TY - JOUR

T1 - VGF is required for recovery after focal stroke

AU - Gillis, Hannah L.

AU - Kalinina, Alena

AU - Xue, Yingben

AU - Yan, Keqin

AU - Turcotte-Cardin, Valerie

AU - Todd, Matthew A. M.

AU - Young, Kevin G.

AU - Lagace, Diane

AU - Picketts, David J.

PY - 2023

Y1 - 2023

N2 - 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.

AB - 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.

KW - Photothrombosis

KW - Stroke

KW - VGF

KW - C3a and C3a receptor

KW - BRAIN

KW - ISCHEMIA

KW - INFLAMMATION

KW - HIPPOCAMPUS

KW - PRECURSOR

KW - BEHAVIOR

KW - INJURY

U2 - 10.1016/j.expneurol.2023.114326

DO - 10.1016/j.expneurol.2023.114326

M3 - Journal article

C2 - 36682400

VL - 362

JO - Experimental Neurology

JF - Experimental Neurology

SN - 0014-4886

M1 - 114326

ER -