Although platelets have been investigated in the context of homeostasis and thrombosis for decades, their role as drivers of inflammation has emerged more recently. This change of paradigm was brought about by evidence that platelets express a surprisingly broad spectrum of receptors and can release a wide range of inflammatory mediators not associated with their classical role, but with inflammation, immunity and tissue repair. Platelets are also exceptionally responsive to stimuli and are typically part of the immediate, first line of response to injury and inflammation, via modulation of neutrophils, lymphocytes, and endothelial cells, as well as adherence to lymphocytes thereby enabling platelet recruitment to sites of tissue injury and inflammation. Finally, they are also known to participate in the capture and sequestration of pathogens within the vasculature.
As a consequence of these newly identified roles of platelets in inflammation in general, these elements have been implicated in the etiology of multiple neuropathologies. These include neurodegenerative disorders such as Alzheimer’s Disease, motor neuron disease, Parkinson’s disease, Huntington’s disease, neuroinflammatory diseases such as traumatic brain injury and multiple sclerosis, as well as stroke, depression, genetic disorders such as Fragile X syndrome and central nervous system (CNS) diseases caused by infectious agents such as meningitis, cerebral malaria and HIV. In view of such a wide range of conditions where a role for platelets has been identified, the immediate question that springs to mind is whether universal pathophysiology underlies their association with neuropathologies. The literature reveals that platelet interactions exhibit modulation over the disease course and while platelets are generally regarded as having a pathogenic role in early disease, this can subsequently reverse to a protective one. In some conditions, their deleterious effect was reported to be mediated by platelet-derived microvesicles rather than by platelets themselves.
Therapeutic targeting of platelets and their microvesicles in the context of neuropathologies will be particularly challenging, not only due to the presence of the blood-brain barrier but also because of obstacles to the drugs reaching their desired sites of action once in the CNS parenchyma. Most importantly, different approaches targeting platelet/platelet microvesicles in both circulation and CNS parenchyma in the same patients are likely to be required. Such issues will have to be met with novel drug formulations and delivery techniques, together with novel imaging approaches to determine drug stability, accurate targeting, and efficacy.
In view of these challenging but simultaneously exciting concepts, this Research Topic will cover the latest developments in platelet pathophysiological mechanisms and changing interactions over the course of a number of neuropathologies. The long-term view will be to identify potential common pathways leading to the development of novel and broad-spectrum platelet-specific therapeutic approaches. We welcome authors to submit Original Research, Review and Mini-Review articles focusing on, but not limited to, the following subtopics:
1. The role of platelets in neurodegenerative disorders
2. The role of platelets in cerebral infections, including cerebral malaria
3. The role of platelets in stroke and other neuroinflammatory conditions
4. Novel therapeutic strategies targeting platelets in the CNS
5. Novel diagnostic strategies targeting platelets in the CNS
Although platelets have been investigated in the context of homeostasis and thrombosis for decades, their role as drivers of inflammation has emerged more recently. This change of paradigm was brought about by evidence that platelets express a surprisingly broad spectrum of receptors and can release a wide range of inflammatory mediators not associated with their classical role, but with inflammation, immunity and tissue repair. Platelets are also exceptionally responsive to stimuli and are typically part of the immediate, first line of response to injury and inflammation, via modulation of neutrophils, lymphocytes, and endothelial cells, as well as adherence to lymphocytes thereby enabling platelet recruitment to sites of tissue injury and inflammation. Finally, they are also known to participate in the capture and sequestration of pathogens within the vasculature.
As a consequence of these newly identified roles of platelets in inflammation in general, these elements have been implicated in the etiology of multiple neuropathologies. These include neurodegenerative disorders such as Alzheimer’s Disease, motor neuron disease, Parkinson’s disease, Huntington’s disease, neuroinflammatory diseases such as traumatic brain injury and multiple sclerosis, as well as stroke, depression, genetic disorders such as Fragile X syndrome and central nervous system (CNS) diseases caused by infectious agents such as meningitis, cerebral malaria and HIV. In view of such a wide range of conditions where a role for platelets has been identified, the immediate question that springs to mind is whether universal pathophysiology underlies their association with neuropathologies. The literature reveals that platelet interactions exhibit modulation over the disease course and while platelets are generally regarded as having a pathogenic role in early disease, this can subsequently reverse to a protective one. In some conditions, their deleterious effect was reported to be mediated by platelet-derived microvesicles rather than by platelets themselves.
Therapeutic targeting of platelets and their microvesicles in the context of neuropathologies will be particularly challenging, not only due to the presence of the blood-brain barrier but also because of obstacles to the drugs reaching their desired sites of action once in the CNS parenchyma. Most importantly, different approaches targeting platelet/platelet microvesicles in both circulation and CNS parenchyma in the same patients are likely to be required. Such issues will have to be met with novel drug formulations and delivery techniques, together with novel imaging approaches to determine drug stability, accurate targeting, and efficacy.
In view of these challenging but simultaneously exciting concepts, this Research Topic will cover the latest developments in platelet pathophysiological mechanisms and changing interactions over the course of a number of neuropathologies. The long-term view will be to identify potential common pathways leading to the development of novel and broad-spectrum platelet-specific therapeutic approaches. We welcome authors to submit Original Research, Review and Mini-Review articles focusing on, but not limited to, the following subtopics:
1. The role of platelets in neurodegenerative disorders
2. The role of platelets in cerebral infections, including cerebral malaria
3. The role of platelets in stroke and other neuroinflammatory conditions
4. Novel therapeutic strategies targeting platelets in the CNS
5. Novel diagnostic strategies targeting platelets in the CNS
