Disparity among neural injury models and the unfolded protein response.
Endoplasmic reticulum stress is activated following both stroke and traumatic brain injury producing reactive oxgygen species, increasing intracellular calcium levels, and inducing inflammation; however, the timing and duration of activation varies between injuries. Preventing the immediate effects of ischemic/reperfusion injury or traumatic brain injury is challenging due to short onset of injury, but mitigating the secondary effects is a therapeutically targetable option. Preventative therapies using pharmacological agents have been utilized in pre-clinical models of neural injury to ameliorate secondary effects such as apoptosis and neurodegeneration. The connection between ER stress activation, apoptosis, and subsequent neurodegeneration has been proposed, but not yet causally linked. Researchers are now pursuing effective treatment strategies to suppress the secondary effects of neural injury in order to mitigate the development of chronic deficits. Secondary effects such as endoplasimic reticulum stress and neuroinflammation can be prevented in pre-clinical models, but the results have yet to translate to meaningful treatment options for patients. Evidence suggests that targeting the right transcription factors, at the right time, will aid in the prevention of apoptosis and neurodegenerative disease development following neural injury. In this review, we examine therapeutic approaches that target secondary injury and how these may correlate to better treatment options for patients.
Department of Pharmaceutical Sciences, West Virginia University, USA; Department of Neurosurgery, West Virginia University, USA.
Aric Flint
AF
Logsdon
Department of Neurosurgery, West Virginia University, USA.
Brandon Peter
BP
Lucke-Wold
Department of Neurosurgery, West Virginia University, USA.
Charles Lee
CL
Rosen
Department of Pharmaceutical Sciences, West Virginia University, USA; Department of Neurosurgery, West Virginia University, USA.
Jason Delwyn
JD
Huber
Apoptosis; Endoplasmic reticulum stress; Inflammation; Ischemic stroke; Neurodegeneration; traumatic brain injury