Summary: Excessive neurogenesis following brain injury may lead to neurological problems and cognitive decline researchers report. The findings challenge common assumptions that excessive brain cell growth following injury is adventageous.
The excessive burst of new brain cells after a traumatic head injury that scientists have traditionally believed helped in recovery could instead lead to epileptic seizures and long-term cognitive decline, according to a new Rutgers New Jersey Medical School study.
In the September issue of Stem Cell Reports, Viji Santhakumar, associate professor in the department of Pharmacology, Physiology and Neuroscience, and her colleagues, challenge the prevailing assumption by scientists in the field that excessive neurogenesis (the birth of new brain cells) after injury is advantageous.
“There is an initial increase in birth of new neurons after a brain injury but within weeks, there is a dramatic decrease in the normal rate at which neurons are born, depleting brain cells that under normal circumstances should be there to replace damaged cells and repair the brain’s network,” said Santhakumar. “The excess new neurons lead to epileptic seizures and could contribute to cognitive decline”
In the United States an estimated 1.7milllion people sustain a TBI each year, making the condition a major cause of death and disability. Symptoms can include impaired thinking or memory, personality changes and depression and vision and hearing problems as well as epilepsy. About 80 percent of those who develop epilepsy after a brain injury have seizures within the first two years after the damage occurs.
Santhakumar said while researchers who study epilepsy have started to look more closely at how preventing excessive neurogenesis after brain injury could prevent seizures, neuroscientists have traditionally viewed the process as helpful to overall brain recovery.
Studying laboratory rats, Rutgers scientists found, however, that within a month after experimental brain injury, the number of new brain cells declined dramatically, below the numbers of new neurons that would have been detected if an injury had not occurred.
When scientists were able to prevent the excessive neurogenesis which occurs within days of the injury with a drug similar to one under trial for chemotherapy treatments, the rate of birth of new brain cells went back to normal levels and risk for seizures was reduced.
“That’s why we believe that limiting this process might be beneficial to stopping seizures after brain injury,” she said.
While the regenerative capability of brain cells, in the hippocampus – the part of the brain responsible for learning and memory – slows down as part of the aging process, the Rutgers scientists determined that the process that occurred after a head injury was related to injury and not age.
“It is normal for the birth of new neurons to decline as we age,” said Santhakumar. “But what we found in our study was that after a head injury the decline seems to be more rapid.”
Funding: The Rutgers study was funded by the NJ Commission on Brain Injury Research. An estimated 12,000 to 15,000 New Jersey residents suffer brain injuries annually.
Source: Robin Lally – Rutgers
Image Source: NeuroscienceNews.com image is credited to Santhakumar et al./Stem Cell Reports.
Original Research: Full open access research for “Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility” by Eric J. Neuberger, Bogumila Swietek, Lucas Corrubia, Anagha Prasanna, and Vijayalakshmi Santhakumar in Stem Cell Reports. Published online August 17 2017 doi:10.1016/j.stemcr.2017.07.015
Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility
•Increase in neurogenesis after TBI is transient and leads to long-term decline
•Altered neural precursor proliferation underlies post-TBI changes in neurogenesis
•Brief antagonism of VEGFR2 restores post-injury neurogenesis to control levels
•Limiting neurogenesis improves excitability and seizure susceptibility after TBI
Hippocampal dentate gyrus is a focus of enhanced neurogenesis and excitability after traumatic brain injury. Increased neurogenesis has been proposed to aid repair of the injured network. Our data show that an early increase in neurogenesis after fluid percussion concussive brain injury is transient and is followed by a persistent decrease compared with age-matched controls. Post-injury changes in neurogenesis paralleled changes in neural precursor cell proliferation and resulted in a long-term decline in neurogenic capacity. Targeted pharmacology to restore post-injury neurogenesis to control levels reversed the long-term decline in neurogenic capacity. Limiting post-injury neurogenesis reduced early increases in dentate excitability and seizure susceptibility. Our results challenge the assumption that increased neurogenesis after brain injury is beneficial and show that early post-traumatic increases in neurogenesis adversely affect long-term outcomes by exhausting neurogenic potential and enhancing epileptogenesis. Treatments aimed at limiting excessive neurogenesis can potentially restore neuroproliferative capacity and limit epilepsy after brain injury.
“Enhanced Dentate Neurogenesis after Brain Injury Undermines Long-Term Neurogenic Potential and Promotes Seizure Susceptibility” by Eric J. Neuberger, Bogumila Swietek, Lucas Corrubia, Anagha Prasanna, and Vijayalakshmi Santhakumar in Stem Cell Reports. Published online August 17 2017 doi:10.1016/j.stemcr.2017.07.015