Neuroinflammation · Lobeworks/17

Neuroinflammation is the inflammatory response inside the brain and spinal cord, carried out by microglia and astrocytes and by signalling proteins (cytokines) arriving from the body, which defends the tissue after infection or injury and, when it lasts, changes how neurons work.

Neuroinflammation. Neuroinflammation is the inflammatory response inside the brain and spinal cord, carried out by microglia and astrocytes and by signalling proteins (cytokines) arriving from the body, which defends the tissue after infection or injury and, when it lasts, changes how neurons work.

The brain is shielded by the blood-brain barrier but not cut off. Inflammation in the body reaches it through the vagus nerve, through spots where the barrier is thin and through the barrier's own cells, and the brain answers with cytokines of its own, mainly IL-1β, IL-6 and TNF-α. The result in the first days of an infection is sickness behaviour: fatigue, loss of appetite, withdrawal, poor sleep and low mood, a program that saves energy for the fight. A response meant for days becomes a problem when the signal does not switch off.

The inflammation hypothesis of depression rests on that overlap with sickness behaviour. On average people with depression have higher IL-6 and C-reactive protein in their blood, and treating other diseases with the cytokine interferon-alpha brings on depressive symptoms in part of the patients; the blood differences are small, overlap widely with healthy people and shrink once body weight is taken into account, so inflammation is a route in a subset, not the cause of depression.

The maternal immune activation line links it to autism research. Infection during pregnancy raises the risk of neurodevelopmental conditions in large registries, and in mice a viral mimic (poly I:C) given to the pregnant mother produces offspring with altered behaviour, through cytokines such as IL-6; how this applies to people is unsettled.

Inflammatory signals raise neuronal excitability, one reason infections and fevers lower the threshold for seizures and why chronic inflammation appears in models of epilepsy.

In neurodegenerative diseases and after injury, prolonged activation of microglia is part of the damage as well as of the repair.

Neuroinflammation is the immune system speaking to the brain.

Brief, it organises recovery; prolonged, the same signals reshape mood, development and excitability.

Questions: What is the inflammation hypothesis of depression? It proposes that for some people depression is partly the brain's response to inflammation. The starting observation is that sickness behaviour, the fatigue, withdrawal and low mood of an infection, is produced by cytokines acting on the brain, and that treating patients with the cytokine interferon-alpha brings on depression in part of them. On average people with depression have raised IL-6 and C-reactive protein, but the differences are small, overlap widely with healthy people and shrink after accounting for body weight, so inflammation looks like one route into depression for a subgroup, not its general cause. What is the maternal immune activation line of autism research? It starts from registries showing that infection during pregnancy is linked to a higher risk of autism and schizophrenia in the child. In mice, giving the pregnant mother a viral mimic (poly I:C) around mid-gestation produces offspring with altered social behaviour and brain development, an effect carried largely by maternal cytokines such as IL-6. The models vary with strain, sex and gut flora, and in people the added risk is small; it is one environmental line beside a condition that is mostly heritable.