A powerful blow can cause significant physical damage to an individual’s skull and brain tissue; however, the trauma does not stop there. The impact initiates chemical reactions that damages neurons and their networks. It was this secondary effect of TBI, which can cause long-term cognitive, psychological and motor systems damage, that piqued the interest of a team of biomedical engineers at the New Jersey Institute of Technology (NJ, USA).
In a study published in the journal ACS Biomaterials Science & Engineering, the team developed a hydrogel therapy engineered to protect neurons whilst promoting their regeneration following injury and tested the efficacy of the treatment in rats.
“ Nerve cells respond to trauma by producing excessive amounts of glutamate, a neurotransmitter that under normal conditions facilitates learning and memory, but at toxic levels overexcites cells, causing them to break down. TBI can also result in the activation and recruitment of immune cells, which cause inflammation that can lead to short- and long-term neural deficits by damaging the structure around cells and creating a chronic inflammatory environment,” explained lead author, Biplab Sarkar (New Jersey of Institute of Technology).
The team’s treatment consisted of lab-created ependymin – a peptide known to protect neurons after injury – that was delivered in a hydrogel. After injection, the peptides reassemble at the site of injury and act as scaffolding to support the structure of cells.
The findings from the study demonstrated that rats injected with the hydrogel retained twice the number of functioning neurons at the site of injury compared with the control group. Further, they also formed new blood cells in the same region.
The idea is to intervene at the right time and place to minimize or reverse damage. We do this by generating new blood vessels in the area to restore oxygen exchange – which is reduced in patients with a TBI – and by creating an environment in which neurons that have been damaged in the injury are supported and can thrive,” commented Director of the New Jersey Institute of Technology, Vivek Kumar. “While the exact mechanism of action for these materials is currently under study, their efficacy is becoming apparent. Our results need to be expanded, however, into a better understanding of these mechanisms at the cellular level, as well as their long-term efficacy and the resulting behavioral improvements.”
The team stated that developing therapy to stimulate the regrowth of blood vessels and tissue after injury was a challenge as brain cells do not regenerate as well as other tissues such as bone. Furthermore, the protective mechanism of the blood–brain barrier makes delivery of medication difficult.
Their developed materials possess mechanical properties similar to brain tissue – which improves biocompatibility – and promote rapid penetration of a stems cell that act as precursors for regeneration.
Conventional biomaterials used in tissue regeneration suffer from a variety of problems with delivery, retention and biocompatibility, which can lead to rejection by the host,” Kumar commented. “We’re trying to address these issues with a technology designed to be universal in its application, delivering materials that persist in the tissue and promote their biologic effects for long periods of time.”
Previously, it has been demonstrated that TBI-related chemical effects, which disrupt vasculature in the blood–brain barrier and promote chronic inflammation, lead to symptoms such as post-traumatic stress disorder and anxiety. Therefore, the research team’s current work provides insight into a potential neuroprotective and neurogenerative therapy option.
Further research will attempt to analyze other mediators of inflammation and blood flow in the brain.
Sources: Sarkar B, Siddiqui Z, Nguyen PK et al. Membrane-disrupting nanofibrous peptide hydrogels. ACS Biomater. Sci. Eng. 5(9), 4657–4670 (2019); https://news.njit.edu/dealing-therapeutic-counterblow-traumatic-brain-injury