Fig. 5

CYLD^−/− mice are protected from posttraumatic brain damage. a Volume of injured brain tissue 15 min and 24 h after experimental traumatic brain injury (TBI) assessed by histomorphological analysis on cresyl violet-stained coronal brain sections. Lesion volume assessed 15 min after TBI represents the primary, untreatable injury, while the lesion volume assessed 24 h after TBI represents the final injury. Accordingly, the difference between the final and the primary injury represents secondary brain damage, i.e., the component of the injury which is mediated by delayed cell death signaling. In wild-type mice, secondary injury is 67% larger than the primary injury, while in CYLD-deficient mice secondary injury is almost halved (+32%; **p < 0.007, Rank-Sum test, n = 8 each group). b Brain edema formation in wild-type and CYLD-deficient mice assessed by measurement of brain water content. Not traumatized mice of either phenotype had a normal brain water content of approximately 78% (wild type: 78.3 ± 0.4%, CYLD^−/−: 78.0 ± 0.7%; n.s.). At the time point of maximal brain edema formation, i.e., 24 h after TBI, CYLD-deficient mice developed significantly less brain edema in both hemispheres that their wild-type littermates (not traumatized hemisphere: 78.5 ± 0.3 vs. 79.3 ± 0.3%, *p < 0.04; traumatized hemisphere: 80.5 ± 0.4 vs. 82.4 ± 0.6%, *p < 0.03; Rank-Sum test; n = 9 each group). c Decreased edema formation translated into significantly lower intracranial pressure in CYLD-deficient mice (19.1 ± 0.8 mmHg) compared to wild type (23.2 ± 1.0 mm Hg, **p < 0.002, n = 8 each group). d Acute neuroprotection observed in CYLD-deficient mice persisted long term. Seven days after experimental TBI, lesion volume was still significantly lower in CYLD-deficient animals (6.8 ± 0.8 mm³) than in wild-type littermates (10.3 ± 1.1 mm³, *p = 0.03, Rank-Sum test, n = 8 each)