Experimental investigations of single mild brain injury (SMI) show relatively little resultant cognitive impairment. However, repeated mild brain injuries (RMI), as those sustained by athletes (e.g., football, hockey, and soccer players) may have cumulative effects on cognitive performance and neuropathology. Numerous clinical studies show persistent, latent, and long-term consequences of RMI, unlike the episodic nature of SMI. The nature of repeated traumatic brain injury (TBI) introduces confounding factors in invasive and even semiinvasive animal models of brain injury (e.g., scar formation). Thus, the present study characterizes SMI and RMI in a noninvasive mouse weight drop model and the cumulative effects of RMI on cognitive performance. Investigation of drop masses and drop distances revealed masses of 50, 100, and 150 g dropped from 40 cm resulted in 0% mortality, no skull fracture, and no difference in acute neurological assessment following sham injury, SMI, or RMI. Cumulative effects of RMI were examined following four mild brain injuries 24 h apart induced by 50-, 100-, or 150-g masses dropped from 40 cm through histological measures, mean arterial pressure, and measures of complex/spatial learning. RMI produced no overt cell death within the cortex or hippocampus, no evidence of blood-brain barrier compromise, and no significant change in mean arterial pressure. Following testing in the Morris water maze (MWM) on days 7-11 after initial injury, mice in the RMI 100-g and RMI 150-g groups had significantly longer MWM goal latencies compared to sham, SMI 150-g, and RMI 50-groups. Additionally, the evident cognitive deficit manifested in the absence of observed cell death. This is the first study to show complex/spatial learning deficits following RMI, similar to the visual/spatial perception and planning deficits observed in clinical studies.

Severe human TBI profoundly disturbs cerebral acid-base homeostasis. The observed pH changes persist for the first 24 hours after the trauma. Brain tissue acidosis is associated with increased tissue PCO2 and lactate concentration; these pathobiochemical changes are more severe in patients who remain in a persistent vegetative state or die. Furthermore, increased brain tissue PCO2 (> 60 mm Hg) appears to be a useful clinical indicator of critical cerebral ischemia, especially when accompanied by increased lactate concentrations.

No abstract

Based on results in the present study one can infer that microdialysate glycerol is a marker of severe tissue damage, as seen immediately after brain injury or during profound tissue hypoxia. Given that brain tissue glycerol levels do not yet add new clinically significant information, however, routine monitoring of this parameter following traumatic brain injury needs further validation.

The goal of this article is to give an overview about the established current treatment concepts of traumatic brain injury, as well as an outlook on possible future developments in pharmacological neuroprotection. Modern medical treatment modalities of traumatic brain injury (TBI), including the preclinical management of severely head-injured patients, are reviewed. Since an increased intracranial pressure represents the most common complication of severe traumatic brain injury, frequently associated with the development of secondary brain damage, special emphasis was given to an updated treatment algorithm for this important condition. New insight into the pathophysiology of severe traumatic brain injury, especially the realization that brain damage develops sequentially, initiated several new treatment approaches aiming at the interruption of pathophysiological mechanisms leading to secondary brain injury. A high number of pharmacological substances have been tested for their ability to ameliorate secondary damage after TBI, or are currently under clinical trial. Although no drug has achieved this goal so far, the most promising of these therapeutical approaches, glutamate receptor antagonists, calcium channel antagonists, free radical scavengers, and cyclosporin A will be discussed in this review. Although a "magical bullet" for the treatment of traumatic brain injury has not been developed yet, several of the currently investigated neuroprotective strategies seem to be encouraging. A promising future approach might be to evaluate treatment strategies that combine several pharmacological agents, and possibly other treatment modalities, such as mild hypothermia, "tailored" according to the special pathology of patient subgroups, or even to every single patient in order to achieve an improvement in outcome after TBI.