Lansoprazole Improves Long-Term Neurological Function via Alleviating Intestinal Injury in a Mouse Model of Intracerebral Hemorrhage

Summary

A collagenase-induced mouse model of intracerebral hemorrhage (ICH) was treated with lansoprazole. Lansoprazole not only alleviated ICH-caused intestinal injury and reduced levels of lipopolysaccharide (LPS) and IL-1β, but it also inhibited brain inflammation. Lansoprazole enhanced learning and memory (long-term neurological function) of ICH mice.

Abstract

Intracerebral hemorrhage (ICH) can compromise the gastrointestinal tract and trigger intestinal injury, contributing to poor clinical outcomes. This study investigated the effects of lansoprazole on intestinal injury and neurological function in mice with ICH. Mice were stereotactically injected with collagenase to establish an ICH model. Neurological function, brain water content, blood-brain barrier permeability, intestinal injury, and intestinal permeability were evaluated. Levels of LPS and IL-1β in the blood and brain were also assayed. Lansoprazole treatment was associated with alleviated intestinal injury, reduced levels of LPS and IL-1β in blood and brain, decreased brain water content, and inhibited brain inflammation in ICH mice. While lansoprazole administration did not lead to improved performance in the Garcia, forelimb placing, and rotarod tests (short-term neurological function), it significantly enhanced learning and memory (long-term neurological function). These findings indicated that lansoprazole treatment was associated with improved long-term neurological outcomes and reduced intestinal injury in ICH mice.

Introduction

Hemorrhagic stroke has high rates of mortality and disability. Recently, the prevalence of stroke in China has increased, making it the leading cause of death¹. Although less common, intracerebral hemorrhage (ICH) is markedly more lethal than ischemic stroke. Studies report a 40% mortality rate within 1 month of ICH; furthermore, approximately 75% of survivors are unable to live independently 1 year later².

The brain communicates with the gastrointestinal tract through several pathways, including the vagus nerve, enteric nervous system, and gut microbial metabolism. The brain-gut axis is a wel....

Protocol

The experiments were performed according to the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health (NIH Publication No. 8023, revised 1978). The protocol was approved by the Ethics Committee of Yantai University (Approval No. YTDX20240526). Hazardous materials were disposed of according to institutional chemical waste protocols. Figure 1 illustrates a schematic diagram of the experimental design. The reagents and the equipment used are listed in the Table of Materials.

1. Animal details

Male CD-1 mice weighing 22-25 g were housed in a....

Results

Effects of lansoprazole on short-term neurological function in ICH mice

Compared with the sham group, mice in the ICH group showed significantly lower scores in the Garcia test (p < 0.01). However, mice in the lansoprazole group did not show improved Garcia scores compared with the ICH group (p > 0.05) (Figure 2A). Similarly, the percentage of left forelimb.......

Discussion

Intestinal injury is a common complication in patients with ICH. ICH-induced intestinal damage can lead to malnutrition, prolonged hospitalization, poor outcomes, and even mortality¹⁷. Using an ICH animal model, this study demonstrated for the first time that lansoprazole attenuates intestinal injury in ICH mice. Although lansoprazole did not show beneficial effects on short-term neurological function, it significantly improved long-term neurological outcomes.

Stroke, w.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
BCA kit	Beyotime Biotechnology	P0009
Collagenase	Sigma-Aldrich	128M4107v
Evans blue dye	Sigma-Aldrich	MKCG7507
FITC-dextran	Sigma-Aldrich	46944
GraphPad Prism 7.0	GraphPad statistical Software, Boston, MA, USA, www.graphpad.com	Prism 7.0
Lansoprazole	Shandong Yuxin pharmaceutical Co., Ltd.	524093053
LPS ELISA kit	Cusabio biotech Co., Ltd.	M25036407
Mice	Jinan Pengyue Experimental Animal Breeding Co., Ltd.	SCXK20220006
Microinfusion pump	World Precision Instruments	Micro 3
Microsyringe	Hamilton Company	SYR 10 μL
Olympus microscope	Olympus Co., Ltd.	IX-70
Rotarod	Panlab Co., Ltd.	LE8205
Stereotaxic frame	Kopf Instruments	Model 902-A
TNF-α ELISA kit	Beyotime Biotechnology	PI301
Transmission electron microscope	JEOL Ltd.	JEM-100SX
Video Tracking Software	Panlab Co., Ltd.	Smart 3.0