Abstract 15119: T2-weighted Magnetic Resonance Imaging Accurately shows Treatment Response of Novel Neuroprotective Compound, Tat-N-dimer, in Ischemic Stroke
Introduction: Tat-N-dimer is a promising drug in stroke therapy targeting the interaction between postsynaptic density protein 95 (PSD-95) and neuronal nitric oxide synthase (nNOS) downstream of the N-methyl-D-aspartate receptor (NMDAR). Studies have shown a neuroprotective effect of the drug with 40% reduction in infarct volume following permanent middle cerebral artery occlusion (pMCAO) in mice. Using high-field, T2-weighted magnetic resonance imaging, the volume of the edema and the total lesion can be estimated precisely.
Hypothesis: Mice undergoing pMCAO have significantly reduced infarct and edema volumes following treatment with Tat-N-dimer, compared to matched controls.
Methods: Thirty-six male C57Bl/6J mice were subjected to pMCAO and randomly assigned to receive either physiological saline (n=16) or 3 nmol/g Tat-N-dimer (n=16) and allowed 28 days of survival. At 6 hours, 48 hours, 7 days and 28 days post-occlusion, mice were subjected to MR imaging on a Bruker BioSpec 700/20 7T pre-clinical scanner. A T2-weighted 3D TurboRARE with TE and TR of 32 ms and 1500 ms, respectively, was used. Ten mice were randomly selected for histological assessment of infarct volumes.
Results: Total lesion volumes were significantly different over the time course of the experiment (p<0.0001, two-way RM ANOVA) peaking at 6 hours and 48 hours after injury and decreasing towards 7 and 28 days after injury. A typical injury development is seen in the figure. The extent of vasogenic edema was evaluated at 6 and 48 hours following pMCAO and found to be significantly reduced in Tat-N-dimer treated mice after 6 hours (p < 0.036, two-tailed t-test). A correlation between infarct volumes obtained from histology and MR lesion volumes revealed T2-weighted MRI as a powerful predictor of tissue destined to infarction (r=0.63, p=0.005).
Conclusions: Tat-N-dimer has a neuroprotective effect on mice exposed to pMCAO, which can be accurately evaluated by T2-weighted MR imaging.
Author Disclosures: A.E. Clemmensen: None. L.K. Kristensen: None. C.H. Nielsen: None. F.F. Johansen: None. A. Kjær: None.
- © 2014 by American Heart Association, Inc.