Gelatin Restores Blood-brain Barrier Function After Brain Injury

Researchers from Lund University in Sweden have established beneficial effects of gelatin following brain injury. Gelatin coatings have been used previously on neurological implants due to their inherent ability to reduce damaging immune responses and improve recovery, but the mechanisms underlying this have remained unknown.

The group found that gelatin aided recovery of the blood-brain barrier (BBB), defending the brain from potentially damaging foreign molecules and cells. The BBB refers to blood vessels which collectively separate blood circulation in the rest of the body from the sensitive central nervous system , of which the brain is a part.

For this research, brain injury was modelled in rats by surgically inserting a needle – with and without gelatin coating – into the brain, creating a stab wound.

Brain Infiltration Reduced By Gelatin

The strict regulation of brain entry allowed for the group to establish the integrity of the BBB, with measurements of infiltrating antibody immunoglobulin G (IgG) being increased in the absence of gelatin. Presence of antibodies in blood within the brain tissue induced an inflammatory and damaging immune response.

The increased inflammatory response when gelatin was not incorporated is supported by the discovery of an increased proportion of ED1 positive microglia. These microglia are damaging as a high proportion of ED1 protein indicates an overactive glial cell, which is associated with phagocytic and damaging behaviour.

This was in contrast with the proportionally increased level of lba1 positive microglia, which signifies an anti-inflammatory and therefore neuroprotective microglial properties

Gelatin Protein Interactions

An additional protective function of gelatin is as a substrate for matrix metalloproteinases (MMPs). These MMPs are upregulated following damage to brain and BBB, but tend to cause unintended damage to the surrounding environment (extracellular matrix) and key BBB cell proteins.

Degradation of extracellular matrix (ECM) and BBB proteins is protected by gelatin effectively quenching the negative effects of MMPs.

Future Applications

The beneficial effects of gelatin shown in this study may translate to improved surgical outcome. The injury which occurs during surgery is similar to the stab wounds inflicted in this animal model.

The authors suggest that the positive effects shown from gelatin coating on the BBB and microglial populations could be used in future for medical device implantation, and to reduce negative tissue reactions from transplantation.

The authors also suggest that further experiments with a chronic implant, instead of the acute stab wound model used, would allow for investigation of the beneficial response of chronic exposure.

Translational Applications

Results from this study also have an impact of other diseases. Blood-brain barrier dysfunction is a common occurrence following brain trauma and even during neurodegenerative diseases like Alzheimer’s disease and Parkinson’s disease.

The beneficial effects of gelatin on the BBB and the anti-inflammatory response from microglia may be of use in therapies for a range of diseases.

The research was supported by a Linnaeus grant from the Swedish Research Council, The Knut and Alice Wallenberg Foundation, and a grant from the Stiftelsen Sven-Olof Jansons livsverk.

Kumosa LS, Zetterberg V, Schouenborg J
Gelatin promotes rapid restoration of the blood brain barrier after acute brain injury
Acta Biomaterialia. Oct 14 2017. DOI: 10.1016/j.actbio.2017.10.020

Author: Geoffrey Potjewyd; Regenerative Medicine & Neuroscience PhD student at the University of Manchester. Image: MRC Toxicology Unit / Wellcome Images