The penumbra is an area of living brain tissue immediately surrounding the
necrotic core of an ischemic or thrombolytic stroke. The penumbra may remain viable
several hours post-stroke due to blood flow from collateral arteries. Thus, this area of
peri-infarct tissue is a therapeutic target for post- stroke and neuroprotective treatment
modalities. Due to the fact that the ratio of viable to non-viable tissue decreases with
time, Factor Xa and Factor II inhibitors such as enoxaparin and thrombolytics such as
recombinant tissue plasminogen activator (r-tPA) must be administered immediately
for optimal, synergistic treatment outcomes. The Broderick Lab is the first to study
penumbral brain neurochemistry after causal acute ischemic stroke (AIS) by middle
cerebral artery occlusion (MCAO) in vivo, as well as to comprehend the effects of
enoxaparin (Lovenox®) and reperfusion via in vivo biochip nanotheranostics actually
imaging the penumbra and its surrounding tissue intravascularly. Indeed, using
Neuromolecular Imaging (NMI) with BRODERICK PROBE® nanobiosensors, animals
were studied as their own control and each side of the brain was imaged in vivo, online,
and in real time. NMI is a technology that uniquely images the baseline state of
subjects before a disease state occurs, thereby establishing an intra-subject control model. In the same subject, with no gliosis, both the infarcted and peri-infarcted
regions were imaged before, during, and after enoxaparin administration. Such imaging
is available only with NMI nanobiosensor technology. In fact, with this new NMI
nanobiosensor technology, the specificity of comparing baselines during drug and
disease states is high because of the ability of NMI to compare baselines in thousands
of previous studies of prescient and non-prescient mammals in vivo. Concurrently,
Dual Laser Doppler Flowmetry (DLDF) was used to monitor cerebral blood perfusion.
The results of this study demonstrate that, using intra-subject studies online (a) NMI
profiles for dorsal striatum in basal ganglia are baseline values, ipsilaterally and
contralaterally. (b) Diminished cerebral blood perfusion from AIS produces a
significant increase of DA and 5-HT neurotransmitter concentrations, as well as
associated metabolites and precursors, in motor neurons. (c) Enoxaparin alleviates
oxygen deficiency by enhancing blood perfusion and reduces DA-induced brain
trauma, enabling brain repair and regeneration. (d) Enoxaparin increases 5-HT release
from motor neurons within the ipsilateral, lesioned hemisphere, as well as in the
contralateral, non-lesioned hemisphere, particularly during the reperfusion stage. This
serotonergic effect demonstrates the potential use of enoxaparin as an antidepressant,
which would be clinically relevant for treating the depression that oftentimes is comorbid
with AIS. (e) The area of post-stroke infarcts is significantly reduced upon
reperfusion; and (f) Cerebral blood perfusion is augmented in a compensatory manner
by both enoxaparin therapy and reperfusion within both hemispheres, particularly the
contralateral hemisphere. Thus, this research demonstrates the efficacy of enoxaparin in
preserving the viability of the penumbra in stroke victims and supports consideration of
the combined use of enoxaparin with r-TPA in standard stroke treatment protocols in
order to harness the brain’s intrinsic repair system. Moreover, these studies
demonstrate the power of NMI nanotechnology in conjunction with BRODERICK
PROBE® theranostic nanobiosensors to reliably study the intricacies of stroke in order
to develop further neuroprotective treatments and allow personalized medicine to be
realized.
Keywords: Anti-platelet, Brain attack, Brain repair, Cerebral blood perfusion,
Enoxaparin, Imaging, Infarct, Intravascular, Ischemia, Lovenox®, Microcirculation,
Nanobiosensors, Nanodiagnostics, Nanotheranostics, Nanotherapeutics,
Neuromolecular Imaging, Occlusion, Peri-infarct, Personalized
medicine, Point of care, Reperfusion, Sensors, Stroke, Surgery, Theranostics,
thrombolytic, Tissue imaging.
