Dennis J Stelzner, PhD

Current Appointments

• Professor of Cell and Developmental Biology

Hospital Campus

• Downtown

Education & Fellowships

• PhD: University of Pennsylvania, 1969

Research Abstract

Olfactory Ensheathing Cells and Spinal Cord Regeneration.

Although axonal regeneration occurs within the peripheral nervous system (PNS), regeneration in the CNS is abortive. The olfactory system is unique in that olfactory receptor neurons are continually being generated to replace neurons that have died and their axons continue to grow and form connections in the olfactory bulb, their CNS target. Olfactory ensheathing cells (OECs), the glia-like cell of the olfactory nerve, have important properties necessary for this CNS ingrowth, and recent results suggest that OECs also may enhance axonal regeneration within the spinal cord. We are testing this possibility by determining if suspensions of adult OECs grown in culture can be implanted within a cryogenic lesion specifically damaging dorsal column (DC) axons of the rat spinal cord. The regeneration of DC axons is being studied morphologically by specifically labeling the axons at different times after the injury/implantation and comparing the results with groups not receiving the OEC implants or receiving Schwann cell (SC) implants, the major PNS glia-like cell. Experiments to transfect the OEC cultures with a construct directing the expression of GFP, a marker protein, are also underway to specifically label these cells to better follow their migration and integration within the host spinal cord. Studies are also underway to enhance the regeneration of dorsal column axons, to compare the regenerative response of DC axons with adjacent corticospinal tract axons, and determine if DC axons are able to reform specific connections in their brainstem target, the gracile nucleus.

2-Deoxyglucose Analysis of CNS Circuitry Activated during Motor Development

A recent modification of the 2-deoxyglucose (2DG) method indicates the level of activation of neurons by mapping their metabolic activity with cellular resolution, and has the ability to double-label neurons using immunohistochemistry. We are using this modification of the 2DG method to study the ontogeny of the central neural circuitry underlying motor development. L-DOPA injection activates stereotypic air-stepping in rats placed in a sling during early postnatal development. The pattern of 2DG labeling of neurons (silver grain density in autoradiographs) in the brainstem and spinal cord of animals involved in L-DOPA induced air-stepping is being compared to that seen in rat pups placed in a sling and injected with vehicle that do not air-step, and in uninjected pups placed in a quiet warm environment. The level of activation of inhibitory neurons in these groups is also being determined, as well as age-related differences. The effect of perinatal CNS injury (anoxia, spinal cord transection) on the functional maturation of the circuits activated by air-stepping is also being determined. Other processes requiring significant metabolic activity occur during CNS development besides neurotransmission, particularly prenatally (e.g. cell division, axonal elongation and synaptogenesis, neuronal migration and differentiation) which potentially may make 2-DG labeling difficult to interpret during this period. However, this period is also being studied pharmacologically activating different types of behavioral responses in utero. Areas of the nervous system which are selectively labeled with this method at different prenatal periods will later be tested to determine if neurons in these regions are selectively vulnerable to different types of prenatal brain insult (e.g. anoxia, alcohol intoxication).

Selected References

Maier, D.L., R.G. Kalb, and D.J. Stelzner 1995 NMDA antagonism during development extends sparing of hindlimb function to older spinally transected rats. Dev. Brain Res. 87:135-144.

Buyan-Dent, L. J., J.S. McCasland, and D.J. Stelzner 1996 Attempts to facilitate dorsal column regeneration in a neonatal spinal environment. J. Comp Neurol. 372:435-456.