The effect of craniectomy treatment for severe TBI on patient outcomes has been debated. Experimental evidence for the therapeutic benefits, including functional recovery, for craniectomy treatment of severe TBI in animal models has been thoroughly examined and primarily indicates that craniectomy is neuroprotective [6, 20]. However, the study by Floyd et al. [6] examined the effect of craniectomy position and found that slight differences in the position of the craniectomy can produce changes in cognitive performance in a rat TBI model. The results of Floyd et al. were mimicked in the study by Lee et al. [12], which also observed a correlation between the location of craniectomy and functional recovery. Clinical reports are also inconsistent on the effect of craniectomy and patient outcome; whereas several reports observed improved patient outcome after decompressive craniectomy [1, 9, 19], the HeADDFIRST [7] and DECRA [5] clinical trials found conflicting and/or inconclusive results of craniectomy treatment on patient outcome. While we wait for the results of the RESCUEicp trial, the need for a treatment of cerebral edema remains of the utmost importance. An OTD has been shown to improve survival rates of water intoxicated mice [14] and reduce brain edema in mice with TBI [15]. Herein, we hypothesized that direct osmotherapy via an OTD is more neuroprotective than craniectomy alone, improving functional outcomes after TBI in mice.

The neurological function of mice after TBI was examined via testing of sensorimotor, proprioception, and balance. The foot fault test found TBI to be associated with functional deficits in the hind limbs of injured animals treated with a craniectomy only compared with those of naïve animals. When injured animals are treated with a craniectomy and an OTD, the number of hind limb faults decreased such that it was not statistically different from the naïve animals. The beam balance test identified that TBI was associated with balance (time to fall) and motor deficits (reduced distance traveled and turning) in animals treated with a craniectomy only compared with naïve animals. When injured animals are treated with a craniectomy plus an OTD, balance is improved and motor deficits are reduced. These tests supported our hypothesis that craniectomy plus OTD (combined therapy) improves functional outcome better than craniectomy alone and further support the therapeutic benefits of direct osmotherapy.