Acid Sphingomyelinase Inhibition Mitigates Histopathological and Behavioral Changes in a Murine Model of Traumatic Brain Injury.

Journal of Neurotrauma
Grace M NiziolekMichael D Goodman

Abstract

Traumatic brain injury (TBI) can lead to the development of chronic traumatic encephalopathy as a result of neuronal phosphorylated tau (p-tau) protein aggregation and neuroinflammation. Acid sphingomyelinase (Asm) may also contribute to post-TBI neurodegenerative disorders. We hypothesized that Asm inhibition would ameliorate p-tau aggregation, neuroinflammation, and behavioral changes after TBI in a murine model. TBI was generated using a weight-drop method. Asm inhibition in wild-type mice was achieved with a single injection of amitriptyline 1 h after TBI. Genetic Asm ablation was achieved using Asm-deficient mice (Asm-/-). Thirty days after TBI, mice underwent behavioral testing with the forced swim test for symptoms of depression or were euthanized for neurohistological analysis. Neuroinflammation was quantified using the microglial markers, ionized calcium-binding adaptor molecule 1 and transmembrane protein 119. Compared to sham mice, TBI mice demonstrated increased hippocampal p-tau. Mice that received amitriptyline after TBI demonstrated decreased p-tau compared to mice that received a saline control. Further, post-TBI Asm-/- mice demonstrated lower levels of p-tau compared to wild-type mice. Though a decrease in neur...Continue Reading

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Citations

Nov 3, 2020·The Journal of Surgical Research·Grace M NiziolekMichael D Goodman
Apr 3, 2021·Frontiers in Endocrinology·Jeffrey B TraversRavi P Sahu
May 4, 2021·The Journal of Trauma and Acute Care Surgery·Kathleen E SingerMichael D Goodman

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