Enhancing CNS Repair in neurological disease

Challenges arising from neurodegeneration and rewiring of the network

Xiaohua Xu, Arthur E. Warrington, Allan J. Bieber, Moses Rodriguez

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Repair of the central nervous system (CNS) constitutes an integral part of treating neurological disease and plays a crucial role in restoring CNS architecture and function. Distinct strategies have been developed to reconstruct the damaged neural tissue, with many tested preclinically in animal models. We review cell replacement-based repair strategies. By taking spinal cord injury, cerebral ischaemia and degenerative CNS disorders as examples for CNS repair, we discuss progress and potential problems in utilizing embryonic stem cells and adult neuralnon-neural stem cells to repair cell loss in the CNS. Nevertheless, CNS repair is not simply a matter of cell transplantation. The major challenge is to induce regenerating neural cells to integrate into the neural network and compensate for damaged neural function. The neural cells confront an environment very different from that of the developmental stage in which these cells differentiate to form interwoven networks.During the repair process, one of the challenges is neurodegeneration, which can develop from interrupted innervations tofrom the targets, chronic inflammation, ischaemia, aging or idiopathic neural toxicity. Neurodegeneration, which occurs on the basis of a characteristic vascular and neural web, usually presents as a chronically progressive process with unknown aetiology. Currently, there is no effective treatment to stop or slow down neurodegeneration. Pathological changes from patients with Alzheimers disease, Parkinsons disease and amyotrophic lateral sclerosis indicate a broken homeostasis in the CNS. We discuss how the blood-brain barrier and neural networks are formed to maintain CNS homeostasis and their contribution to neurodegeneration in diseased conditions.Another challenge is that some inhibitors produced by CNS injury do not facilitate the regenerating neural cells to incorporate into a pre-existing network. We review glial responses to CNS injury. Of note, the reactive astrocytes not only encompass the lesionspathogens but may also form glial scars to impede regenerating axons from traversing the lesions. In addition, myelin debris can prevent axon growth. Myelination enables saltatory transduction of electrical impulses along axonal calibers and actually provides trophic support to stabilize the axons. Therefore, repair strategies should be designed to promote axonal growth, myelination and modulate astrocytic responses. Finally, we discuss recent progress in developing human monoclonal IgMs that regulate CNS homeostasis and promote neural regeneration.

Original languageEnglish (US)
Pages (from-to)555-573
Number of pages19
JournalCNS Drugs
Volume25
Issue number7
DOIs
StatePublished - 2011

Fingerprint

Central Nervous System
Nervous System Trauma
Axons
Homeostasis
Neuroglia
Neural Stem Cells
Central Nervous System Diseases
Cell Transplantation
Amyotrophic Lateral Sclerosis
Embryonic Stem Cells
Growth
Myelin Sheath
Brain Ischemia
Blood-Brain Barrier
Spinal Cord Injuries
Astrocytes
Cicatrix
Blood Vessels
Parkinson Disease
Regeneration

Keywords

  • Alzheimers-disease
  • Cerebral-ischaemia
  • Monoclonal-antibodies
  • Multiple-sclerosis
  • Neurodegenerative-disorders
  • Parkinsons-disease
  • Spinal-cord-injuries
  • Stem-cell-therapies

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Psychiatry and Mental health
  • Clinical Neurology

Cite this

Enhancing CNS Repair in neurological disease : Challenges arising from neurodegeneration and rewiring of the network. / Xu, Xiaohua; Warrington, Arthur E.; Bieber, Allan J.; Rodriguez, Moses.

In: CNS Drugs, Vol. 25, No. 7, 2011, p. 555-573.

Research output: Contribution to journalArticle

Xu, Xiaohua ; Warrington, Arthur E. ; Bieber, Allan J. ; Rodriguez, Moses. / Enhancing CNS Repair in neurological disease : Challenges arising from neurodegeneration and rewiring of the network. In: CNS Drugs. 2011 ; Vol. 25, No. 7. pp. 555-573.
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