytokine levels were measured. Polymorphonuclear cell (PMN) oxidative burst and marker expression were assessed after incubation with the IF. Immunohistochemistry was used to identify intracerebral CD68(+) cells (microglia/macrophages).


RESULTS
The proinflammatory cytokines interleukin (IL)-1alpha, IL-1beta, IL-6, and tumor necrosis factor-alpha were significantly elevated after CCI in the injury and penumbral regions. Increases in the same cytokines were localized to the cortex and the hippocampus. Increased PMN expression of CD11b and L-selectin was identified after incubation with injury or penumbral area IF, without change in PMN oxidative burst. CD68(+) cells were noted in the direct injury and penumbral areas.


CONCLUSIONS
The local cerebral milieu in the first 48 hours after TBI is highly proinflammatory. This response is most pronounced in areas at or proximal to the direct injury. The local, acute proinflammatory response after TBI may serve as a therapeutic target of early cell therapy or, conversely, may create an unfavorable local milieu, limiting the efficacy of early cellular therapy.
Harting
Matthew T
MT
Department of Pediatric Surgery, University of Texas Medical School at Houston and Children's Memorial Hermann Hospital, Houston, Texas 77030, USA.
Jimenez
Fernando
F
Adams
Sasha D
SD
Mercer
David W
DW
Cox
Charles S
CS
D000210:Acute-Phase Reaction / Q000209:etiology* / Q000378:metabolism / Q000628:therapy; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism* / Q000473:pathology* / Q000628:therapy; D039481:CD11b Antigen / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism; D019041:L-Selectin / Q000378:metabolism; D051381:Rats; D016897:Respiratory Burst / Q000502:physiology; D013481:Superoxides / Q000378:metabolism; D013997:Time Factors
D039481:CD11b Antigen; D016207:Cytokines; D013481:Superoxides; D019041:L-Selectin