Challenging the role of adaptive immunity in neurotrauma: Rag1(-/-) mice lacking mature B and T cells do not show neuroprotection after closed head injury.

The role of adaptive immunity in contributing to post-traumatic neuroinflammation and neuropathology after head injury remains largely unexplored. The present study was designed to investigate the pathophysiological sequelae of closed head injury in Rag1(-/-) mice devoid of mature B and T lymphocytes. C57BL/6 wild-type and Rag1(-/-) mice were subjected to experimental closed head injury, using a standardized weight-drop device. Outcome parameters consisted of neurological scoring, quantification of blood-brain barrier (BBB) function, measurement of inflammatory markers and mediators of apoptosis in serum and brain tissue, and assessment of neuronal cell death, astrogliosis, and tissue destruction. There was no difference between wild-type and Rag1(-/-) mice with regard to injury severity and neurological impairment for up to 7 days after head injury. The extent of BBB dysfunction was in a similar range for both groups. Quantification of complement activation fragments in serum revealed significantly attenuated C3a levels in Rag1(-/-) mice compared to wild-type animals. In contrast, the levels of pro- and anti-inflammatory cytokines and pro-apoptotic and anti-apoptotic mediators remained in a similar range for both groups, and the histological analysis of brain sections did not reveal a difference in reactive astrogliosis, tissue destruction, and neuronal cell death in Rag1(-/-) compared to wild-type mice. These findings suggest that adaptive immunity is not of crucial importance for initiating and sustaining the inflammatory neuropathology after closed head injury. The attenuated extent of post-traumatic complement activation seen in Rag1(-/-) mice implies a cross-talk between innate and adaptive immune responses, which requires further investigation in future studies.

Update in the treatment of traumatic brain injury.

This review focuses on recent advances in the treatment of traumatic brain injury (TBI) during 2004 and 2005. Injured brain is a very heterogeneous structure, significantly evolving over time. Implementation of multimodal neuromonitoring will certainly provide more insights into pathophysiology of TBI. More studies are needed to determine how to best incorporate these new parameters into effective management protocols. Based on current literature, corticosteroids should not be indicated for the treatment of TBI. Avoidance or immediate treatment of secondary insults remains a mainstream of clinical care for patients with TBI. It seems that the therapy should focus on control of intracranial hypertension, and values of cerebral perfusion pressure around 60 mm Hg appear to correlate with favorable outcome in most patients. Hypertonic saline may become a preferred osmotherapeutic agent in severely head-injured patients, especially those with refractory intracranial hypertension. Benefit and indications for performing a decompressive craniectomy remain to be determined. Overall, individualized treatment respecting actual status of a patient's intra- and extracranial homeostasis should be the key principle of our current therapeutic approach toward severely head-injured patients.