Biosensors for brain trauma and dual laser doppler flowmetry: enoxaparin simultaneously reduces stroke-induced dopamine and blood flow while enhancing serotonin and blood flow in motor neurons of brain, in vivo

Sensors (Basel). 2011;11(1):138-61. doi: 10.3390/s11010013. Epub 2010 Dec 24.

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.

Keywords: Factor II; Factor Xa; Factor Xa inhibitors; L-Tryptophan; acute ischemic stroke; anticoagulants; biochemical sensors; blood clots; cerebral blood flow; dopamine; dorsal striatum; dual laser Doppler flowmetry; edema; electrochemistry; enoxaparin; glycoprotein IIb/IIIa inhibitors; heparin; homovanillic acid; in vivo microvoltammetry; integrin; laser sensors; middle cerebral artery occlusion; monoclonal antibodies; motor neurons; neuromolecular imaging; optic fiber; platelets; reperfusion; serotonin; thrombosis; thrombospondin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticoagulants / therapeutic use*
  • Biosensing Techniques*
  • Blood Flow Velocity
  • Brain Injuries / metabolism*
  • Brain Injuries / pathology
  • Dopamine / metabolism*
  • Electrochemical Techniques
  • Enoxaparin / therapeutic use*
  • Laser-Doppler Flowmetry
  • Male
  • Motor Neurons / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Serotonin / metabolism*
  • Stroke / drug therapy
  • Stroke / metabolism*
  • Stroke / pathology

Substances

  • Anticoagulants
  • Enoxaparin
  • Serotonin
  • Dopamine