Subacute intranasal administration of tissue plasminogen activator improves stroke recovery by inducing axonal remodeling in mice.

ABSTRACT: In addition to thrombolysis, tissue plasminogen activator (tPA) can evoke neurorestorative processes. We therefore investigated the therapeutic effect of subacute intranasal administration of tPA post stroke on neurological recovery and on corticospinal innervation in mice. A transgenic mouse line, in which the pyramidal neurons and corticospinal tract (CST) axons are specifically labeled by yellow fluorescent protein (YFP) was employed. Adult CST-YFP mice were subjected to right unilateral middle cerebral artery occlusion (MCAo), and were randomly divided into groups treated with saline or tPA intranasally in the subacute phase. Pseudorabies virus (PRV)-614-monomeric red fluorescent protein (RFP) was injected into the left forelimb. The cervical spinal cord and brain were processed for fluorescent microscopy to detect YFP and RFP labeling. Primary embryonic neurons were cultured with tPA at different concentrations. Neurite length and branch numbers were then measured. In vivo, subacute tPA treatment significantly enhanced functional recovery (p?

SUBMITTER: Chen N 

PROVIDER: S-EPMC5916497 | biostudies-literature | 2018 Jun

REPOSITORIES: biostudies-literature