Elucidating Microglial Immune Regulation Targets to Remove Protein Aggregates in TBI
Abstract
Objectives and Rationale: The proposed research in this application addresses one of the major health issues facing Soldiers wounded in combat, an alarming increase of post-head trauma Alzheimer’s disease (AD) and related dementias, imposing enormous emotional and economic burdens on families, their communities, and society as a whole. Currently, there is no effective tool to either diagnose or treat such conditions, due to poor understanding of mechanisms of post-head trauma AD development. We will investigate how a known toxic compound, amyloid beta peptides (Aß), a factor previously shown to cause AD, accumulates and leads to AD following head trauma. Using unique animal models, we will study how the body naturally removes these toxic compounds and how this endogenous protective mechanism is compromised in the event of head trauma. Knowing these mechanisms may help us restore and stimulate such neuroprotective capabilities following head trauma to prevent the occurrence of AD. Applicability of the Research: We intend to develop an effective immunotherapy that can empower the human immune system to remove toxic compounds that are known to cause AD. We predict that such immunotherapy, which has shown tremendous success in cancer therapy, will significantly reduce the incidence of post-head trauma mental illness, particularly AD. Military Benefit: This project is highly relevant to the military, in that our men and women routinely suffer such injuries and there is an alarming trend in the increasing reports of post-TBI AD and related dementias among wounded Soldiers. Head trauma can directly result from exposure to explosive blasts to which our Soldiers are routinely exposed in combat and training exercises. Furthermore, intense combat conditions will also increase the incidence of traumatic brain injury in situations such as severe car accidents or accidental falls from varying heights. Therefore, uncovering the mechanisms responsible for this epidemic, which detracts from the quality of life of thousands of Veterans, could profoundly benefit our Soldiers whom sacrifice a great deal to ensure our freedom.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010665
Entities
People
- Gaurav Chopra
Organizations
- Purdue University
- United States Army