Name: an in vivo rodent model of contraction-induced injury and non-invasive monitoring of recovery
Uploaded: 2011-05-11T12:00:00
Description: Watch this Scientific Journal Video about An in vivo Rodent Model of Contraction-induced Injury and Non-invasive Monitoring of Recovery at JoVE.com

The authors would like to thank Dr., Robert Bloch for his generous donation of laboratory space and facilities and Dr. Rao Gullapalli and Da Shi in the Core for Translational Imaging at Maryland (C-TRIM) and the Magnetic Resonance Research Center (MRRC) for technical support. This work was supported by grants to RML from the National Institutes of Health (K01AR053235 and 1R01AR059179) and from the Muscular Dystrophy Association (#4278), and by a grant to JAR from the Jain Foundation.

1. in vivo injury Model and measurement of isometric torque.
<ol>
 <li> These procedures can be used for rats or mice7,17,18. To begin, place the animal supine under inhalation anesthesia (~ 4-5% isoflurane 
 for induction in an induction chamber,then ~ 2% isoflurane via a nosecone for maintenance) using a precision vaporizer (cat # 91103, Vet Equip, Inc, 
 Pleasanton, CA). Apply sterile ophthalmic cream (Paralube Vet Ointment, PharmaDerm, Floham Park, NJ) to each eye to protect the corneas ...

<ol>
	<li>Aldridge, R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Muscle+pain+after+exercise+is+linked+with+an+inorganic+phosphate+increase+as+shown+by+31P.">Muscle pain after exercise is linked with an inorganic phosphate increase as shown by 31P.</a> NMR. Biosci. Rep. 6, 663-663 (1986).</li><li>Argov, Z., Lofberg, M., Arnold, D. L. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Insights+into+muscle+diseases+gained+by+phosphorus+magnetic+resonance+spectroscopy.">Insights into muscle diseases gained by phosphorus magnetic resonance spectroscopy.</a> Muscle Nerve. 23, 1316-1316 (2000).</li><li>Brooks, S. V., Zerba, E., Faulkner, J. A. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Injury+to+muscle+fibres+after+single+stretches+of+passive+and+maximally+stimulated+muscles+in+mice.">Injury to muscle fibres after single stretches of passive and maximally stimulated muscles in mice.</a> J. Physiol. 488, 459-459 (1995).</li><li>Burkholder, T. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Relationship+between+muscle+fiber+types+and+sizes+and+muscle+architectural+properties+in+the+mouse+hindlimb.">Relationship between muscle fiber types and sizes and muscle architectural properties in the mouse hindlimb.</a> J. Morphol. 221, 177-177 (1994).</li><li>Hakim, M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dexamethasone+and+Recovery+of+Contractile+Tension+after+a+Muscle+Injury.">Dexamethasone and Recovery of Contractile Tension after a Muscle Injury.</a> Clin. Orthop. Relat Res. 439, 235-235 (2005).</li><li>Hamer, P. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Evans+Blue+Dye+as+an+in+vivo+marker+of+myofibre+damage:+optimising+parameters+for+detecting+initial+myofibre+membrane+permeability.">Evans Blue Dye as an in vivo marker of myofibre damage: optimising parameters for detecting initial myofibre membrane permeability.</a> J. Anat. 200, 69-69 (2002).</li><li>Hammond, J. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Use+of+Autologous+Platelet-rich+Plasma+to+Treat+Muscle+Strain+Injuries.">Use of Autologous Platelet-rich Plasma to Treat Muscle Strain Injuries.</a> Am. J. Sports Med. , (2009).</li><li>Heemskerk, A. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Determination+of+mouse+skeletal+muscle+architecture+using+three-dimensional+diffusion+tensor+imaging.">Determination of mouse skeletal muscle architecture using three-dimensional diffusion tensor imaging.</a> Magn Reson. Med. 53, 1333-1333 (2005).</li><li>Ho, K. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Skeletal+muscle+fiber+splitting+with+weight-lifting+exercise+in+rats.">Skeletal muscle fiber splitting with weight-lifting exercise in rats.</a> Am. J. Anat. 157, 433-433 (1980).</li><li>Huijing, P. A., Baan, G. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Myofascial+force+transmission+causes+interaction+between+adjacent+muscles+and+connective+tissue:+effects+of+blunt+dissection+and+compartmental+fasciotomy+on+length+force+characteristics+of+rat+extensor+digitorum+longus+muscle.">Myofascial force transmission causes interaction between adjacent muscles and connective tissue: effects of blunt dissection and compartmental fasciotomy on length force characteristics of rat extensor digitorum longus muscle.</a> Arch. Physiol Biochem. 109, 97-97 (2001).</li><li>Ingalls, C. P. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Dihydropyridine+and+ryanodine+receptor+binding+after+eccentric+contractions+in+mouse+skeletal+muscle.">Dihydropyridine and ryanodine receptor binding after eccentric contractions in mouse skeletal muscle.</a> J. Appl. Physiol. 96, 1619-1619 (2004).</li><li>Lee, D., Marcinek, D. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Noninvasive+in+vivo+small+animal+MRI+and+MRS:+basic+experimental+procedures.">Noninvasive in vivo small animal MRI and MRS: basic experimental procedures.</a> J. Vis. Exp. , (2009).</li><li>Lovering, R. M., Deyne, P. G. D. e. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Contractile+function,+sarcolemma+integrity,+and+the+loss+of+dystrophin+after+skeletal+muscle+eccentric+contraction-induced+injury.">Contractile function, sarcolemma integrity, and the loss of dystrophin after skeletal muscle eccentric contraction-induced injury.</a> Am. J. Physiol Cell Physiol. 286, C230-C238 (2004).</li><li>Lovering, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+contribution+of+contractile+pre-activation+to+loss+of+function+after+a+single+lengthening+contraction.">The contribution of contractile pre-activation to loss of function after a single lengthening contraction.</a> J. Biomech. 38, 1501-1501 (2005).</li><li>Lovering, R. M. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Recovery+of+function+in+skeletal+muscle+following+2+different+contraction-induced+injuries.">Recovery of function in skeletal muscle following 2 different contraction-induced injuries.</a> Arch. Phys. Med. Rehabil. 88, 617-617 (2007).</li><li>Provencher, S. W. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Automatic+quantitation+of+localized+in+vivo+1H+spectra+with+LCModel.">Automatic quantitation of localized in vivo 1H spectra with LCModel.</a> NMR Biomed. 14, 260-260 (2001).</li><li>Roche, J. A., Lovering, R. M., Bloch, R. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Impaired+recovery+of+dysferlin-null+skeletal+muscle+after+contraction-induced+injury+in+vivo.">Impaired recovery of dysferlin-null skeletal muscle after contraction-induced injury in vivo.</a> Neuroreport. 19, 1579-1579 (2008).</li><li>Stone, M. R. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Absence+of+keratin+19+in+mice+causes+skeletal+myopathy+with+mitochondrial+and+sarcolemmal+reorganization.">Absence of keratin 19 in mice causes skeletal myopathy with mitochondrial and sarcolemmal reorganization.</a> J. Cell Sci. 120, 3999-3999 (2007).</li><li>Van Donkelaar, C. C. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=Diffusion+tensor+imaging+in+biomechanical+studies+of+skeletal+muscle+function.">Diffusion tensor imaging in biomechanical studies of skeletal muscle function.</a> J. Anat. 194, 79-79 (1999).</li><li>Vogl, T. J. <a target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed&cmd=Search&doptcmdl=Citation&defaultField=Title+Word&term=The+value+of+in-vivo+31-phosphorus+spectroscopy+in+the+diagnosis+of+generalized+muscular+diseases.+The+clinical+results+and+the+differential+diagnostic+aspects.">The value of in-vivo 31-phosphorus spectroscopy in the diagnosis of generalized muscular diseases. The clinical results and the differential diagnostic aspects.</a> Rofo. 162, 455-455 (1995).</li></ol>

"Muscle damage" has been defined and measured in many ways. Structural damage is evident in histological findings6,9, but one problem with many of the biological markers used to assess muscle injury, including those used in animal studies, is that they usually do not correlate with the loss of force. Muscle damage is often defined within the context of the assay used to examine it and no one finding can account for the changes in contractility after injury. Since full contractile function can persist...

(All equipment is the same for mice and rats except for the footplate)
<ul>
	<li>BUD Value Line Cabinet (Newark, 06M4718)</li>
	<li>Multifunction l/O USB-6221M (National Instruments, 779808-01)</li>
	<li>Stepper motor controller (Newark, 16M4189)</li>
	<li>Stepper Motor (Newark, 16M4198)</li>
	<li>Strain Gauge Amplifier (Honeywell, Sensotec, DV-05)</li>
	<li>Torque Sensor (Honeywell, QWLC-8M)</li>
	<li>Foot plate and stabilization device (custom made, patent pending)</li>
</ul>

an in vivo rodent model of contraction-induced injury and non-invasive monitoring of recovery

Muscle strains are one of the most common complaints treated by physicians. A muscle injury is typically diagnosed from the patient history and physical exam alone, however the clinical presentation can vary greatly depending on the extent of injury, the patient's pain tolerance, etc. In patients with muscle injury or muscle disease, assessment of muscle damage is typically limited to clinical signs, such as tenderness, strength, range of motion, and more recently, imaging studies. Biological markers, such as serum creatine kinase levels, are typically elevated with muscle injury, but their levels do not always correlate with the loss of force production. This is even true of histological findings from animals, which provide a "direct measure" of damage, but do not account for all the loss of function. Some have argued that the most comprehensive measure of the overall health of the muscle in contractile force. Because muscle injury is a random event that occurs under a variety of biomechanical conditions, it is difficult to study. Here, we describe an in vivo animal model to measure torque and to produce a reliable muscle injury. We also describe our model for measurement of force from an isolated muscle in situ. Furthermore, we describe our small animal MRI procedure.

Watch this Scientific Journal Video about An in vivo Rodent Model of Contraction-induced Injury and Non-invasive Monitoring of Recovery at JoVE.com

An in vivo Rodent Model of Contraction-induced Injury and Non-invasive Monitoring of Recovery

An in vivo animal model of injury is described. The method takes advantage of the subcutaneous position of the fibular nerve. Velocity, timing of muscle activation, and arc of motion are all pre-determined and synchronized using commercial software. Post injury changes are monitored in vivo using MR imaging/spectroscopy.

An in vivo Rodent Model of Contraction-induced Injury and Non-invasive Monitoring of Recovery

Muscle strains are one of the most  common complaints treated by physicians. A muscle injury is typically diagnosed from the patient history and  physical ...

Research

JoVE Journal

Medicine

Non-invasive Optical Measurement of Cerebral Metabolism and Hemodynamics in Infants

Perinatal brain injury remains a significant cause of infant mortality  and morbidity, but there is not yet an effective bedside tool that can  accurately ...

Non-invasive Assessment of Microvascular and Endothelial Function

The authors have utilized capillaroscopy and forearm blood flow techniques to investigate the role of microvascular dysfunction in pathogenesis of ...

Transplantation into the Anterior Chamber of the Eye for Longitudinal, Non-invasive In vivo Imaging with Single-cell Resolution in Real-time

Transplantation into the Anterior Chamber of the Eye for Longitudinal, Non-invasive In vivo Imaging with Single-cell Resolution in Real-time

Intravital imaging has emerged as an indispensable tool in biological research.  In the process, many imaging techniques have been developed to study ...

An Alkali-burn Injury Model of Corneal Neovascularization in the Mouse

Under normal conditions, the cornea is avascular, and this transparency is essential for maintaining good visual acuity. Neovascularization (NV) of the ...

Murine Model for Non-invasive Imaging to Detect and Monitor Ovarian Cancer Recurrence

Epithelial ovarian cancer is the most lethal gynecologic malignancy in the United States. Although patients initially respond to the current standard of ...

A Methodological Approach to Non-invasive Assessments of Vascular Function and Morphology

The endothelium is the innermost lining of the vasculature and is involved in the maintenance of vascular homeostasis.  Damage to the endothelium may ...

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring

Use of Ultra-high Field MRI in Small Rodent Models of Polycystic Kidney Disease for In Vivo Phenotyping and Drug Monitoring

Several in vivo pre-clinical studies in Polycystic Kidney Disease (PKD) utilize orthologous rodent models to identify and study the genetic and molecular ...

Depletion of Mouse Cells from Human Tumor Xenografts Significantly Improves Downstream Analysis of Target Cells

The use of in vitro cell line models for cancer research has been a useful tool. However, it has been shown that these models fail to reliably mimic ...

Non-invasive Assessments of Subjective and Objective Recovery Characteristics Following an Exhaustive Jump Protocol

Fast recovery after strenuous exercise is important in sports and is often studied via cryotherapy applications. Cryotherapy has a significant ...

Non-invasive Assessment of Dorsiflexor Muscle Function in Mice

Assessment of skeletal muscle contractile function is an important measurement for both clinical and research purposes. Numerous conditions can negatively ...