Fly model of repetitive head trauma speeds up time

Behnke and Zheng describe their model as a platform for future studies on repetitive head injury, in which they can unleash all of the genetic tools fruit flies have to Read more

Brain organoid model shows molecular signs of Alzheimer’s before birth

In a model of human fetal brain development, Emory researchers can see perturbations of epigenetic markers in cells derived from people with familial early-onset Alzheimer’s disease, which takes decades to appear. This suggests that in people who inherit mutations linked to early-onset Alzheimer’s, it would be possible to detect molecular changes in their brains before birth. The results were published in the journal Cell Reports. “The beauty of using organoids is that they allow us to Read more

The earliest spot for Alzheimer's blues

How the most common genetic risk factor in AD interacts with the earliest site of neurodegeneration Read more

brain injury

Strategy to defend vs double hit at beginning of life

Chorioamnionitis is a complication of pregnancy: inflammation of the membranes surrounding the fetus, caused by a bacterial infection. It has the potential to inflict damage to the brain of the fetus, especially when combined with fetal hypoxia, and is a known risk factor for developing cerebral palsy.

Chia-Yi (Alex) Kuan and his team, who study fetal brain injury in the Department of Pediatrics, have a new paper in Journal of Neuroscience on a strategy for inhibiting fetal brain inflammation. Postdoctoral fellows Dianer Yang, Yu-Yo Sun and Siddhartha Kumar Bhaumik are co-first authors.

The researchers show that a type of immune cells called Th17 cells seems to be driving inflammation because the rest of the fetal immune system is still immature. A marker of Th17 cells is elevated in blood samples from human infants with chorioamnionitis, the researchers found. Th17 cells are thought to be important for both autoimmunity and anti-microbial responses.

A drug called fingolimod, which stops immune cells from circulating out of the lymph nodes, was effective in reducing inflammation-induced fetal brain injury in animal models. Fingolimod has been approved by the FDA for use with multiple sclerosis and has been studied in clinical trials of kidney transplantation. The authors write that it may be a potential add-on to hypothermia as a treatment for infants in danger of hypoxia + infection-induced brain damage.

Posted on by Quinn Eastman in Immunology, Neuro Leave a comment

Next steps in progesterone for brain injury

At a recent Society for Neuroscience (SFN) meeting, Emory researchers described their efforts to learn about optimizing progesterone for treatment of traumatic brain injury.

Researcher Donald Stein, PhD, Asa G. Candler Professor of Emergency Medicine at Emory School of Medicine, has shown that progesterone can protect damaged brain tissue. Stein is director of the Department of Emergency Medicine’s Brain Research Laboratory.

Donald G. Stein, PhD

Donald G. Stein, PhD

One of the Emory SFN presentations covered efforts to find progesterone analogues that are more water soluble. This work comes from Stein and his colleagues in collaboration with the laboratory of Dennis Liotta, PhD, Emory professor of chemistry.

Currently, the lack of water solubility limits delivery of progesterone, in that the hormone must be prepared hours ahead and cannot be kept at room temperature. Small chemical modifications may allow similar compounds with the same effects as progesterone to be given to patients closer to the time of injury.

According to the results, two compounds similar to progesterone showed an equivalent ability to reduce brain swelling in an animal model of traumatic brain injury.

The second Emory report described evidence that adding vitamin D to progesterone enhances the hormone’s effectiveness when applied to neurons under stress in the laboratory. Like progesterone, vitamin D is a steroid hormone that is inexpensive, has good safety properties and acts on many different biochemical pathways.

David Wright, MD

David Wright, MD

The authors showed that a low amount of vitamin D boosted the ability of progesterone to protect neurons from excito-toxicity , a principal cause of brain injury and cell death.

A new study at Emory, slated to begin early 2010, will evaluate progesterone’s effectiveness for treating traumatic brain injury in a multisite phase III clinical trial called ProTECT III.

The study follows earlier findings that showed giving progesterone to trauma victims shortly after brain injury appears to be safe and may reduce the risk of death and long-term disability.

David Wright, MD, assistant professor of emergency medicine at Emory School of Medicine is the national study’s lead investigator.

Michael Frankel, MD, Emory professor of neurology, will serve as site principal investigator of the clinical trial at Grady Memorial Hospital.

Posted on by Quinn Eastman in Neuro Leave a comment