Spatiotemporal pathological alternations during syringomyelia formation and resolution
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE217697 | GEO | 2023/05/29
REPOSITORIES: GEO
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Project description:Syringomyelia is a common clinical lesion associated with arachnoid adhesion, traumatic injury, intramedullary tumor, and congenital or acquired spinal deformities. However, the mechanism of syringomyelia formation and resolution remains controversial. We previously constructed a reversible rat model with extradural compression to closely reproduce the canalicular syringomyelia in the human condition. It is quite necessary to depict the spatiotemporal pathophysiological changes of syringomyelia more precisely by transcriptomic analyses during syrinx development and regression.
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Project description:The arachnoid barrier delineates the border between the central nervous system and dura mater. Although the arachnoid barrier creates a partition, communication between the central nervous system and the dura mater is crucial for waste clearance and immune surveillance. How the arachnoid barrier balances separation and communication is poorly understood. Leveraging transcriptomic data, we developed novel transgenic mice to examine specific anatomical structures that serve as routes across the arachnoid barrier. Bridging veins create discontinuities where they cross the arachnoid barrier, forming structures that we termed arachnoid cuff exit (ACE) points. The openings that ACE points create allow the exchange of fluids and molecules between the subarachnoid space and the dura, enabling the drainage of cerebrospinal fluid and limited entry of molecules from the dura to the subarachnoid space. In healthy human volunteers, MRI tracers transit along bridging veins in a similar fashion to access the subarachnoid space. Interestingly, in neuroinflammatory conditions such as experimental autoimmune encephalomyelitis, ACE points also allow cellular trafficking, representing a previously unknown route for immune cells to directly enter the subarachnoid space from the dura mater. Collectively, our results indicate that ACE points are a critical part of the anatomy of neuroimmune communication in both mice and humans that links the central nervous system with the dura and its immunological diversity and waste clearance systems.
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Project description:The complexity and low accessibility of the human brain make it challenging to understand its development, function, and disorders. Brain diseases including neurodegenerative disease and psychiatric diseases incur huge medical and social burdens without effective treatments. While mouse has substantially contributed to our current understanding of brain, the translational value of mouse models may limit to certain aspects of a disease due to the apparent differences in brain structure (gyrencephalic versus lissencephalic) and behavior between mice and humans. Nonhuman primates are, in theory, the best animals to understand human brains. However, monkeys are extremely expensive and inefficient to reproduce (5 years to reach sexual maturity and only one progeny per pregnancy). Dogs have similar gyrencephalic brain structure as humans. Due to the human selection and domestication, dogs have developed exquisite and complex dog-human heterospecific social capabilities. For example, dogs can learn by observing human social and communicative behaviors such as a pointing gesture to find hidden food. Indeed, psychologists have learned that average dogs can count, reason and recognize words and gestures on par with a human 2-year-old. Compared with nonhuman primates, dogs have relatively lower costs of husbandry and shorter breeding times, with multiple offspring per pregnancy. Given that gene editing and animal cloning by somatic nuclear transfer have been available in dogs in recent years and other advantages described above, dogs are thus a potential model for studying human brain development and disease. However, to what extent the dog brain is conserved with the human brain at the molecular level remains unclear.
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