Regionally Specific Human Pre-Oligodendrocyte Progenitor Cells Produce Both Oligodendrocytes and Neurons after Transplantation in a Chronically Injured Spinal Cord Rat Model after Glial Scar Ablation.

Chronic spinal cord injury (SCI) is a devastating medical condition. In the acute phase after injury, there is cell loss resulting in chronic axonal damage and loss of sensory and motor function including loss of oligodendrocytes that results in demyelination of axons and further dysfunction. In the chronic phase, the inhibitory environment within the lesion including the glial scar can arrest axonal growth and regeneration and can also potentially affect transplanted cells.

Safety and Efficacy of Rose Bengal Derivatives for Glial Scar Ablation in Chronic Spinal Cord Injury.

There are no effective therapies available currently to ameliorate loss of function for patients with spinal cord injuries (SCIs). In addition, proposed treatments that demonstrated functional recovery in animal models of acute SCI have failed almost invariably when applied to chronic injury models. Glial scar formation in chronic injury is a likely contributor to limitation on regeneration.

Role of endogenous Schwann cells in tissue repair after spinal cord injury.

Schwann cells are glial cells of peripheral nervous system, responsible for axonal myelination and ensheathing, as well as tissue repair following a peripheral nervous system injury. They are one of several cell types that are widely studied and most commonly used for cell transplantation to treat spinal cord injury, due to their intrinsic characteristics including the ability to secrete a variety of neurotrophic factors. This mini review summarizes the recent findings of endogenous Schwann cells after spinal cord injury and discusses their role in tissue repair and axonal regeneration.

Somatosensory evoked potentials can be recorded on the midline of the skull with subdermal electrodes in non-sedated rats elicited by magnetic stimulation of the tibial nerve.

Somatosensory evoked potentials (SSEPs) are a sensitive quantitative measure of conduction in somatosensory pathways of the central nervous system and are increasingly used in both clinical trials and animal experiments. SSEPs can be recorded in non-sedated rodents by magnetic stimulation (MS) of peripheral nerves. To overcome some disadvantages caused by using anesthesia and implanted recording electrodes, we used subdermal needle electrodes located on the midline of the skull to successfully record SSEPs in non-sedated rats, elicited by stimulating the tibial nerve with a magnetic stimulator.

Tail nerve electrical stimulation combined with scar ablation and neural transplantation promotes locomotor recovery in rats with chronically contused spinal cord.

To date, few treatment strategies applying cellular transplantation to the chronically injured spinal cord have yielded significant functional improvement in animal experiments. Here we report that significant improvement of locomotor function was achieved in rats with chronic spinal cord injury (SCI) by the application of combination treatments with tail nerve electrical stimulation (TANES), which can activate the central pattern generator, inducing active weight-supported stepping. Contusion injury (25 mm) to spinal cord T10 was produced by using the NYU impactor device in female, adult Long-Evans rats.

Scar ablation combined with LP/OEC transplantation promotes anatomical recovery and P0-positive myelination in chronically contused spinal cord of rats.

We have successfully removed an existing glial scar in chronically contused rat spinal cord using a rose Bengal-based phototoxic method. The purpose of this study is to examine if scar ablation benefits the anatomical recovery by cell/tissue transplantation, and thus provides a more permissive physical and biochemical environment for axonal growth, which may lead to functional recovery. Immediately after scar ablation, we transplanted lamina propria (LP) of the olfactory mucosa alone or in combination with cultured olfactory ensheathing cells (OEC) into the lesion cavity 6 weeks after contusion injury (NYU impactor device, 25 mm height setting) at spinal cord segment T10 of adult female Long-Evans rats.

Histological repair of damaged spinal cord tissue from chronic contusion injury of rat: a LM observation.

The spinal cord has an intrinsic, limited ability of spontaneous repair; the endogenous repair of damaged tissue starts a few days after spinal cord injury (SCI). To date, however, detailed observation in histology at the injury site has not been well documented. In the present study we analyzed the histological structure of the repaired tissue from injury site of rats 6 or 14 weeks after contusion injury (NYU impactor device, 25 mm height setting) on T10, and rats 8 weeks after transplantation of lamina propria (LP) or acellular lamina propria.

Extensive scarring induced by chronic intrathecal tubing augmented cord tissue damage and worsened functional recovery after rat spinal cord injury.

Intrathecal infusion has been widely used to directly deliver drugs or neurotrophins to a lesion site following spinal cord injury. Evidence shows that intrathecal infusion is efficient for 7 days but is markedly reduced after 14 days, due to time dependent occlusion. In addition, extensive fibrotic scarring is commonly observed with intrathecal infusion.

Tail nerve electrical stimulation induces body weight-supported stepping in rats with spinal cord injury.

Walking or stepping has been considered the result from the activation of the central pattern generator (CPG). In most patients with spinal cord injury (SCI) the CPG is undamaged. To date, there are no noninvasive approaches for activating the CPG.

Statins decrease chondroitin sulfate proteoglycan expression and acute astrocyte activation in central nervous system injury.

Statins elicit numerous favorable effects on central nervous system (CNS) injury, including inhibition of the rhoA/ROCK pathway. In the present study, we show that statins decrease acute astrocyte activation in CNS injury, and decrease chondroitin sulfate proteoglycan (CSPG) levels in astrocyte cultures as well as CNS injury. CSPG levels decreased by up to 45% in simvastatin-treated astrocyte cultures compared to control cultures.

Artifactual dendritic beading in rat spinal cord induced by perfusion with cold saline and paraformaldehyde.

Extensive dendritic beading of MAP2 (microtubule-associated protein 2) immunoreactivity has previously been observed in the contused rat spinal cord. However, we have also observed dendritic beading in occasional uninjured animals. The purpose of this study was to examine the possibility that perfusion conditions contributed to the dendritic beading.

Photochemical scar ablation in chronically contused spinal cord of rat.

Glial scar represents a physical and molecular barrier to axonal regeneration and has become an important target for regeneration research in chronic spinal cord injury. Although many methods have been proven useful for the prevention of scar formation in an acute injury model, to date no effective method has been described to remove an existing glial scar in a chronic injury. The chronic lesion possesses an irregular shaped scar that lines the entire perimeter of the cavity.

Simvastatin promotes neurite outgrowth in the presence of inhibitory molecules found in central nervous system injury.

Statins (3-hydroxy-3-methylglutaryl-CoA [HMG-CoA] reductase inhibitors) inhibit the rate-limiting step in the mevalonate pathway, conversion of HMG-CoA to mevalonate, by competitive inhibition with the enzyme HMG-CoA reductase. Statins not only lower cholesterol levels, but are also thought to exert neuroprotective and neurogenic effects that may be beneficial in treating brain and spinal cord injuries. Data presented here illustrate that simvastatin enables neurite outgrowth in the presence of growth-inhibitory molecules commonly found at central nervous system (CNS) injury sites.