Preventing Neurodegeneration in Traumatic Brain Injury

The immune system is the new focus of much work on traumatic brain injury (TBI). In a challenge to the paradigm that the blood brain barrier prevents harmful leukocytes from entering the brain, a Texas team tried to neutralize the impact of these cells. Peripheral lymphocytes are activated after TBI. They may then act as potential antigen presenting cells and get into the brain, causing cells there to degenerate.

The immune system is the new focus of much work on traumatic brain injury (TBI). In a challenge to the paradigm that the blood brain barrier prevents harmful leukocytes from entering the brain, a Texas team documented in a mouse study that they do get into the brain. The team then tried to neutralize the impact of these cells. The team said peripheral lymphocytes are activated after TBI. They may then act as potential antigen presenting cells and get into the brain, causing cells there to degenerate.

After subjecting mice to a percussive head injury—a control group got sham injuries—the researchers targeted the resulting expression of lymphocytes using a competitive antagonist (CAP) for the MCH Class II-associated invariant peptide (CLIP) needed for antigen processing and presentations. Their hypothesis was that peptide competition could reverse of prevent neurodegeneration after TBI.

As expected, after the injury, peripheral splenic lymphocytes increased. But they used CAP treatment and found it worked worked to decrease them.

To further test that theory, they used a mouse deficient in CD74, the precursor of CLIP and again found that after the injury the animals had decreased peripheral lymphocyte activation, decreased neurodegeneration, and a significantly smaller lesion size.

“Taken together, the data support the hypothesis that neurodegeneration following TBI is dependent up antigen processing and presentation that requires CD74.

The researchers, Richard Tobin, a postdoctoral fellow at the department of surgery at Texas A&M University College of Medicine and colleagues, published their findings in Acta Neuropathologica Communications, an open access online journal.

Four of the co-authors are consultants for VG Life Sciences Inc. which has a patent pending for CAP.