1. |
- Heslegrave, A. J., et al.
(author)
-
A Selected reaction monitoring protocol for the measurement of sTREM2 in cerebrospinal fluid
- 2018
-
In: Biomarkers for Preclinical Alzheimer’s Disease. Perneczky R. (red.). - New York, NY : Springer. - 0893-2336. - 9781493976744 ; , s. 169-177
-
Book chapter (peer-reviewed)abstract
- Mass spectrometry plays an increasingly important role in the biomarker field with the advent of targeted proteomics. Tryptic peptides from a protein of interest can be used to create a targeted assay to interrogate cerebrospinal fluid (CSF) for biomarkers. Since heterozygous mutations in the TREM2 gene have been associated with an increased risk of Alzheimer’s disease, measuring this soluble protein in CSF has become a priority. This chapter demonstrates the development, optimization, and validation of a method to measure soluble TREM2 using a single reaction monitoring (SRM) targeted mass spectrometry assay. © 2018, Springer Science+Business Media, LLC.
|
|
2. |
- Andreasson, Ulf, 1968, et al.
(author)
-
Method and Clinical Validation of Biomarkers for Neurodegenerative Diseases
- 2021
-
In: Cerebrospinal Fluid Biomarkers. Neuromethods, vol 168. Teunissen C.E., Zetterberg H. (eds). - New York, NY : Springer. - 0893-2336. - 9781071613184 ; , s. 163-173
-
Book chapter (other academic/artistic)abstract
- In the Merriam-Webster dictionary, one definition of the word valid is “well-grounded or justifiable: being at once relevant and meaningful.” Validation is then the process of determining the degree of validity. From this broad definition, it follows that validations can be made in many different fields with quite different implications. When talking about validation, it is therefore important to specify the subject under scrutiny and in this chapter the focus will be on validation of biomarkers. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.
|
|
3. |
- Burmeister, Jason J., et al.
(author)
-
In vivo electrochemical studies of optogenetic control of glutamate signaling measured using enzyme-based ceramic microelectrode arrays
- 2018
-
In: Neuromethods. - New York, NY : Springer New York. - 1940-6045 .- 0893-2336. ; 130, s. 327-351
-
Book chapter (peer-reviewed)abstract
- Direct electrochemical measurements of glutamate release in vivo were combined with optogenetics in order to examine light-induced control of glutamate neurotransmission in the rodent brain. Self-referenced recordings of glutamate using ceramic-based microelectrode arrays (MEAs) in hippocampus and frontal cortex demonstrated precise optical control of light-induced glutamate release through channelrhodopsin (ChR2) expression in both rat hippocampus and frontal cortex. Although the virus was only injected unilaterally, bilateral and rostro-caudal expression was observed in slice imaging, indicating diffusion and active transport of the viral particles. Methodology for the optogenetic control of glutamate signaling in the rat brain is thoroughly explained with special attention paid to MEA enzyme coating and cleaning for the benefit of other investigators. These data support that optogenetic control of glutamate signaling is robust with certain advantages as compared to other methods to modulate the in vivo control of glutamate signaling.
|
|
4. |
- Cenci, M. Angela, et al.
(author)
-
Toxin-Based Rodent Models of Parkinson’s Disease
- 2021
-
In: Neuromethods. - New York, NY : Springer US. - 0893-2336 .- 1940-6045. - 9781071609125 - 9781071609118 ; 160, s. 3-19
-
Book chapter (peer-reviewed)abstract
- A major pathological hallmark of Parkinson’s disease (PD) is a severe degeneration of dopamine (DA)-producing neurons in the substantia nigra pars compacta (SNc) projecting to the motor part of the striatum. Therefore, there is a long-standing interest in using animal models with severe nigrostriatal degeneration for experimental research. Pathophysiological and behavioral features of PD are best studied in mammalian species endowed with well-developed corticobasal ganglia thalamocortical loops, such as rodents. Different toxins can be used to generate nigrostriatal damage, including 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), paraquat, and rotenone. Models based on 6-OHDA lesions provide the main advantage of a severe and reproducible DA lesions. Models based on MPTP provide easy and versatile tools to rapidly evaluate potential neuroprotective treatments. Models based on paraquat and rotenone are appealing for their relevance to some well-known environmental risk factors of the human PD, although they yield only partial dopaminergic degeneration and entail a considerable risk of nonspecific toxicity. The main general limitation of neurotoxin-based models is that they do not replicate some characterizing features of PD pathology, such as the formation of Lewy body–like proteinaceous aggregates or the anatomical pattern of neurodegeneration, which also affects nondopaminergic brain regions.
|
|
5. |
- Clausen, Fredrik, et al.
(author)
-
The Fluid Percussion Injury Rodent Model in Preclinical Research on Traumatic Brain Injury
- 2019
-
In: Animal Models of Neurotrauma. - New York, NY : Springer New York. - 0893-2336 .- 1940-6045. - 9781493997091 - 9781493997114 ; 149, s. 3-18
-
Book chapter (peer-reviewed)abstract
- There is still a lack of pharmacological treatment options for traumatic brain injury (TBI), the dominant cause of death and disability in persons under the age of 40 in the developed part of the world. Clinical TBI is a markedly complex disease, categorized into different subtypes that differ in their pathophysiology, treatment requirements, and long-term consequences. For successful development of novel treatment options, refined preclinical evaluation in rodent TBI models is mandatory. Since persisting cognitive deficits, impaired motor function, depression, and personality changes are common sequelae in TBI patients, preclinical models must produce clinically relevant behavioral deficits. Additionally, clinical TBI is a markedly heterogeneous disease with a severity span from immediately fatal to mild injuries with minor and passing symptoms. Ideally, a rodent TBI model should thus be adjustable in terms of injury severity. One of the most widely used rodent TBI model is the fluid percussion injury (FPI), which meets many of the criteria for a clinically relevant experimental model. The FPI technique relies on a fluid pressure pulse being transmitted into the skull cavity of the animal, allowing for a degree of brain displacement. By placing the craniectomy and the injury site either over the midline of the skull (the central FPI; cFPI) or over one hemisphere (the lateral FPI; lFPI) the injury shows either more diffuse (cFPI) or more focal (lFPI) characteristics. Although FPI has many advantages over other TBI models, including the possibility to vary important injury characteristics, the outcome after TBI may be influenced by other features such as gender, age, species, and even strain which should be considered in the design of the rodent models. In this chapter, we discuss the limitations and advantages, as well as the special considerations necessary when using the FPI model in rodents.
|
|
6. |
- Corona, Rebeca, et al.
(author)
-
Methods to Assess the Role of Neurogenesis in Reproductive Behaviors of Birds, Rats, and Sheep
- 2023
-
In: Neuromethods. - 0893-2336 .- 1940-6045. ; , s. 313-337
-
Book chapter (other academic/artistic)abstract
- Reproduction represents one of the most important biological events for the organism due to its relevance in perpetuating life. It allows the production of offspring with similar characteristics to the progenitor. The behavioral events of reproduction comprise several changes that prepare the organisms and favor the display of specific behaviors. Reproduction starts with the localization and selection of a possible partner, and this specific moment requires the detection of chemosensory cues that guides their attention and behavior. After the adequate partner is selected, the sexual interaction takes place, usually regulated by females. If pregnancy happens, a series of changes and adaptations occurs within the brain that prepares the mother for the future interaction with the offspring. After delivery, interaction with the offspring during early postpartum along with the pregnancy adaptations of the new mother allows the display of a complex set of parental behaviors that facilitate the care and survival of the newborn. During all these reproductive steps, several adaptations occur within the brain that prepare the organism for its current needs and, in some cases, maintain the changes until the next reproductive episode. The aim of the present chapter is to discuss one of the most complex plastic adaptations, namely adult neurogenesis that occurs in the brain and accompanies the different steps of reproduction in life. From partner attraction and selection through sexual interaction to the parental care of the offspring, we selected three different species in which evidence has shown that neurogenesis plays an important role. We will describe how in songbirds, neurons recently incorporated to the high-vocal center are necessary for the female attraction by facilitating a new singing repertoire of the male each reproductive season. In rats, from the first sexual behavior encounter, neurogenesis in the olfactory bulb is stimulated allowing a facilitation of the following interactions. The deployment of maternal behavior in sheep requires an early and highly specialized odor recognition of the offspring by the mother in which newly born olfactory bulb neurons participate. Additionally, in this chapter we overview two of the most used techniques to visualize and study adult neurogenesis, the use of endogenous and exogenous markers revealed by immunostainings and neuronal precursor labeling by electroporation.
|
|
7. |
- Dahlin, Lars B., et al.
(author)
-
Traumatic Peripheral Nerve Injuries : Experimental Models for Repair and Reconstruction
- 2019
-
In: Animal Models of Neurotrauma. - New York, NY : Springer New York. - 0893-2336 .- 1940-6045. - 9781493997114 - 9781493997091 ; 149, s. 169-186
-
Book chapter (peer-reviewed)abstract
- Peripheral nerve injuries are difficult to treat, and the clinical outcome after surgical repair and reconstruction is still insufficient, particularly concerning recovery of sensory function. To improve the clinical treatment strategies, experimental models are used to systematically examine the mechanisms behind nerve regeneration and assess the improvement of nerve regeneration by introduction of new surgical nerve repair and reconstruction methods (e.g., novel devices made by bioartificial materials). Rat models, where the sciatic nerve has essentially a similar size as a human digital nerve, are widely used to evaluate nerve regeneration with the inherent advantages and disadvantages of the experimental models. Estimations revealing that a large number of diabetic patients will eventually suffer from peripheral nerve injury have motivated development of suitable experimental diabetes models for studying the nerve regeneration process and novel treatment approaches. We have successfully used the Goto-Kakizaki rat model, which shows moderately increased blood sugar closely resembling type 2 diabetes, for assessing the surgical peripheral nerve regeneration potential with and without artificial scaffolds. In order to improve outcome after repair and reconstruction of nerve injuries, one has to have a clear concept concerning how to evaluate novel repair and reconstruction techniques in experimental models before clinical studies can be initiated in an accurate way.
|
|
8. |
- Davidsson, Johan, 1967, et al.
(author)
-
A Model for Research on Penetrating Traumatic Brain Injuries
- 2019
-
In: Neuromethods. - New York, NY : Springer New York. - 1940-6045 .- 0893-2336. ; 149, s. 47-59
-
Book chapter (other academic/artistic)abstract
- The animal model presented here produces high-speed penetrating traumatic brain injuries (pen-TBI) to simulate a form of neurotrauma that is severe and is the prevailing TBI in warzones and in areas with high incidence of violence. Commonly, these neurotraumas involve laceration of brain tissue, accompanying hemorrhage, edema, and inflammation. This also occurs in the pen-TBI model designed for rats that is presented here. During trauma, a probe, constructed in one single unit in aluminum and guided by a probe holder, is propelled by a lead bullet and penetrates at high speed into the brain parenchyma of the anesthetized animal. The animal’s head is held in position in a purposely built stereotactic frame. This frame can be adjusted in position relative the tip of the probe so that the tip of the probe is positioned on the exposed dura, using three orthogonally arranged horizontal slides. This procedure will facilitate high similarity in probe penetration location. By adjusting the air pressure in the air-driven accelerator used to accelerate the lead bullet, a large range of probe velocities can be achieved; 110 m/s probe velocity is commonly used. Several probe tip shapes are available for use in the pen-TBI model; pointy, blunt, and flat. The distance the probe penetrates the brain can be controlled. A typical distance is 5.5 mm, and this distance has been found to be almost independent of probe velocity and probe tip shape. After the probe has penetrated the animal, the pen-TBI device facilitates removal of the probe without causing additional brain damage. To do so, the animal is removed using the horizontal slider on the device that moves the animal’s head away from the probe in the direction of probe travel. The pen-TBI device is easy to operate and requires limited pre-trauma and post-trauma surgery. The device induces a small cavity, primary injury in a greater volume of the brain than the cavity and secondary injuries in an even greater volume that is several times that of the primary injury volume. The model appears to produce identical injuries in terms of appearance and dimensions in-between animals of same sex and body mass. The device also produces substantial but short-lived intracranial brain pressure changes, some 8-bar overpressure in the contralateral ventricle has been recorded, with high repeatability.
|
|
9. |
- Davidsson, Johan, 1967, et al.
(author)
-
A Sagittal Plane Rotational Injury Rodent Model for Research on Traumatic Brain Injuries
- 2019
-
In: Neuromethods. - New York, NY : Springer New York. - 1940-6045 .- 0893-2336. ; 149, s. 61-75
-
Book chapter (other academic/artistic)abstract
- The model presented here produce brain injuries following sagittal plane rearward rotational acceleration in rats. During trauma, a rotating bar, which is tightly secured to the animal head, is impacted by a striker that causes the rotating bar and the animal head to rotate rearward; the acceleration phase is followed by a rotation at constant speed and gentle deceleration when the rotating bar contacts a padded stop. The total head angle change range from 25° to 30°. By adjusting the air pressure in the air-driven accelerator used to accelerate the striker, a large range of rotational accelerations can be achieved. This model can, depending on the striker velocity, produce subdural bleedings, graded widespread axonal injuries in the corpus callosum, the border between the corpus callosum, cortex, cerebellum, olfactory bulbs, and in some of the tracts in the brain stem. The model has been shown to produce degenerating axons. For lower rotational accelerations no apparent axonal injuries can be observed. The model produces only limited signs of contusion injury, and macrophage invasions, glial fibrillary acidic protein redistribution or hypertrophy, and blood–brain barrier changes are unusual. The model produces distinct S100 and Neurofilament Light serum concentration changes, thus indicating that blood vessel and glia cell injuries may occur. The rotational acceleration trauma model presented can produce graded axonal injury, is repeatable, and produce limited other types of TBIs and as such is useful in the study of injury biomechanics, diagnostics, and treatment strategies following diffuse axonal injury and most likely also following concussion.
|
|
10. |
- Davidsson, Johan, 1967, et al.
(author)
-
Concluding Remarks
- 2019
-
In: Neuromethods. - New York, NY : Springer New York. - 1940-6045 .- 0893-2336. ; 149, s. 297-299
-
Book chapter (other academic/artistic)abstract
- In this chapter we summarize the arguments for the use of animal models for neurotrauma experiments. We also stress the need for well-controlled and well-validated models. The use of guidelines for animal experiments is an important way to increase the value of the animal models and facilitate translation to real-life situations.
|
|