Ultrastructural changes in the sinuatrial and atrioventricular nodes of the heart of the monkey (Macaca fascicularis) after bilateral vagotomy

This study describes the ultrastructural changes in the sinu-atrial (SA) and atrio-ventricular (AV) nodes of the monkey (Macaca fascicularis) after bilateral mid-cervical vagotomy at 1, 3, 5, 7 and 14 days post-operations. The changes were similar in both types of nodal cells. The most obvious feature of the degenerating nodal cells was the swollen mitochondria with disrupted cristae. Other changes include increased granular sarcoplasmic reticulum, increased glycogen particles, vacuolation of mitochondria and increased lysosomal activity. Axonal profiles in the vicinity of the nodal cells showed swelling and vacuolation. Cardiac neurons also showed some changes such as distended granular endoplasmic reticulum, increased accumulation of glycogen particles and increased lipofuscin granules. Macrophages and Schwann cells were the main scavengers in removing the degenerated nodal cells and axonal profiles. In the case of affected cardiac neurons, satellite cells seemed to act as main scavenger cells. It is postulated that the nodal cells are dependent on the incoming fibres of the vagus nerve for their survival. By an understanding of the ultrastructural changes in the nodal cells after bilateral vagotomy, it may help in developing new strategies to explore in depth of the conducting system of the heart.     

Enkephalins and functionally specific vagal preganglionic neurons to the heart: ultrastructural studies in the cat

In cat, distinct populations of vagal preganglionic and postganglionic neurons selectively modulate heart rate, atrioventricular conduction and left ventricular contractility, respectively. Vagal preganglionic neurons to the heart originate in the ventrolateral part of nucleus ambiguus and project to postganglionic neurons in intracardiac ganglia, including the sinoatrial (SA), atrioventricular (AV) and cranioventricular (CV) ganglia, which selectively modulate heart rate, AV conduction and left ventricular contractility, respectively. These ganglia receive projections from separate populations of vagal preganglionic neurons. The neurochemical anatomy and synaptic interactions of afferent neurons which mediate central control of these preganglionic neurons is incompletely understood. Enkephalins cause bradycardia when microinjected into nucleus ambiguus. It is not known if this effect is mediated by direct synapses of enkephalinergic terminals upon vagal preganglionic neurons to the heart. The effects of opioids in nucleus ambiguus upon AV conduction and cardiac contractility have also not been studied. We have tested the hypothesis that enkephalinergic nerve terminals synapse upon vagal preganglionic neurons projecting to the SA, AV and CV ganglia. Electron microscopy was used combining retrograde labeling from the SA, AV or CV ganglion with immunocytochemistry for enkephalins in ventrolateral nucleus ambiguus. Eight percent of axodendritic synapses upon negative chronotropic, and 12% of axodendritic synapses upon negative dromotropic vagal preganglionic neurons were enkephalinergic. Enkephalinergic axodendritic synapses were also present upon negative inotropic vagal preganglionic neurons. Thus enkephalinergic terminals in ventrolateral nucleus ambiguus can modulate not only heart rate but also atrioventricular conduction and left ventricular contractility by directly synapsing upon cardioinhibitory vagal preganglionic neurons.     

Atrioventricular nodal re-entrant tachycardia associated with stimulant treatment.

A 13-year-old African-American female taking sertraline for obsessive compulsive disorder was diagnosed with her first episode of atrioventricular (AV) nodal re-entrant tachycardia five days after beginning Mixed Salts of a Single-Entity Amphetamine Product (Adderall) for treatment of attention-deficit hyperactivity disorder (ADHD). She received successful cardioversion with 6 mg of intravenous adenosine, but developed a second episode of possible AV nodal re-entrant tachycardia twelve days after Adderall was reinitiated at half the previous dose. The patient had clinically similar cardiac episodes five and six months after treatment was changed to slow-release methylphenidate. Stimulant medication may evoke onset of AV nodal tachyarrhythmias in patients who have the potential to develop them, possibly in combination with a selective serotonergic reuptake inhibitor (SSRI).     

Ultrastructural circuitry of cardiorespiratory reflexes: there is a monosynaptic path between the nucleus of the solitary tract and vagal preganglionic motoneurons controlling atrioventricular conduction in the cat

We have tested the hypothesis: (1) that presumptive negative dromotropic vagal preganglionic neurons in the ventrolateral nucleus ambiguus (NA-VL) can be selectively labelled from the heart, by injecting one of two fluorescent tracers into the two intracardiac ganglia which independently control sino–atrial (SA) rate or atrioventricular (AV) conduction; i.e., the SA and AV ganglia, respectively. The NA-VL was examined for the presence of single and/or double labelled cells. Over 91% of vagal preganglionic neurons in the NA-VL projecting to either intracardiac ganglion did not project to the second ganglion. Consequently, we also tested the hypothesis: (2) that there is a monosynaptic connection between neurons of the medial, and/or dorsolateral nucleus of the solitary tract (NTS), rostral to obex, and negative dromotropic neurons in the NA-VL. An anterograde tracer was injected into the NTS, and a retrograde tracer into the AV ganglion. The anterograde marker was found in both myelinated and unmyelinated axons in the NA-VL, as well as in nerve terminals. Axo–somatic and axo–dendritic synapses were detected between terminals labelled from the NTS, and retrogradely labelled negative dromotropic neurons in the NA-VL. This is the first ultrastructural demonstration of a monosynaptic pathway between neurons in the NTS and functionally associated (negative dromotropic) cardioinhibitory neurons. The data are consistent with the hypothesis that the neuroanatomical circuitry mediating the vagal baroreflex control of AV conduction may be composed of as few as four neurons in series, although interneurons may also be interposed within the NTS.     

Cardiotopic organization of the nucleus ambiguus? An anatomical and physiological analysis of neurons regulating atrioventricular conduction

Previous data indicate that there are anatomically segregated and physiologically independent parasympathetic postganglionic vagal motoneurons on the surface of the heart which are capable of selective control of sinoatrial rate, atrioventricular conduction and atrial contractility. We have injected a retrograde tracer into the cardiac ganglion which selectively regulates atrioventricular conduction (the AV ganglion). Medullary tissues were processed for the histochemical detection of retrogradely labeled neurons by light and electron microscopic methods. Negative dromotropic retrogradely labeled cells were found in a long column in the ventrolateral nucleus ambiguus (NA-VL), which enlarged somewhat at the level of the area postrema, but reached its largest size rostral to the area postrema in an area termed the rostral ventrolateral nucleus ambiguus (rNA-VL). Three times as many cells were observed in the left rNA-VL as compared to the right (P < 0.025). Retrogradely labeled cells were also consistantly observed in the dorsal motor nucleus of the vagus (DMV). The DMV contained one third as many cells as the NA-VL. The right DMV contained twice as many cells as the left (P < 0.05). These data are consistent with physiological evidence that suggests that the left vagus nerve is dominant in the regulation of AV conduction, but that the right vagus nerve is also influential. While recording the electrocardiogram in paced and non-paced hearts,l-glutamate (GLU) was microinjected into the rNA-VL. Microinjections of GLU caused a 76% decrease in the rate of atrioventricular (AV) conduction (P < 0.05) and occasional second degree heart block, without changing heart rate. The effects of GLU were abolished by ipsilateral cervical vagotomy. These physiological data therefore support the anatomical inference that CNS neurons that are retrogradely labeled from the AV ganglion selectively exhibit negative dromotropic properties. Retrogradely labeled negative dromotropic neurons displayed a round nucleus with ample cytoplasm, abundant rough endoplasmic reticulum and the presence of distinctive somatic and dendritic spines. These neurons received synapses from afferent terminals containing small pleomorphic vesicles and large dense core vesicles. These terminals made both asymmetric and symmetric contacts with negative dromotropic dendrites and perikarya, respectively. In conclusion, the data presented indicate that there is a cardiotopic organization of ultrastructurally distinctive negative dromotropic neurons in the NA-VL. This central organization of parasympathetic preganglionic vagal motoneurons mirrors the functional organization of cardioinhibitory postganglionic neurons of the peripheral vagus nerve. These data are further discussed in comparison to a recent report on the light microscopic distribution and ultrastructural characteristics of negative chronotropic neurons in the NA-VL⁴². The data support the hypothesis that anatomically separated and functionally selective parasympathetic preganglionic vagal motoneurons in the NA may independently control AV conduction and cardiac rate.     

Horseradish peroxidase localization of the sympathetic postganglionic neurons innervating the cat heart

The localization of the sympathetic postganglionic neurons innervating the cat heart has been investigated by using retrograde axonal transport of horseradish peroxidase (HRP). HRP was injected into the subepicardial layers of 4 different cardiac regions. The animals were sacrificed 72-96 h later and fixed by perfusion via the left ventricle. The paravertebral sympathetic ganglia from the superior cervical, middle cervical and stellate ganglia to T10 ganglia were removed and processed for HRP identification. Following injections of HRP into the apex of the heart, the sinoatrial (SA) nodal region and the ventral wall of the right ventricle, we observed that HRP-labeled sympathetic neurons were localized predominantly in the right stellate ganglia, and to a lesser extent, in the right superior and middle cervical ganglia, and left stellate ganglia. Fewer labeled cells were found in the right T4-T6. T8 and T9. After HRP injection into the dorsal wall of the left ventricle, HRP-labeled cells were present mainly in the left stellate ganglia.     

Neuronal-glial and synaptic plasticity in the adult rat paraventricular nucleus

Using quantitative ultrastructural analysis on cells identified by immunogold postembedding immunocytochemistry, we show that magnocellular oxytocinergic neurons in the adult rat paraventricular nucleus (PVN) undergo significant neuronal-glial and synaptic changes upon stimulation. Thus, during lactation, the surface membranes of most PVN oxytocinergic somata and dendrites were directly juxtaposed; many were also contacted synaptically by the same axonal terminal ('shared' synapses). Non-oxytocinergic profiles showed few plasmalemma juxtapositions and 'shared' synapses. These ultrastructural changes are similar to those that modify oxytocin neurons in the supraoptic nucleus under the same conditions, and indicate that the whole oxytocinergic system in the hypothalamus is capable of neuronal-glial and synaptic plasticity when stimulated to release its neurohormone.     

The olivocerebellar system. II. Some ultrastructural correlates of inferior olive destruction in the rat

Short- and long-term ultrastructural changes induced in rat inferior olivary nucleus (ION) and cerebellum by a single injection of 3-acetylpyridine (3-AP) were investigated. Evidence of perikaryal and dendritic alterations was already present in numerous ION neurons at 3 h after injection. All ION neurons were affected at 6 h. Complete destruction of the entire ION was achieved within 8–10 h. Time-course and cytological features of this degeneration were discribed. Total absence of axonal terminal degeneration in the ION or at its periphery rules out the existence of recurrent olivary axons in these locations.Climbing fiber (CF) terminal degeneration in the cerebellar cortex apparently was restricted to the molecular layer, which cast serious doubts on the existence of glomerular collaterals of CFs. Evidence of axonal terminal degeneration was observed within all cerebellar nuclei at 24 and 25 h after 3-AP treatment, but degenerating profiles were unexpectedly infrequent.Consequential to CF deafferentation, Purkinje cells (P.cells) underwent both precocious and delayed ultrastractural changes. Delayed and long-range changes involved mainly dendrites and perikarya. Axon terminals underwent precocious but prolonged alterations which were interpreted as evidence supporting enhanced synaptic activity of P. cells deprived of CFs.     

Central control of atrio-ventricular conduction and left ventricular contractility in the cat heart: Synaptic interactions of vagal preganglionic neurons in the nucleus ambiguus with neuropeptide Y-immunoreactive nerve terminals

In the cat, vagal postganglionic controls of heart rate, atrio-ventricular (AV) conduction and left ventricular contractility are mediated by three separate intrinsic cardiac ganglia, the sinoatrial (SA), AV and cranioventricular (CV) ganglia, respectively. The vagal preganglionic neurons (VPNs) that project to these ganglia are located in the ventrolateral nucleus ambiguus (NA-VL). We have previously shown that the VPNs projecting to the SA, AV and CV ganglia are distinct from one another. We have also demonstrated that neuropeptide Y-immunoreactive (NPY-IR) axon terminals synapse upon VPNs projecting to the SA ganglion. In the present study, we test the hypothesis that those VPNs projecting to the AV ganglion (negative dromotropic VPNs) and those projecting to the CV ganglion (negative inotropic VPNs) are innervated by NPY-IR terminals in NA-VL. A retrograde tracer was injected into the AV or CV ganglion of the cat, and the brains subsequently processed for visualization of tracer and the immunocytochemical visualization of NPY by dual labeling electron-microscopic methods. We observed that 11+/-5% of all axodendritic synapses and 8+/-6% of all axosomatic synapses upon negative inotropic VPNs were NPY-IR. Furthermore, 19+/-14% of all axodendritic synapses upon negative dromotropic VPNs were NPY-IR. A few NPY-IR axosomatic synapses upon negative dromotropic neurons were also observed. NPY-IR terminals in NA-VL occasionally formed axosomatic synapses with NPY-IR neurons and axoaxonic synapses with unlabeled terminals. These results suggest that central NPY afferents to the NA-VL modulate the vagal preganglionic control of AV conduction and left ventricular contractility.     

Cerebellar injury due to phenytoin. Identification and evolution of Purkinje cell axonal swellings in deep cerebellar nuclei of mice

Summary The present study describes the identification and the ultrastructural and numerical evolution of Purkinje cell axonal swellings induced by phenytion. Thirty male C57BI/6J mice received phenytion orally in doses up to 100 mg/kg daily and were killed after 3, 6, 10, 14, and 48 days of treatment. Light and electron microscopic investigations as well as morphometric analysis of cut surface area and numerical density of axonal swellings were performed. The swellings appeared as early as 6 days after initiation of treatment and gradually increased in size and frequency. Use of an anti-lymphocyte monoclonal antibody (CD 3), specifically cross-reacting with Purkinje cells, identified the swellings as dystrophic Purkinje cell axons. On grounds of their ultrastructural appearance they were classified into three distinct types occurring at different time intervals after phenytoin exposure. At 6 days, most axonal swellings contained loosely aggregated membranous vesicles and tubules in a finely granulated matrix (type 1). At 14 days, larger axonal swellings appeared characterized by the presence of three-dimensional networks of branched and anastomosing membranous tubules (type 2). At 48 days, even larger axons contained bodies of highly condensed membranous material of sometimes paracrystalline appearance (type 3). It is suggested that phenytoin-induced axonal pathology of Purkinje cells is a dynamic process characterized by the progressive accumulation of proliferating membranous material arranged in an increasingly complex fashion.Supported by the Deutsche Forschungsgemeinschaft, grant VO 272, 5-1     

Ultrastructural changes in the atrioventricular valves of streptozotocin-induced diabetic rats

The present study describes ultrastructural changes in the atrioventricular (AV) valves of diabetic rats at 3, 6, 9 and 12 months. At 3 and 6 months of diabetes, the interstitial cells were characterized by an accumulation of vacuoles, lysosomes, electron-dense vesicles, mitochondria and cisternae of rough endoplasmic reticulum in the cytoplasm. There were numerous collagen fibres in the interstitial space. Unmyelinated axons were ensheathed by Schwann cells. Infiltration of macrophages was observed near the interstitial cells. Each macrophage showed a large round or oval nucleus containing heterochromatin masses at the periphery of the cell nucleus. At 9 and 12 months of diabetes, the interstitial cells contained numerous vacuoles, dilated mitochondria, agranular vesicles and a prominent multivesicular body in the cytoplasm. Degenerating unmyelinated nerve fibres were encountered near the interstitial cells. Phagocytic macrophages contained numerous vacuoles of various sizes, which occupied most of the cytoplasmic area. Several vacuoles and degenerated electron-dense granules (some of them appeared to be fragmented) were present in the cytoplasm of interstitial cells and macrophages. It is concluded that interstitial cells in the AV valves contribute to valvular dysfunction in the streptozotocin-induced diabetic rats.     

Spatially divergent cardiac responses to nicotinic stimulation of ganglionated plexus neurons in the canine heart

Ganglionated plexuses (GPs) are major constituents of the intrinsic cardiac nervous system, the final common integrator of regional cardiac control. We hypothesized that nicotinic stimulation of individual GPs exerts divergent regional influences, affecting atrial as well as ventricular functions. In 22 anesthetized canines, unipolar electrograms were recorded from 127 atrial and 127 ventricular epicardial loci during nicotine injection (100 mcg in 0.1 ml) into either the 1) right atrial (RA), 2) dorsal atrial, 3) left atrial, 4) inferior vena cava-inferior left atrial, 5) right ventricular, 6) ventral septal ventricular or 7) cranial medial ventricular (CMV) GP. In addition to sinus and AV nodal function, neural effects on atrial and ventricular repolarization were identified as changes in the area subtended by unipolar recordings under basal conditions and at maximum neurally-induced effects. Animals were studied with intact AV node or following ablation to achieve ventricular rate control. Atrial rate was affected in response to stimulation of all 7 GPs with an incidence of 50–95% of the animals among the different GPs. AV conduction was affected following stimulation of 6/7 GP with an incidence of 22–75% among GPs. Atrial and ventricular repolarization properties were affected by atrial as well as ventricular GP stimulation. Distinct regional patterns of repolarization changes were identified in response to stimulation of individual GPs. RAGP predominantly affected the RA and posterior right ventricular walls whereas CMVGP elicited biatrial and biventricular repolarization changes. Spatially divergent and overlapping cardiac regions are affected in response to nicotinic stimulation of neurons in individual GPs.     

Ultrastructural appearance of intentionally frustrated axonal regeneration in rat sciatic nerve

The ultrastructural appearance of axons regenerating after crush injury was examined in rat sciatic nerves in which proximodistal growth was interrupted (frustrated regeneration) by placement of a tight ligature 1 cm distal to the original crush injury, and in nerves lacking a distal tie (unimpeded regeneration). Examination of unimpeded regenerating axons four and seven days after injury showed minute axonal sprouts as well as scattered dilated (2-10 microns) axonal profiles containing large numbers of anastomosing tubulovesicular elements and vacuoles. These dilated profiles were consistent with the appearance of growth cones, the motile tips of regenerating axons, as described in various in vivo and in vitro systems. The ultrastructural appearance of regenerating axons accumulating proximal to a frustrating tie was a function of time after arrival at the ligature. At the earliest time examined (one week) large numbers of axonal profiles accumulated at the ligature which were qualitatively similar to growth cones seen in unimpeded regeneration, although slightly larger in diameter. With time, the uniform population of growth cones proximal to the frustrating ligature was replaced by dilated axons containing large numbers of neurofilaments, dense collections of heterogeneous membranous organelles, or delicate to coarse tubulovesicular elements admixed with a variety of subcellular organelles. Rare examples of axonal dystrophy were demonstrated after chronic frustration of regeneration; however, they represented only a small percentage (less than 1%) of frustrated axons. Frustrated regeneration was accompanied by scattered examples of demyelination/remyelination of large axons proximal to the ligature as well as transperineurial growth of axons as microfascicles to escape the site of ligation.     

Effects of posture, effort and psychophysiological activation on atrio-ventricular node and Kent bundle refractoriness.

A new protocol is described for non-invasive evaluation of electrophysiological effects of autonomic nervous system on both normal and abnormal atrio-ventricular conduction in patients with Wolff-Parkinson-White (WPW) syndrome. In 64 WPW patients with stable Kent-type ventricular preexcitation transoesophageal atrial pacing has been carried out to quantify changes in both atrioventricular (AV) node and Kent bundle refractoriness and maximal conductive capability induced by posture, physical exercise and psychophysiological activation. A significant shortening of AV nodal and accessory pathway refractory periods was found, induced by manoeuvres enhancing the sympathetic outflow, being the AV node the most sensitive structure. This finding suggests that an exhaustive investigation protocol of WPW patients should include the evaluation of the neurovegetative effects on cardiac electrophysiological parameters, under conditions which can reproduce as close as possible the individual situations a patient has to face in his real life.     

Axonal dystrophy of dorsal root ganglion sensory neurons in a mouse model of Niemann-Pick disease type C

Niemann-Pick disease type C (NP-C) is a progressive and fatal neurological disorder characterized by intracellular accumulation of cholesterol and glycolipid. A Balb/c-npc1 mutant strain is a genetically authentic murine model of NP-C, and homozygous mice show progressive weight loss and tremor or ataxia until death at 12-14 weeks of age. Neuropathologically, this model is known to faithfully reproduce the cardinal histologic features of NP-C including neuronal storage, appearance of swollen axons (spheroids), and neuronal loss, although the cellular mechanisms of neural degeneration are largely unknown. To investigate the mode of neural degeneration of sensory neurons in NP-C, we studied the central processes of dorsal root ganglion (DRG) neurons at the level of the medullary dorsal column nuclei and the spinal dorsal horn with special attention to the ultrastructural changes of presynaptic axon terminals. The appearance of axonal spheroids in the dorsal column nuclei and the loss of axons in the spinal nerve roots were assessed quantitatively. We show that the gracile nuclei develop numerous axonal spheroids after only 3 weeks. At 6 and 9 weeks, dystrophic axons, which were separated from simple axonal spheroids by the ultrastructural presence of distinctive tubulo-vesicular elements, progressively increased in size and number. These neuropathological findings are identical to those of gracile axonal dystrophy (GAD) of the normal aging mouse. Presynaptic elements were exclusively involved in spheroid formation. The cuneate nuclei and the spinal dorsal horn revealed fewer axonal spheroids and only rare dystrophic changes. This was associated with a significant drop in the number of L4-5 dorsal root axons in NP-C mouse at 9 weeks of age compared with controls. These results support the existence of a length-dependent axonopathy in the central processes of DRG neurons and are consistent with the view that altered axonal transport, which is implicated in the pathogenesis of GAD in physiological aging, may be an underlying mechanism in neuronal degeneration in NP-C. Clinically, the premature development of GAD may be responsible for ataxia, one of the early manifestations of this disease.     

An Ultrastructural Study of the Ciliary Ganglia of the Cat and Monkey (Macaca fascicularis) Following Preganglionic Axotomy

The present study describes ultrastructural changes in the ciliary ganglia of the cat and monkey following preganglionic axotomy. At 3, 5 and 7 days after operation, the nucleus of some neurons was irregular, with prominent indentations, and displaced to the periphery of the neuron. The surface of most neurons was irregular. Neurofilaments and glycogen-like granules were much increased in some neurons. At 21 and 28 days after operation, neurons again appeared normal. Dendritic profiles, packed with many mitochondria and glycogen-like granules, could often be observed from 3 days after operation. In longitudinal section such profiles represented expanded trunks of dendrites; dilated mitochondria and dense bodies were sometimes encountered within them. At later stages after operation, some of these profiles were synaptically contacted by, or closely associated with, axon terminals. In myelinated axons, mitochondria and glycogen-like granules were also increased in number and dilated profiles and dense bodies were found within the axoplasm. In unmyelinated axons, dilated profiles and myelin-like figures were present, as were vesiculo-tubular structures and dense bodies. Electron-dense and -lucent changes could both be observed in myelinated and unmyelinated axons. Almost all the axon terminals were affected 3 days after operation. Within such degenerating axon terminals, the synaptic vesicles had accumulated to form one or several clumps, sometimes the degenerating axon terminals had undergone filamentous hyperplasia. At 45 days after operation, hardly any axon terminals were encountered. Non-neuronal cells, including satellite cells, macrophages and Schwann cells, were actively involved in removing degenerating axons and other cell debris.     

Comparison of the axonal and glial reactions between the caudal and rostral border in the cryoinjured dorsal funiculus of the rat spinal cord

Axonal and glial reactions to traumatic injury were compared between the caudal and rostral border of the lesion after freeze-injury to the C3 dorsal funiculus by attaching a liquid nitrogen-cooled copper probe to the dorsum of the rat spinal cord. The axonal and glial changes were examined up to 60 days postoperative by light and electron microscopy and immunohistochemistry for neurofilaments. Regenerative axonal changes and the appearance of numerous undifferentiated cells were found at the caudal border 7 days after cryoinjury. In contrast, such axonal and cellular reactions were scarce at the rostral border. Undifferentiated cells clearly manifested their phenotypes by differentiating into oligodendrocytes or astrocytes 11 days postinjury. The results indicated that glial cell reactions occurred in association with regenerative axonal changes at the proximal stump of the injured nerve fibers, suggesting that regenerating and demyelinated naked axons could be responsible for the appearance of the immature glial cells.     

Comparison of ultrastructural changes in proximal and distal segments of transected giant fibers of the cockroach Periplaneta americana

When the giant axons of the cockroach Periplaneta americana are transected the proximal segment (the part connected to the soma) regenerates by tip sprouting and the distal segment degenerates. The initial ultrastructural response (24-48 h post-transection) occurring in the cut ends of the proximal and distal segments are similar. This response includes the disappearance of neurotubules; appearance of amorphous material in the axoplasm and a gradual accumulation of large numbers of small mitochondria, vesicles of various sizes and smooth endoplasmic reticulum. The axolemma in the region of organelle accumulation invaginates and glial processes are present in the invagination. The similarity of the changes that occur in the cut ends of the proximal and distal segments indicates that the primary reaction to axotomy is of a local nature and does not depend on the soma. Two to four days after transection, the cut end of the distal axonal segment reveals signs of degeneration. These include the appearance of swollen mitochondria, lysosomes, myelinated bodies and shrinking of the axon. In addition there is a massive proliferation of glial processes around the degenerating axons. Sprouting from the tip of the proximal segment starts 5--7 days post axotomy. Sprouts were identified as profiles containing few neurotubules, many vesicles and abundant smooth endoplasmic reticulum. 'Growth cone-like' structures were identified. The ultrastructural reorganization of the cut end of the proximal segment is discussed in relation to changes in membrane properties of the regenerating tip, as previously described by us.     

Ultrastructural changes in the hypothalamic secretory nuclei of rats depending on the duration of clinical death.

The studies were carried out on neurosecretory nuclei of rat hypothalamus following complete circulatory arrest for 5 min (group I) and 10 min (group II). The surviving time of the animals after the experiment was 6 weeks. In group I, the ultrastructural appearance of the perikaryonic areas of the neurons indicates increased metabolic activity of these cells. Crinophagocytic bodies were noted near the Golgi apparatus. In the processes of neurons changes in the structure of the cytoskeletal elements were observed. In group II significant differences were noted, as compared with group I. They consisted in the desolation of the rough endoplasmic reticulum membranes from ribosomes, dilatation of the Golgi area cisternae, and swelling of mitochondria. In the perivascular region cells with the surface of the cytoplasmic processes membranes covered by the product of the Alcian blue reaction were noticed. In our opinion these cells may represent "cerebral macrophages". The ultrastructural changes were more pronounced in animals of group II, as compared with animals of group I.     

Induction of Presynaptic Reexpression of an Adhesion Protein in Lamina II after Dorsal Root Deafferentation in Adult Rat Spinal Cord

Limbic system-associated membrane protein (LAMP), a 64-kDa membrane protein, is an axon guidance adhesion molecule expressed by neurons in limbic system-related areas of the CNS. During development, LAMP is expressed on growing axons, growth cones, and their target neurons, but in adults it is restricted to membranes of somata and dendrites. In the adult spinal cord, LAMP immunoreactivity is found only on neurons of lamina II, lamina X, and the intermediolateral cell column and its ultrastructural localization is entirely postsynaptic. We studied changes in the expression of LAMP in lamina II of adult rat spinal cord after L1–S2 dorsal rhizotomy, a procedure that partially deafferents lamina II neurons and induces axonal sprouting by spared systems in lamina II. At the light microscopic level, LAMP immunoreactivity in lamina II was decreased in density at 3, 10, and 60 days postoperatively. This decrease in immunoreactivity suggests that LAMP expression by lamina II neurons may normally be regulated by specific afferent activity. Ultrastructurally, in control lamina II and after deafferentation in both control and deafferented lamina II at 3 and 60 days postoperatively, LAMP expression was restricted to postsynaptic membranes. Ten days after deafferentation, however, when axons are actively sprouting, LAMP was expressed on both axonal and postsynaptic membranes. The reexpression of LAMP on axonal profiles after deafferentation may identify axons that undergo sprouting in response to deafferentation.