Pycnogenol and traumatic brain injury

Traumatic brain injury (TBI) is a global health problem that is financially crippling for many families because of not only lost financial income but also the specialized care that is involved. Following the initial trauma, a secondary injury cascade begins that leads to neuronal death and subsequent cognitive dysfunction. This secondary injury cascade appears to be amenable to pharmacologic intervention but may require a multi-faceted approach in order to achieve a favorable outcome. Oxidative stress, neuronal death, and neuronal inflammation all appear to play major roles in the ensuing cognitive dysfunction. Naturally occurring flavonoids are unique in possessing a variety of different properties that can modulate cellular homeostasis leading to a reduction in inflammation, oxidative stress, and cell toxicity. The proposed studies will investigate the idea that Pycnogenol® (PYC), a combination of bioflavonoids, can significantly suppress the secondary injury cascade following TBI. This is a novel approach to TBI therapy since it utilizes a family of very closely related biologically active polyphenols. The first series of studies explore the best possible doing of PYC to maximally reduce the secondary injury and to determine the effective therapeutic window. The second set of studies will explore the neuroprotective qualities of PYC on hippocampal cell survival and hippocampal plasticity using slice electrophysiology. The third aim will assess functional and cognitive recovery of PYC at its optimal dose and if PYC offers neuroprotection in another model of TBI. Successful completion of these studies will pave the way for using PYC in more involved experimental TBI studies and contribute to the development of a rational therapy leading to a more favorable outcome.