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For evaluation of novel therapeutic regimens against brain edema in experimental models, it is important to know the temporal profile of edema formation. Since development of brain swelling and edema following a cryogenic injury is poorly documented in rats, these parameters have been investigated in this study. 17 Sprague-Dawley rats were used. Three rats (controls) were sham-operated. Their brains were removed 15 min after sham-operation. In all other animals a right parietal cryogenic lesion was applied in ketamine-xylazine anesthesia. Systemic blood pressure was monitored during the perioperative period. Brains were removed in defined intervals following cryogenic injury (0.25, 0.5, 1, 3, 6, 12, 24, and 72 h; n = 3 each). Hemispheres were then separated and weighed for determination of brain swelling, dried and weighed again. Cerebral water content was calculated as the difference of hemispheric wet- and dry-weight. Posttraumatic hemispheric swelling reached its maximum (7.9 +/- 0.4%) as early as 12 h post trauma. During the first hour after injury, brain swelling showed a steep, linear increase to 3.9%, i.e. swelling amounted to 50% of its maximum within one hour. 6 h post trauma swelling was 5.7%. After 12 h brain swelling started to decline. 72 h post cryogenic injury, 6.1% hemispheric swelling were found. Development of brain swelling was paralleled by a linear increase in brain water content of the lesioned hemisphere. The maximum of hemispheric water content was seen 24 h post trauma. In non-lesioned hemispheres only a marginal transient increase in cerebral water content was observed. edema has to be considered when planning therapeutic protocols.

21-Aminosteroids have been shown to attenuate neuronal damage and to improve neurological outcome after experimental ischemia. The aim of this study was to determine whether brain edema induced by a cryogenic injury can be influenced by the 21-aminosteroid U-74389F. A cortical freezing lesion was applied to the right parietal region of Sprague-Dawley rats under ketamine-xylazine anesthesia. Systemic blood pressure was monitored in the peritraumatic period. Four different doses of U-74389F (A-D) were studied for their effect on post-traumatic brain swelling and edema. Respective control groups received only the solvent, citric acid buffer. (A) 3 mg/kg b.w.i.p. (total dose) 30 min before, 1 and 12 h; post trauma (p.t.); (B) 9 mg/kg b.w.i.v. 30 min before, 1 and 12 h p.t.; (C) 25 mg/kg b.w.i.v. 30 min before, 1, 6, and 12 h p.t.; (D) 50 mg/kg b.w.i.v. 15 min before, 15 and 30 min as well as 1, 2, 6, and 12 h p.t. 24 h after trauma, brains were removed and hemispheric swelling and water content were determined from the difference between wet and dry weight. Application of the 21-aminosteroid U-74389F moderately reduced post-traumatic brain swelling in all treatment groups: (A) 5%, (B) 9%, (C) 12%, and (D) 14%. In parallel with this, the increase in water content of the traumatized hemisphere was marginally lowered by U-74389F in all groups; in (C) e.g. from 1.9 +/- 0.1% to 1.7 +/- 0.1%, p = 0.07. These two findings taken together indicate that the 21-aminosteroid U-74389F moderately reduces post-traumatic swelling and edema.

Mannitol is frequently used to reduce elevated intracranial pressure often associated with brain edema. In cases of a damaged blood-brain barrier, however, mannitol might aggravate vasogenic cerebral edema, as has recently been stressed. The aim of this study was to investigate whether multiple doses of mannitol administered during development of vasogenic brain edema following a cryogenic cortical injury affect hemispheric swelling and edema. Sprague-Dawley rats were anesthetized with ketamine and xylazine. A cortical freezing lesion was applied to the right parietal region. A first series of eight rats received four doses of 20% mannitol (0.4 g/kg within 10 minutes) thirty minutes, 3, 6 and 9 hours after trauma. Twelve hours after cryogenic injury, the brains were removed for determination of hemispheric swelling and cerebral water content. Eight control rats were infused with saline only. In a second series nine rats received eight doses of 20% mannitol 30 minutes, 3, 6, 9, 12, 15, 18 and 21 hours after trauma. In this series, the brains were removed 24 hours after freezing. Again respective control animals were infused with saline only. Hemispheric swelling was 7.2 +/- 0.5% after four doses of mannitol compared to 7.6 +/- 0.5% in control animals (n.s.). Following eight doses of mannitol hemispheric swelling was 8.9 +/- 0.4% compared to 10.1 +/- 0.4% in control rats (p < 0.05). Accordingly, the water content of traumatized hemispheres was lower following repeated mannitol treatment (80.5 versus 80.8%). Water content in control hemispheres was not affected by mannitol. Taken together, these results indicate that multiple doses of mannitol do not aggravate total hemispheric swelling, nor global water content following induction of vasogenic edema.(ABSTRACT TRUNCATED AT 250 WORDS)

Age is an important factor of mortality and morbidity following traumatic brain injury. The causes for the adverse effect of old age remain obscure. The aim of this study was to clarify whether age affects the development of posttraumatic brain edema. In Wistar rats, a cortical freezing lesion was applied to the parietal region in ketamine-xylazine anesthesia. 18 young rats (4-6 months) were compared to 15 old animals (36-40 months). In the early peritraumatic and late posttraumatic period blood pressure was monitored. 24 hours after trauma, the brains were removed and hemispheric swelling, water- und electrolyte-contents were measured. In addition, the brains of 3 animals of each group were histologically evaluated. In the old age group, 3 animals died during the 24 hours observation period (mortality 20%), whereas all young rats survived (p < 0.01). The cortical freezing lesion resulted in a hemispheric swelling of 6.9 +/- 0.5% in young, and 10.4 +/- 0.8% in old animals (p < 0.001). Accordingly, the increase of cerebral water content due to the lesion was significantly more pronounced in the group of old rats, i.e. 2.05% in old versus 1.50% in young animals (p < 0.01). The increase of swelling and edema in the old age group could not be attributed to arterial hypertension. On the contrary, mean arterial blood pressure was significantly lower in old animals. Histological examinations did not reveal significant differences between the two groups. Edema generation following a standardized cryogenic lesion is markedly enhanced in old versus young rats. This might be one factor among others for higher mortality and morbidity following traumatic brain injury in old versus young individuals.

Elevation of the head as a common practice to reduce raised intracranial pressure (ICP) has been discussed controversially of late. Some investigators were able to show that besides lowering ICP head elevation may also reduce cerebral perfusion pressure (CPP). For a new evaluation of optimal head position in neurosurgical care it would be of importance to know the influence of body position on cerebral perfusion. We therefore employed continuous jugular venous oximetry, monitoring cerebral oxygenation, to study the effect of 0 degrees, 15 degrees, 30 degrees, and 45 degrees head elevation on ICP, CPP and jugular venous oxygen saturation (SJVO2) in 25 comatose patients with reduced intracranial compliance. As expected, head elevation significantly reduced ICP from 19.8 +/- 1.3 mmHg at 0 degrees to 10.2 +/- 1.2 mmHg at 45 degrees. Already at 30 degrees 92% of the possible effect on ICP was detected. There was no statistically significant change in CPP and SJVO2 associated with varying head position. Individual reactions of CPP to changes in head position, however, were quite unpredictable. The data suggest that an individual approach to head elevation is to be preferred. A moderate head elevation between 15 degrees and 30 degrees significantly reduces ICP and, in general, does not impair cerebral perfusion. Jugular venous oximetry may be used to optimize ICP, CPP and cerebral oxygenation.

To prevent secondary cerebral ischemia in comatose patients it would be of great importance to assess cerebral blood flow. Recently monitoring of the jugular venous oxygen saturation (SJVO2) has been shown to continuously evaluate cerebral oxygenation and to estimate cerebral blood flow. While most of these studies have dealt with severely head injured patients, we investigated cerebral oxygenation in 50 comatose patients due to an intracerebral haematoma (n = 14), subarachnoid haemorrhage (n = 12) and severe head injury (n = 24). In these groups of patients, the reaction of SJVO2 to hyperventilation and to lowering of blood pressure was studied. Moderate hyperventilation from 35 to 28 mmHg resulted in a significant decrease of SJVO2 in all groups. A critical SJVO2 between 50 and 55% was found in one half of the patients studied, a pathological SJVO2 below 50% was seen in 23% of the cases. Lowering of arterial blood pressure within the limits of autoregulation resulted in decreases of SJVO2 in patients with intracerebral haematomas only. 55% of these patients showed signs of insufficient cerebral oxygenation. Furthermore the frequency of spontaneous desaturation episodes was studied retrospectively and comparison made between the different groups. These episodes were found more frequently in patients with intracerebral haematomas compared to patients with severe head injury. In conclusion, monitoring of jugular venous oxygen saturation is a valuable tool for detecting and treating insufficient cerebral oxygenation in comatose patients following intracerebral haemorrhage, subarachnoid haemorrhage and severe head injury.