Investigating the neuroproductive effects of hypothermia as a potential therapeutic for traumatic brain injuries using a 4D neronal cell model
Abstract
Abstract Traumatic brain injury (TBI) is one of the worldÕs major causes of death and disability, and is a direct result of blast impact or rapid acceleration and deceleration of the brain [1-4]. At a cellular level TBI is generally classified morphologically as diffuse axonal injury (DAI) or axonal swelling, the precursor to neuronal degeneration and neuronal apoptosis [5-7]. Traumatic brain injury (TBI) is one of the worldÕs major causes of death and disability [8, 9].Hypothermic treatment is of great interest as a clinical therapeutic due to its simplicity in administering. However, its effectiveness in reducing cellular damage due to TBI is still being investigated even after several decades [10-12]. Part of the challenge has been in understanding the precise mechanism by which hypothermia affects different cells in the brain from the vasculature endothelium down to astrocytes and neurons. Clinical applications of hypothermic treatment have seen some benefit, in particular in reducing intracranial pressure in more severe brain injuries, but have shown only limited success in stopping diffuse axonal injury in animal models [10, 11, 13, 14]. A key question on whether a particular combination of hypothermic temperature and exposure ranges will significantly improve the neuroprotective outcome still remains to be answered. Given the brainÕs complexity in cell numbers and cell phenotypes in-vitro models are ideal candidates to identify the specific mechanism by which hypothermia affects neurons. Recent completed work by our laboratory has shown that application of mild hypothermia (33¡C) significantly reduced neuronal cell death lending significant support to the use of hypothermia as a neuroprotective therapeutic for treating traumatic brain injuries. Based on these prior results, we will systematically investigate the timetemperature parameter space that renders hypothermia neuroprotective against traumatic brain injuries using our previously established 3D neuronal in-vitro model.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- May 22, 2016
- Source ID
- N000141512406
Entities
People
- Christian Franck
Organizations
- Brown University
- Office of Naval Research
- United States Navy