J. Douglas Balentine

Ca2+-accumulation in experimental spinal cord trauma

Quantitative measurements of the time course of calcium levels in experimental spinal cord trauma have been made. The injury was produced in rats by dropping a 10 g weight from 30 cm upon exposed dura-invested spinal cord. Lumbar sections of traumatized spinal cord and internal controls from remote cervical cord were excised and analyzed for calcium using atomic absorption spectroscopy. Total calcium levels in the lesioned cord were significantly elevated over control values within 45 min post-trauma (P less than 0.005), with maximal increase at 8 h. The increased levels of calcium in the lesion tissue confirm the previous morphologic finding of calcium deposits within axons in the lesion.

Evidence for glycoconjugate in nociceptive primary sensory neurons and its origin from the Golgi complex

Glycoconjugates with terminal galactose residues were localized in rat spinal cord and spinal ganglia using lectin-HRP conjugates of Griffonia simplicifolia and Glycine max agglutinins. Alternate staining of serial sections with HRP-labelled lectins and an antibody for substance P (SP) showed staining in identical primary sensory neurons with both methods. Similarly, lectin-reactive as well as SP-positive fibers were found in Rexed laminae I and II, Lissauers tract, the spinal nucleus and tract of the trigeminal nerve, the nucleus commissuralis and a small bundle of fibers just ventral to the central canal. Administration of capsaicin to neonatal rats produced a significant decrease in lectin-reactive fibers of the substantia gelatinosa, and in the number of lectin-reactive sensory neurons. The coexistence of SP with galactose-containing glycoconjugates in spinal ganglion neurons, as well as sensitivity of these cells to capsaicin, provided a basis for classifying the reactive neurons as nociceptive in type. Ligation of dorsal roots resulted in disappearance of lectin reactivity in the spinal cord and caused accumulation of lectin-positive material proximal to the ligature, indicating somatofugal transport of galactose-containing glycoconjugates. Colchicine injection caused an increase in SP reactivity in dorsal ganglion neurons but no change in lectin staining of galactoconjugate. At the ultrastructural level affinity for the lectin conjugates was confined to the Golgi cisternae and the plasmalemma of B-type sensory neurons in the dorsal ganglion. The axolemma of unmyelinated processes stained selectively in dorsal roots and the substantia gelatinosa of the spinal cord. These findings provide evidence for the presence in certain sensory cells of a characteristic galactosylconjugate which may prove to be of significance in nerve function.

Orthostatic hypotension with brainstem tumors

Three patients with brainstem tumors had orthostatic hypotension as the major presenting manifestation. Two patients had primary tumors that involved the dorsal medulla, pons, and rostra1 spinal cord; one was a malignant astrocytoma and the other a hemangioblastoma. The third patient had an oat cell carcinoma of the lung with subependymal spread to the medulla, pons, hypothalamus, and thalamus. Evaluation of baroreceptor function in the patient with the malignant astrocytoma showed a defect in the efferent sympathetic limb of the baroreceptor reflex arc.

Ultrastructural Pathology of Nerve Fibers in Calcium-Induced Myelopathy

Calcium has been proposed as a mediator of nerve fiber degeneration following traumatic injury of the spinal cord. It induces a spongy, necrotizing myelopathy similar in its evolution to that observed in experimental spinal cord trauma. The current study was undertaken to determine the ultrastructural changes in the central nervous system (CNS) nerve fibers associated with calcium-induced myelopathy. A 10% calcium chloride (CaCl2) solution (pH 7.4) was slowly dripped on the dorsal surface of the surgically exposed lower thoracolumbar spinal cord of adult male Sprague-Dawley rats. The posterior and lateral columns of the spinal cords were fixed and processed for electron microscopy. Controls consisted of tissue from normal and sham-operated animals, as well as those receiving equal volumes and osmolalities of sodium chloride (NaCl), magnesium chloride (MgCl2), and potassium chloride (KC1) at the same pH. In the CaCl2 treated animals, spongiosis of increasing severity developed in white matter, as the result of periaxonal, adaxonal and intramyelinic swelling. Vesicular demyelination was consistently observed, beginning within one hour (h) and progressing with increasing severity up to 24–72 h. Axonal changes included pleomorphic spheroids, granular degeneration and intra-axonal calcification. The ultrastructural changes in the nerve fibers provoked by calcium were indistinguishable from those previously reported in experimental spinal cord trauma. These observations strengthen the hypothesis that calcium initiates the nerve fiber degeneration following spinal cord injury.

Oxygen tension in the globus pallidus and neostriatum of unanesthetized rats during exposure to hyperbaric oxygen

Abstract Unanesthetized rats were exposed 1 h to 100% oxygen at 60 psig (5 atmospheres absolute). Utilizing platinum semimicroelectrodes, oxygen tension was recorded from the globus pallidus and the neostriatum. Oxygen tension increased from control values (room air at ambient pressure) during the exposure period in both experimental groups. In the globus pallidus, oxygen tension reached the first stable peak in an average of 27.8 min, whereas in the neostriatum the first stable peak was reached in an average of 3.0 min. The results of this study suggest a correlation between oxygen tension and pathologic changes observed in the basal ganglia.

Retroperitoneal Ganglioneuroblastoma: A Kaleidoscope of Neuronal Degeneration: A Light and Electron Microscopic Study

The light and electron microscopic features of an unique retroperitoneal ganglioneuroblastoma in a four-year-old female are described. The unprecedented concurrence of Hirano, zebra, membranous cytoplasmic (MCB), and Pick bodies in the same population of neoplastic, sympathetic ganglion cells provides further evidence for their non-specificity. Although the pathogenesis of the membranous cytoplasmic bodies in this tumor is unclear, they ostensibly arise within endoplasmic cisterns, similar to the proposed origin of membranous cytoplasmic bodies in Tay-Sachs disease. Both the apparent continuum between argyrophilic bodies and central chromatolysis, and the incorporation of various cytoplasmic constituents within neurofilamentous proliferations reflect some of the dynamic factors involved in the formation of Pick bodies.

Complex oligodendroglial invaginations within myelinated nerve fibers of the central nervous system during axonal degeneration.

Ultrastructural studies of spinal cord in rats subjected to hyperbaric oxygen exposure and experimental spinal cord trauma have resulted in frequent degeneration of axons. In both experimental situations central nervous system myelinated fibers containing complex cytoplasmic interdigitations of electron lucent, normal appearing cytoplasm, and dense cytoplasm, interpreted as degenerative, were observed. In some of the complex profiles the electron lucent cytoplasm could be traced back to the inner mesaxon, where its relation to the latter indicated a glial origin. Cytochemical evaluation of acid phosphatase activity in the complex cytoplasmic interdigitations revealed that both components contain significant lysosomal activity. The complex structures are interpreted as being sequestrations of degenerating axoplasm by distal adaxonal oligodendroglial processes, possibly representing an unusual form of heterophagocytosis.

Tissue calcium levels in CaCl2-induced myelopathy

CaCl2-induced myelopathy was produced in rats by the application of a solution of CaCl2 to exposed leptomeninges of lumbosacral spinal cord. Equal lengths of remote cervical and lumbar cord were removed at intervals following Ca2+ application. The total Ca2+ in tissue from lumbar cord was significantly elevated over autologous cervical cord and homologous lumber controls after after 2 h. The maximum Ca2+ increase in lumbar cord was 3.9-fold that of homogolous control and was reached by 8 h post Ca2+ application. The time course for the elevation of Ca2+ as measured by atomic absorption spectrophotometry, resembles that found in spinal cord following direct physical trauma. These findings as well as similar changes in morphology and neural proteins from previous studies suggest that Ca2+ is involved in and may potentiate the degeneration of axons and myelin via Ca2+-activated neutral proteinases.

Selective Vulnerability of the Central Nervous System to Hyperbaric Oxygen

The adverse effects of hyperoxia on the central nervous system (CNS) have been well known since the 19th century writing of Paul Bert. Acute CNS oxygen toxicity is manisfested by grand mal convulsions and may result in death following status epilepticus. Bean and Seigfried2 reported a delayed or chronic type of oxygen poisoning in rats subjected to repeated brief intermittent exposures to hyperbaric oxygen (HO), which resulted in permanent limb paralysis. The paralyses observed in this type of oxygen toxicity usually affect the forelimbs bilaterally with the animals assuming a kangaroolike posture. Rigidity of the paralyzed limbs is common. Animals capable of locomotion are ataxic. A few rats become quadriplegic.

Oxygen Tensions in the Deep Gray Matter of Rats Exposed to Hyperbaric Oxygen

Selective necrosis of neurons and nuclei consistently occurs within the central nervous system (CNS) of rats paralyzed by repeated 1 hour exposures to 5 atmospheres of oxygen.l The distribution of the lesions differs from those of hypoxia in the same animal species. Excessive oxygen inhibits many enzymes vital to cellular metabolism in the CNS and it is reasonable to hypothesize that the neuronal necrosis produced by hyperbaric oxygen exposure is related to elevated tissue oxygen tensions. However, hyperbaric oxygen notedly produces cerebral vasospasm and a reduction in cerebral blood flow, and regional ischemia has been a tenable hypothesis for the occurrence of the CNS lesions. This latter mechanism seems unlikely because unilateral carotid artery ligation protects the ipsilateral but not the contralateral cerebral hemisphere from the occurrence of the oxygen induced lesions.2 (see Fig. 1)Selective necrosis of neurons and nuclei consistently occurs within the central nervous system (CNS) of rats paralyzed by repeated 1 hour exposures to 5 atmospheres of oxygen.l The distribution of the lesions differs from those of hypoxia in the same animal species. Excessive oxygen inhibits many enzymes vital to cellular metabolism in the CNS and it is reasonable to hypothesize that the neuronal necrosis produced by hyperbaric oxygen exposure is related to elevated tissue oxygen tensions. However, hyperbaric oxygen notedly produces cerebral vasospasm and a reduction in cerebral blood flow, and regional ischemia has been a tenable hypothesis for the occurrence of the CNS lesions. This latter mechanism seems unlikely because unilateral carotid artery ligation protects the ipsilateral but not the contralateral cerebral hemisphere from the occurrence of the oxygen induced lesions.2 (see Fig. 1)