Handbook of Experimental Neurology: Methods and Techniques in Animal Research

Cover......Page 1
Half-title......Page 3
Title......Page 5
Copyright......Page 6
Contents......Page 7
Contributors......Page 10
Part I Principles and general methods......Page 17
1 Introduction: Animal modeling – a precious tool for developing remedies to neurological diseases......Page 19
2.1 Introduction......Page 22
2.1.1 Ethical issues and considerations......Page 23
2.2.1 Council of Europe (CoE) and Convention ETS/123......Page 25
2.2.2 European Union (EU) and Directive 86/609......Page 27
2.3.1 The work......Page 29
2.3.3 The people......Page 31
References......Page 33
3.1 Introduction......Page 35
3.2 Environmental enrichment......Page 36
3.3 Caging......Page 40
3.4 Environmental control......Page 41
3.4.3 Ventilation......Page 42
3.4.5 Noise......Page 43
3.5.1 Feeding and watering......Page 44
3.5.2 Cage cleaning......Page 45
References......Page 46
4.1 Dyes......Page 49
4.3 Ear tags......Page 51
4.4 Removing digits......Page 53
4.6 Electronic tagging......Page 54
Acknowledgments......Page 55
5.1 Overview......Page 56
5.2 Preoperative medication......Page 57
5.3 Analgesia......Page 58
5.4 Systemic anesthesia......Page 60
5.4.1 Injectable anesthesia......Page 61
5.4.2 Inhalation anesthesia......Page 66
Anesthetic breathing systems......Page 67
Anesthetic machine components......Page 71
Inhalation anesthetics......Page 74
5.5 Monitoring of anesthesia......Page 76
5.6 Postoperative care......Page 77
5.7 Local anesthesia......Page 78
Anesthesia using hypothermia......Page 79
References......Page 80
6 Euthanasia in small animals......Page 83
6.1.2 Carbon dioxide and carbon monoxide......Page 84
6.2 Mechanical/physical methods......Page 85
6.2.1 Cervical dislocation......Page 86
6.2.2 Decapitation......Page 87
6.2.6 Head trauma......Page 88
Acknowledgments......Page 89
References......Page 90
7.1.1 The surgeon......Page 91
Planning......Page 92
Anatomy......Page 93
7.2.1 Surgical instruments......Page 94
7.2.2 The operating area......Page 95
7.2.3 The animals......Page 96
Temperature......Page 97
7.2.4 Suture materials......Page 98
Tying knots......Page 99
Wound closure and care......Page 100
Surgical asepsis......Page 101
7.2.6 Anesthesia......Page 102
7.3.1 Blood sampling......Page 103
Catheters and their preparation......Page 104
Catheterization of the jugular vein......Page 105
Catheterization of the carotid artery......Page 106
Catheterization of the jugular vein......Page 107
Cardiac perfusion-fixation and removal of the brain......Page 112
Stereotaxic brain surgery......Page 113
Microdialysis......Page 117
7.5 Non-invasive and invasive measurement of blood pressure in rodents......Page 118
7.5.2 Exteriorized catheters......Page 119
Data acquisition system......Page 120
Blood pressure transmitters......Page 121
7.7 Recording of body, brain, and muscle temperature......Page 124
7.7.2 Muscular temperature......Page 125
References......Page 126
8.1 Introduction......Page 130
8.2 Beyond the link between gene and disorder......Page 131
8.3 Methods for the production of transgenic mice......Page 134
8.3.1 Making the human SOD1 transgenic mouse......Page 135
8.4 Methods for the production of knockout mice......Page 136
8.5 The production of transgenic rats......Page 137
8.6 Challenges of gene targeting and emerging strategies......Page 138
8.7 The impact of transgenic technology......Page 140
8.8 Summary......Page 141
References......Page 142
9.2 Magnetic resonance imaging......Page 148
9.3 Computed X-ray tomography......Page 154
9.4 Positron emission tomography......Page 157
References......Page 158
10.2 General hazards......Page 163
10.3 Personal hygiene and protective clothing......Page 164
10.4 Infectious hazards and zoonoses......Page 165
10.5 Chemical and radiation hazards......Page 166
10.6 Laboratory animal allergies......Page 167
10.7 Risk assessment......Page 168
References......Page 169
11.1 Limitations and principles......Page 170
11.2 General experimental considerations......Page 171
11.3 Individual behavioral tests......Page 172
11.3.2 Tactile placing (forelimb and hindlimb)......Page 173
11.3.6 Resistance to lateral pressure......Page 174
11.3.10 Beam-walking......Page 175
11.3.12 Somatosensory asymmetry test......Page 176
11.3.13 Limb-use asymmetry (cylinder) test......Page 177
11.4 Use in focal ischemia models......Page 178
11.4.4 Open field behavior......Page 179
11.4.5 Resistance to lateral pressure......Page 180
11.4.7 Foot-fault test......Page 181
11.4.12 Corner test......Page 182
References......Page 184
12.2 Fixation of brain tissue......Page 189
12.5 Staining methods for brain: analysis of different cellular components......Page 190
12.7 Brain for immunocytochemical analysis......Page 191
12.9 Brain for molecular biological analysis......Page 195
References......Page 196
13.1 Introduction......Page 197
Materials......Page 198
Procedure......Page 200
13.2.2 Rat cerebral microvascular endothelial cells......Page 201
Materials......Page 202
Procedure......Page 203
Materials......Page 205
Procedure......Page 206
Procedure......Page 207
Solutions......Page 208
Materials......Page 209
13.3.2 Assessment of apoptotic injury (two independent pathways)......Page 210
Materials......Page 211
Materials......Page 212
13.4.1 Anoxia......Page 213
Procedure......Page 214
Procedure......Page 215
Materials......Page 216
Materials......Page 217
13.5.3 Embolic model of focal cerebral ischemia......Page 218
Procedure......Page 219
Procedure......Page 220
Procedure......Page 221
Procedure......Page 222
13.6.2 Cylinder test......Page 223
13.6.4 Morris water maze test......Page 224
References......Page 225
14.1.1 Systemic immunology......Page 228
Blood-brain barrier......Page 229
Resident cells of the central nervous system......Page 230
Immune response of the CNS......Page 235
Resident cells of the peripheral nervous system......Page 238
Immune response of the peripheral nervous system......Page 239
14.3.1 Experimental autoimmune encephalomyelitis......Page 240
Cellular immunity in EAE......Page 241
Humoral immunity in EAE......Page 242
14.3.2 Experimental autoimmune myasthenia gravis......Page 243
Humoral immunity in EAMG......Page 244
14.3.3 Experimental autoimmune neuritis......Page 245
Cellular immunity in EAN......Page 246
14.3.4 Immunotherapeutic strategies in CNS and PNS autoimmune diseases......Page 247
Therapeutic targets directed at co-stimulatory signals......Page 248
Therapeutic targets directed at gene delivery......Page 249
14.4 Concluding remarks......Page 250
References......Page 252
15.1 Overview......Page 255
15.2.2 Refinement of the concept......Page 256
15.3 Sex differences in brain anatomy......Page 257
15.3.2 Steroid receptors......Page 258
15.4.1 Dopamine and serotonin......Page 259
15.4.2 Other neurotransmitters......Page 260
15.5.1 Female sensitivity......Page 261
Take-home points......Page 262
15.6.2 Locomotor activity......Page 263
15.6.5 Dimorphic immune system......Page 264
15.7.1 Cognition......Page 265
15.7.2 Alzheimer’s disease......Page 266
15.7.4 Depression......Page 267
Take-home points......Page 268
References......Page 269
16.1 Introduction......Page 273
16.2 The ependymal route......Page 275
16.3.1 Herpes simplex type 1-derived vectors......Page 277
16.3.4 Adeno-associated virus vectors......Page 278
Preparation of the injecting device......Page 279
Preparation of the working area......Page 280
Follow-up......Page 281
References......Page 283
17.1 Introduction......Page 285
17.2.1 Source, dissection, and age of donor tissue......Page 287
17.2.2 Status of the host target......Page 288
17.2.3 Hypothesized mechanism of graft function......Page 290
17.2.4 Immunological compatibility of donor and host......Page 291
Facilities and equipment......Page 293
Instruments, disposables, and glassware......Page 294
Preparation......Page 295
17.3.2 Staging pregnant rats......Page 296
17.3.4 Removing the embryo brains......Page 298
17.3.5 Dissecting embryonic tissues......Page 299
17.3.6 Preparing dissociated cell suspensions......Page 300
17.3.7 Counting cell viability......Page 301
The suspension microsyringe......Page 303
The suspension injection......Page 304
17.4 Refinements in the cell suspension protocols......Page 305
17.5.1 Alternative fetal tissue dissections......Page 308
17.5.2 Peripheral, adult, and non-neuronal sources......Page 309
17.5.3 Labeling cells for transplantation......Page 311
17.5.4 Neonatal transplantation......Page 313
Surgery......Page 315
References......Page 316
Part II Experimental models of major neurological diseases......Page 325
18.1 Introduction......Page 327
18.3.1 Intraluminal suture (monofilament) MCA occlusion model......Page 328
18.3.2 Thromboembolic model......Page 331
18.3.3 Direct surgical MCA occlusion model......Page 334
18.3.4 Embolus model......Page 335
18.4 Why do drugs work in animals but not in humans?......Page 336
18.4.4 Mortality......Page 337
18.4.7 Treatment initiation time point and time window studies......Page 338
18.4.11 Lack of sufficient data......Page 339
References......Page 340
19.1 Introduction......Page 345
19.2.2 Rat......Page 346
19.2.3 Mouse......Page 349
19.3 Cardiac arrest models......Page 350
19.3.1 Rats......Page 351
19.3.2 Mouse......Page 353
19.4 Other global cerebral ischemia models......Page 354
References......Page 355
20.1 Introduction......Page 361
20.2.1 Intracerebral hemorrhage......Page 362
Blood injection model......Page 363
Bacterial collagenase injection model......Page 364
Balloon inflation model......Page 365
20.2.2 Intraventricular hemorrhage......Page 366
Hemodynamic IVH models......Page 367
20.2.3 Subarachnoid hemorrhage......Page 368
Endovascular filament model of SAH......Page 369
Blood injection model......Page 370
20.2.4 Subdural hemorrhage......Page 371
Blood injection model......Page 372
Chronic SDH......Page 373
References......Page 374
21.2 Closed head injury......Page 382
21.3 Fluid percussion......Page 383
21.5 Rotational injury......Page 384
21.7 Cryogenic injury......Page 385
References......Page 387
22.1 Introduction......Page 391
22.3 Models that are best utilized for assessing therapeutics and diagnostics......Page 392
22.3.1 Tumor cell lines......Page 393
22.3.2 Location......Page 394
22.4 Models that are better for assessing biological issues......Page 396
22.4.1 Chemical carcinogenesis......Page 397
22.4.2 Virus-induced tumors......Page 398
22.4.3 Murine transgenic models......Page 399
22.5 Summary......Page 403
References......Page 404
23.1 Introduction......Page 409
23.2 Models of disease......Page 412
23.4 Relapsing models......Page 416
23.5 Immunization site and adjuvants can modulate EAE......Page 417
23.6 Passive transfer of disease......Page 418
23.7 Transgenic models......Page 419
References......Page 421
24.2 6-Hydroxydopamine model of PD......Page 427
24.3 MPTP-induced model of PD......Page 429
24.4 Paraquat-induced model of neurodegeneration......Page 433
24.5 Rotenone-induced PD model......Page 435
24.6 Proteosomal inhibitor-induced PD model......Page 437
24.7 Genetic models of PD......Page 438
24.8 Knockout mouse models of PD......Page 441
References......Page 442
25.2 Experimental models of temporal lobe epilepsy......Page 454
25.2.1 Kindling model......Page 455
25.2.2 Pilocarpine model......Page 457
25.2.3 Kainic acid model......Page 459
25.3 Experimental models of epilepsy in the developing brain......Page 460
Kainic acid model......Page 462
Pentylenetetrazol (PTZ) model......Page 463
25.4 Models of malformations of cortical development......Page 464
25.4.1 Non-genetic models of MCD......Page 465
25.4.2 Genetic models of MCD......Page 466
References......Page 467
26.1 Introduction......Page 473
hyh mouse......Page 474
H-Tx rat......Page 475
Injections into the cisterna magna......Page 476
Kaolin......Page 477
Cyanoacrylic gel......Page 478
26.3.1 Behavior......Page 479
26.3.2 Imaging......Page 480
26.4 Summary......Page 481
References......Page 482
27.2 Bacterial meningitis......Page 488
27.3 Experimental models of bacterial meningitis in the infant rat......Page 489
27.4.1 Intracisternal route of infection......Page 491
27.4.2 Intracerebral administration of bacteria......Page 493
27.4.4 Assessing therapeutic modalities for the potential treatment of bacterial meningitis......Page 494
27.5 Brain abscess......Page 495
27.5.1 Induction of experimental brain abscess in the mouse......Page 496
27.5.2 Experimental brain abscess models in the rat......Page 497
27.5.3 Citrobacter koseri-induced experimental brain abscess......Page 498
27.6 Conclusions and perspectives......Page 500
References......Page 501
28.1 Introduction......Page 503
28.2.3 Mice expressing human midsized neurofilament......Page 505
28.3.1 Inbred strains......Page 506
28.3.2 F hybrids......Page 508
Strain name B6.Cg-Tg (SOD1-G93A)dl1Gur/J (Jackson Laboratories stock number 002299)......Page 509
Strain name B6SJL-Tg (SOD1-G93A)dl1Gur/J (Jackson Laboratories stock number 002300)......Page 510
28.4.1 Assessment of disease onset and progression......Page 512
Motor score......Page 513
Body weight......Page 514
28.4.5 Late-stage animals......Page 515
28.4.6 Timescale......Page 516
28.5 ALS rat model......Page 517
References......Page 518
29.1 Introduction......Page 520
29.2 Current classification of sleep disorders......Page 521
29.2.2 Hypersomnias......Page 522
29.2.5 Parasomnias......Page 523
29.3 Physiology of sleep......Page 524
29.4 Overview of sleep disorders with genetic backgrounds......Page 527
29.5.1 Spontaneous occurring models......Page 528
Canine narcolepsy......Page 529
Hypocretin-deficient human narcolepsy......Page 531
Continuing animal studies in narcolepsy research......Page 533
PLMS associated with narcolepsy......Page 534
29.5.3 Brain lesion models......Page 535
29.6.1 Random mutagenesis......Page 536
29.6.2 Sleep phenotype variations and quantitative trait loci......Page 537
29.7.1 Transgenic and gene targeting in mice......Page 539
29.7.2 General considerations for interpreting the results using knockout and transgenic mice......Page 543
29.7.3 Functional genomics in rats......Page 544
29.8 Simpler animal models......Page 545
29.8.1 Drosophila melanogaster......Page 546
29.8.2 Danio rerio......Page 548
29.9 Conclusions......Page 549
References......Page 550
30.2 Muscle individuality......Page 560
30.3 Muscle sampling and histological analysis......Page 563
30.4 Muscle satellite cells, differentiation, and muscle cell culture......Page 564
30.6 Genetically modified mice as models for muscle phenotypes......Page 565
30.7 Functional testing of murine muscle......Page 567
30.8 In vitro measurement of single fiber and skinned fiber force......Page 569
30.10.1 Upregulation of alternative genes......Page 570
30.10.3 Cell replacement......Page 571
References......Page 572
Index......Page 578