The crucial cortex

Lance Millar_Developmental Anatomy_14Oct2017.jpg-large

University of Oxford PhD student Lance Millar recently ran one of our Brain Spotlight events as part of the Brain Diaries exhibition programme. Here, Lance explains his research into neurodevelopmental disorders and possible treatments.

The brain has always been a fascinating organ for me. It is the site of our intelligence, our problem-solving and social skills, and it allows us to connect our senses to the world around us.

The large, folded outer part of the human brain is called the cortex, and is responsible for decision-making, language, face recognition, and a lot of the other things that I like to think are what make us human. The word cortex comes from the Greek for husk or outer shell, which underestimates the importance of what the cortex does.

Humans can survive with damage to the cortex, but depending on the part of the cortex that is damaged, a range of disabilities can result. People who have had a stroke can lose part of their cortex, leading to limb paralysis, loss of speech, or loss of memory, depending on the site of the damage.

B0009564 Human brain, coronal section, LM

Cerebral cortex – Professor Michael R Peres – Wellcome Images

Some people are also born with a developmental problem in the cortex, and are said to have a neurodevelopmental disorder. Such conditions are thought to include autism, schizophrenia, ADHD, and even dyslexia – all fairly common conditions. The damage to the cortex is subtle and complex in these conditions, and scientists are still working out exactly what happens to the brain during its prenatal development.

I am studying one particular neurodevelopmental disorder caused by lack of oxygen at birth. It is known to medical specialists as neonatal hypoxia ischaemia. The image on the right shows a cross-section MRI scan of a normal newborn human brain, alongside some babies who have been damaged by oxygen deprivation. You can see that the brains are smaller, the cortex is less folded and it takes up less space inside the skull.

Woodward

MRI scans of normal newborn brains alongside those of babies who have been damaged by oxygen deprivation. Image: Woodward et al., New England Journal of Medicine, 2006

Scientists still don’t know how to protect the newborn brain from these injuries. Some are caused by inflammation which is a normal response to illness, but can wreak havoc in the confined space of the skull. Some is caused by the presence of free radicals, which are thought to contribute to ageing and organ failure, as the newborn brain doesn’t have many antioxidants to fight these chemicals. It’s also possible that the electrical signals that neurons within the brain send to each other contribute to the damage when there isn’t enough oxygen to feed them.

So what can we do to treat oxygen deprivation at birth? One breakthrough treatment currently available is known known as hypothermia. In this technique, the baby is cooled to 33℃ which slows down the brain-damaging chemical reactions which in turn protects the brain. This is currently the only treatment available, but I am involved in the study of possible alternatives.

We don’t want to introduce any drugs to the baby’s system as they might be harmful to normal development. So scientists are currently working on treatments which help the baby’s natural body proteins to protect the brain. I do this by looking at neurons under the microscope, and identifying proteins expressed by these neurons using fluorescent probes known as antibodies.

Neurons under the microscope

An example of neurons under the microscope. Image: Lancelot Millar

These neurons are expressing neuroserpin, a natural brain protein which decreases inflammation and cell death. I’m looking at exactly where neuroserpin is expressed in the brain, how it can be upregulated in response to oxygen deprivation, and how its chemical reactions could be used to protect the brain.

Another way to help people with neurodevelopmental disorders is to better understand how the cortex connects to other parts of the brain and how it can carry out complicated decisions. There is still so much to understand about the complexity of the human brain, and what seems like fundamental research could generate the springboard for new ideas for neurodevelopmental disorder treatments.

To explore the structure of the human brain and compare it to that of other animals see the Brain Diaries Brain Explorer below.

 

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