Tuesday, October 22, 2019

Immune cells rewire, repair brain while we sleep

Researchers have found that immune cells called microglia, which play an important role in reorganising the connections between nerve cells, fighting infections, and repairing damage, are also primarily active while we sleep.

Microglia serve as the brain’s first responders, patrolling the brain and spinal cord and springing into action to stamp out infections or gobble up debris from dead cell tissue.

“This research shows that the signals in our brain that modulate the sleep and awake state also act as a switch that turns the immune system off and on,” said study lead author Ania Majewska, Professor at University of Rochester in the US.

In previous studies, Majewska’s lab has shown how microglia interact with synapses, the juncture where the axons of one neuron connects and communicates with its neighbours.

The microglia help maintain the health and function of the synapses and prune connections between nerve cells when they are no longer necessary for brain function.

For the findings, researchers conducted the study on mice.

The current study points to the role of norepinephrine, a neurotransmitter that signals arousal and stress in the central nervous system.

This chemical is present in low levels in the brain while we sleep, but when production ramps up it arouses our nerve cells, causing us to wake up and become alert.

The study showed that norepinephrine also acts on a specific receptor, the beta2 adrenergic receptor, which is expressed at high levels in microglia.

When this chemical is present in the brain, the microglia slip into a sort of hibernation.

The study, which employed an advanced imaging technology that allows researchers to observe activity in the living brain, showed that when mice were exposed to high levels of norepinephrine, the microglia became inactive and were unable to respond to local injuries and pulled back from their role in rewiring brain networks.

“This work suggests that the enhanced remodeling of neural circuits and repair of lesions during sleep may be mediated in part by the ability of microglia to dynamically interact with the brain,” said the study's first author.

“Altogether, this research also shows that microglia are exquisitely sensitive to signals that modulate brain function and that microglial dynamics and functions are modulated by the behavioural state of the animal,” the first author said.

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Sunday, January 07, 2018

Advanced MRI detect placental perfusion abnormalities in pregnancies complicated by fetal CHD


In pregnancies complicated by fetal congenital heart disease (CHD), global placental perfusion was significantly decreased and regional variation of placental perfusion significantly increased as pregnancies progressed, findings that point to non-invasive imaging providing an early warning of placental dysfunction. A Children’s National Health System research team is thought to be the first to report non-invasive, whole placenta perfusion imaging in utero in a study.
 
According to the researchers, congenital heart defects are the most common type of birth defect, affecting 8 in 1,000 newborns. Early in pregnancy, the fetal heart follows a parallel developmental course as the placenta, which supplies the growing fetus with oxygen and nutrients while ferrying out waste products. The study authors write that placental arteries are dynamic during pregnancy, remodeling themselves to accommodate increased blood flow as fetuses undergo explosive growth spurts in later stages of pregnancy. If this crucial remodeling does not occur, the placenta may not supply sufficient oxygen and nutrients to the fetus, leading to fetal growth restriction or preeclampsia.

The research team, enrolled 48 pregnant women who underwent at least one fetal magnetic resonance imaging (MRI) session during their second or third trimester of pregnancy. Thirty-one of the women were healthy volunteers whose mean gestational age was 30 weeks (range: 21 to 39 gestational weeks). Seventeen women were pregnant with fetuses diagnosed with CHD whose mean gestational age was 32 weeks (range: 22 to 38 gestational weeks).

The researchers used velocity-selective arterial spin labeling (VSASL), a powerful MRI technique that directly measures the rate of delivery of arterial blood to organs like the brain. ASL tracks water molecules within the blood as blood flows through arteries, eliminating the need to use a contrast agent. The team was able to distinguish the placenta perfusion contributions by the fetus and the mother.

“In pregnancies complicated by fetal CHD, global placental perfusion significantly decreased and regional variation of placental perfusion significantly increased with advancing gestational age,” says  the study’s lead author.

“Just like the human brain, heart and kidneys—organs that can commandeer heightened blood flow when needed—the placenta may employ an auto-regulatory mechanism to optimize perfusion,” adds  the study’s senior author. “The early increased global placental profusion in pregnancies complicated by CHD may represent an attempt to correct for insufficient fetal blood flow.”

The research team writes that the findings demonstrate that placental dysfunction due to CHD can be apparent as early as the second trimester of pregnancy using this imaging technology.

“The predictive value of VSASL imaging, which we continue to study, holds the promise of detecting dysfunction before placental abnormalities become irreversible,” the author says. 

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