Poststroke dendritic arbor regrowth requires the actin nucleator Cobl

Ischemic stroke is a major cause of death and long-term disability. We demonstrate that middle cerebral artery occlusion (MCAO) in mice leads to a strong decline in dendritic arborization of penumbral neurons. These defects were subsequently repaired by an ipsilateral recovery process requiring the actin nucleator Cobl. Ischemic stroke and excitotoxicity, caused by calpain-mediated proteolysis, significantly reduced Cobl levels. In an apparently unique manner among excitotoxicity-affected proteins, this Cobl decline was rapidly restored by increased mRNA expression and Cobl then played a pivotal role in poststroke dendritic arbor repair in peri-infarct areas. In Cobl knockout (KO) mice, the dendritic repair window determined to span day 2 to 4 poststroke in wild-type (WT) strikingly passed without any dendritic regrowth. Instead, Cobl KO penumbral neurons of the primary motor cortex continued to show the dendritic impairments caused by stroke. Our results thereby highlight a powerful poststroke recovery process and identified causal molecular mechanisms critical during poststroke repair.

Automated summary

Ischemic stroke in mice leads to a decline in dendritic arborization of penumbral neurons, which is repaired by the actin nucleator Cobl. The decreased Cobl levels caused by stroke and excitotoxicity are rapidly restored by increased mRNA expression, playing a pivotal role in dendritic arbor repair poststroke. Cobl knockout mice show impaired dendritic repair poststroke, highlighting the crucial role of Cobl in poststroke recovery.