Abstract

Neuromolecular Imaging (NMI) based on adsorptive electrochemistry, combined with Dual Laser Doppler Flowmetry (LDF) is presented herein to investigate the brain neurochemistry affected by enoxaparin (Lovenox®), an antiplatelet/antithrombotic medication for stroke victims. NMI with miniature biosensors enables neurotransmitter and neuropeptide (NT) imaging; each NT is imaged with a response time in milliseconds. A semiderivative electronic reduction circuit images several NT’s selectively and separately within a response time of minutes. Spatial resolution of NMI biosensors is in the range of nanomicrons and electrochemically-induced current ranges are in pico- and nano-amperes. Simultaneously with NMI, the LDF technology presented herein operates on line by illuminating the living brain, in this example, in dorso-striatal neuroanatomic substrates via a laser sensor with low power laser light containing optical fiber light guides. NMI biotechnology with BRODERICK PROBE® biosensors has a distinct advantage over conventional electrochemical methodologies both in novelty of biosensor formulations and on-line imaging capabilities in the biosensor field. NMI with unique biocompatible biosensors precisely images NT in the body, blood and brain of animals and humans using characteristic experimentally derived half-wave potentials driven by oxidative electron transfer. Enoxaparin is a first line clinical treatment prescribed to halt the progression of acute ischemic stroke (AIS). In the present studies, BRODERICK PROBE® laurate biosensors and LDF laser sensors are placed in dorsal striatum (DStr) dopaminergic motor neurons in basal ganglia of brain in living animals; basal ganglia influence movement disorders such as those correlated with AIS. The purpose of these studies is to understand what is happening in brain neurochemistry and cerebral blood perfusion after causal AIS by middle cerebral artery occlusion in vivo as well as to understand consequent enoxaparin and reperfusion effects actually while enoxaparin is inhibiting blood clots to alleviate AIS symptomatology. This research is directly correlated with the medical and clinical needs of stroke victims. The data are clinically relevant, not only to movement dysfunction but also to the depressive mood that stroke patients often endure. These are the first studies to image brain neurotransmitters while any stroke medications, such as anti-platelet/anti-thrombotic and/or anti-glycoprotein are working in organ systems to alleviate the debilitating consequences of brain trauma and stroke/brain attacks.

Highlights

  • Neuromolecular Imaging (NMI) with BRODERICK PROBE® biosensors selectively detect neurotransmitters, metabolites and precursors of neurotransmitters, excitatory and inhibitory neuropeptides (NT) in vivo in specific neuroanatomic substrates of brain, body and blood

  • Dopaminergic motor neurons in basal ganglia of brain within dorsal striatum (DStr) are selected because these dopaminergic neurons influence movement behaviors and disorders

  • Investigations into the effectiveness of tissue platelet activating factor (tPA) as a stroke medication is recently advanced by a group of German researchers who have employed recombinant tissue plasminogen factor (r-tPA) during the reperfusion period of the nylon suture monofilament method for middle cerebral artery occlusion [41]

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Summary

Introduction

NMI with BRODERICK PROBE® biosensors selectively detect neurotransmitters, metabolites and precursors of neurotransmitters, excitatory and inhibitory neuropeptides (NT) in vivo in specific neuroanatomic substrates of brain, body and blood. Investigations into the effectiveness of tPA as a stroke medication is recently advanced by a group of German researchers who have employed recombinant tissue plasminogen factor (r-tPA) during the reperfusion period of the nylon suture monofilament method for middle cerebral artery occlusion [41] These researchers performed monitoring studies on recanalization and in sonothrombolysis, contrast-enhanced ultrasound (CEUS) and found that r-tPA partially improved hemispheric perfusion and r-tPA combined with CEUS significantly reduced ischemic lesion (infarct) volume, edema and microcirculatory malfunctioning. In the present experimental design, investigations into the efficacy of enoxaparin as a stroke medication are dramatically advanced by imaging cerebral neurotransmitters in basal ganglia using neuromolecular imaging (NMI) while at the same time monitoring cerebral blood flow with dual laser

Conventional Voltammetry and Microvoltammetry
Experimental Design
In Vitro Calibration Procedures
In Vivo Surgical Procedures
Image Scanning Procedures with a Semiderivative Circuit
Interpretation and Analysis of Data
Dual Laser Doppler Flowmetry
Results and Discussion
Conclusions
Full Text
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