Integrating Molecular, Cellular, and Systems Approaches to Repairing the Brain After Stroke

  • Max O. KrucoffEmail author
  • Stephen C. Harward
  • Shervin Rahimpour
  • Keith Dombrowski
  • Erik F. Hauck
  • Shivanand P. Lad
  • Dennis A. Turner
Part of the Springer Series in Translational Stroke Research book series (SSTSR)


A stroke implies a sudden and spontaneous onset of neurological symptoms due to a vascular insult. Despite the brain’s inherent capacity for plasticity and spontaneous improvement, strokes still leave many patients with devastating deficits that can permanently affect independence and quality of life. This chapter focuses on ways to help restore the functionality of the central nervous system (CNS) after this type of injury. Understanding how neurons interact on both individual (i.e. cellular and molecular) and population (i.e. synapses and circuits) levels is crucial to developing successful restorative strategies, as is appreciating how these interactions change over the injury-recovery timeline. The CNS has several characteristics that make its restitution exceptionally difficult; beyond even its incredible intricacy, its parenchymal cells, or neurons, do not regenerate well after injury, and this damaged neuronal substrate embodies a consciousness system that must be engaged in its own recovery. In fact, there is now data suggesting that conscious intention, often invoked through goal-oriented rehabilitation, plays a crucial role in facilitating functional plasticity and long-range axonal sprouting. To capitalize on this principle, neural interfaces and electrical stimulation strategies are being integrated into rehabilitation paradigms to provide critically-timed feedback that can reinvigorate injured circuits. Combining these approaches with interventions at the cellular and molecular level (e.g. immunological or genetic modulations aimed at promoting neuronal outgrowth, or stem cells that can replace damaged parenchyma) has the chance to improve neurological recovery to back toward baseline levels. Ultimately, because cells of the CNS do not regrow on their own, and because regrowth and synapse formation does not necessarily ensure restoration of function, harmonious application of synergistic approaches at both the micro- and macroscopic levels will be needed to establish long-lasting functional plasticity and meaningful recovery.


Neural repair Neural regeneration Stroke Neurorehabilitation Brain-machine interface Brain-computer interface Neural interface Axonal regeneration Neural restoration 



α-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid


Action potential


Brain-computer interface




Brain-machine interface


Brain state dependent stimulation


Cyclic adenosine monophosphate


Constraint-induced movement therapy


Central nervous system


Ciliary neurotrophic factor


Cerebral perfusion pressure


Chondroitin sulfate proteoglycans


Deep brain stimulation


Disorder of consciousness


Dorsal root ganglion


Federal Drug Administration


Functional electrical stimulation


Gamma-aminobutyric acid


Growth associated protein 43


Growth and differentiation factor 10


Internal carotid artery


Intracranial pressure


Insulin-like growth factor 1


Long-term depression


Long-term potentiation


Primary motor cortex




Myelin-associated inhibitory molecule


Middle cerebral artery


Mechanistic target of rapamycin


Nogo receptor




Non-steroidal anti-inflammatory drug


Oligodendrocyte-myelin glycoprotein




Paired associative stimulation


Premotor cortices


Phosphatase and tensin homolog


Retinal ganglion cell


Repetitive transcranial magnetic stimulation


Spinal cord injury


Subgranular zone


Spike-timing dependent plasticity


Subventricular zone


Transforming growth factor beta


Transforming growth factor beta receptor


Transcranial magnetic stimulation


Conflict of Interest

The authors declare they have no conflict of interest.


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Copyright information

© Springer International Publishing AG 2018

Authors and Affiliations

  • Max O. Krucoff
    • 1
    Email author
  • Stephen C. Harward
    • 1
  • Shervin Rahimpour
    • 1
  • Keith Dombrowski
    • 2
  • Erik F. Hauck
    • 1
  • Shivanand P. Lad
    • 1
  • Dennis A. Turner
    • 1
    • 3
    • 4
  1. 1.Department of NeurosurgeryDuke University Medical CenterDurhamUSA
  2. 2.Department of NeurologyDuke University Medical CenterDurhamUSA
  3. 3.Department of NeurobiologyDuke UniversityDurhamUSA
  4. 4.Research and Surgery ServicesDurham Veterans Affairs Medical CenterDurhamUSA

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