# Urapidil as a neuroprotective agent: targeting hypoxia, inflammation, and oxidative stress in traumatic brain injury

## TL;DR

This study shows that Urapidil reduces brain damage in a rat model of traumatic brain injury by targeting inflammation, oxidative stress, and cell death pathways.

## Contribution

The study demonstrates Urapidil's neuroprotective effects in TBI through modulation of key molecular pathways like HMGB1, BNIP3L, and HIF1α.

## Key findings

- Urapidil reduced histopathological damage and inflammatory markers in TBI rats.
- Urapidil lowered oxidative stress and apoptosis-related protein expressions in injured brains.
- Both Urapidil doses improved tissue integrity and antioxidant levels compared to the TBI group.

## Abstract

One of the important causes of morbidity and mortality in the world is traumatic brain injury (TBI), which is a process that triggers damaging mechanisms such as inflammation, oxidative stress, and apoptosis. The results of current pharmaceutical methods are not enough, and researches into new therapy modalities are needed. This study aimed to evaluate the neuroprotective effects of Urapidil (Ura), which is an alpha-1 adrenergic receptor antagonist with serotonergic activity, in a TBI model and investigating signaling pathways like high mobility group box 1 (HMGB1), BCL2-interacting protein 3-like (BNIP3L), and hypoxia-inducible factor-1 alpha (HIF1α).

Thirty-two rats were divided into four groups: control, TBI, TBI + Ura0.5 (0.5 mg/kg), TBI + Ura5 (5 mg/kg) groups. Tissue integrity and expressions of tumor necrosis factor-alpha (TNF-α), caspase-3 (Cas-3), tyrosine hydroxylase (TH), HIF1α, BNIP3L, and HMGB1 were assessed. Ura’s biochemical oxidative stress indicators were also assessed.

Ura treatment at both doses, significantly decreased histopathological findings, BNIP3L, HMGB1, and HIF1α expressions, TNF-α, Cas-3, TH immunexpressions, and TOS and OSI levels, and elevated TAS levels compared to TBI group. These results show that Ura regulates molecular pathways related to TBI, including neuroinflammation, mitochondrial dysfunction, and hypoxia.

Ura shows promising tissue-protective effects in TBI by targeting inflammation, oxidative stress, and apoptosis. This study provides a new perspective on the need for further development of Ura for therapeutic use.