# The Dynamics of Neuroinflammation in Traumatic Brain Injury: Molecular Markers Useful for Establishing the Post-Traumatic Interval in Forensic Practice

## TL;DR

This paper reviews molecular markers of neuroinflammation after traumatic brain injury to help estimate the time since injury in forensic cases.

## Contribution

The paper identifies a range of molecular markers with specific time windows for detection, offering a multiparametric approach for forensic time-of-injury estimation.

## Key findings

- Microglial activation markers like allograft inflammatory factor 1 appear within 10 minutes to 2 hours after injury.
- Cytokine fluctuations and leukocyte infiltration patterns provide time-specific indicators for injury timing.
- A multiparametric approach combining multiple markers is suggested to improve accuracy in forensic assessments.

## Abstract

In forensic pathology, accurately estimating the time since injury is essential. Current histological and imaging approaches commonly miss subtle temporal changes, especially in deaths occurring within hours of injury. This review discusses the timing of neuroinflammation after traumatic brain injury and emphasizes possible markers for estimating the time of injury in forensic cases. Promising markers include microglial activation (allograft inflammatory factor 1 and transmembrane protein 119, detectable within 10 min to 2 h), β-amyloid precursor protein accumulation (20–35 min), high-mobility group box 1 translocation (2–6 h), cytokine fluctuations (IL-1β and TNF-α peak between 4 and 24 h, IL-6 shows delayed, extended elevation), sequential leukocyte infiltration (neutrophils from 2 to 48 h, lymphocytes after 3–5 days), blood–brain barrier breakdown markers such as fibrinogen and IgG leakage, loss of tight junction proteins (2–3 h), matrix metalloproteinase-9 activity (peaking at 24–48 h), and reactive astrocytosis with increased glial fibrillary acidic protein levels (from 12 to 24 h onward). The association between injury severity and inflammation is influenced by factors such as age, genetics (e.g., APOE ε4), coexisting conditions, and preexisting inflammation, which reduce the reliability of individual markers. A multiparametric approach may offer the best prospects to improve the accuracy of post-traumatic and post-mortem interval assessment in medicolegal cases.