“It should be done as early as possible, before the injury has occurred, or as soon as there is any suspicion that the child could suffer a brain injury. Immediately after birth in cases of infection in the child, and before birth if the mother is carrying something that could be passed on to the fetus,” says Amin Mottahedin, a doctoral student at the Institute of Neuroscience and Physiology.
Brain injury in newborns is the most common cause of neurological problems such as cerebral palsy (CP). In Sweden, two out of every one thousand infants are diagnosed with this form of disrupted muscle control. It occurs more commonly in premature births but also occurs after full-term pregnancies.
Common causes of brain injury include lack of oxygen (hypoxia), low blood flow (ischemia) to the brain, and a combination of these. Another risk factor is infections in the infant or mother around the time of birth, and it is precisely how infections increase the risk that is the main issue in Amin Mottahedin’s doctoral thesis.
Activated immunity in the brain
Studies of newborn mice showed that brain injury after induced hypoxia and ischemia was exacerbated when the animal’s immune system was first activated. This occurred through two toll-like receptors (TLR), which are found on the surface of various cells and detect infections. TLR3 primarily reacts to viruses, while TLR2 reacts to a particular group of bacteria.
Activating these particular receptors was also shown to increase brain injury, like that an infant can suffer, in both nerve cells and nerve fibres in mice. Viral and bacterial infections make the brain more sensitive to a lack of oxygen and poor blood supply.
Continued studies also provided answers to how the increased sensitivity arises. When TLR3 was activated, the brain responded with severe inflammation, which via cellular changes led to the brain’s own immune cells becoming more reactive. Activation of TLR2 was followed by an invasion of white blood cells to the brain coupled with a poorer supply of energy.
An injury that can be stopped
However, it was demonstrated that the effects could be dampened with N-acetylcysteine. In experiments with rats, the flow of white blood cells could also be blocked through targeted treatment against what proved to be their passage into the brain, the organ known as the choroid plexus.
According to Amin Mottahedin, there is still a lot of research left to do in relation to the choroid plexus before the results can make an impact in healthcare. However, he believes things will progress more quickly when it comes to treating expectant mothers and newborns with the drug NAC, orally or intravenously, to prevent brain injury.
“We modelled viral infections and bacterial infections and have seen that both – in combination with lack of oxygen and poor blood supply to the brain – can exacerbate a brain injury. We may prevent this by stopping the communication between the infection and the inflammation in the brain using a proven drug, which previous studies have shown to be harmless,” says Amin Mottahedin.
GUPEA: Developing brain and systemic inflammation: a "Toll-like" link with consequences