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  4. In Vivo Imaging of CNS Injury and Disease

In Vivo Imaging of CNS Injury and Disease

The Journal of Neuroscience, 2017 · DOI: 10.1523/JNEUROSCI.1826-17.2017 · Published: November 8, 2017

NeurologyMedical Imaging

Simple Explanation

In vivo optical imaging is a powerful tool for studying cellular responses to injury and disease in the mammalian central nervous system (CNS). It provides new insights into axonal degeneration and regeneration, glial responses and neuroinflammation, changes in the neurovascular unit, and neural transplantations. Time-lapse imaging of cellular structures depicts the dynamic responses to injury and disease at a high spatiotemporal resolution, revealing unanticipated new principles and mechanisms at both acute and chronic time points. This review highlights recent advances in using in vivo optical imaging to understand the multicellular responses to CNS injury and disease, considering both a 2017 SfN Mini-Symposium and the published literature.

Study Duration
Not specified
Participants
Rodent models (mice, rats)
Evidence Level
Not specified

Key Findings

  • 1
    In vivo imaging reveals reversible axon damage in clinically relevant models of CNS injury and disease, suggesting axonal rescue as a promising therapeutic strategy.
  • 2
    Serotonergic axons in the brain exhibit an unusual capacity to regrow after injury, and this regrowth is functional and approximates the prelesion state.
  • 3
    In vivo imaging of the neurovascular interface reveals the sequence of events leading to neurologic impairment, with BBB leakage and fibrin deposition preceding microglial activation and demyelination in neuroinflammatory disease models.

Research Summary

In vivo optical imaging has revolutionized the study of cellular responses to injury and disease in the CNS, providing insights into axonal degeneration/regeneration, glial responses, neuroinflammation, and the neurovascular unit. The development of techniques to image the neurovascular unit, transplanted human iPSC-derived neurons, and retinal axons has broadened the scope of in vivo imaging, allowing for the study of complex neurological diseases and potential therapeutic interventions. Technological advancements, such as deeper imaging capabilities, genetically encoded indicators, and multiomics approaches, are expected to further enhance the utility of in vivo imaging in uncovering new therapeutic avenues for neurological diseases.

Practical Implications

Therapeutic Development

Axonal rescue by manipulating intra-axonal calcium could be a promising strategy to preserve connectivity and function following spinal cord injury.

Understanding Disease Mechanisms

In vivo imaging of the neurovascular interface may reveal the sequence of events that leads to neurologic impairment.

Drug Discovery

In vivo two-photon imaging allows the study of the sequence of events that lead to neurological disease, thus revealing the early triggers and apical mechanisms responsible for disease pathogenesis.

Study Limitations

  • 1
    Monitoring activity in single axons still remains an unmet challenge.
  • 2
    Animal models of complex neurological diseases often do not recapitulate the full extent of human phenotypes.
  • 3
    The degree to which visual representations of normal optic nerve inputs to brain targets is recapitulated after regeneration remains unclear.

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