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A quantitative method for microstructural analysis of myelinated axons in the injured rodent brain
Erik van Tilborg1, Caren M van Kammen1, Caroline G M de Theije1
1Laboratory of Neuroimmunology and Developmental Origins of Disease, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.
Abstract:
MRI studies (e.g. using diffusion tensor imaging) revealed that injury to white matter tracts, as observed in for instance perinatal white matter injury and multiple sclerosis, leads to compromised microstructure of myelinated axonal tracts. Alterations in white matter microstructure are also present in a wide range of neurological disorders including autism-spectrum disorders, schizophrenia and ADHD. Whereas currently myelin quantity measures are often used in translational animal models of white matter disease, it can be an important valuable addition to study the microstructural organization of myelination patterns in greater detail. Here, we describe methods to extensively study the microstructure of cortical myelination by immunostaining for myelin. To validate these methods, we carefully analyzed the organization of myelinated axons running from the external capsule towards the outer layers of the cortex in three rodent models of neonatal brain injury and in an adult stroke model, that have all been associated with myelination impairments. This unique, relatively easy and sensitive methodology can be applied to study subtle differences in myelination patterns in animal models in which aberrations in myelination integrity are suspected. Importantly, the described methods can be applied to determine efficacy of novel experimental treatments on microstructural organization of cortical myelination.
Insights
Researchers developed a new method to study the microstructural organization of myelination in the brain. This technique uses immunostaining to analyze myelinated axonal tracts, aiding research into neurological disorders and treatment efficacy.
Area of Science:
- Neuroscience
- Histology
- Biomedical Engineering
Background:
- White matter tract injury, seen in conditions like multiple sclerosis and perinatal brain injury, compromises myelinated axonal tracts.
- Altered white matter microstructure is implicated in various neurological disorders, including autism spectrum disorder, schizophrenia, and ADHD.
- Current animal models often focus on myelin quantity, but detailed microstructural analysis of myelination patterns is needed.
Purpose of the Study:
- To introduce and validate a novel immunostaining method for detailed analysis of cortical myelination microstructure.
- To assess the utility of this method in rodent models of neonatal brain injury and adult stroke.
- To provide a sensitive tool for investigating myelination integrity and treatment efficacy in neurological disease models.
Main Methods:
- Development of an immunostaining protocol targeting myelin.
- Application of the method to analyze myelinated axon organization in rodent models.
- Validation of the technique using established models of white matter injury.
Main Results:
- The described immunostaining method allows for extensive study of cortical myelination microstructure.
- The technique was successfully applied to analyze myelinated axon organization in multiple rodent models.
- The methods provide a sensitive approach to detect subtle differences in myelination patterns.
Conclusions:
- This novel immunostaining methodology offers a valuable and sensitive approach to study cortical myelination microstructure.
- The technique is applicable to various animal models of neurological disorders affecting white matter.
- It can be instrumental in evaluating the effectiveness of experimental treatments on myelination integrity.
