Related Experiment Video
Updated: Jan 21, 2026
A Fibrin-Enriched and tPA-Sensitive Photothrombotic Stroke Model
Published on: June 4, 2021
N-Acetyl-Seryl-Aspartyl-Lysyl-Proline Augments Thrombolysis of tPA (Tissue-Type Plasminogen Activator) in Aged Rats
Chao Li1, Li Zhang1, Chunyang Wang1
1From the Department of Neurology, Henry Ford Hospital, Detroit, MI (C.L., L.Z., C.W., H.T., B.F., M.C., Z.G.Z.).
Abstract:
Background and Purpose- Stroke is a leading cause of disability worldwide, mainly affecting the elderly. However, preclinical studies in aged ischemic animals are limited. N-acetyl-seryl-aspartyl-lysyl-proline (AcSDKP) is a naturally occurring tetrapeptide with vascular-protective properties. The present study investigated the effect of AcSDKP on tPA (tissue-type plasminogen activator)-induced thrombolysis in aged rats after ischemic stroke. Methods- Aged male rats (18 months) were subjected to embolic middle cerebral artery occlusion. Rats subjected to 4 hours of middle cerebral artery occlusion were randomized into the following groups: (1) AcSDKP; (2) tPA; (3) AcSDKP in combination with tPA; and (4) saline. Neurological deficits, cerebral microvascular patency and integrity, and infarction were examined at 1 day and 7 days after middle cerebral artery occlusion. In vitro experiments were performed to examine the effect of AcSDKP on aged cerebral endothelial cell permeability. Results- Compared with saline, AcSDKP, or tPA as monotherapy did not have any therapeutic effects, whereas AcSDKP in combination with tPA significantly reduced cerebral tissue infarction and improved neurological outcome without increasing cerebral hemorrhage. Concurrently, the combination treatment significantly augmented microvascular perfusion and reduced thrombosis and blood-brain barrier leakage. In vitro, compared with cerebral endothelial cells from ischemic adult rats, the endothelial cells from ischemic aged rats exhibited significantly increased leakage. AcSDKP suppressed tPA-induced aged endothelial cell leakage and reduced expression of ICAM-1 (intercellular adhesion molecule 1) and NF (nuclear factor)-κB. Conclusions- The present study provides evidence for the therapeutic efficacy of AcSDKP in combination tPA for the treatment of embolic stroke in aged rats at 4 hours after stroke onset. AcSDKP likely acts on cerebral endothelial cells to enhance the benefits of tPA by increasing tissue perfusion and augmenting the integrity of the blood-brain barrier. Visual Overview- An online visual overview is available for this article.
Related Concept Videos
01:19The Effect of Aging on Tissues
01:19Nervous Tissue: Neuron Types
Structurally, neurons are categorized into three main types: multipolar, bipolar, and unipolar (or pseudounipolar). Multipolar neurons, which are the most common type in the brain and spinal cord, as well as all motor neurons, possess multiple dendrites and a single axon.
Bipolar neurons, on the other hand, have one primary dendrite and one axon. They are...
01:22Connective Tissue Cell Types
Fat cells (adipocytes), smooth muscle cells (myoblasts), and bone cells (osteoblasts) are some connective tissue cell types. Some immune system cells...
01:24Phase II Reactions: Acetylation Reactions
The substrates for acetylation are typically drugs or their metabolites with an amino, sulfonamide, or hydrazine functional group. Acetylation can occur at several points in the drug molecule, including primary, secondary, and...
02:04Co-activators and Co-repressors
01:26Aging
Cellular Clock Theory
The cellular clock theory posits that the human lifespan is closely tied to the finite capacity of cells to divide, a phenomenon governed by telomeres, which are protective caps at the ends of...