Time Course of Cerebral Edema after Traumatic Brain Injury in Rats: Effects of Riluzole and Mannitol

Abstract

Brain trauma is the main cause of morbidity and mortality in young adults. One delayed events that occurs after a head trauma and compromises the survival of patients is cerebral edema. The present study examined first the occurrence of cerebral edema after a traumatic brain injury (TBI) induced by moderate fluid percussion in rats. Brain water content was measured from 1 h to 7 days posttrauma, in the hippocampus and cortex, on both ipsi- and contralateral hemispheres. Second, the effects of mannitol, an osmotic agent frequently used in the clinic, and riluzole, a neuroprotective compound, were investigated on regional edema formation. After TBI, the ipsilateral edema began early at 1-6 h, was maximal at 48 h and was resorbed by 5-7 days. No edema was observed in the contralateral hemisphere. Mannitol at 1 g/kg or vehicle was administered iv 15 min, 2 h and 4 h postinjury. At this dose, mannitol significantly attenuated the ipsilateral injured cortex edema measured at 6 h (p < 0.05). Riluzole at 4 and 8 mg/kg or vehicle was administered 15 min (IV) and 6 h, 24 h, and 30 h (SC) post-TBI. Riluzole at 4 x 4 mg/kg significantly reduced edema measured at 48 h, in the ipsilateral hippocampus (p < 0.05), whereas at 4 x 8 mg/kg, the reduction was observed in the hippocampus (p < 0.01) and the injured cortex (p < 0.05). Our results demonstrate that (1) cerebral edema begins early after the injury and is resorbed over 1 week; (2) mannitol could attenuate cerebral edema; and (iii) riluzole in addition to its neuroprotective effects reduces the brain edema. Thus, riluzole could be useful in human TBI treatment.

Intracranial biomechanics following cortical contusion in live rats

“…10,21 We observed an evolution of the contusion-related histological features similar to those described in more detail previously. 7,28 In previous rat experiments, others have shown that intra-and extracellular edema formation peaks from 12 hours to 2 days following contusion, 3,15 which corresponds to a peak in the intracranial pressure. 9 Many different descriptors are used for designating the physical properties of materials, and lay usage does not always equal the scientific definitions.…”

Combination Therapy with Fenofibrate, a Peroxisome Proliferator-Activated Receptor α Agonist, and Simvastatin, a 3-Hydroxy-3-methylglutaryl-Coenzyme A Reductase Inhibitor, on Experimental Traumatic Brain Injury

“…In this experimental model of TBI, edema develops early after trauma, increases within the first 15 h, and persists up to 48 h after injury (Bareyre et al, 1997). Our data showed that monotherapies and combination therapy reduced the posttraumatic brain edema by 70% at 24 h. More importantly, the combination still reduced 50% of the brain edema at 48 h after injury, exhibiting a potent long-lasting antiedematous effect, whereas fenofibrate and simvastatin, when given alone, had no more effect at this time point.…”

Autologous Bone Marrow Mononuclear Cells Reduce Therapeutic Intensity for Severe Traumatic Brain Injury in Children

“…In brief, the filtered mononuclear cell fraction was isolated using Ficoll-Paque PLUS (GE Healthcare Bio-Sciences Corp., New Jersey, USA) density gradient separation. The mononuclear cells were washed with human serum albumin in normal saline and adjusted to the appropriate concentration of 6×10 6 BMMNC/kg at a volume of 1cc/kg of body weight. Prior to release, the cells were tested for viability and presence of endotoxin.…”

“…The second and often long term goal is directed towards treating the secondary effects of the initial impact, which involves a neuroinflammatory response exacerbated by the breakdown of the blood brain barrier, resulting in sub-acute, life threatening cerebral edema. This second stage classically peaks approximately 48-72 hours after the initial trauma [5][6][7] . Subsequent chronic inflammation and cellular dysfunction manifests as chronic motor and cognitive disabilities.…”