Alleviating tinnitus and memory deficits induced by blast exposure

Va Western New York Healthcare System, Buffalo NY

Investigators

Abstract

Abstract Tinnitus and mental illness are common disorders in veterans caused by blast exposure. Convergent evidence found that tinnitus response is highly affected by the limbic impairment which may affect neurogenesis and memory deficits. Although management of emotional and mental status has become a critical treatment for tinnitus, the connection of tinnitus and memory deficits has rarely been studied. Our preliminary study found that blast exposure can induce neural inflammation in the auditory brainstem and reduced neural neurogenesis in the hippocampus. We hypothesize that blast caused damage in the auditory and limbic system is critical in exacerbating the severity of chronic tinnitus, and reducing the neural damage in the limbic system will rescue memory deficits and alleviate tinnitus. Three specific aims of this study are: (1) To determine the correlation of blast waves induced memory deficits and chronic tinnitus/hyperacusis. In our preliminary study we have shown tinnitus, hyperacusis and impaired memory retention deficits induced by blast exposure in our animal model. We will continue to investigate the cause and correlation of these disorders and determine if memory impairment will increase the likelihood of developing chronic tinnitus/hyperacusis; (2) To identify whether blast exposure activates brain immune cells in the central auditory system and disturbs ongoing adult neurogenesis in the hippocampus. In our preliminary study, we found that blast exposure impaired adult neurogenesis and activated brain immune cells in the auditory brainstem and the hippocampus. In this study, we will determine the neural pathway of blast waves induced neural inflammation and neurogenesis. Immunostaining of neural inflammation and neurogenesis markers will be used to detect blast induced neural impairment blasts; (3) To determine if improving neuron survival using minocycline, a sage tetracycline derivative, can reduce neuroinflammation in the brainstem and hippocampus and reduce chronic tinnitus and memory deficits after blast. We predict that treatment of minocycline will reduce brain inflammation, memory deficits and tinnitus/hyperacusis in the blast exposure animals. In summary, this project will address tinnitus and mental illness caused by blast wave injury. The success of this study will provide neural mechanisms and clinically relevant data on ameliorating these auditory disorders and memory deficits. [Type here]