The timing of decompressive craniectomy for the treatment of increased intracranial pressure (ICP) after traumatic brain injury (TBI) is a widely discussed clinical issue. Although we showed recently that early decompression is beneficial following experimental TBI, it remains unclear to what degree decompression craniectomy reduces secondary brain damage and if craniectomy is still beneficial when it is delayed by several hours as often inevitable during daily clinical practice. The aim of the current study was therefore to investigate the influence of craniectomy on secondary contusion expansion and brain edema formation and to determine the therapeutic window of craniectomy. Male C57/Bl6 mice were subjected to controlled cortical impact injury. Contusion volume, brain edema formation, and opening of the blood-brain barrier were investigated 2, 6, 12, and 24 h and 7 days after trauma. The effect of decompression craniectomy on secondary brain damage was studied in control mice (closed skull) and in animals craniotomized immediately or with a delay of 1, 3, or 8 h after trauma. Twenty-four hours after trauma, the time point of maximal lesion expansion (+60% vs. 15 min after trauma) and brain edema formation (+3.0% water content vs. sham), contusion volume in craniotomized mice did not show any secondary expansion; that is, contusion volume was similar to that observed in mice sacrificed immediately after trauma (18.3 +/- 5.3 vs. 22.2 +/- 1.4 mm(3)). Furthermore, brain edema formation was reduced by 52% in craniotomized animals. The beneficial effect of craniectomy was still present even when treatment was delayed by up to 3 h after trauma (p < 0.05). The current study clearly demonstrates that early craniectomy prevents secondary brain damage and significantly reduces brain edema formation after experimental TBI. Evaluation of early craniectomy as a therapeutic option after TBI in humans may therefore be indicated.

Inflammatory mechanisms are known to contribute to the pathophysiology of traumatic brain injury (TBI). Since bradykinin is one of the first mediators activated during inflammation, we investigated the role of bradykinin and its receptors in posttraumatic secondary brain damage. We subjected wild-type (WT), B(1)-, and B(2)-receptor-knockout mice to controlled cortical impact (CCI) and analyzed tissue bradykinin as well as kinin receptor mRNA and protein expression up to 48 h thereafter. Brain edema, contusion volume, and functional outcome were assessed 24 h and 7 days after CCI. Tissue bradykinin was maximally increased 2 h after trauma (P<0.01 versus sham). Kinin B(1) receptor mRNA was upregulated up to four-fold 24 h after CCI. Immunohistochemistry showed that B(1) and B(2) receptors were expressed in the brain and were significantly upregulated in the traumatic penumbra 1 to 24 h after CCI. B(2)R(-/-) mice had significantly less brain edema (-51% versus WT, 24 h; P<0.001), smaller contusion volumes ( approximately 50% versus WT 24 h and 7 d after CCI; P<0.05), and better functional outcome 7 days after TBI as compared with WT mice (P<0.05). The present results show that bradykinin and its B(2) receptors play a causal role for brain edema formation and cell death after TBI.

Molecular stereotactic biopsy is feasible and safe, can be implemented in daily clinical practice, improves diagnostic precision and enables personalized treatment.