Traumatic brain injury is the main cause of death and disability in the world. Bluntly injects brain trauma, usually caused by falls or traffic accidents, with more than 61,000 Americans dead each year. More than 80,000 will develop some long-term disabilities.

While most brain injuries occur immediately - called the main stage of injury, a destructive chemical process occurs minutes to days after the initial impact. Unlike the primary stage of injury, this secondary stage can be prevented by targeting molecules that drive the damage.

I am a materials science engineer and my colleagues and I are working to design treatments to neutralize the hazards of secondary traumatic brain injury and reduce neurodegeneration. We designed a new material that targets and neutralizes brain-destructive molecules in mice, improves their cognitive recovery and provides people with potential new treatments.

Biochemical consequences

The main stages of traumatic brain injury can severely damage and even damage the blood-brain barrier - protecting the brain by limiting the interfaces that can be accessed.

The disruption of this disorder can trigger the release of certain chemicals by damaged neurons or immune systems, resulting in a destructive biochemical process. When too much calcium ions are allowed to enter the neurons, activate fragmented DNA and enzymes that damage cells, resulting in death, a process called excitotoxicity occurs. Another process, neuroinflammation, is caused by activation called microglia, which can trigger inflammation in damaged areas of the brain.

These secondary processes also produce harmful molecules called reactive oxygen species. These molecules include free radicals that chemically modify and deform essential proteins in cells, making them useless. They can also break DNA strands, resulting in potentially disrupting genetic mutations.

If not examined by tissue, this harm from oxidative stress can have devastating consequences for long-term health and neurocognitive recovery. Researchers have linked biochemical changes and by-products that disrupt the molecular cascade to the development of long-term neurological diseases such as Alzheimer's, Parkinson's, and ALS.

However, compounds called antioxidants can target this oxidative stress and improve long-term neurocognitive recovery by interacting with reactive oxygen species in a way that can neutralize its destructive properties.

Find the ideal antioxidant

My team and I looked at whether an antioxidant called the thiol group could help treat traumatic brain injury.

A thiol group is a compound containing sulfur atoms bound to a hydrogen atom. The sulfur atom is much larger than the hydrogen atom, which means that the sulfur atom in the thiol has a strong tension on the lonely electrons of the hydrogen atom. This weakens the bond between hydrogen and its electrons, making it easy for hydrogen to abandon its electrons to other atoms.

As a result, thiols can easily interact with many different reactive oxygen species, including oxygen that damages DNA. We chose not only thiols for their antioxidant properties, but also their ability to bind and neutralize other brain-impaired molecules called lipid peroxidation products. When reactive oxygen species damage body fat, these neurotoxic compounds are formed as by-products.

To get these thiols into the body, we incorporate them into a material called polymers. These are long chains of organic molecules made from single units called monomers. To connect the monomers together, lonely electrons (or free radicals) use monomers to initiate bonds, triggering chain reactions. Think of this process, such as knocking down a series of dominoes: The push of your hand (in this case free radicals) hits the dominoes (single) and then knocks down the rest of the dominoes to form a line ( polymer).

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Since thiols can inhibit this polymerization process, we have to make a monomer made of so-called protective groups that can be chemically removed after polymerization to become our thiol. Since a common supplement found in pharmacies contains this protective thiol group, we use it to make monomers.

We then made chains of these monomers with a raft, a controlled process through which polymers can be designed to allow the body to pass through the urine. To this end, water-soluble co-mergers can be added to the chains, thereby allowing the polymer to dissolve in the blood.

Finally, we processed the polymer removal protection group, resulting in the thiol polymer prepared for further testing.

Testing on TBI

Next, we tested our thiol polymer neutralizing reactive oxygen species.

First, we used a technique called UV-visible spectrophotometry, which irradiates laser light into a cell sample containing our polymers and damaged brain molecules. If reactive oxygen species are present in the sample, light will absorb minimally. However, if our polymer neutralizes these compounds, the light will be absorbed in large quantities. Through these studies, we found that our thiol polymer neutralizes reactive oxygen species (such as hydrogen peroxide) up to 50%, while other neurotoxic molecules (such as acrolein) up to 100%, thus protecting neurons Be protected from damage.

We conducted additional tests by exposing the fluorescent protein to free radicals and found that proteins not treated with our thiol polymer were destroyed. The treated proteins continued to be fluorescent, indicating that our thiol polymer neutralizes free radicals and protects the protein.

Finally, we injected thiol polymer into mice with trauma. Brain scans show that our polymers are not only successfully concentrated in damaged areas of the brain, but also can immediately protect further damage. Our thiol polymers were able to reduce the reactive oxygen species in injured mice to only 3% of normal levels in uninjured mice. Untreated mice with cerebral trauma increased by 45% compared with uninjured mice.

Future work on thiol polymers

Our findings suggest that these thiol polymers may be potential treatments for secondary stages of brain injury. Further testing can help determine whether the material has the potential to reduce the risk of long-term disability.

We are currently developing a cheap process that combines thiols with tiny nanoparticles. This may help increase the amount of thiol in the material, while also improving its ability to circulate in the blood for longer protection.

Many other studies are needed in animals to confirm the effectiveness of our material in the treatment of traumatic brain injury. If our results continue to be positive, we aim to test the effectiveness of materials in people through clinical trials. We hope these treatments can improve long-term outcomes for victims of car accidents, falls and even sports-related brain crashes.