Brain Injuries May Cause Astrocytes to Kill the Very Nerves They Normally Nourish
After a brain injury, cells that normally nourish nerves may actually kill them instead, a new study in rodents finds. This 鈥渞eactive鈥 phenomenon may be the driving factor behind neurodegenerative diseases like glaucoma, a leading cause of blindness.
Led by researchers at 好色tv Grossman School of Medicine, the study examined what happens when pressure builds up in the eye and damages the nerve cells that connect the eyes and brain. Although experts have long linked this condition to glaucoma, it remained unclear how excess pressure leads to cell death.
The new investigation revealed that increased pressure drove astrocytes鈥攁 star-shaped glial cell of the central nervous system鈥攖o release as-yet-unidentified neuron-killing toxins, possibly to 鈥渃lear away鈥 damaged cells. Meanwhile, excess pressure had little effect on nerves when astrocytes were not present. In addition, when astrocytes were prevented from reacting to pressure, neurons were damaged, but not as badly.
鈥淥ur findings point to astrocytes as the true culprits behind nerve cell death and highlight a new way of treating a neurodegenerative disease like glaucoma,鈥 says study senior author , an assistant professor in the at 好色tv Langone Health. 鈥淧erhaps targeting astrocytes after an injury may be the way to keep neurons healthy and help prevent further deterioration.鈥
Dr. Liddelow, also an assistant professor in 好色tv Langone鈥檚 , adds that while half of all brain cells are astrocytes, most research on glaucoma has historically focused on neurons, the electrically active cells that send messages throughout nerve tissue.
The study findings, he says, make clear that in order to understand neurodegenerative diseases, experts must look beyond neurons to the cells that surround them, including astrocytes, which are named after the Greek word for star.
His previous research in rodents showed that astrocytes could become reactive immediately after nerves are physically damaged. The new investigation, , is believed to be the first to show that reactive astrocytes kill cells over time in a process similar to what occurs in glaucoma, the study authors say.
In addition, the findings may help explain why brain cells continue to die long after excess pressure has been controlled. According to Dr. Liddelow, dying neurons spill inflammatory compounds into the surrounding tissue, which may further aggravate astrocytes and lead to a continuous cycle of cell destruction.
For their investigation, the study authors increased eye pressure for two weeks in several dozen rats and mice, some of which had been genetically engineered to lack these neuron-killing reactive astrocytes.
They found that while the unmodified mice lost up to half of the neurons in the injured area, those without toxic astrocytes saw little cell death. In addition, neurons that survived continued to send electrical signals.
To examine whether neurons survive if astrocytes are prevented from releasing toxins, the researchers increased pressure again, this time disrupting inflammation in some of the animals to prevent their astrocytes from becoming reactive.
Although the findings suggest that blocking astrocytes is a potential means of preventing nerve damage in people with glaucoma, he cautions that researchers do not yet know whether the resulting effects are permanent or what side effects may occur.
Next, the research team plans to investigate whether this treatment can actually improve vision in animals with glaucoma, as well as to study astrocyte behavior in related conditions like Alzheimer鈥檚 disease, Parkinson鈥檚 disease, and Lou Gehrig鈥檚 disease.
Funding for the study was provided by the National Institutes of Health grants R01 EY026100, R01 EY027713, and P30 EY026877. Additional support was provided by the Cure Alzheimer鈥檚 Foundation and the Glenn Foundation Glenn Award. Dr. Liddelow maintains a financial interest in AstronauTx Ltd, a company targeting astrocytes as a possible treatment target for Alzheimer鈥檚 disease. The terms and conditions are being managed in accordance with the policies of 好色tv Langone.
In addition to Dr. Liddelow, other 好色tv Langone investigators involved in the study are Rana El-Danaf, PhD; Indigo Rose, MS; and Medical Scientist Training Program student Drew Adler. Additional research support was provided by Alexandra M眉nch, BA; Maya Weigel, BA; and Andrew Huberman, PhD, at Stanford University in California. Kevin Guttenplan, PhD, also at Stanford University, is the study lead investigator.
Media Inquiries
Shira Polan
Phone: 212-404-4279
shira.polan@nyulangone.org