FAU researchers prove that the cortex cannot regenerate
In the past, experimental studies repeatedly kept the hope alive that the cortex is able to generate new nerve cells after a stroke, reducing the consequential damage. Unfortunately, scientists at FAU have had to put an end to this hope: working with a Swedish team of researchers, they were able to determine the exact age of the nerve cells using radiocarbon dating – and confirm that the vast majority were exactly as old as the patient themselves, i.e. they were not generated more recently. The scientists have now published their findings in the journal ‘Nature Neuroscience’.
The cortex is the part of the human brain which houses the higher cognitive functions. Strokes which affect the cortex in particular often lead to consequential damage such as paralysis and speech disorders. ‘The stroke is one of the most common causes of death in the western world and many patients who survive are disabled or in need of care in their day-to-day lives,’ explains the Erlangen-based neurologist Dr. Hagen Huttner, Department of Neurology at Universitätsklinikum Erlangen. For this reason, the question of whether new nerve cells can or cannot be generated in patients with cortex diseases has always been one of the key clinically relevant factors for the success of the rehabilitation of stroke patients.
Led by Huttner and the head of the department, Prof. Dr. Stefan Schwab, a team of German and Swedish researchers at FAU and at the Karolinska Institute in Stockholm has now been able to clarify this. A side effect of the more than 500 above-ground nuclear bomb tests carried out during the Cold War which released increased amounts of a radio-active carbon isotope into the atmosphere which was incorporated into the DNA of nerve cells was useful for their investigations.
‘Radiocarbon dating is often used by archaeologists to date their finds, for instance,’ Hagen Huttner explains. ‘However, for millennia, the ratio of normal to radioactive carbon was relatively constant, meaning that the accuracy of the dating method was not optimal. But the nuclear bomb tests changed this carbon ratio dramatically and it is now slowly returning to normal after nuclear test ban treaties have been implemented. This means that the temporal resolution of radiocarbon dating has become very accurate and we can use it for our precise scientific experiments to find out whether any regeneration of nerve cells occurs after a stroke.’
Radiocarbon dating of nerve cells makes use of the fact that the radioactive carbon was absorbed into humans via plants and animals in the food chain and was incorporated into the DNA of every new cell at exactly the same ratio to normal carbon as the atmospheric value during the year of the cell’s birth. If one isolates the DNA of nerve cells that do not divide after their development and examines them with regard to the ratio of normal to radioactive carbon, the birth year can be determined with great accuracy.
‘We were able to show that the age of the surviving cells after a stroke corresponded almost exactly to the age of the stroke patients and that a significant amount of new nerve cells had not formed in the cortex,’ Huttner says. This data was supported by immunohistochemical analyses. ‘The result is quite sobering upon first sight but, unfortunately, it correlates with our clinical experiences. Interestingly, however, the nerve cells which survived the stroke demonstrated the ability to repair their DNA which was damaged due to insufficient blood supply, meaning that a more or less intact genome was present.’
The scientists now want to continue their research, as many strokes affect not the cortex but the basal ganglia. These are located much closer to other regions in the human brain in which Huttner and his colleagues strongly suspect neurogenesis takes place. Only recently, the researchers published the discovery that the human brain can produce new nerve cells through its entire lifetime in a small area of the brain, the hippocampus, in the journal ‘Cell’. ‘An analysis of basal ganglia infarctions could produce positive results and leave the door open for therapeutic options,’ hopes Huttner.
PD Dr. Hagen Huttner
Phone.: +49 9131 8533001