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How the brain compensates for disorders when damaged
How the brain compensates for disorders when damaged How the brain compensates for disorders when damaged

The greater number of new neurons (red dots) in the right image indicates an increase in neurogenesis in a brain structure, the hippocampus, after injury. Source: eNeuro.

Since childhood, we have been used to hearing the phrase: “Nerve cells don’t regenerate.” But is that really the case? Is our brain really so vulnerable that when it is damaged or under stress it irretrievably loses its main cells – neurons? Does such an intricate structure really lack the mechanisms to recover after, or compensate for, diseases and injuries? Today we can confidently say that our brain has a much greater margin of safety than was previously thought. It turns out that, like skin or bones, the brain also has the ability to ‘heal itself', and the range of strategies and tactics for this is rather wide.

Brain damage can be caused by various factors, including trauma, tumours, strokes, neurological and infectious diseases, hypoxia (lack of oxygen), ischemia (lack of blood supply), poisoning, and drug or alcohol dependence.  However, regardless of the cause, the main consequence in all cases is nerve cell death and impaired brain function.

Let's imagine we have a complex structure of many elements.  What actions can be taken to preserve it after an impact which has destroyed and damaged some of its elements, and has violated the stability of the structure?  Firstly, it is possible to compensate for the destruction with the remaining elements.  Secondly, one may try to insert new elements to replace the destroyed ones.  Thirdly, it is possible to repair and fix the elements which are damaged but not completely destroyed.  Finally, it is possible to somehow strengthen the intact elements in order to prevent the very possibility of their subsequent destruction under new conditions.  With certain assumptions, it can be said that a similar scenario is also played out with brain damage.

As studies in recent decades have shown, our brains are unusually flexible, that is, they are able to adapt and restructure themselves in response to new situations, changes in the environment, as well as injuries and diseases, reorganising existing connections between neurons and forming new ones throughout their lifespan.  Thus, after an injury, the surviving neurons take over the functions of the dead neurons.  The effectiveness of this strategy can be illustrated, for example, by Parkinson's disease.  With this disease, there is a gradual death of neurons in a particular area of the brain - the substantia nigra (“black substance”), responsible for organising motor function.  Clinical symptoms of the disease (trembling of the extremities, limited mobility, and an unstable gait) appear only when 60-80% of neurons have already died in this area [1], up to this point the brain can compensate for disorders.  The enhanced formation of new contacts between neurons – synapses – forms the basis of an injured brain's plasticity [2–4].  This is facilitated by stimulated growth and neuron process branching – dendrites and axons [3, 5-6].  These processes start within a few minutes after the injury and are aimed at restoring the lost connections and information transfer routes in the brain [7].

At the end of the 20th century, an amazing discovery was made: neurogenesis, the emergence of new nerve cells, and another mechanism of the brain's response to damage.  It transpired that adult mammal brains, including those of humans, contain stem cells, from which the precursors of all basic brain cell types can be formed [8–9]. These precursors can divide, move, and become involved in the work of existing neuron systems [10-11], thus replacing dying elements in an adult or even aging brain [7].  It is worth noting, however, that neurogenesis is still limited in the adult brain, and occurs only in certain areas [12].  An article recently published in the authoritative scientific journal Science stated that after damaging effects such as a stroke, neurons can also be formed from pre-existing brain cells: astrocytes, the main support and assistance to neurons [13].  Moreover, there is evidence that more than 50% of mature nerve cells are able, under certain conditions, to 'forget' their specialisation and regain their ability to divide [14].

Neurons also have another important quality: they are, much like a salamander, capable of regeneration.  Today, the death of adult specialised neurons after damage to their branches is not as inevitable as previously thought.  Dramatic changes can occur in the damaged neuron, but, in most cases, these are only temporary reactions, and survival and recovery are possible [7].  For instance, the ability of the auditory pathway to regenerate, with the recovery of sensitivity to sound, has been demonstrated [15], as has the survival of one type of retinal cell, with the restoration of dark-light discrimination [16], and the recovery of spinal cord axons with the normalisation of motor functions [17-18].

There are many mechanisms in the brain to protect against death of surviving nerve cells.  There are also mechanisms to start and implement the processes of neurogenesis, regeneration, and the formation of new connections, which replace those lost due to damage.  Moving from the cellular level to the molecular level, it has been found that damaging effects activate the genes in the brain cells that encode proteins regulating cell growth and specialisation (for example, GAP-43) [3, 5, 19].  These proteins are involved in the formation of new neuron processes and the regeneration of damaged ones.  The number of so-called neurotrophic factors (BDNF, GDNF, NGF, NT-3, bFGF), which promote the survival of neurons and stimulate regeneration and neurogenesis, also increases [4, 20].  The expression of antioxidant enzymes (Mn-SOD, GSSG-R) is enhanced [4].  These enzymes remove active oxygen forms — extremely reactive molecules that, when overproduced (which is characteristic of damage), cause serious cell damage.

When the brain malfunctions occur, neurons often become unable to fully utilise their main energy supply, glucose.  However, the brain even tries to solve this problem itself: astrocytes come to the aid of neurons, attempting to provide an alternative source of energy: lactate, a form of lactic acid [21].

On the whole, scientists view the brain's ability to heal itself following damage more optimistically today than they did half a century ago.  The brain has exceptional self-regulatory and function-restoring capabilities.  Special dependable systems support the normal operation of their cells, much like conductors of an orchestra, and contribute towards increased resistance to damaging influences.  Of course, the brain’s potential is not limitless, but we can increase its resistance to negative factors ourselves.  Thus, physical [30-32] and mental [33-34] exercise enhance neurogenesis and switch on new neurons in the brain, while chronic stress affects these processes adversely [35].  What is more, if the brain is continuously kept active, much more contact between the neurons is formed in it, which increases the brain's resistance to damage [36-38], because the more connections there are, the more difficult it is to break them all at once.



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