Earl R. Feringa

A ventral uncrossed corticospinal tract in the rat

By studying cross-section autoradiograms of the spinal cord with dark field microscopy we demonstrated a ventral uncrossed corticospinal tract in the rat. Corticospinal fibers were labeled by the slow axoplasmic flow of a minute volume of high specific activity tritiated proline injected directly into the motor sensory cortex. The uncrossed ventral corticospinal tract was small but easily identifiable in the cervical region. More caudally the tract became less distinct and could not be traced below midthoracic levels. Only two corticospinal tracts were identified in this study: the well-known crossed dorsal corticospinal tract and the ventral uncrossed corticospinal tract described in this study. The corticospinal tract in the rat has been described as an easily identified group of fibers situated in the most ventral portion of the dorsal white funiculus of the spinal cord (1, 3, 5). Aside from a single abstract (2), we know of no report of ancillary corticospinal tracts in the rat spinal cord. Other reports indicate that the corticospinal tract in the rat spinal cord is completely crossed at the level of the caudal medulla oblongata and lies in the most ventral portion of the dorsal white columns. In the course of study of transport of tritiated proline by corticospinal axons in the rat (6), we discovered a constant ventral corticospinal tract which was easily identified by dark field illumination of cross-section autoradiographs of the spinal cord.

Immunosuppressive treatment to enhance spinal cord regeneration in rats

Various immunosuppressive regimens were used in an effort to enhance spinal cord regeneration in isologous rats. Ninety-six animals were evaluated six months after transection and immunosuppressive treatment. No evidence of regeneration was found in the control group, in animals inoculated with central nervous system tissue at birth, or in animals receiving some of the immunosuppressive regimens. Injection of 200 mg per kilogram of alpha methyl tyrosine before transection did not enhance regeneration. We did find electrophysiologic evidence of regeneration in one of 13 animals receiving a combination of immunosuppressive drugs and in four of 12 animals receiving one injection of 75 mg per kilogram of cyclophosphamide within one hour after spinal cord transection.

Descending spinal motor tract regeneration after spinal cord transection

In spite of evidence that mammalian axons do sprout in areas of central nervous system (CNS) injury and in some cases cross the gap in a transected spinal cord, the goal of useful regeneration after human cord injury remains elusive.’-6 Glial scars can be reduced and regenera t ion enhanced by a variety of methods,7-‘ but long motor tract regeneration in mammals has been claimed only by Freeman and associates.’ -2 Other investigators have not repeated their experiments, and the reliability of their endpoints of functional r e t u r n and electromyographic evidence of regeneration is disputed. Treatments have been successful in decreasing the amount of scar tissue, but the remaining scar always appears to inhibit regenerating axons. We investigated reports of those animnls in which cord regeneration did occur to search for a clue as to why it occurred in the simpler animals2 ’ -2 and in embryo^^^-^ but not in mature mammals.’ A remarkable parallel was recognized: Each group in which cord regeneration had been recorded was also known to accept skin hornograft~.~ 9 3 We decided to test the hypothesis that autoimmunity to brain antigens in those that do not produce regeneration in their spinal cords is a causal factor in their inability to regenerate. The newborn rat is still immunologically in the “plastic period” in which he can be made tolerant to foreign antigens by exposure to the antigens during the first two days of life.3 ’ 3 3 2 P a t e r ~ o n ~ ~ 3 3 4 has shown that rats exposed to emulsified spinal cord from animals of the same inbred strain on day 1 or 2 of life will have a decreased susceptibility to experimental allergic encephalomyelitis when they are challenged with spinal cord antigen in later adult life. We confirmed this ability to induce tolerance to spinal cord antigen in our own rats with similar experiments. This report will discuss our efforts to increase the potential for spinal cord regeneration in rats by methods that should be effective in inhibiting the development of homograft-type allergic responses to CNS antigen.

Axoplasmic flow of tritiated proline in the corticospinal tract of the rat

SummaryThe rates of axoplasmic transport were studied in the corticospinal tract of the rat by injecting tritiated proline into the sensory-motor cortex and subsequently analyzing the distribution of incorporated label in the spinal cord at intervals after injection. A mathematical model of the anatomy of the corticospinal tract was developed and used in analysis of the data. The rate of a fast component was calculated to be 240–420 mm per day, which is comparable with rates of fast components in the peripheral nervous system (PNS), but considerably greater than rates in other tracts in the central nervous system. A slow component was calculated to have a transport rate of 3–8 mm per day which is greater than rates found either in the CNS or PNS. This higher rate may be related to the greater length of the corticospinal tract as compared to other CNS tracts studied.

Effects of sympatholytic agents on CNS regeneration, cystic necrosis after spinal cord transection.

In rats with complete spinal cord transection, one group received alpha methyl tyrosine to block norepinephrine production, one group received dibenamine to block the effect of excess norepinephrine on the blood vessels, and one group served as a control group. None of the animals showed any evidence of long motor tract regeneration. The amount of cystic change in the rostral and caudal ends of the transected cord was unaffected by either treatment. The reported decrease in hemorrhagic necrosis that occurs when production of norepinephrine is inhibitled in animals with blunt cord trauma could not be reproduced in animals with complete cord transection. Attempts to block the effect of excess norepinephrine on blood vessels with dibenamine failed to inhibit local cord necrosis in the rats.

Darvon® and the EEG

Abstract Eighty normal male volunteers were employed in an acute and chronic double blind study of the effects on the EEG of dextropropoxyphene hydrochloride (Darvon ® ) and a similar appearing placebo. Each subject served as his own control. Dextropropoxyphene produced no statistically significant change in the EEG of normal subjects.