The exact mechanism of hypothermic cerebroprotection after traumatic brain injury (TBI) is not fully understood. The present study was conducted to investigate the effects of mild hypothermia on trauma-induced synthesis of nitric oxide (NO), which has been implicated in the pathogenesis of ischemic brain damage associated with glutamate neurotoxicity. Cerebral contusion was created in the rat parietal cortex by a weight-drop method, and extracellular concentrations of the NO end products nitrite and nitrate were measured using in vivo brain microdialysis and capillary electrophoresis under normothermic (37 degrees C) and mild hypothermic (32 degrees C) conditions. In normothermic animals, the level of NO end products increased markedly 10 min after contusion, reaching a maximum level at 20 min. In the hypothermic rats, such increases were absent. Although it is unknown whether endothelial NO synthase, neuronal NO synthase, or both caused the elevation of the NO end products seen in the normothermic animals, the present results indicate that inhibition of NO synthesis may play a part in hypothermic cerebroprotection following TBI.

A study was conducted to investigate the role of serum protein exudation in the aetiology of chronic subdural haematoma (SDH). Scintigraphy after intravenous injection of 99mTc-labelled human serum albumin (HSA) was performed in three patients with chronic SDH and a patient with subdural effusion. In another 60 haematomas, the amounts of total protein and albumin as indices of serum exudation were measured, and then compared among low-density, iso-density and high-density haematomas. Accumulation of 99mTc-HSA in the haematoma cavity was seen 6 h after isotope injection and became more evident at 24 h. However, the protein concentrations and albumin ratios in the haematomas exhibited a reciprocal relationship, suggesting that not all the protein in the haematomas was derived from serum exudation. The higher the total protein concentration in the haematoma became, the higher the haematoma density which was observed on CT. The albumin concentration in low-density haematomas was lower than that in iso-density and high-density haematomas, whereas no significant difference was seen between the latter two haematoma types. These results provide morphological evidence for serum protein exudation into the haematoma cavity, and therefore it is possible that serum protein exudation plays a role in the progression of chronic SDH and is related to changes in haematoma density on CT.

The titration method of mild hypothermia to control intracranial hypertension in severely head-injured patients is clinically feasible. However, the method failed to reduce the incidence of infectious and hematological complications.

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Acute subdural hematoma (SDH) complicates about 20% of severely head-injured patients, and death and severe disability frequently result, yet over half of these patients may have been conscious, at some time after injury, implying secondary mechanisms of brain damage. Drugs that block the "excitotoxic" effects of glutamate at the N-methyl-D-aspartate (NMDA) receptor have generally been effective in reducing ischemic brain damage associated with SDH in animal models, yet these agents all appear to be associated with major behavioral side effects, in conscious patients, at neuroprotective doses. We therefore evaluated the effects of treatment with a novel antagonist for the glycine binding site of the NMDA receptor (ACEA1021) upon ischemic brain damage, in the rat SDH model. ACEA1021 may be free of psychomotor effects, and may thus permit high dose therapy in conscious trauma and stroke patients. SDH was produced by the slow injection of 0.4 mL autologous blood into the subdural space overlying the parietal cortex. brain damage was assessed histologically at 8 coronal planes, in animals sacrificed 4 h after induction of hematoma. Both pre- and posttreatment with ACEA1021 significantly reduced hemispheric ischemic damage produced by SDH. The magnitude of neuroprotection with this compound (26 to 39% reduction in infarct size) is similar to other NMDA antagonists, and the robust posttreatment effect implies that human studies with this compound should be performed in head injured patients, subject to completion of toxicology testing.