Secondary Degeneration of Oligodendrocyte Precursor Cells Occurs as Early as 24 h after Optic Nerve Injury in Rats.

Optic nerve injury causes secondary degeneration, a sequela that spreads damage from the primary injury to adjacent tissue, through mechanisms such as oxidative stress, apoptosis, and blood-brain barrier (BBB) dysfunction. Oligodendrocyte precursor cells (OPCs), a key component of the BBB and oligodendrogenesis, are vulnerable to oxidative deoxyribonucleic acid (DNA) damage by 3 days post-injury. However, it is unclear whether oxidative damage in OPCs occurs earlier at 1 day post-injury, or whether a critical 'window-of-opportunity' exists for therapeutic intervention.

Cuprizone feed formulation influences the extent of demyelinating disease pathology.

Cuprizone is a copper-chelating agent that induces pathology similar to that within some multiple sclerosis (MS) lesions. The reliability and reproducibility of cuprizone for inducing demyelinating disease pathology depends on the animals ingesting consistent doses of cuprizone. Cuprizone-containing pelleted feed is a convenient way of delivering cuprizone, but the efficacy of these pellets at inducing demyelination has been questioned.

Damage Mechanisms to Oligodendrocytes and White Matter in Central Nervous System Injury: The Australian Context.

Traumatic brain injury (TBI) and spinal cord injury (SCI) present a significant contribution to the global disease burden. White matter tracts are susceptible to both the physical forces of trauma and cascades of pathological secondary degeneration. Oligodendrocytes, the myelinating cells of the central nervous system (CNS), and their precursors are particularly vulnerable cell populations and their disruption results in a loss of white matter, dysmyelination, and poor myelin repair.

Comparing modes of delivery of a combination of ion channel inhibitors for limiting secondary degeneration following partial optic nerve transection.

Injury to the central nervous system is exacerbated by secondary degeneration. Previous research has shown that a combination of orally and locally administered ion channel inhibitors following partial optic nerve injury protects the myelin sheath and preserves function in the ventral optic nerve, vulnerable to secondary degeneration. However, local administration is often not clinically appropriate.

The effects of a combination of ion channel inhibitors on pathology in a model of demyelinating disease.

Background: Multiple sclerosis (MS) has been shown to feature oxidative damage, which can be modelled using the cuprizone model of demyelinating disease. Oxidative damage can occur as a result of excessive influx of calcium ions (Ca) and oligodendroglia are particularly vulnerable. However, the effects of limiting excess Ca influx on oxidative damage, oligodendroglia and myelin structure are unknown.

Elucidating the Inability of Functionalized Nanoparticles to Cross the Blood-Brain Barrier and Target Specific Cells in Vivo.

The adsorption of serum proteins on the surface of nanoparticles (NPs) delivered into a biological environment has been known to alter NP surface properties and consequently their targeting efficiency. In this paper, we use random copolymer (p(HEMA- ran-GMA))-based NPs synthesized using 2-hydroxyethyl methacrylate (HEMA) and glycidyl methacrylate (GMA). We show that serum proteins bind to the NP and that functionalization with antibodies and peptides designed to facilitate NP passage across the blood-brain barrier (BBB) to bind specific cell types is ineffective.

Comparison of ion channel inhibitor combinations for limiting secondary degeneration following partial optic nerve transection.

Following neurotrauma, secondary degeneration of neurons and glia adjacent to the injury leads to further functional loss. A combination of ion channel inhibitors (lomerizine + oxATP + YM872) has been shown to be effective at limiting structural and functional loss due to secondary degeneration. Here we assess efficacy of the combination where oxATP is replaced with Brilliant Blue G (BBG), a more clinically applicable P2X receptor inhibitor.

Oligodendroglia Are Particularly Vulnerable to Oxidative Damage after Neurotrauma .

Loss of function following injury to the CNS is worsened by secondary degeneration of neurons and glia surrounding the injury and is initiated by oxidative damage. However, it is not yet known which cellular populations and structures are most vulnerable to oxidative damage Using Nanoscale secondary ion mass spectrometry (NanoSIMS), oxidative damage was semiquantified within cellular subpopulations and structures of optic nerve vulnerable to secondary degeneration, following a partial transection of the optic nerve in adult female PVG rats. Simultaneous assessment of cellular subpopulations and structures revealed oligodendroglia as the most vulnerable to DNA oxidation following injury.

Limiting oxidative stress following neurotrauma with a combination of ion channel inhibitors.

Following injury to the central nervous system, secondary degeneration is mediated by Ca2+ imbalances and overproduction of reactive oxygen species from mitochondria, and is associated with myelin deficits and loss of function. Preventing intracellular Ca2+ influx at the acute phase of injury is a potential strategy for limiting these deficits and preserving function. The use of single ion channel inhibitors has had little success in attenuating morphological and functional deficits, potentially due to the many pathways by which calcium can traverse the cell membrane.