# Mild TBI Changes Brain and Plasma Neurosteroid Levels in Mice

## TL;DR

This study shows that mild brain injury in mice leads to changes in brain and blood levels of specific neurosteroids, suggesting they could be used as biomarkers for diagnosis.

## Contribution

The study identifies ISODOC as a potential blood biomarker for mild traumatic brain injury in mice.

## Key findings

- Traumatized mice showed prolonged wake-up time and mild astrogliosis but no skull fractures or mortality.
- Isopregnanolone and ISODOC levels in the brain decreased significantly after mTBI.
- ISODOC levels in plasma also decreased significantly after mTBI.

## Abstract

Mild traumatic brain injury (mTBI) accounts for 80% of all TBI, may be associated with chronic impairments, and is difficult to diagnose due to a lack of objective markers. In this study, we investigated whether neurosteroids can serve as blood biomarkers for mTBI. Two cohorts of C57BL/6 mice were subjected to a model of mTBI combining impact with rotational acceleration or sham surgery. The first cohort underwent neurological testing for anxiety, balance, and locomotion before and after mTBI. For the second cohort, brains and plasma were collected 6 or 24 h after mTBI to measure steroid and neurosteroid levels by gas chromatography-tandem mass spectrometry. Traumatized mice exhibited significantly prolonged wake-up time from anesthesia, transiently increased beam-walk time, and mild astrogliosis compared with their control counterparts, but did not suffer from skull fractures, intracranial hemorrhage, or mortality. Isopregnanolone and 3β,5α-tetrahydrodeoxycorticosterone (ISODOC) were significantly decreased by more than 50% in brain parenchyma at 6 and 24 h after mTBI, while ISODOC was also significantly decreased in plasma (−75%). Therefore, ISODOC may be a candidate diagnostic biomarker for mTBI.