Cognitive assessment of pycnogenol therapy following traumatic brain injury

Abstract

We have previously shown that pycnogenol (PYC) increases antioxidants, decreases oxidative stress, suppresses neuroinflammation and enhances synaptic plasticity following traumatic brain injury (TBI). Here, we investigate the effects of PYC on cognitive function following a controlled cortical impact (CCI). Adult Sprague-Dawley rats received a CCI injury followed by an intraperitoneal injection of PYC (50 or 100mg/kg). Seven days post trauma, subjects were evaluated in a Morris water maze (MWM) and evaluated for changes in lesion volume. Some animals were evaluated at 48h for hippocampal Fluoro-jade B (FJB) staining. The highest dose of PYC therapy significantly reduced lesion volume, with no improvement in MWM compared to vehicle controls. PYC failed to reduce the total number of FJB positive neurons in the hippocampus. These results suggest that the reduction of oxidative stress and neuroinflammation are not the key components of the secondary injury that contribute to cognitive deficits following TBI.

Keywords: Bioflavonoids; Cortical contusion; Head injury; Natural compounds; Recovery of function; Water maze.

Figure 1

Beginning seven days post injury, animals were trained to locate a submerged platform in a standard Morris water maze. (A) The time to locate the submerged platform (Escape Latency) was averaged over the four trials on each day of training. Inset shows the different groups’ performance on day 5. (B) Total distance required to find the submerged platform (Escape Path Length) was averaged over the four trials on each day of training. The inset shows the different groups’ performance on day 5. (C) Following the final acquisition trial on day five of training in the Morris water maze, animals were tested for spatial memory during a probe trial. Horizontal dashed line represents chance performance. Points represent group means (n=7/group) * p < 0.05 ** 0.01 Sham vehicle compared to all other groups. Bars represent group mean ± SD.

Figure 2

(A) Photomicrograph of a coronal cresyl violate stained section showing a representative lesion resulting from a unilateral cortical impact at 12 days post injury. Tissue loss (***) on the right side resulted from the cortical impact. T (B) Changes in injury volume assessed by measuring the total amount of spared tissue using unbiased stereology. The high dose PYC group showed greater tissue sparing. The sham group is not included because there was no injury. (C) Photomicrograph of a FJB stained coronal section in the dentate gyrus. The arrows indicate a few of the FJB-positive stained granule cells ipsilateral to the injury. (D) Estimates of the total number of FJB positive neurons in two different regions of the hippocampus. There was no significant difference between the vehicle and high-PYC treatment group. * p < 0.05 compared to other groups. Calibration bar = 100 µm. Bars represent group mean ± SD.