Traumatic brain injury (TBI) remains a major public health problem, effecting more than 1.7 million people in the United States. In 2010, the center for disease controlled estimated the direct and indirect costs of TBI were $76.5 billion. Patients with TBI have impaired cognition, learning and memory deficits are also observed in animal models of TBI. In addition to direct, immediate primary injury, delayed molecular and cellular changes contribute to cell death and neurological dysfunction caused by TBI. One well-supported secondary injury mechanism is cell cycle activation (CCA). TBI induced CCA results in apoptosis of post-mitotic cells such as neurons and oligodendroglial cells as well as microglia proliferation, causing neuroinflammation and secondary neurotoxicity. Pharmacological inhibition of CCA with selective cyclin-dependent kinase inhibitors prevents activation of microglia and astrocytes and improves cognitive function. The well-established rodent TBI model of controlled cortical impact will be used to investigate downstream mechanisms behind inhibiting CCA. The proposed research will determine the neuroprotective potential of systemic treatment with a selective cell cycle inhibitor to attenuate CCA, and microglial and astrocyte activation, and cognitive deficits. Understanding the mechanisms responsible for continued cell death and cognitive deficits may facilitate development of novel targeted therapeutic interventions potentially increasing the quality of life of individuals suffering from TBI.

Public Health Relevance

Traumatic brain injury (TBI) remains a major public health problem, effecting more than 1.7 million people in the United States, those that survive often suffer from disabilities. Delayed molecular and cellular changes contribute to cell death and neurological dysfunction caused by TBI. Understanding the mechanism behind secondary injury would provide a potential target for therapeutic treatment of TBI.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Postdoctoral Individual National Research Service Award (F32)
Project #
5F32NS096895-02
Application #
9412762
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Bellgowan, Patrick S F
Project Start
2017-02-01
Project End
2019-01-31
Budget Start
2018-02-01
Budget End
2019-01-31
Support Year
2
Fiscal Year
2018
Total Cost
Indirect Cost
Name
University of Maryland Baltimore
Department
Anesthesiology
Type
Schools of Medicine
DUNS #
188435911
City
Baltimore
State
MD
Country
United States
Zip Code
21201