Neuroscience

Research identifies the mechanism that protects our brains from turning stress and trauma into post-traumatic stress disorder

Researchers from the University of Exeter Medical School have for the first time identified the mechanism that protects us from developing uncontrollable fear.

Our brains have the extraordinary capacity to adapt to changing environments – experts call this ‘plasticity’. Plasticity protects us from developing mental disorders as the result of stress and trauma.

Researchers found that stressful events re-programme certain receptors in the emotional centre of the brain (the amygdala), which the receptors then determine how the brain reacts to the next traumatic event.

These receptors (called protease-activated receptor 1 or PAR1) act in the same way as a command centre, telling neurons whether they should stop or accelerate their activity.

Before a traumatic event, PAR1s usually tell amygdala neurons to remain active and produce vivid emotions. However, after trauma they command these neurons to stop activating and stop producing emotions – so protecting us from developing uncontrollable fear.

This helps us to keep our fear under control, and not to develop exaggerated responses to mild or irrelevant fear triggers – for example, someone who may have witnessed a road traffic accident who develops a fear of cars or someone who may have had a dog jump up on them as a child and who now panics when they see another dog.

The research team used mice in which the PAR1 receptors were genetically de-activated and found that the animals developed a pathological fear in response to even mild, aversive stimuli.

The study was led by Professor Robert Pawlak of University of Exeter Medical School. He said: “The discovery that the same receptor can either awaken neurons or ‘switch them off’ depending on previous trauma and stress experience, adds an entirely new dimension to our knowledge of how the brain operates and emotions are formed.”

Professor Pawlak added: “We are now planning to extend our study to investigate if the above mechanisms, or genetic defects of the PAR1 receptor, are responsible for the development of anxiety disorders and depression in human patients. There is more work to be done, but the potential for the development of future therapies based on our findings is both exciting and intriguing.”

The article describing the above findings has recently been published in one of the most prestigious psychiatry journals, Molecular Psychiatry.

By exploring parts of the brain that trigger during periods of daydreaming and mind-wandering, neuroscientists from Western University have made a significant breakthrough in understanding what physically happens in the brain to cause vegetative state and other so-called “disorders of consciousness.”
Vegetative state and related disorders such as the minimally conscious state are amongst the least understood conditions in modern medicine because there is no particular type of brain damage that is known to cause them. This lack of knowledge leads to an alarmingly high level of misdiagnosis.

In support of the study titled, “A role for the default mode network in the bases of disorders of consciousness,” Davinia Fernandez-Espejo, a post doctoral fellow at Western’s Brain and Mind Institute, utilized a technique called diffusion tensor imaging tractography to investigate more than 50 patients suffering from varying degrees of brain injury.

This state-of-the-art magnetic resonance imaging (MRI) technique allows researchers to virtually reconstruct the pathways that connect different parts of the brain in the patients while detecting subtle differences in their brain damage.

Specifically, Fernandez-Espejo was able to show that in vegetative state patients, a group of brain regions known as the default mode network that are known to activate during periods of daydreaming and mind-wandering were significantly disconnected, relative to healthy individuals.

"These findings are a first step towards identifying biomarkers that will help us to improve diagnosis and to find possible therapies for these patients" says Fernandez-Espejo. "But they also give us new information about how the healthy brain generates consciousness."

Strokes often cause loss or impairment of vital brain functions – such as speech, movement, vision or attention. Restoration of these functions is often possible, but difficult. One of the factors impeding brain plasticity is inflammation.  A study on rats, carried out at the Nencki Institute in Warsaw, suggests that effectiveness of neurorehabilitation after a stroke can be improved by anti-inflammatory drugs.

Post-stroke inflammation slows down recovery and impairs brain plasticity, reveal the results from the lab of Professor Małgorzata Kossut at the Nencki Institute in Warsaw. The popular anti-inflammatory drug ibuprofen restores the ability of brain cortex to reorganize – a process necessary for recovery of stroke-damaged functions. “Our research was conducted on rats, but we have good reasons to suppose that in future our results will help improve effectiveness of rehabilitation of stroke patients”, says Prof. Kossut.

The Nencki Institute team stresses that so far there are no proofs that the treatment will be effective in humans and that they did not investigate if the ibuprofen therapy prevents strokes, but concentrated on post-stroke recovery.

The most frequent cause of stroke is blocking of brain arteries. Without supply of oxygen, neurons die quckly. In the region of stroke-induced damage pathological changes cause decrease of brain tissue metabolism, impairment of neurotransmission and edema.

Brain control over physiological and voluntary functions may be lost, depending on the localization of the infarct. Impairments of movement, vision, speech and attention are frequent. In most cases these functions return either partially or completely. Sometimes they return spontaneously, more often after neurorehabilitation.

“In both instances recovery is based on neuroplasticity, the ability of the brain to reorganize, that is to change the properties of neurons and to alter the connections between them”, says Dr. Monika Liguz-Lęcznar (Nencki Institute).

After a stroke, neuroplasticity is impaired. Scientists from the Nencki Institute suppose that this may be due to inflammation developing at the site of the stroke. The proof that decreasing inflammation helps neurorehabilitation came from experiments done on rats with experimentally induced stroke. The stroke was localized in a special region of the brain cortex, receiving information from whiskers.

The whiskers are important sensory organs of rodents, allowing the animals to orient themselves in their environment in darkness. Every whisker activates a small, precisely delineated chunk of brain cortex.

In healthy rats neuroplastic changes can be induced by cutting off some of the whiskers, that is by eliminating part of the sensory input to the brain. The brain reacts to that by letting the remaining whiskers take over more cortical space, expand their cortical representation, at the expense of the cut off ones.

“This plastic change does not occur when the site of stroke-induced damage is near the region of cortex ‘belonging’ to the whiskers. We showed that application of ibuprofen decreases inflammation and restores neuroplasticity – the brain cortex reorganizes like in healthy animals”, says Prof. Kossut.