Experimental diffuse brain injury results in regional alteration of gross vascular morphology independent of neuropathology

Abstract

Primary objective: A dynamic relationship exists between diffuse traumatic brain injury and changes to the neurovascular unit. The purpose of this study was to evaluate vascular changes during the first week following diffuse TBI. It was hypothesized that pathology is associated with modification of the vasculature.

Methods: Male Sprague-Dawley rats underwent either midline fluid percussion injury or sham-injury. Brain tissue was collected 1, 2 or 7 days post-injury or sham-injury (n = 3/time point). Tissue was collected and stained by de Olmos amino-cupric silver technique to visualize neuropathology or animals were perfused with AltaBlue casting resin before high-resolution vascular imaging. The average volume, surface area, radius, branching and tortuosity of the vessels were evaluated across three regions of interest.

Results: In M2, average vessel volume (p < 0.01) and surface area (p < 0.05) were significantly larger at 1 day relative to 2 days, 7 days and sham. In S1BF and VPM, no significant differences in the average vessel volume or surface area at any of the post-injury time points were observed. No significant changes in average radius, branching or tortuosity were observed.

Conclusions: Preliminary findings suggest gross morphological changes within the vascular network likely represent an acute response to mechanical forces of injury, rather than delayed or chronic pathological processes.

Keywords:

• Neurovascular unit
• traumatic brain injury
• neuropathology
• vascular casting
• midline fluid percussion

Acknowledgements

The animals for this study were prepared at the University of Kentucky. The authors wish to thank Amanda Lisembee for the preparation of the animals and Dr. Pooja Talauliker for investigating the vascular casting techniques.

Declaration of interest

The authors report no conflicts of interest. Research reported in this manuscript was supported, in part, by National Institute of Neurological Disorders and Stroke of the National Institutes of Health under award number NIH R01 NS-065052, and Phoenix Children’s Hospital Mission Support Funds. RKR was supported by a Bisgrove Fellowship from Science Foundation Arizona. JLH was supported by the Bruce and Diane Halle Foundation.