Technology-based approaches toward a better understanding of neuro-coagulation in brain homeostasis

Abstract

Blood coagulation factors can enter the brain under pathological conditions that affect the blood–brain interface. Besides their contribution to pathological brain states, such as neural hyperexcitability, neurodegeneration, and scar formation, coagulation factors have been linked to several physiological brain functions. It is for example well established that the coagulation factor thrombin modulates synaptic plasticity; it affects neural excitability and induces epileptic seizures via activation of protease-activated receptors in the brain. However, major limitations of current experimental and clinical approaches have prevented us from obtaining a profound mechanistic understanding of “neuro-coagulation” in health and disease. Here, we present how novel human relevant models, i.e., Organ-on-Chips equipped with advanced sensors, can help overcoming some of the limitations in the field, thus providing a perspective toward a better understanding of neuro-coagulation in brain homeostasis.

Modulating scar formation for improving brain repair: from coagulation and inflammation to cell therapy

“…The relevance of the coagulation cascade and coagulation factors was not considered for a long time in neuroscience, at least with regard to their role in defining physiological brain functions, such as neural excitability and synaptic plasticity. Maoz et al ( 2021 ) review how “brain born” coagulation factors affect brain physiology and pathology. They focus on the role of thrombin/PAR1 in synaptic plasticity and how its misregulation in changes to the blood–brain interface affects complex brain functions.…”

Traumatic Brain Injury in a Well: A Modular Three-Dimensional Printed Tool for Inducing Traumatic Brain Injury In vitro

“… 2 Although TBI poses a major problem in human health; we are limited in our ability to study it, and thus far translation to the clinic has failed, for various reasons. 3 , 4 …”

Inducing Mechanical Stimuli to Tissues Grown on a Magnetic Gel Allows Deconvoluting the Forces Leading to Traumatic Brain Injury

“…and protective factors (neurogenesis, gliogenesis, angiogenesis, synaptic plasticity, and axonal sprouting) that determine the extent and severity of the injury, as well as the recovery. 6 Despite significant progress in modeling 7 , 8 and understanding the complex molecular mechanisms underlying TBI, such as activation of the inflammatory response, 9 , 10 disruption of the blood–brain barrier, 11 and release of excitatory neurotransmitters, 12 there is still a gap in translating this knowledge into clinical practice and effective therapy.…”