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.
Highlights
Around 40% of the human brain consists of white matter, which mainly contains myelinated axons that allow rapid transmission of action potentials to distant brain areas[1,2]
In order to study cortical myelination after neonatal brain injury in great detail, brain sections were stained for MBP and various analyses were performed
Myelination was investigated in three rodent models: a rat 2-hit model of neonatal diffuse WMI (fetal inflammation and postnatal hypoxia (FIPH)), a P5 mouse 2-hit model of neonatal unilateral WMI (hypoxia-ischemia (HI) + LPS), and a P9 mouse model of neonatal unilateral asphyxia comprising both grey and white matter injury (HI)
Summary
Around 40% of the human brain consists of white matter, which mainly contains myelinated axons that allow rapid transmission of action potentials to distant brain areas[1,2]. We demonstrate using four different rodent models of both neonatal brain injury and adult stroke that staining brain sections for myelin-basic-protein (MBP) enables highly detailed analysis of the microstructural integrity of myelinated axons running from the external capsule in the deep white matter towards the outer cortical layers.
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