Platelets are blood cells that are involved in blood clotting and also play a key role in the initiation of inflammation. Platelets are known to be involved in later stages of MS, however, there has been very little done to investigate the role platelets may play in inflammation in the early stages of MS.
Mr Nair aims to demonstrate whether platelet-mediated inflammation plays a role in MS and if so, he will apply the group’s expertise in platelet imaging to track the progression of early stage MS in a laboratory model.
Mr Nair will be working in the laboratory of Professor Karlheinz Peter, an experienced vascular biologist. Professor Peter and colleagues have developed new methods to detect atherosclerosis (blocked blood vessels) before it leads to a heart attack. They have also created a novel imaging agent that targets platelet-rich blood clots, the indicators of inflammation in blood vessels, so that they show up in MRI scans.
Using microscopy, Mr Nair aims to investigate whether activated platelets are present in animal models of early MS. If present, he will use the platelet-specific imaging agent to track the inflammatory events that may contribute to myelin damage and lesion formation.
To understand the molecular events leading to lesion formation in MS, he will also investigate the interaction between thrombospondin, a protein found on platelets, and myelin basic protein (MBP), a major component of the myelin sheath. The binding of these two proteins may have a possible role in the inflammation and resulting damage to myelin.
Ultimately, Mr Nair’s research seeks to develop a sensitive, accurate and easy method to track the progression of MS, particularly in the early stages when there are no clinical signs.
Mr Nair has already achieved success in creating a novel nanoparticle-based imaging agent, specific to activated platelets. This agent is able to successfully target platelet-rich blood clots. Mr Nair has also confirmed the interaction between thrombospondin, a protein found on platelets, and myelin basic protein (MBP), a major component of the myelin sheath and found that MBP has a high affinity for thrombospondin.
Using the new imaging agent, Mr Nair has confirmed the presence of activated platelets in early stages of illness in the brains of mice with MS-like disease, indicating a potential role for platelets in early MS. More importantly, platelet presence was seen in the brains of these mice before the onset of observable clinical symptoms or brain lesions, supporting the idea of using them as diagnostic targets in early MS. In addition, preliminary experiments have demonstrated that mice with platelet depletion also show delayed onset of symptoms. Mr Nair showed these delays in two different types of mice with MS-like illness.
The next stage of the research has attempted to track the activated platelets within the animal models at the early stage of MS. Using positron emission tomography / computerised tomography (PET/CT), this work demonstrated higher levels of platelets in MS-like mice, compared to healthy mice. This important work suggests that PET/CT imaging could be used for imaging the early stages of MS.
The final study undertaken in this project tested the relationship between platelets and the brain lesions observed in MS. In continuation of the microscopy study reported above, where platelets were found in the brains of mice with MS-like disease, further analyses revealed that the platelets were located in close proximity to brain lesions. Platelets were correlated with the presence of microglial cells, the immune cells of the brain, whose presence is a hallmark of illness in MS-like mice. Higher platelet levels were also associated with reduced levels of a structural filament that supports nerve cells, suggesting platelets may play an important role in the brain pathology associated with MS.
Updated: 14 May 2015
Updated: 04 January, 2012