title: Intra-arterial injection of neural stem cells using a microneedle technique does not cause microembolic strokes.
abstract: Intra-arterial (IA) injection represents an experimental avenue for minimally invasive delivery of stem cells to the injured brain. It has however been reported that IA injection of stem cells carries the risk of reduction in cerebral blood flow (CBF) and microstrokes. Here we evaluate the safety of IA neural progenitor cell (NPC) delivery to the brain. Cerebral blood flow of rats was monitored during IA injection of single cell suspensions of NPCs after stroke. Animals received 1 × 10(6) NPCs either injected via a microneedle (microneedle group) into the patent common carotid artery (CCA) or via a catheter into the proximally ligated CCA (catheter group). Controls included saline-only injections and cell injections into non-stroked sham animals. Cerebral blood flow in the microneedle group remained at baseline, whereas in the catheter group a persistent (15 minutes) decrease to 78% of baseline occurred (P<0.001). In non-stroked controls, NPCs injected via the catheter method resulted in higher levels of Iba-1-positive inflammatory cells (P=0.003), higher numbers of degenerating neurons as seen in Fluoro-Jade C staining (P<0.0001) and ischemic changes on diffusion weighted imaging. With an appropriate technique, reduction in CBF and microstrokes do not occur with IA transplantation of NPCs.
authors.affiliation: Department of Neurosurgery, Stanford University School of Medicine, 300 Pasteur Drive, Stanford, CA 94305, USA.
authors.forename: Joshua Y
authors.initials: JY
authors.lastname: Chua
authors.forename: Arjun V
authors.initials: AV
authors.lastname: Pendharkar
authors.forename: Nancy
authors.initials: N
authors.lastname: Wang
authors.forename: Raymond
authors.initials: R
authors.lastname: Choi
authors.forename: Robert H
authors.initials: RH
authors.lastname: Andres
authors.forename: Xavier
authors.initials: X
authors.lastname: Gaeta
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Mike E
authors.initials: ME
authors.lastname: Moseley
authors.forename: Raphael
authors.initials: R
authors.lastname: Guzman
mesh_terms: D000818:Animals; D002560:Cerebrovascular Circulation / Q000502:physiology*; D005260:Female; D007269:Injections, Intra-Arterial; D020766:Intracranial Embolism / Q000209:etiology*; D017078:Laser-Doppler Flowmetry; D051379:Mice; D058953:Neural Stem Cells / Q000637:transplantation*; D051381:Rats; D017208:Rats, Wistar; D033581:Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods*; D020521:Stroke / Q000209:etiology*