Explosive-driven double-blast exposure: molecular, histopathological, and behavioral consequences

Abstract

Traumatic brain injury generated by blast may induce long-term neurological and psychiatric sequelae. We aimed to identify molecular, histopathological, and behavioral changes in rats 2 weeks after explosive-driven double-blast exposure. Rats received two 30-psi (~ 207-kPa) blasts 24 h apart or were handled identically without blast. All rats were behaviorally assessed over 2 weeks. At Day 15, rats were euthanized, and brains removed. Brains were dissected into frontal cortex, hippocampus, cerebellum, and brainstem. Western blotting was performed to measure levels of total-Tau, phosphorylated-Tau (pTau), amyloid precursor protein (APP), GFAP, Iba1, αII-spectrin, and spectrin breakdown products (SBDP). Kinases and phosphatases, correlated with tau phosphorylation were also measured. Immunohistochemistry for pTau, APP, GFAP, and Iba1 was performed. pTau protein level was greater in the hippocampus, cerebellum, and brainstem and APP protein level was greater in cerebellum of blast vs control rats (p < 0.05). GFAP, Iba1, αII-spectrin, and SBDP remained unchanged. No immunohistochemical or neurobehavioral changes were observed. The dissociation between increased pTau and APP in different regions in the absence of neurobehavioral changes 2 weeks after double blast exposure is a relevant finding, consistent with human data showing that battlefield blasts might be associated with molecular changes before signs of neurological and psychiatric disorders manifest.

Document Details

Document Type
Pub Defense Publication
Publication Date
Oct 15, 2020
Source ID
10.1038/s41598-020-74296-2

Entities

People

  • Daniel P. Perl
  • Diego Iacono
  • Erin K. Murphy
  • Fabio Leonessa
  • Hongna Pan
  • Jamie B. Grimes
  • Sorana Raiciulescu
  • Steven Parks

Organizations

  • United States Department of Defense

Tags

Fields of Study

  • Biology

Readers

  • Neurotrauma and Rehabilitation Medicine.
  • Toxicology/Environmental Toxicology
  • Traumatic Brain Injury (TBI) and Cognitive Aging in the Guam and Border Populations Affected by Alzheimer's Disease and Tau-Associated Dementias.