MS Society-supported researchers shed light on critical mechanisms for cell entry into the central nervous system in MS
The blood-brain and blood-spinal cord barriers (BBB and BSCB, respectively) are important features of the body that regulate the passage of cells into the brain or spinal cord from the bloodstream. It has been shown in mice that exhibit MS-like characteristics that when the physical integrity of the BSCB is affected, aggressive immune cells can enter the central nervous system (CNS) and cause damage to myelin, the protecting sheath around nerve fibers. Myelin loss disrupts communication between nerve cells and leads to the development of MS. Thus, dysfunction of the BBB and BSCB is associated with MS and other neurologic conditions such as stroke and neuromyelitis optica (NMO) - a condition similar to MS that involves myelin loss of the spinal cord and optic nerve. The exact triggers for these barriers becoming compromised are still unknown.
A study recently published in The Journal of Immunology sought to examine how cells known as neutrophils affect the disruption of the BSCB. Neutrophils are a type of white blood cell that migrate quickly to a site of inflammation to help fight infections.
Researchers in Montreal, including several MS Society funded researchers and neurologists, induced MS-like characteristics in a strain of mice (to read about the use of animals in research, click here). They then performed a specific imaging procedure with the mice, which involves looking at tissues in real time to view how cells behave. Using this method, the research team examined themovement of cells during BSCB disruption. They also examined postmortem CNS tissue from one human subject with MS and two subjects with NMO. Finally, the researchers therapeutically removed neutrophils from the mice to determine how their absence would affect the barrier disruption process.
Imaging results demonstrated that disruption of the BSCB occurred within a day after the MS-like disease was induced in mice. Neutrophils made up a large portion of the cells that entered the CNS and infiltration of these cells took place just before the onset of MS-like symptoms in the mice. When the researchers therapeutically eliminated neutrophils from the mice, they observed a noticeable delay in the appearance of MS-like symptoms, along with decreased severity of the symptoms and maintained integrity of the BSCB.
Additional findings from the postmortem human brain and spinal cord tissue revealed increases of neutrophil concentration associated with leakage of the BBB or BSCB.
Taken together, the data collected from this study supports the notion that neutrophils are likely involved in the initial events that take place in MS, likely through a mechanism that involves the breakdown of the protective barriers that separate the CNS from circulating blood cells. Although still preliminary, these findings offer implications for therapeutic strategies, including blocking the action of neutrophils in order to delay the onset of MS.
Aubé B et al. Neutrophils mediate blood-spinal cord barrier disruption in demyelinating neuroinflammatory disease. The Journal of Immunology 2014 July 21 [Epub ahead of print]