# Assessment of cerebrovascular alterations induced by inflammatory response and oxidative–nitrative stress after traumatic intracranial hypertension and a potential mitigation strategy

## TL;DR

This study explores how traumatic brain injury causes cerebrovascular changes and shows that a drug targeting inflammation can help reduce damage and improve blood flow recovery.

## Contribution

The study identifies a novel mitigation strategy using Infliximab to counteract cerebrovascular damage caused by traumatic intracranial hypertension.

## Key findings

- Traumatic intracranial hypertension activates the TNF-α/NF-κB/iNOS axis, leading to oxidative–nitrative stress and capillary injury.
- Infliximab treatment reduces inflammation and oxidative stress, improving microcirculation and venous blood flow recovery.
- Capillary wall cell injury and blood–brain barrier disruption persist after decompressive craniectomy without treatment.

## Abstract

The rapid perfusion of cerebral arteries leads to a significant increase in intracranial blood volume, exposing patients with traumatic brain injury to the risk of diffuse brain swelling or malignant brain herniation during decompressive craniectomy. The microcirculation and venous system are also involved in this process, but the precise mechanisms remain unclear. A physiological model of extremely high intracranial pressure was created in rats. This development triggered the TNF-α/NF-κB/iNOS axis in microglia, and released many inflammatory factors and reactive oxygen species/reactive nitrogen species, generating an excessive amount of peroxynitrite. Subsequently, the capillary wall cells especially pericytes exhibited severe degeneration and injury, the blood–brain barrier was disrupted, and a large number of blood cells were deposited within the microcirculation, resulting in a significant delay in the recovery of the microcirculation and venous blood flow compared to arterial flow, and this still persisted after decompressive craniectomy. Infliximab is a monoclonal antibody bound to TNF-α that effectively reduces the activity of TNF-α/NF-κB/iNOS axis. Treatment with Infliximab resulted in downregulation of inflammatory and oxidative–nitrative stress related factors, attenuation of capillary wall cells injury, and relative reduction of capillary hemostasis. These improved the delay in recovery of microcirculation and venous blood flow.