VGF is required for recovery after focal stroke

Research output: Contribution to journalJournal articlepeer-review

  • Hannah L. Gillis
  • Alena Kalinina
  • Yingben Xue
  • Keqin Yan
  • Valerie Turcotte-Cardin
  • Todd, Matthew
  • Kevin G. Young
  • Diane Lagace
  • David J. Picketts

The high incidence of ischemic stroke worldwide and poor efficacy of neuroprotective drugs has increased the need for novel therapies in stroke recovery. Transcription of the neurosecretory protein VGF (non-acronym) is enhanced following ischemic stroke and proposed to be important for stroke recovery. To determine the requirement for VGF in recovery, we created Vgffl/fl:Nestin-Cre conditional knockout (Vgf cKO) mice and induced a photothrombotic focal ischemic stroke. Naive Vgf cKO mice had significant less body weight in the absence of gross defects in brain size, cortical lamination, or deficits in locomotor activity compared to wildtype controls. Following a focal stroke, the Vgf cKO mice had greater deficits including impaired recovery of forepaw motor deficits at 2- and 4-weeks post stroke. The increase in deficits occurred in the absence of any difference in lesion size and was accompanied by a striking loss of stroke-induced migration of SVZ-derived immature neurons to the peri-infarct region. Importantly, exogenous adenoviral delivery of VGF (AdVGF) significantly improved recovery in the Vgf cKO mice and was able to rescue the immature neuron migration defect observed. Taken together, our results define a requirement for VGF in post stroke recovery and identify VGF peptides as a potential future therapeutic.

Original languageEnglish
Article number114326
JournalExperimental Neurology
Volume362
Number of pages12
ISSN0014-4886
DOIs
Publication statusPublished - 2023
Externally publishedYes

    Research areas

  • Photothrombosis, Stroke, VGF, C3a and C3a receptor, BRAIN, ISCHEMIA, INFLAMMATION, HIPPOCAMPUS, PRECURSOR, BEHAVIOR, INJURY

ID: 337586963