Mark P. Dentinger

Ultrastructure of the central nervous system in a myelin deficient rat

Myelin deficiency (md) is a new mutant in the Wistar rat caused by an X-linked recessive lethal gene. One-half of the male offspring develop tremor and ataxia at 10-12 days of age and seizures at 16-21 days. Usually, the animals die 24-28 days postnatally unless survival is prolonged by anticonvulsants. Light microscopic examination of the C.N.S. shows a complete lack of myelin. The P.N.S. is normally myelinated, however. Frontal cortex, corpus callosum, optic nerves, cerebellum and spinal cord were studied routinely in affected animals aged 3-46 days. Abnormal males were identified three days after birth by the absence of myelinated axons from the ventral funiculus of the cervical cord. In mutants aged 3-16 days, axons had the usual ultrastructural features but were either entirely non-myelinated or, rarely, were invested by poorly organized, non-compacted, myelin-like loops of membranes, 2 to 4 in number. In mutants aged 17-20 days, axonal swellings appeared. These increased in number with longer survival times and contained large numbers of microtubules, neurofilaments, mitochondria and dense bodies. Normal C.N.S. myelin was not observed at any age. Two types of abnormal glial cell occur in md. The first, present in white matter at three days of age, is an abnormal oligodendrocyte. The cytoplasm contains dilatation of the rough-surfaced endoplasmic reticulum and the nuclear envelope is widened. A second cell-type, conspicuous by 10 days, has an electron-dense nucleus with prominently clumped chromatin and large cytoplasmic lipid droplets. This second cell type is believed to be a microgliacyte. The number of cytologically-normal oligodendrocytes decreases as mutants age while hypertrophied, filament-rich astrocytes occur in increasing numbers. The myelin defect in md C.N.S. is probably due to an abnormality of oligodendrocytes. Axonal alterations are probably secondary. Myelin deficiency resembles the murine mutant, Jimpy (jp), although ultrastructural changes in oligodendrocytes appear to be dis-similar and md, in contrast to jp, contains no normal-appearing C.N.S. myelin.

Ultrastructure of Axonal Reaction in Red Nucleus Of CAT

Described here are ultrastructural changes in neurons of feline red nucleus exhibiting axon reaction after unilateral rubropsinal tratotomy at the C-2 level and surviving 2 to 65 days. Ultrastructural alterations included neurofilamentous hyperplasia; proliferation of smooth ER; temporary disappearance of organized granular ER with partial substitution by haphazardly arranged, broad cisternal profiles; loss of rosette ribosomes and occurrence of single ribonucleoprotein granules or an intercisternal amorphous density; increased numbers of subsurface cisterns and allied structures, often disposed in stacks; vesiculation and vacuolation of Golgi cisternae; prevalence of autophagic bodies derived in part from Golgi complexes; probable mitochondrial hyperplasia and various qualitative changes in these organelles; an increase in lipofuscin. Dendritic changes paralleled those of perikarya save that proliferation of subsurface cisterns and autophagic bodies was absent. Abnormalities of myelinated axons and boutons occurred and may have originated from retrograde degeneration of cortical neurons induced by lateral funiculotomy. Some perikarya were devoid of axosomatic boutons. Ultrastructural changes varied with the length of postoperative survival and were, at least partly, reversible. Chromatolysis was detectable light microscopically before ultrastructural abnormality appeared. The bearing of transneuronal mechanisms on axon reaction of central neurons and the protective effect of section of axons beyond the site of origin of collaterals are discussed.

Glial and axonal development in optic nerve of myelin deficient rat mutant

Development of glial cell lines and axons is reported for the optic nerve of the myelin deficient rat mutant, md, 3-46 days postnatally. In mutants, optic nerves do not increase in area after 16 days of age whereas, in normal rats, they enlarge through 46 days of postnatal life. The density of glial cells, determined in cross-sections, is similar in md and normal littermates through 19 days postnatally. Thereafter, glial densities are greater in the mutant. Nonetheless, total glial counts are reduced in md as compared to the normal, because cross-sectional areas and lengths of mutant nerve 30-46 days after birth are smaller than those of age-matched, normal littermates. Differential counts of glial cells, made by ultrastructural criteria, show that md optic nerves contain abnormal, vacuolated, immature oligodendroglia from the third postnatal day. Furthermore, oligodendrocytes are reduced in number in older mutants; they constitute 1% of optic nerve neuroglia at 46 days. Astrocytic numbers are increased in relative, not in absolute, terms from 19 days, and microglial numbers are greater than normal in the oldest mutants. Reactive microglia, containing large cytoplasmic lipid droplets, constitute 4-8% of the glia of md nerve 19-46 days postnatally. Mean axonal areas are similar in normal rats and mutants at 19 and 43-46 days of age. However, mitochondrial density is greater in md axons 19 days after birth and mean areas of axonal mitochondria are significantly larger in 43-46 day mutants than in age-matched, normal littermates. Additionally, the percent area of axoplasm occupied by mitochondria is increased in md at both 19 and 43-46 days of age. The myelination defect in md appears to be due primarily to an oligodendroglial abnormality which precedes the normal age of onset of myelination. Astrocytic and microglial changes are secondary. Axonal enlargement proceeds normally over 46 days of postnatal life. Overall, the data do not provide definitive support for an axonal basis for the myelination defect, although measurable differences in axonal mitochondria between mutants and normals are demonstrable and qualitative abnormalities do occur in the axons of the mutant.

The role of home practice in thermal biofeedback

The role of regular home practice of hand warming was examined in the thermal biofeedback (TBF) treatment of vascular (migraine and mixed migraine and tension) headache (HA) by giving 12 sessions (over 6 weeks) of TBF to two groups of vascular HA patients (n = 23 per group). One group was asked to practice regularly at home with a home trainer between clinic sessions, whereas no mention of practice was made to the other group. A third group merely monitored HAs. Treatment was superior to no treatment. There was no advantage for the group receiving home practice, either in headache reduction or in acquisition of the hand-warming response.

Incorporation of triated leucine by axotomized rubral neurons

Fourteen kittens, 7--10 weeks of age, were injected with [3H]leucine 0.5--24 h before sacrifice 1--30 days after unilateral high cervical rubrospinal tractotomy. Histoautoradiographs of the red nuclei were prepared and counterstained with thionin. Axon reaction, evident histologically 24 h after surgery, was manifested by central chromatolysis or diffuse cytoplasmic chromophobia. Partial reversion toward a normal cytologic appearance was apparent 10--30 days postoperatively. Nucleolar and nuclear shrinkage and cytoplasmic atrophy were conspicuous accompaniments of axon reaction in rubral neurons. Expressed per cell the radioactivity of axotomized rubral nerve cells was consistently less than controls in animals surviving operation from 5 to 30 days. The data indicate that axon reaction in red nucleus is regressive in character and early associated with diminished protein synthesis. The frequently regressive nature of axon reaction in intrinsic neurons, such as those of red nucleus, probably is important in accounting for failure of regeneration of many mammalian CNS fiber tracts after injury.

Fine structure of neurons of the hypertrophied human inferior olive.

Ultrastructural study of hypertrophied inferior olives from three cases of palatal myoclonus revealed that nerve cells not infrequently contained numerous round, homogeneously electron-dense granules (mean diameter, 360 nm) located within expanded cisternal profiles of rough endoplasmic reticulum (RER). Control tissue did not contain similar structures. These granules may consist of proteinaceous secretion of the RER which, for reasons unknown, accumulates during transsynaptic degeneration of the inferior olive. Additional noteworthy electron microscopic features of neurons of the hypertrophied olive were as follows: 1. neurofilamentous hyperplasia, greater in dendrites than in perikarya: 2. vacuoles in intermediate and large (up to 15 µ) size, derived from RER; and 3. prominent intracytoplasmic protrusions by boutons containing dense core vesicles (mean diameter, 98 nm). Glomeruloids were identified ultrastructurally and consisted of numerous boutons interspersed among neurofilament-rich dendrites and occasional, filament-packed astrocytic profiles. Frequently, these boutons also contained dense-core vesicles. It seems possible that the boutons mentioned may arise from collateral axonal sprouts

Direction of Temperature Control in the Thermal Biofeedback Treatment of Vascular Headache

In order to test for the specific therapeutic effects of thermal biofeedback (TBF) for hand warming on vascular headache (HA), 70 patients with chronic vascular HA were randomly assigned to TBF for hand warming, TBF for hand cooling, TBF for stabilization of hand temperature, or biofeedback to suppress alpha in the EEG. Patients in each condition initially had high levels of expectation of therapeutic benefit and found the treatment rationales highly credible. Participants in each condition received 12 treatment sessions on a twice-per-week basis. Based on daily HA diary data gathered for 4 weeks prior to treatment and 4 weeks after treatment, HA Index was significantly (p=.003) reduced as was HA medication consumption. There were no differential reducations in HA Index or Medication Index among the four conditions. Global self-reports of improvement gathered at the end of the post-treatment monitoring period also did not differ among the four conditions. We were unable to demonstrate a specific effect of TBF for hand warming on vascular HA activity.

Preliminary results from the self-regulatory treatment of high-medication-consumption headache

Data are presented from a prospective clinical replication series of ten consecutive high-medication headache patients who presented for nondrug treatment of their headaches. For the first eight, an attempt was made to withdraw the patients from medication, with the assistance of relaxation training, prior to entering a comprehensive self-regulatory treatment program. For the last two, drug withdrawal accompanied the treatment. Six of the ten patients showed clinically significant reductions in headache activity, which held up over follow-ups of up to 12 months. Psychological tests provide some discrimination between success and failures.

The refractory headache patient—I. Chronic, daily, high intensity headache☆

Two studies on patients with Chronic, Daily, High Intensity Headache (CDHIHA) are presented. In the first, their response to various self-regulatory (biofeedback, relaxation) treatments was compared to that of case controls matched for age, duration and Ad Hoc Committee diagnoses who had 1-2 headache-free days per week (Group II) and 3-5 headache-free days per week (Group III). The CDHIHA patients had a significantly poorer response to treatment (12.7 vs 49.8% improvement for Groups II and III combined). In the second study, the psychological profiles of an enlarged sample of CDHIHA patients were compared to matched case controls from Group II and Group III. The CDHIHA patients tended to be more anxious, more hysterical and to have more non-headache somatic complaints than Groups II and III combined.

Platelet morphology in Parkinson's disease: An electron microscopic study

There are no peripheral diagnostic markers for Parkinsons disease (PD). However, recent studies of platelets in PD patients indicate that mitochondrial and monoamine oxidase function may be abnormal. This investigation examines platelets in PD from a morphological standpoint utilizing transmission electron microscopy (EM). Fourteen PD patients (seven treated, seven untreated) and seven age matched controls had platelets separated from other blood components, fixed in a standardized fashion and examined by EM. Platelets (in the activated form because they were collected in glass tubes) were evaluated at magnifications of 15,000x and 40,000x. Abnormalities observed in treated and untreated PD patients included the presence of numerous large intracytoplasmic vacuoles formed from the open canalicular system. Morphometric examination performed at 40,000x magnification indicated that the mean area of vacuoles and the cytoplasmic volume percent of platelets occupied by vacuoles were significantly greater in PD (p < 0.05) than controls. However, differences observed between treated and untreated PD groups suggest that these changes could be caused by the disease or the treatment or both. No abnormalities were found in relation to mitochondria, storage granules and glycogen. From EM assessment, we conclude that platelets in PD are morphologically abnormal.