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The incidence and virulence of C. difficile infection are increasing. Antibiotic use and length of hospital stay correlate strongly with infection. Oral or intravenous metronidazole is the recommended first-line therapy, with discontinuation of systemic antibiotics if possible. Forty percent of patients may have a prolonged course and 20% will relapse despite adequate therapy. Fulminant colitis develops in 3-8% of patients; diagnosis can be difficult with diarrhea absent in 20% of the subgroup. Once diagnosed, subtotal colectomy with ileostomy is usually required. In patients with a marked leukocytosis or bandemia, surgery is advisable because the leukocytosis frequently precedes hypotension and the requirement for vasopressor therapy, which carries a poor prognosis.

While 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. Rats underwent a controlled cortical impact (CCI) injury or sham injury, were sacrificed at 6, 12, 24, 48, and 72 hours, and intracerebral fluid (IF) was isolated from the direct injury, penumbral, ipsilateral frontal, contralateral regions. Cortical and hippocampal areas were also isolated. Regional cytokine levels were measured. PMN oxidative burst and marker expression were assessed after incubation with the IF. Immunohistochemistry identified intracerebral CD68+ cells (microglia/macrophages). The pro-inflammatory cytokines IL-1α, IL-1β, IL-6, and TNF-α 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. The local cerebral milieu in the first 48 hrs after TBI is highly pro-inflammatory. This response is most pronounced in areas at or proximal to the direct injury. The local, acute pro-inflammatory 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.

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