No abstract

If, how, and when decompressive craniotomy should be used for the treatment of increased intracranial pressure after traumatic brain injury are widely discussed clinical subjects. Despite the large number of clinical studies addressing this issue, experimental evidence of a beneficial or detrimental role of decompressive craniotomy after brain trauma is sparse. Therefore, we investigated the influence of craniotomy on intracranial pressure, contusion volume, and functional outcome in a model of traumatic brain injury in mice. Male C57/Bl6 mice were craniotomized above the right parietal cortex and were subjected to controlled cortical impact injury. In control mice, the craniotomy was closed immediately after trauma, whereas in treated animals the craniotomy was left open. In control mice intracranial pressure (ICP) increased to a maximum of 23.7 +/- 3.1 mm Hg 6 h after trauma (p < 0.001), while in craniotomized animals, no ICP increase was observed. Twenty-four hours after trauma, the point in time of maximal lesion expansion, contusion volume in craniotomized mice was 40% smaller as compared to controls (18.3 +/- 2.0 vs. 30.2 +/- 3.5 mm(3), p < 0.04). Furthermore, craniotomized mice showed significantly improved motor function in a beam walking task (p < 0.04) and faster recovery of body weight after trauma (p < 0.02). Our results demonstrate that craniotomy blunts post-traumatic ICP increase, significantly reduces secondary brain damage and improves functional outcome after experimental TBI. Careful clinical evaluation of craniotomy as a therapeutic option after TBI in man may therefore be indicated.

Summary: Effects of severe lactacidosis were analyzed in vitro by employment of C6 glioma cells and astrocytes from primary culture. The cells were suspended in a physiological medium, which was rendered acidotic by addition of lactic acid in rising concentrations. A pH range of 7.4-4.2 was studied under maintenance of isoto nicity and a normal electrolyte concentration of the me dium. Cell swelling was quantified by flow cytometry us ing an advanced Coulter system with hydrodynamic fo cusing. The method was also utilized for assessment of cell viability by exclusion of the fluorescent dye propid ium iodide. The volume of C6 glioma cells was found to increase if the pH was titrated to pH 6.8 or below. From this level downward, the extent of cell swelling depended on the degree of acidosis and the duration of exposure. For example, lactacidosis of pH 6.2 for 60 min led to an increase in cell size to 124.5% of normal, while pH 5.0 or 4.2 led to a cell size of 151.1 or 190.9%, respectively. A comparative analysis of the acidosis-induced cell swelling was made by using sulfuric acid. Swelling of C6 glioma at a given pH was only half of what was found when using lactic acid. This indicates specific swelling-inducing prop erties of lactic acid, while cell viability was not differently affected by both acids. Of the C6 glioma cells, 89.1 % were viable under control conditions at pH 7.4. The via bility remained unchanged down to pH 6.2. At pH 5.6, viability remained normal for 30 min, but it decreased to 73.4% after 60 min. Further lowering of pH to 5.0 or 4.6 respectively, decreased the number of viable cells to 47.8 Cerebral ischemia, seizures, and severe head in jury are associated with an enhancement of anaer obic metabolism resulting in intra-and extracellular lactacidosis (Siesj6, 198 1, 1988). Lactacidosis may be involved in the formation of cytotoxic brain edema and irreversible damage of nerve and glial

Background and Purpose-The intraluminal thread model for middle cerebral artery occlusion (MCAO) has gained increasing acceptance. Numerous modifications have been reported in the literature, indicating that the technique has not been standardized. The present study was performed to evaluate and optimize the reliability of this model. Methods-One hundred Sprague-Dawley rats were subjected to MCAO by 2 different intraluminal filaments. Cortical blood flow was continuously monitored over both hemispheres by laser-Doppler flowmetry (LDF). In part I (3-0 filament), we evaluated the incidence of adequate MCAO, subarachnoid hemorrhage (SAH), intraluminal thrombus formation, and the effects of heparinization. In part II (silicone-coated 4-0 filament), we also determined the influence of insufficient MCAO on morphological and functional outcome and the incidence of postischemic hyperthermia. Results-In part I, SAH occurred in 30% and premature reperfusion in 24%. All animals with a decrease in contralateral flow had suffered SAH. Thrombus formation was not observed in any group. In part II, SAH occurred in 8% and premature reperfusion in 26%. There was no difference in outcome between rats with primary MCAO and rats with filament correction. Animals with uncorrected premature reperfusion had significantly smaller infarct volumes and fewer neurological deficits. Conclusions-SAH and insufficient MCAO may be more common in the intraluminal thread model than previously reported. Inadvertent premature reperfusion contributes to the interanimal variability associated with this model. The incidence of valid experiments increases with the use of a silicone-coated 4-0 filament. Continuous bilateral LDF is indispensable to monitor adequate MCAO and is highly sensitive to recognize SAH. (Stroke. 1998;29:2162-2170.)

Background and Purpose Preischemic spontaneous locomotor activity was distinguished in this laboratory as a factor influencing outcome after 15 and 20 minutes of forebrain ischemia in gerbils. Histological investigations were carried out to analyze potential relations between postischemic survival and a reduction of cerebral damage by spontaneous locomotor activity.Methods Male Mongolian gerbils were divided into two groups, one with access to running wheels ("runners") and one kept in conventional cages ("nonrunners") for 2 weeks preceding forebrain ischemia of 15 or 20 minutes. A total of 99 gerbils were divided in subgroups and were allowed to recover for 2 weeks for assessment of survival. Other subgroups (n=7 to 9) were killed at day 4 for quantitative histology of selectively vulnerable areas such as hippocampus, cortex, striatum, and thalamus.Results Two weeks after 15-minute ischemia, 44% of nonrunners had survived compared with 90% of runners (P<.01).