Gadolinium-Based Neuroprognostic Magnetic Resonance Imaging Agents Suppress COX‑2 for Prevention of Reperfusion Injury after Stroke

Advancements
in recanalization therapies have rendered reperfusion
injury an important challenge for stroke management. It is essential
to work toward effective therapeutics that protect the ischemic brain
from reperfusion injury. Here, we report a new concept of neuroprognostic
agents, which combine molecular diagnostic imaging and targeted neuroprotection
for treatment of reperfusion injury after stroke. These neuroprognostic
agents are inflammation-targeted gadolinium compounds conjugated with
nonsteroidal anti-inflammatory drugs (NSAIDs). Our results demonstrated
that gadolinium-based MRI contrast agents conjugated with NSAIDs suppressed
the increase in cyclooxygenase-2 (COX-2) levels, ameliorated glial
activation, and neuron damage that are phenotypic for stroke by mitigating
neuroinflammation, which prevented reperfusion injury. In addition,
this study showed that the neuroprognostic agents are promising T1 molecular MRI contrast agents for detecting
precise reperfusion injury locations at the molecular level. Our results
build on this new concept of neuroprognostics as a novel management
strategy for ischemia-reperfusion injury, combining neuroprotection
and molecular diagnostics.