An investigation of cerebral edema and injury volume assessments for controlled cortical impact injury.

UNLABELLED: Using the controlled cortical impact (CCI) model, our laboratory compared edema in contralateral and ipsilateral regions to help clarify conflicting reports of contralateral edema and for enhanced assessment and interpretation of CCI injury pathophysiology. This investigation examined regional edema in response to graded injury severities over time with regards to tissue damage. Prior to injury rats were anesthetized with ketamine and xylazine (1:1). CCI injury parameters were set at 4.0m/s and 120 to 130 ms. Rats were randomized to receive moderate or severe injuries set at 2.0 and 3.0mm depths, respectively. Cerebral edema and injury volume were examined separately following euthanasia with pentobarbital. Cerebral edema was measured using the wet-dry weight technique at 24 or 48 h after injury. Sham animals underwent all surgical procedures except the impact injury. Injury volume was quantified using 2,3,5-triphenyltetrazolium chloride staining at 24h or 7 days after injury. The results of this investigation confirm that cerebral edema is absent in the uninjured, contralateral hemisphere after moderate and severe CCI injury. There were regional differences in cerebral edema formation in the hemisphere ipsilateral to injury that were dependent on injury severity and the length of time after injury. Tissue damage was reduced over 7 days following moderate CCI injury. CONCLUSIONS: (1) the absence of edema in the contralateral hemisphere allows it to serve as a valid control for edema formation, (2) misrepresenting injury volume because of edema continues to be a problem for evaluating CCI injury and treatment efficacy, and (3) reduced injury volume over 7 days following CCI injury suggests tissue recovery after initial dysfunction.

Effects of crystalloid-colloid solutions on traumatic brain injury.

The purpose of this study was to compare the effects of crystalloid and crystalloid-colloid solutions administered at different times after isolated traumatic brain injury. Male Sprague-Dawley rats were randomized to receive one of three intravenous treatments (4 mL/kg body weight) at 10 min or 6 h after moderate traumatic brain injury. Treatments included hypertonic saline, hypertonic albumin, and normal albumin. Moderate injuries were produced using the controlled cortical impact injury model set at 2.0 mm, 4.0 m/sec, and 130 msec. Tissue damage and cerebral edema were measured to evaluate the effect of treatments for traumatic brain injury. Blood brain barrier permeability was assessed at different time points after injury to identify a mechanism for treatment effectiveness. Injury volume was the smallest for animals treated with hypertonic albumin at 6 h after injury compared to all other treatments and administration times. Ipsilateral brain water content was significantly attenuated with immediate normal saline-albumin treatment. The presence of colloid in the infusion solutions was associated with an improvement in tissue damage and edema following isolated head injury while hypertonic saline alone, when given immediately after injury, worsened tissue damage and edema. When hypertonic saline was administered at 6 h after injury, tissue damage and edema were not worsened. In conclusion, the presence of colloid in solutions used to treat traumatic brain injury and the timing of treatment have a significant impact on tissue damage and edema.

Hypertonic saline attenuates tissue loss and astrocyte hypertrophy in a model of traumatic brain injury.

Hypertonic saline is currently being used in the treatment of patients with post-traumatic cerebral edema and elevated intracranial pressure resulting from TBI. A limited number of studies show the cellular effects of hypertonic saline and no studies, to our knowledge, have investigated the effects on astrocytes. The role of astrocyte responses after traumatic brain injury remains unclear. There is evidence that reduced astrocyte proliferation is detrimental while increased hypertrophy and proliferation are signs of increased injury severity. Therefore, this study focused on the hypothesis that hypertonic saline-induced improvements in histological outcome are time dependent and may be associated with alterations in astrocyte hypertrophy after cortical contusion injury. Histopathological changes at 7 days after controlled cortical impact (CCI) injury were examined. Brain tissue loss determined using cresyl violet staining and astrocyte hypertrophy and proliferation were assessed using glial fibrillary acidic protein immunostaining in hypertonic saline and normal saline treated rats, and untreated, injured controls. Effects of the timing of hypertonic saline treatment administration on tissue loss were also examined. Plasma osmolarity and sodium levels were measured over 4 h and again at 24 h following hypertonic saline administration. Results show that hypertonic saline treatment reduced tissue loss that correlated with attenuated astrocyte hypertrophy characterized by reductions in astrocyte immunoreactivity without changes in the number of astrocytes after CCI injury. Delayed treatment of hypertonic saline resulted in the greatest reduction in tissue loss compared to all other treatments indicating that there is a therapeutic window for hypertonic saline use after traumatic brain injury.