Summary of "Fibrin promotes oxidative stress and neuronal loss in traumatic brain injury via innate immune activation"

Fibrinogen is a blood protein that is crucial in coagulation. Fibrogen can be found in the blood-brain barrier (BBB), which can be compromised years after a TBI. This protein is converted to fibrin, exposing the CD11b/CD18 integrin receptor on microglial cells in the nervous system is the zone where an antibody would attach to an invader. The interactions between fibrin and CD11b-CD18 cause signaling between immune cells and induce the release of less chemically stable oxygen species that have been linked to the degeneration of neurons in Alzheimer’s and multiple sclerosis models. Fibrinogen effects inflammation and neurodegeneration after a traumatic brain injury.

This study examined the distribution of fibrinogen, how deposits of the protein are regulated, and whether blood products entering the brain through a disrupted BBB worsen neuroinflammation and neuron loss. Adult male mice were used with Fggy390-396A knock-in mice (a gene was added to their DNA), constituting the group without an increase in fibrinogen after a TBI, and C5BL/6 mice constituting the wildtype control group. Fggy390-396A knock-in mice constituting express mutant fibrinogen that remains normal in its clotting responses and lacks the binding function of y390-396 to CD11b/CD18 integrin. C5BL/6 mice are a commonly used mice strain that expresses mutations well because of their resistance to tumors and audiogenic seizures, their macrophages are also resistant to anthrax and lethal toxins. Each group had those with a TBI, and a sham group that underwent a surgical procedure, but no injury was induced.

Using tissue adjacent to the TBI lesion as well as tissue far from it, the cells containing fibrinogen were counted without the origin of each sample being known. Amoeboid cells that are immune cells can change their shape and function expressed two calcium-binding proteins which are activated by microglia in monocytic (1 cell) white blood cells, similar to Alzheimer's disease and multiple sclerosis.The findings suggest that oxidative microglia are activated by CD11b/CD18 fibrin signaling after a TBI, which lasted longer in the wild-type mice that Fgg^y390-396A mice, increasing the oxidative damage, cortical loss, and deterioration of the BBB in all wild-type groups.

This fibrinogen response cannot be treated by dampening the entire immune system, which is vitally important to recovery after a traumatic brain injury. Instead, the dampening of fibrin-CD11b signaling specifically can reduce cognitive impairment and reduce paralysis in AD and MS. Targeting could be done with monoclonal (laboratory produced) antibodies, that are aimed at the fibrin y377-395 epitope.