Hyperbaric oxygen brain injury treatment (HOBIT) trial: a multifactor design with response adaptive randomization and longitudinal modeling

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134231/1/pst1755_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134231/2/pst1755.pd

Bayesian hierarchical EMAX model for doseâ response in early phase efficacy clinical trials

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149669/1/sim8167_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/149669/2/sim8167.pd

Effects of hyperbaric oxygen therapy on cerebral oxygenation and mitochondrial function following moderate lateral fluid-percussion injury in rats

In the current study, the authors examined the effects of hyperbaric O2 (HBO) following fluid-percussion brain injury and its implications on brain tissue oxygenation (PO2) and O2 consumption (VO2) and mitochondrial function (redox potential). Cerebral tissue PO2 was measured following induction of a lateral fluid-percussion brain injury in rats. Hyperbaric O2 treatment (100% O2 at 1.5 ata) significantly increased brain tissue PO2 in both injured and sham-injured animals. For VO2 and redox potential experiments, animals were treated using 30% O2 or HBO therapy for 1 or 4 hours (that is, 4 hours 30% O2 or 1 hour HBO and 3 hours 100% O2). Microrespirometer measurements of VO2 demonstrated significant increases following HBO treatment in both injured and sham-injured animals when compared with animals that underwent 30% O2 treatment. Mitochondrial redox potential, as measured by Alamar blue fluorescence, demonstrated injury-induced reductions at 1 hour postinjury. These reductions were partially reversed at 4 hours postinjury in animals treated with 30% O2 and completely reversed at 4 hours postinjury in animals on HBO therapy when compared with animals treated for only 1 hour. Analysis of data in the current study demonstrates that HBO significantly increases brain tissue PO2 after injury. Nonetheless, treatment with HBO was insufficient to overcome injury-induced reductions in mitochondrial redox potential at 1 hour postinjury but was able to restore redox potential by 4 hours postinjury. Furthermore, HBO induced an increase in VO2 in both injured and sham-injured animals. Taken together, these data demonstrate that mitochondrial function is depressed by injury and that the recovery of aerobic metabolic function may be enhanced by treatment with HBO

The Effect of Reductive Ventricular Osmotherapy on the Osmolarity of Artificial Cerebrospinal Fluid and the Water Content of Cerebral Tissue Ex Vivo

The purpose of this study was to explore a novel treatment involving removal of free water from ventricular cerebrospinal fluid (CSF) for the reduction of cerebra]l edema. The hypothesis is that removal of free water from the CSF will increase the osmolarity of the CSF, which will favor movement of tissue-bound water into the ventricles, where the water can be removed. Reductive ventricular osmotherapy (RVOT) was tested in a flowing solution of artificial CSF (aCSF) with two end-points: (1) the effect of RVOT on osmolarity of the CSF, and (2) the effect of RVOT on water content of ex vivo cerebral tissue. RVOT catheters are made up of membranes permeable only to water vapor. When a sweep gas is drawn through the catheter, free water in the form of water vapor is removed from the solution. With RVOT treatment, aCSF osmolarity increased from a baseline osmolarity of 318.8 ± 0.8 mOsm/L to 339.0 ± 3.3 mOsm/L (mean ± standard deviation) within 2 h. After 10 h of treatment, aCSF osmolarity approached an asymptote at 344.0 ± 4.2 mOsm/L, which was significantly greater than control aCSF osmolarity (p <<0.001 by t-test, n = 8). Water content at the end of 6 h of circulating aCSF exposure was 6.4 ± 0.9 g H2O (g dry wt)−1 in controls, compared to 6.1 ± 0.7 g H2O (g dry wt)− after 6 h of RVOT treatment of aCSF (p = 0.02, n = 24). The results support the potential of RVOT as a treatment for cerebral edema and intracranial hypertension