Implantation of Miniosmotic Pumps and Delivery of Tract Tracers to Study Brain Reorganization in Pathophysiological Conditions.

Abstract

Pharmacological treatment in animal models of cerebral disease imposes the problem of repeated injection protocols that may induce stress in animals and result in impermanent tissue levels of the drug. Additionally, drug delivery to the brain is delicate due to the blood brain barrier (BBB), thus significantly reducing intracerebral concentrations of selective drugs after systemic administration. Therefore, a system that allows both constant drug delivery without peak levels and circumvention of the BBB is in order to achieve sufficiently high intracerebral concentrations of drugs that are impermeable to the BBB. In this context, miniosmotic pumps represent an ideal system for constant drug delivery at a fixed known rate that eludes the problem of daily injection stress in animals and that may also be used for direct brain delivery of drugs. Here, we describe a method for miniosmotic pump implantation and post operatory care that should be given to animals in order to successfully apply this technique. We embed the aforementioned experimental paradigm in standard procedures that are used for studying neuroplasticity within the brain of C57BL6 mice. Thus, we exposed animals to 30 min brain infarct and implanted with miniosmotic pumps connected to the skull via a cannula in order to deliver a pro-plasticity drug. Behavioral testing was done during 30 days of treatment. After removal the animals received injections of anterograde tract tracers to analyze neuronal plasticity in the chronic phase of recovery. Results indicated that neuroprotection by the delivered drug was accompanied with increase in motor fibers crossing the midline of the brain at target structures. The results affirm the value of these techniques for drug administration and brain plasticity studies in modern neuroscience.

• Authors: Eduardo H Sanchez-Mendoza, Jeismar Carballo, Marines Longart, Dirk M Hermann, Thorsten R Doeppner
• Journal: Journal of visualized experiments : JoVE (J Vis Exp) Issue 107 Pg. e52932 (Jan 18 2016) ISSN: 1940-087X [Electronic] United States
• PMID: 26863287 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Video-Audio Media)

Chemical References

• 2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt
• Dextrans
• Fluorescent Dyes
• Stilbamidines
• biotinylated dextran amine
• Biotin

Topics

• Animals
• Biotin (administration & dosage, analogs & derivatives)
• Brain (drug effects, physiopathology)
• Brain Diseases (physiopathology)
• Brain Infarction (physiopathology)
• Dextrans (administration & dosage)
• Drug Delivery Systems
• Fluorescent Dyes (administration & dosage)
• Infusion Pumps, Implantable
• Mice
• Mice, Inbred C57BL
• Motor Cortex (drug effects, physiopathology)
• Neuronal Plasticity (drug effects)
• Stilbamidines (administration & dosage)