Treatment of TBI with Hormonal and Pharmacological Support, Preclinical Validation Using Diffuse and Mechanical TBI Animal Models
Technical Report,01 Sep 2008,28 Feb 2016
University of Alabama at Birmingham Birmingham United States
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We established the lateral fluid percussion model for induction of TBI, and applied it to a substantial panel of in vivo tests to evaluate the effects of E2-SO4 early years test article or ethinyl estradiol-3-sulfate EE-3-SO4 later years test article on ameliorating early events for TBI pathology. This panel of TBI tests included standard clinical evaluations for physiological deficits i.e., intracranial pressure, brain O2 tension, cranial perfusion pressure. In vivo testing also included behavioral and physical activity evaluations, including memory, cognition, vestibulomotor function, fear and anxiety. These behavioral tests were conducted under the direction of Dr. Thomas van Groen Neurobiology Core Facility Director. In addition we examined general physical activity, using a custom-fabricated instrumental system of our design. This was applied to measuring generalized nocturnal activity, confirming that EE-3-SO4 treated TBI rats have higher activity levels vs. vehicle-treated TBI rats. Our in vivo tests also included MRI imaging, focusing on edema resolution and reduction of diffuse axonal damage fractional anisotropy. Here we found that EE-3-SO4 was protective if given within the first hour post injury. For in vitro testing, we performed histochemical and immunohistochemical analyses for neuronal damage and integrity plus in vitro examinations of neuronal stretch damage mitigation by E2-SO4. All assays showed a protective advantage for EE-3-SO4. These data, which are published, confirm that EE-3-SO4 is as effective as or better than the previously used drug, E2-SO4 whose results are also published. We have applied for and received two patent awards one for the use of EE-3-SO4 for treating severe hemorrhage and the other for treating TBI. In addition, we have received a contract from DoD to move toward clinical trials with EE-3-SO4 for severe hemorrhage.
- Medicine and Medical Research