• KSBNS 2024


Original Article

Exp Neurobiol 2022; 31(2): 105-115

Published online April 30, 2022

© The Korean Society for Brain and Neural Sciences

Time Course of Remote Neuropathology Following Diffuse Traumatic Brain Injury in the Male Rat

Katherine R. Giordano1,2,3†, L. Matthew Law1,2,3†, Jordan Henderson1,2, Rachel K. Rowe4 and Jonathan Lifshitz1,2,3*

1BARROW Neurological Institute at Phoenix Children’s Hospital, Phoenix, AZ 85013, 2Department of Child Health, University of Arizona College of Medicine – Phoenix, Phoenix, AZ 85004, 3Phoenix Veterans Affairs Health Care System, Phoenix, AZ 85012, 4Department of Integrative Physiology, University of Colorado, Boulder, CO 80309, USA

Correspondence to: *To whom correspondence should be addressed.
TEL: 1-602-827-2346
These authors contributed equally to this article.

Received: December 15, 2021; Revised: December 15, 2021; Accepted: April 12, 2022

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Traumatic brain injury (TBI) can affect different regions throughout the brain. Regions near the site of impact are the most vulnerable to injury. However, damage to distal regions occurs. We investigated progressive neuropathology in the dorsal hippocampus (near the impact) and cerebellum (distal to the impact) after diffuse TBI. Adult male rats were subjected to midline fluid percussion injury or sham injury. Brain tissue was stained by the amino cupric silver stain. Neuropathology was quantified in sub-regions of the dorsal hippocampus at 1, 7, and 28 days post-injury (DPI) and coronal cerebellar sections at 1, 2, and 7 DPI. The highest observed neuropathology in the dentate gyrus occurred at 7 DPI which attenuated by 28 DPI, whereas the highest observed neuropathology was at 1 DPI in the CA3 region. There was no significant neuropathology in the CA1 region at any time point. Neuropathology was increased at 7 DPI in the cerebellum compared to shams and stripes of pathology were observed in the molecular layer perpendicular to the cerebellar cortical surface. Together these data show that diffuse TBI can result in neuropathology across the brain. By describing the time course of pathology in response to TBI, it is possible to build the temporal profile of disease progression.

Graphical Abstract

Keywords: Traumatic brain injury, Neuropathology, Diffuse axonal injury, Silver stain, Hippocampus, Cerebellum