# Traumatic Brain Injury Induces Senescence in Brain Microvasculature

## TL;DR

Traumatic brain injury causes different types of brain cells to enter a state of permanent cell cycle arrest, with effects varying by cell type and injury severity.

## Contribution

This study reveals cell-type-specific patterns of senescence in the neurovascular unit following traumatic brain injury in a rat model.

## Key findings

- Astrocyte senescence increased acutely after severe TBI in the neocortex.
- Endothelial cell senescence was significantly elevated four weeks after severe TBI.
- Microglial senescence was observed in both mild and severe TBI samples in the neocortex.

## Abstract

Background: Traumatic brain injury (TBI) frequently leads to long-term neurological deficits. Recent research also implicates cellular senescence—a state of permanent cell cycle arrest driven by DNA damage—as a key contributor to neuroinflammation and cognitive decline. This study investigates the cell-type specificity of senescence within glial and vascular cells of the neurovascular unit (NVU) following experimental TBI in a rat model. Methods: Rats underwent various TBI scenarios, including single severe TBI (sTBI), single mild TBI (mTBI), repetitive mild TBI (rmTBI) and repetitive sham-operated control (rSham). Twenty-four hours or four weeks later, brains were harvested and brain sections were co-stained for γH2AX and cell type-specific markers. Immunofluorescence microscopy was used to comprehensively assess senescence in both glial and vascular cells of the NVU, specifically astrocytes, microglia, endothelial cells, and pericytes. Results: We observed acute increased astrocyte senescence in sTBI samples and microglial senescence in mTBI and sTBI samples in the neocortex, while endothelial cell senescence was significantly elevated in the neocortex of the sTBI group after four weeks. Pericytes did not exhibit significant signs of senescence at either time point. Conclusion: These findings demonstrate differential γH2AX labelling of NVU components following TBI, suggesting that vulnerability to TBI-induced senescence can be specific both to the cell type and the time after the injury. This has implications on therapies targeting senescent cells for mitigating the long-term consequences of TBI.