Reductions in blood flow to the brain of sufficient duration and extent lead to stroke, which results in damage to neuronal networks and the impairment of sensation, movement or cognition. Evidence from animal models suggests that a time-limited window of neuroplasticity opens following a stroke, during which the greatest gains in recovery occur. Plasticity mechanisms include activity-dependent rewiring and synapse strengthening. The challenge for improving stroke recovery is to understand how to optimally engage and modify surviving neuronal networks, to provide new response strategies that compensate for tissue lost to injury.

Plasticity during stroke recovery: from synapse to behaviour.

Damage to the adult CNS often leads to persistent deficits due to the inability of mature axons to regenerate after injury. Mounting evidence suggests that the glial environment of the adult CNS, which includes inhibitory molecules in CNS myelin as well as proteoglycans associated with astroglial scarring, might present a major hurdle for successful axon regeneration. Here, we evaluate the molecular basis of these inhibitory influences and their contributions to the limitation of long-distance axon repair and other types of structural plasticity. Greater insight into glial inhibition is crucial for developing therapies to promote functional recovery after neural injury.

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Glial inhibition of CNS axon regeneration

CNS Injury, Glial Scars, and Inflammation: Inhibitory extracellular matrices and regeneration failure

Chondroitin sulfate proteoglycans (CSPGs) present a barrier to axon regeneration. However, no specific receptor for the inhibitory effect of CSPGs has been identified. We showed that a transmembrane protein tyrosine phosphatase, PTPσ, binds with high affinity to neural CSPGs. Binding involves the chondroitin sulfate chains and a specific site on the first immunoglobulin-like domain of PTPσ. In culture, PTPσ–/– neurons show reduced inhibition by CSPG. A PTPσ fusion protein probe can detect cognate ligands that are up-regulated specifically at neural lesion sites. After spinal cord injury, PTPσ gene disruption enhanced the ability of axons to penetrate regions containing CSPG. These results indicate that PTPσ can act as a receptor for CSPGs and may provide new therapeutic approaches to neural regeneration.

https://science.sciencemag.org/content/sci/326/5952/592.full.pdf

PTPσ Is a Receptor for Chondroitin Sulfate Proteoglycan, an Inhibitor of Neural Regeneration

Traumatic spinal cord injury (SCI) is a life changing neurological condition with substantial socioeconomic implications for patients and their care-givers. Recent advances in medical management of SCI has significantly improved diagnosis, stabilization, survival rate and well-being of SCI patients. However, there has been small progress on treatment options for improving the neurological outcomes of SCI patients. This incremental success mainly reflects the complexity of SCI pathophysiology and the diverse biochemical and physiological changes that occur in the injured spinal cord. Therefore, in the past few decades, considerable efforts have been made by SCI researchers to elucidate the pathophysiology of SCI and unravel the underlying cellular and molecular mechanisms of tissue degeneration and repair in the injured spinal cord. To this end, a number of preclinical animal and injury models have been developed to more closely recapitulate the primary and secondary injury processes of SCI. In this review, we will provide a comprehensive overview of the recent advances in our understanding of the pathophysiology of SCI. We will also discuss the neurological outcomes of human SCI and the available experimental model systems that have been employed to identify SCI mechanisms and develop therapeutic strategies for this condition.

/pdf/traumatic-spinal-cord-injury-an-overview-of-pathophysiology-2kheasgwgf.pdf

Traumatic Spinal Cord Injury: An Overview of Pathophysiology, Models and Acute Injury Mechanisms.

Upregulation of extracellular chondroitin sulfate proteoglycans (CSPGs) after CNS injuries contributes to the impediment of functional recovery by restricting both axonal regeneration and synaptic plasticity In the present study, the effect of degrading CSPGs with the application of the bacterial enzyme chondroitinase ABC (chABC) into the cuneate nucleus of rats partially denervated of forepaw dorsal column axons was examined A dorsal column transection between the C6-C7 dorsal root entry zones was followed immediately by an ipsilateral brainstem injection of either chABC or a bacterial-derived control enzyme [penicillinase (P-ase)] and then subsequently (1 week later) followed with a second brainstem enzyme injection and cholera toxin B subunit (CTB) tracer injection into the ipsilateral forepaw digits and pads After 1 additional week, the rats underwent electrophysiological receptive field mapping of the cuneate nucleus and/or anatomical evaluation Examination of the brainstems of rats from each group revealed that CSPGs had been reduced after chABC treatment Importantly, in the chABC-treated rats (but not in the P-ase controls), a significantly greater area of the cuneate nucleus was occupied by physiologically active CTB traced forepaw afferents that had been spared by the initial cord lesion These results demonstrate, for the first time, a functional change directly linked to anatomical evidence of sprouting by spinal cord afferents after chABC treatment

https://www.jneurosci.org/content/jneuro/26/16/4406.full.pdf

Chondroitinase ABC Digestion of the Perineuronal Net Promotes Functional Collateral Sprouting in the Cuneate Nucleus after Cervical Spinal Cord Injury

Adult rat forelimb dysfunction after dorsal cervical spinal cord injury

Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury

Julie A. Decker

Papers

Chondroitinase ABC Digestion of the Perineuronal Net Promotes Functional Collateral Sprouting in the Cuneate Nucleus after Cervical Spinal Cord Injury

Adult rat forelimb dysfunction after dorsal cervical spinal cord injury

Loss and spontaneous recovery of forelimb evoked potentials in both the adult rat cuneate nucleus and somatosensory cortex following contusive cervical spinal cord injury