Quercetin in an animal model of spinal cord compression injury: correlation of treatment duration with recovery of motor function.

OBJECTIVES: We have shown previously that administration of quercetin after spinal cord injury in a rat model induced significant recovery of motor function. In the same model for spinal cord compression injury, we now have correlated the treatment duration with the extent to which motor function is recovered. METHODS: Seventy-four male Wistar rats were assigned to eight experimental groups. Mid-thoracic spinal cord injury was produced in the animals of seven groups. Quercetin was administered intraperitoneally in individual doses of 25 micromol kg(-1). Treatment onset was 1 h after the injury. The length of treatment ranged from one single injection to 10 days, with injection frequencies of two or three times daily. BBB (Basso, Beattie and Bresnahan) scores were obtained and tissue preservation at the site of injury was analyzed. RESULTS: None of the untreated control animals recovered motor function sufficient to walk. When quercetin was administered twice daily over a period of either 3 or 10 days, about 50% of the animals recovered sufficient motor function to walk. Stepping/walking (BBB > or =10) were seen in two of six animals receiving only a single injection and in one of the six animal receiving three injections. Surprisingly, none of the animals that received quercetin injections three times daily recovered the ability to walk (all BBB < or = 9). CONCLUSION: Quercetin administration results in preservation of tissue bridges at the site of injury. Treatment success depends on frequency of administration and overall dose.

Olfactory ensheathing cells: historical perspective and therapeutic potential.

Olfactory ensheathing cells (OECs) are the glial cells that ensheath the axons of the first cranial nerve. They are attracting increasing attention from neuroscientists as potential therapeutic agents for use in the repair of spinal cord injury and as a source of myelinating glia for use in remyelinating axons in demyelinating diseases such as multiple sclerosis. This review mainly addresses the cell biological aspects of OECs pertinent to addressing two questions. Namely, where do OECs fit into the groupings of central nervous system (CNS)/peripheral nervous system (PNS) glial cells and should OECs be viewed as a clinically relevant alternative to Schwann cells in the treatment of spinal cord injury? The evidence indicates that OECs are indeed a clinically relevant alternative to Schwann cells. However, much more work needs to be done before we can even come close to answering the first question as to the lineage and functional relationship of OECs to the other types of CNS and PNS glial cells.

LacZ-expressing olfactory ensheathing cells do not associate with myelinated axons after implantation into the compressed spinal cord.

Studies have shown that implanting olfactory ensheathing cells (OECs) may be a promising therapeutic strategy to promote functional recovery after spinal cord injury. Several fundamental questions remain, however, regarding their in vivo interactions in the damaged spinal cord. We have induced a clip compression injury at the T10 level of the spinal cord in adult rats. After a delay of 1 week, OECs isolated from embryonic day 18 rats were implanted into the cystic cavity that had formed at the site of injury. Before implantation, OECs were infected with a LacZ-expressing retrovirus. At 3 weeks after implantation, LacZ-expressing OECs survived the implantation procedure and remained localized to the cystic cavity. At the electron microscopic level, the cystic cavity had clusters of LacZ-expressing OECs and numerous Schwann cells lacking LacZ expression. Although labeled OECs made no direct contact with axons, unlabeled Schwann cells were associated with either a single myelinated axon or multiple unmyelinated axons. Positively labeled OEC processes often enveloped multiple Schwann cell-axon units. These observations suggest that the role of OECs as the primary mediators of the beneficial effects on axon growth, myelination, and functional recovery after spinal cord injury may require re-evaluation.

Amelioration of experimental allergic encephalitis (EAE) through phase 2 enzyme induction.

The multiple sclerosis (MS) lesion is characterized by an inflammatory cell mediated attack on white matter. Oxidative stress appears to play a role in the onset and progression of MS. We reasoned that decreasing oxidative stress might ameliorate MS. One way of decreasing oxidative stress is to induce phase 2 enzymes. The model chosen to test this hypothesis was experimental allergenic encephalomyelitis (EAE) induced in the Lewis rat. The 26 animals were placed into two groups: 1) those on normal rat chow, 2) those on rat chow containing 250 mumoles t-butylhydroxyanisole (BHA)/kg. After 2 weeks, animals were administered 100 micrograms guinea pig myelin basic protein and examined daily in a blinded fashion. Twenty-nine days later, animals were sacrificed, blood collected for glutathione (GSH) measurements and tissues collected for histology. Six of the 13 control chow animals developed hindlimb weakness or paralysis while 5 developed tail weakness only. Only 1 BHA fed animal exhibited symptoms--hindlimb weakness. Clinical symptoms correlated well with the extent of perivascular lymphocyte infiltration. Animals with BHA in the diet had 20% higher red cell GSH indicting induction of phase 2 enzymes. We conclude that dietary phase 2 enzyme inducers should be examined for their ability to ameliorate MS.