Gelatin promotes rapid restoration of the blood brain barrier after acute brain injury

Abstract

The neural interfaces field holds great promise to enable elucidation of neural information processing and to develop new implantable devices for stimulation based therapy. Currently, this field is struggling to find solutions for reducing tissue reactions to implanted micro and nanotechnology. Prior studies have recently shown that gelatin coatings lower activation of digestive microglia and mitigate the ubiquitous loss of neurons adjacent to implanted probes, both of which impede implant function. The underlying mechanisms remain to be elucidated, however. Our findings demonstrate for the first time that gelatin has a significant effect on the BBB by promoting rapid restoration of integrity after injury. Moreover, gelatin alters microglia phenotypes and modulates gelatinase activity for up to 2weeks favoring anti-inflammation and restoration of the tissue. Given the key importance of the BBB for normal brain functions, we believe our findings have substantial significance and will be highly interesting to researchers in the biomaterial field.

Local delivery of minocycline-loaded PLGA nanoparticles from gelatin-coated neural implants attenuates acute brain tissue responses in mice

“…Using non-crosslinked gelatin as the load-carrying coating material, has previously been shown to preserve the integrity of the neural implant without compromising its function [5]. In the present study, no traces of gelatin were seen in the surrounding tissue at either timepoints which is consistent with known rapid dissolution at body temperature and subsequent enzymatic breakdown into amino acids by upregulation of gelatinases (MMP-2 and MMP-9) in rodent brain [6]. The voids in the brain tissue remaining after explanting the implants were of the same dimensions as the implanted needles, which also suggest that the tissue contract tightly around the implant after the gelatin is dissolved.…”

“…We have previously reported that gelatin can be used as a coating-material to provide structural support during implantation of ultrathin flexible electrodes in the brain [5,33] and that gelatin itself can significantly reduce microglia activation but not the astrocytic response [4,6]. Here we developed a novel method for local delivery of nanoparticles from gelatin coatings allowing the amount of drug to be kept several orders of magnitude lower as compared to systemic administration.…”

“…However, it was only when combining ultra-flexible mechanical properties with a gelatin embedding that the ubiquitous loss of nearby neurons was, for the first time, abolished [4]. Moreover, we recently found that gelatin coating promotes healing of the blood-brain barrier [6]. Nevertheless, glial cell responses remain to some extent in the immediate vicinity of the electrodes.…”

Silver nanoparticle-induced expression of proteins related to oxidative stress and neurodegeneration in an in vitro human blood-brain barrier model

“…Since astrocytes play a major role in the functioning of the BBB, we were interested in studying the astrocyte proteome after exposure to AgNPs for different time periods (Kumosa, Zetterberg, and Schouenborg 2018;Banks, Kovac, and Morofuji 2018;Moura, Almeida, and Sarmento 2017). It has been reported that astrocytes have a prominent function in metal metabolism in the brain (Dringen et al 2007).…”

Regenerative Medicine Therapies for Targeting Neuroinflammation After Stroke

“…Isolation of single ECM components for hydrogels enables the determination of the positive or negative effects of different biopolymers on brain tissue, with some native ECM biopolymers inducing an anti-inflammatory response on their own; Hyaluronic acid (HA) hydrogels in particular have been used frequently in stroke studies ( 43 , 115 , 122 – 126 ), owing to their anti-inflammatory effects through CAPs binding to CD44, which inhibits inflammation ( 127 ) as well as leukocyte rolling and extravasation through the BBB to the brain parenchyma ( 128 ). Similarly, gelatin has been shown to exhibit native anti-inflammatory effects in the brain following injury through repairing the BBB, reducing circulatory molecules and cells from entering the brain parenchyma and shifting the microglial response from neurotoxic to a neuroreparative phenotype ( 129 ).…”