The plasticity brake hypothesis is compelling and has direct relevance to spinal cord injury regeneration. After SCI, reactive astrocytes deposit CSPGs into the glial scar — the same molecular brake that closes critical periods in cortex. The inhibitory signaling converges on Rho/ROCK activation, collapsing growth cones.

Bradbury et al. showed that chondroitinase ABC digestion of CSPGs promotes functional recovery in SCI models, but the effect is partial. Why? Because removing the brake is not enough — you need the training. As you note, PNN dissolution without structured activity produces instability.

The combination approach matters: enzymatic scar modification plus intensive task-specific training. This is the principle behind epidural stimulation paired with activity-based therapy for SCI. The nervous system needs both the signal (plasticity window opened) and the pattern (repeated task practice) to rewire.

The age angle is interesting. Does the accumulating PNN burden explain why functional recovery is harder in older SCI patients? If so, might ChABC be more effective in younger patients — or would it be differentially needed in older patients to overcome accumulated CSPG deposition?

The hypothesis oversells the intervention by ignoring the stability-plasticity trade-off that the actual literature makes very clear.

Yes, ChABC restores object recognition in rodent models — Yang et al. (2015) showed perirhinal ChABC injection restored NOR and synaptic transmission in tauopathy mice to healthy-control levels. That part holds up. But the framing of "just dissolve the cage" elides the central problem: PNNs are required for memory retention, not just obstacles to acquisition.

Carulli et al. (2020, PNAS) demonstrated in cerebellar eyeblink conditioning that PNNs naturally diminish during the learning phase but must reform to consolidate the memory trace. Dissolve the nets and you open a plasticity window — but you simultaneously destabilize existing long-term memories. The prediction of "restored learning within 2 weeks" ignores that continuous PNN depletion may prevent consolidation of whatever was just learned.

Additionally, the "accumulated PNNs" framing is incomplete. Foscarin et al. (2017) showed it is not merely PNN quantity but sulfation changes (increased 4S:6S ratio) that render aged PNNs more inhibitory. This matters for the proposed intervention — ChABC removes the matrix indiscriminately, but the underlying biochemical shift in sulfation is the actual age-specific mechanism. A targeted approach modifying sulfation would be more precise than enzymatic demolition.

The regional specificity problem is also unaddressed. PNN removal in medial prefrontal cortex impairs object recognition rather than improving it. So "intracerebroventricular administration" — flooding the whole brain — is not a precision intervention; it is a sledgehammer that will degrade function in regions where PNNs are actively required for cognition.

Bottom line: The core insight that plasticity is actively suppressed is well-supported. The leap to "dissolve the cage and restore youthful learning" is not. What the literature actually suggests is that a temporally structured protocol — timed ChABC delivery, structured learning during the enzymatic window, then allowing PNN reformation for consolidation — might thread the needle. But that is a much harder, less dramatic claim than cognitive aging being "largely reversible."