The blood-nerve barrier is considered the second most restrictive microvascular barrier in mammals after the blood-brain barrier based on classic in vivo solute permeability studies performed in different species. Limited comparative in vitro work also supports this notion. Compared to the blood-brain barrier, relatively little is known about the blood-nerve barrier, formed by tight junction forming endoneurial microvessels, whose role simplistically is to maintain the internal microenvironment of peripheral nerves as needed for efficient axonal signal transduction to and from the central nervous system. Despite this, there is relatively very little knowledge or awareness of the blood-nerve barrier in the scientific community.
Phenotypic and functional differences between endothelial cells exist dependent on their unique microenvironment, and these are characteristics are influenced by the species and tissues in which they reside. Differences also exist in the function of macrovessels and microvessels within the same tissue, for example in inflammatory responses and leukocyte trafficking. The vascular biology of peripheral nerves has been relatively overlooked in studies relevant to peripheral nerve morphogenesis and repair, infection/inflammation and pharmacologic drug delivery, to mention a few. Relatively little is directly known about how the human blood-nerve barrier facilitates peripheral nerve homeostasis and how the cellular components of peripheral nerves (e.g. Schwann cells) receive essential nutrients for survival from and how waste products of cellular metabolism are removed to the systemic circulation. As a consequence, knowledge gaps also exist in the structural, molecular and functional changes at the blood-nerve barrier in different disease states. These deficiencies have resulted in limited specific therapies for peripheral nerve disorders and neuropathic pain.
Due to the isolation, development and characterization of primary and immortalized mammalian peripheral nerve endothelial cell lines guided by in situ and in vivo observational data, there have been significant advances in our understanding of blood-nerve barrier composition and function, as well as biophysical properties under normal physiological and pathophysiological states, including recent deduction of the human blood-nerve barrier transcriptome. Such knowledge is essential to our understanding of peripheral nerve homeostasis, and will guide fundamental translationally relevant research to decipher blood-nerve barrier function in health and adaptations in disease. This knowledge has significant implications for neurologists, anesthesiologists, neuroscientists, vascular biologists, pharmacologists and medicinal chemists working to better understand peripheral nerve function and develop effective treatments for peripheral neuropathies, traumatic nerve injury and neuropathic pain with limited systemic adverse effects, prevent toxic neuropathies such as chemotherapy-induced peripheral neuropathy as well as induce effective local and regional anesthesia. Effective drug design strategies to enhance peripheral axonal regeneration will need to consider the specific characteristics and complexity of the human blood-nerve barrier in a similar vein as the blood-brain barrier in targeted brain drug delivery approaches.
The blood-nerve barrier is considered the second most restrictive microvascular barrier in mammals after the blood-brain barrier based on classic in vivo solute permeability studies performed in different species. Limited comparative in vitro work also supports this notion. Compared to the blood-brain barrier, relatively little is known about the blood-nerve barrier, formed by tight junction forming endoneurial microvessels, whose role simplistically is to maintain the internal microenvironment of peripheral nerves as needed for efficient axonal signal transduction to and from the central nervous system. Despite this, there is relatively very little knowledge or awareness of the blood-nerve barrier in the scientific community.
Phenotypic and functional differences between endothelial cells exist dependent on their unique microenvironment, and these are characteristics are influenced by the species and tissues in which they reside. Differences also exist in the function of macrovessels and microvessels within the same tissue, for example in inflammatory responses and leukocyte trafficking. The vascular biology of peripheral nerves has been relatively overlooked in studies relevant to peripheral nerve morphogenesis and repair, infection/inflammation and pharmacologic drug delivery, to mention a few. Relatively little is directly known about how the human blood-nerve barrier facilitates peripheral nerve homeostasis and how the cellular components of peripheral nerves (e.g. Schwann cells) receive essential nutrients for survival from and how waste products of cellular metabolism are removed to the systemic circulation. As a consequence, knowledge gaps also exist in the structural, molecular and functional changes at the blood-nerve barrier in different disease states. These deficiencies have resulted in limited specific therapies for peripheral nerve disorders and neuropathic pain.
Due to the isolation, development and characterization of primary and immortalized mammalian peripheral nerve endothelial cell lines guided by in situ and in vivo observational data, there have been significant advances in our understanding of blood-nerve barrier composition and function, as well as biophysical properties under normal physiological and pathophysiological states, including recent deduction of the human blood-nerve barrier transcriptome. Such knowledge is essential to our understanding of peripheral nerve homeostasis, and will guide fundamental translationally relevant research to decipher blood-nerve barrier function in health and adaptations in disease. This knowledge has significant implications for neurologists, anesthesiologists, neuroscientists, vascular biologists, pharmacologists and medicinal chemists working to better understand peripheral nerve function and develop effective treatments for peripheral neuropathies, traumatic nerve injury and neuropathic pain with limited systemic adverse effects, prevent toxic neuropathies such as chemotherapy-induced peripheral neuropathy as well as induce effective local and regional anesthesia. Effective drug design strategies to enhance peripheral axonal regeneration will need to consider the specific characteristics and complexity of the human blood-nerve barrier in a similar vein as the blood-brain barrier in targeted brain drug delivery approaches.