The UT Southwestern researchers are currently taking steps toward moving into human clinical trials based on findings in their preclinical two-hit model
. With time, they expect that all heart failure patients will have treatment options.
The two-hit model was induced as previously described (10).
Hemorrhage/resuscitation and subsequent endotoxemia are common in clinical practice, and multiple organ damage induced by this two-hit model is more in line with clinical practice.
Platonin mitigates lung injury in a two-hit model of hemorrhage/ resuscitation and endotoxemia in rats.
Thus, in this two-hit model, LPS-induced inflammation accelerated [alpha]-syn accumulation, aggregation, and nitration.
2007), our two-hit model created by a moderately toxic dose of LPS (3 x [10.sup.6] EU/kg) revealed accelerated DA neurodegeneration and provided additional insight into [alpha]-syn pathologic alterations under inflammatory states.
As expected, rats exposed to the two-hit model with glucocorticoid insensitivity displayed increased HMGB1, TLR4, and p-NF-[kappa]B, and decreased VE-cadherin, GR[alpha], and I[kappa]B[alpha] protein expression, which is indicative of severe lung injury.
We chose to intraperitoneally inject LPS at 2 mg/kg, then performed tracheal infusion using LPS at 4 mg/kg to create a two-hit model. This resulted in lung injury in the model, including more neutrophils within the alveolar and the interstitial areas, and proteinaceous refuse covering the airspaces and alveolar septum.
"A two-hit model
would explain much better than a single-hit model the regulation of the vascular permeability.
A model exploring this hypothesis should explore the possibility that early damage to the DA system could result in cell loss or high vulnerability to a second environmental risk factor associated with PD (two-hit model