Periostin aggravates the early phase of traumatic brain injury via the MAPK/ERK pathway

ABSTRACT

Objectives

Periostin is found associated with trauma severity and mortality following head injury. In this study, the role and mechanism of periostin in the traumatic brain injury were investigated.

Methods

Male Sprague-Dawley adult rats underwent sham or TBI modeling. Vehicle or recombinant periostin was administered intracerebroventricularly at 30 minutes post-TBI, and U0126, a specific MEK1/2 inhibitor, was administered intravenously at 30 minutes pre-TBI. Garcia neuroscore, limb function and brain water content assessments, as well as TUNEL and Western blotting assays were performed to evaluate the status of the above rats at 24 hours post-TBI. Finally, the motor test and Morris water maze test were performed to measure the effects of periostin and U0126 in the late phase of TBI.

Results

Periostin expression significantly increased 24 hours post-TBI. Treatment with R-periostin aggravated post-TBI neurobehavioral impairment, brain edema, induced apoptosis and raised the quantity of phospho-p38, phospho-JNK, phospho-ERK and MMP-9, and lowered the expression of ZO-1. However, U0126, a kind of inhibitor of MEK, lowered the quantities of phospho-ERK and MMP-9, raised the expression of ZO-1, and suppressed apoptosis. U0126 also ameliorated the neurobehavioral impairments and brain edema induced by R-periostin. Additionally, U0126 didn’t inhibit the expression of periostin in the early phase of TBI model. IU0126 was also able to ameliorate the pathological conditions in the late phase of TBI.

Discussion

Periostin could aggravate neurobehavioral impairments and brain edema following TBI, and was involved in the early phase of TBI via the MAPK/ERK pathway.

KEYWORDS:

• Traumatic brain injury (TBI)
• periostin
• ERK
• U0126

Disclosure statement

No potential conflict of interest was reported by the author(s).

Ethics approval and consent to participate

The study protocol conforms to the official recommendations of the National Institutes of Health guidelines and the Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine.

Additional information

Funding

This work was supported by the Natural Science Foundation of Zhejiang Province (Grant Number: LGD19H150002).