Imatinib on target in stroke recovery

Abstract

Ischemic stroke causes scars in the CNS that impede functional recovery, and there is a need for therapeutics to improve recovery after the acute phase. Scar-resident myofibroblasts and the PDGF pathway have been implicated in stroke pathology. In this issue of the JCI, Protzmann et al. report that inhibition of PDGF-CC or its receptor, PDGFRα, reduces the myofibroblast population and improves functional recovery after ischemic stroke in mice. Importantly, PDGFRα inhibition was effective in improving functional recovery even when initiated 24 hours after stroke, which suggests opportunities for later treatment by targeting the PDGF pathway. This study demonstrates the therapeutic potential of enhancing stroke recovery even after acute damage and blood-brain barrier dysfunction has already occurred.

Figure 1. Protzmann et al. demonstrate benefits of PDGF-CC/PDGFRα pathway inhibition for stroke recovery.

Experimental stroke was induced using middle artery occlusion in mice, resulting in immediate ischemia, rapid BBB breakdown, and inflammation. Within a few days, a multilayered scar formed with an ECM-rich core, a rim of PDGFRα⁺ myofibroblasts, and an outermost glial layer. Imatinib blocked PDGFRα tyrosine kinase activity. This treatment reduced myofibroblasts and ECM in the scar, and improved BBB integrity and function in sensory-motor integration tests. Similar results were obtained from specifically blocking PDGF-CC with neutralizing antibody, or from genetic deletion of PDGFRα.