Original Article
A self-assembly peptide nanofibrous scaffold reduces inflammatory response and promotes functional recovery in a mouse model of intracerebral hemorrhage

https://doi.org/10.1016/j.nano.2015.12.387Get rights and content

Abstract

Self-assembly peptide nanofibrous scaffold (SAPNS), such as RADA16-I, has been shown to reduce acute brain injury and enhance functional recovery in rat intracerebral hemorrhage (ICH) models. The acidic property of RADA16-I, however, limits its application in patients. In the present study, by using a modified neutral SAPNS (the RADA16mix) in collagenase IV induced ICH mice, we detected there were less microglial and apoptotic cells in mice injected with RADA16mix, meanwhile, more cells survived in this group. In addition, behavioral tests indicated that mice treated with RADA16mix showed better functional recovery than RADA16-I. Local delivery of RADA16mix reduces acute brain injury by lowering the number of apoptotic cells, decreasing glial reaction, reducing inflammatory response and, therefore promotes functional recovery. Moreover, new nerve fibers have grown into this new SAPNS, which indicates RADA16mix is able to serve as a bridge for nerve fibers to grow through.

From the Clinical Editor

Acute brain injury, such as intracerebral hemorrhage is a serious problem. In this work, self-assembly peptide nanofibrous scaffold (SAPNS) were tested in a rat model to aid functional recovery. Several items have been considered, such as histology, brain water content, hematoma volume, cell death and survival, inflammatory response, and nerve fiber growth. The positive data generated should pave the way towards better treatment options.

Graphical abstract

Intracranial injection of collagenase IV caused acute brain injury. In order to access whether local delivery of this new synthetic neutral self-assembly peptide nanofibrous scaffold called RADA16mix could lessen such kind of injury or not, several items has been estimated as follows: histology, brain water content, hematoma volume, cell death and survival, inflammatory response, nerve fiber growth and functional recovery.

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Section snippets

Methods

All surgical procedures done in mice were approved by Laboratory Animal Ethics Committee at Jinan University. Adult C57BL/6 mice (purchased from Guangdong Medical Laboratory Animal Center), 2-3 months old and weighting 22-28 g, were used in this study. All surgery was performed under 2.5% avertin anesthesia, and all efforts were made to minimize the suffering and number of animals used. Animals were kept on a 12/12 light/dark cycle with ad libitum access to food and water. The animal holding

Histology

Nissl staining was to show the overall morphology of the injured brain in the acute phase of ICH. Collagenase IV injection induced intracerebral hematoma, which caused a considerable loss of neurons (Figure 2, A). However, the injection of SAPNS filled the void and the boundary between the material and host fits quite tightly (Figure 2, B and C).

Hematoma

The amount of hematoma three days after ICH was 68.65 ± 9.239 μg/mL in RADA16mix group, 45.74 ± 4.531 μg/mL in RADA16-I group and 75.56 ± 8.343 μg/mL in saline

Discussion

Recently, several attempts have been made to exploit new biologically compatible scaffolds for drug sustained-release and tissue regeneration.16, 17, 18, 19 There were several types of collagen-based scaffold together with their derivatives showed great promise in tissue engineering.20, 21, 22, 23 Self-assembly is a commonly used method to produce nanofibers, it is the spontaneous organization of molecules and components into structures without intervention.24 Molecular self-assembly is

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    There was no prior or upcoming presentation of abstracts at meetings regarding the research.

    Conflict of interest: There was no conflict of interest.

    This work was supported by National Basic Research Program of China (973 Program, 2014CB542205), Hong Kong Health and Medical Research Fund (02132826), foundation for Distinguished Young Talents in Higher Education of Guangdong (Yq2013023) and the Leading Talents of Guangdong Province (87014002).

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