Putative glutamatergic and/or aspartatergic cells in the main and accessory olfactory bulbs of the rat.

The "transmitter-specific" retrograde axonal tracer 3H-D-aspartate has been used to demonstrate neurons in the olfactory bulb which putatively utilize aspartate and/or glutamate as their neurotransmitter and which send an axon either to the piriform cortex or within the bulb itself. Injections of 3H-D-aspartate into layer I of the anterior piriform cortex, in the zone of termination of axons from the olfactory bulb, labeled only a few cells in the main olfactory bulb, located in the mitral and external plexiform layers. Although these cells resembled mitral and tufted cells, they tended to have smaller somata than other mitral or tufted cells and apparently form a distinct subpopulation of relay cells. In contrast, many of the mitral cells of the accessory olfactory bulb were labeled by the same injections of 3H-D-aspartate, probably as a result of involvement of the accessory olfactory tract or its bed nucleus in the injection site. Similar injections of the "nonspecific" tracer HRP into the anterior piriform cortex labeled most of the cells in the mitral cell layer of both the main and accessory olfactory bulbs, and some tufted cells in the external plexiform layer. It is concluded that only a small, distinct subpopulation of the mitral or tufted cells of the main olfactory bulb are aspartatergic and/or glutamatergic, while many (at least) of the mitral cells of the accessory olfactory bulb use the excitatory amino acids as transmitters. Injections of 3H-D-aspartate directly into the main olfactory bulb also failed to label the mitral and deeply situated tufted cells. However, a few cells were labeled in the periglomerular region, the superficial external plexiform layer, and the granule cell layer near the injection site. These labeled cells were smaller than mitral and tufted cells but generally larger than periglomerular or granule cells. They may represent a population of glutamatergic or aspartatergic short axon cells. In addition, small cells of an unknown type were labeled in the olfactory nerve layer following injections in the deepest part of the bulb. These cells do not correspond to any of the well characterized cell types of the olfactory bulb.

Sources of presumptive glutamergic/aspartergic afferents to the rat ventral striatopallidal region.

The distribution of presumptive glutamergic and/or aspartergic neurons retrogradely labeled following injections of 3H-D-aspartate (3H-D-Asp) into the ventral striatopallidal region was compared with the distribution of neurons labeled by comparable injections of wheat germ agglutinin-horseradish peroxidase (WGA-HRP). The afferents labeled by 3H-D-Asp were a subset of those labeled by WGA-HRP. The major sources of afferents to the nucleus accumbens and olfactory tubercle that could be labeled by 3H-D-Asp were in the medial frontal and insular cortices; the olfactory cortex; the lateral, basolateral, and basomedial amygdaloid nuclei; and the midline nuclear complex of the thalamus. The corresponding afferents to the ventral pallidum arose in the central, medial, and basomedial amygdaloid nuclei and the midline thalamic nuclei. In addition, the nucleus of the lateral olfactory tract was moderately or heavily labeled by 3H-D-Asp injections into all three areas, and cells were labeled in the subiculum following injection in the anteromedial part of the nucleus accumbens. Conversely the ventral striatopallidal structures themselves were, at best, sparsely labeled by any of the 3H-D-Asp injections. Neurons in the substantia nigra, ventral tegmental area, dorsal raphe, and locus coeruleus were labeled by WGA-HRP but not by 3H-D-Asp, except for an occasional cell in the raphe. The results indicate that 3H-D-Asp is a specific retrograde tracer and suggest that there are widespread, presumably excitatory, glutamergic and/or aspartergic inputs to the ventral striatum and pallidum.

Sources of presumptive glutamatergic/aspartatergic afferents to the magnocellular basal forebrain in the rat.

The distribution of presumptive glutamatergic and/or aspartatergic neurons retrogradely labeled following injections of [3H]-D-aspartate into the magnocellular basal forebrain of the rat was compared with the distribution of neurons labeled by comparable injections of the nonspecific retrograde axonal tracer wheat germ agglutinin conjugated to horseradish peroxidase. Cells retrogradely labeled by wheat germ agglutinin-horseradish peroxidase were found in a wide range of limbic and limbic-related structures in the forebrain and brainstem. In the telencephalon, labeled neurons were seen in the orbital, medial prefrontal, and agranular insular cortical areas, the amygdaloid complex, and the hippocampal formation. Labeled cells were also seen in the olfactory cortex, the lateral septum, the ventral striatopallidal region, and the magnocellular basal forebrain itself. In the diencephalon, neurons were labeled in the midline nuclear complex of the thalamus, the lateral habenular nucleus, and the hypothalamus. In the brainstem, labeled cells were found bilaterally in the ventral midbrain, the central gray, the reticular formation, the parabrachial nuclei, the raphe nuclei, the laterodorsal tegmental nucleus, and the locus coeruleus. A significant fraction of the afferents to the magnocellular basal forebrain appear to be glutamatergic and/or aspartatergic. Only a few of the regions labeled with wheat germ agglutinin-horseradish peroxidase were not also labeled with [3H]-D-aspartate in the comparable experiments. Most prominent among the non-glutamatergic/aspartatergic projections were those from fields CA1 and CA3 of the hippocampus, the hilus of the dentate gyrus, the dorsal subiculum, the tuberomammillary nucleus, and the ventral pallidum. In addition, most of the lateral hypothalamic and brainstem projections to the magnocellular basal forebrain were not significantly labeled with [3H]-D-aspartate. In addition to these inputs, a commissural projection from the region of the contralateral nucleus of the horizontal limb of the diagonal band was confirmed with both wheat germ agglutinin-horseradish peroxidase and the anterograde axonal tracer Phaseolus vulgaris leucoagglutinin. This projection did not label with [3H]-D-aspartate or [3H]-GABA, suggesting that it is not glutamatergic/aspartatergic or GABAergic. Furthermore, double labeling experiments with the fluorescent retrograde tracer True Blue and antibodies against choline acetyltransferase indicate that the projection is not cholinergic.

Sources of presumptive glutamatergic/aspartatergic afferents to the mediodorsal nucleus of the thalamus in the rat.

The distribution of presumptive glutamatergic and/or aspartatergic neurons retrogradely labeled following injections of 3HD-aspartate into the mediodorsal nucleus of the thalamus (MD) in the rat was compared to the distribution of neurons labeled by comparable injections of the nonspecific retrograde tracer wheat germ agglutinin conjugated horseradish peroxidase (WGA-HRP). Cells retrogradely labeled by WGA-HRP were found in the prefrontal and agranular insular cortices; in forebrain structures such as the amygdaloid complex, the piriform cortex, the ventral pallidum and the reticular nucleus of the thalamus; and in several different parts of the brainstem, such as the superior colliculus, central grey, and substantia nigra, pars reticulata. Some, but not all, of these projections are presumably glutamatergic and/or aspartatergic. The projections to MD from the prefrontal and agranular insular cortices are well labeled with 3H-D-aspartate, as are projections from the anterior cortical amygdaloid nucleus. Projections from the superior colliculus to the lateral portion of MD also label with this tracer. However, other forebrain and brainstem projections to MD are not labeled with 3H-D-aspartate, and apparently do not use glutamate or aspartate as a neurotransmitter. These include the projections from the basal and accessory basal amygdaloid nuclei, as well as possibly GABAergic projections from the ventral pallidum and the substantia nigra, pars reticulata. A small fraction of the cells in the piriform cortex that project to MD label with 3H-D-aspartate, suggesting that this projection may be heterogeneous. In other experiments, presumptive GABAergic projections to MD were studied by using 3H-GABA as a retrograde tracer. Although in these cases the thalamic reticular nucleus is well labeled, the ventral pallidum and the substantia nigra, pars reticulata are only poorly labeled. Pallidal projections to the ventromedial thalamic nucleus (VM), which are likely to be GABAergic, were also studied with this technique. After injections of 3H-GABA into VM, only a few cells in the substantia nigra, pars reticulata, or entopeduncular nucleus were labeled. This result suggests 3H-GABA has limited usefulness as a transmitter-specific retrograde tracer.

Carbon dioxide rapid superpulsed laser treatment of erythroplasia of Queyrat.

A single case of erythroplasia of Queyrat successfully treated by rapid superpulsed carbon dioxide laser emission is presented. The results of this single case and previous studies are compared with thos obtained by different modalities used in the past.

Intrastriatal folic acid mimics the distant but not local brain damaging properties of kainic acid.

Folic acid (pteroyl-L-glutamine acid, PGA), when injected into the rat striatum, has the kainic acid (KA) property of inducing sustained seizures and a disseminated pattern of distant brain damage, but lacks the KA property of destroying neurons locally at the injection site. This suggests the interesting possibility that one component of KA neurotoxicity (seizure-related distant damage) may involve interaction with a folate system. Folates are promising tools for exploring the neurotoxic properties of KA and, more importantly, for studying mechanisms of epilepsy and epileptic brain damage.

The anti-excitotoxic effects of certain anesthetics, analgesics and sedative-hypnotics.

Various agents were tested for their ability to antagonize the acute excitotoxic action of N-methyl-DL-aspartate (NMA) and kainic acid (KA) on neurons in the in vitro chick embryo retina. The following compounds (in order of descending potencies) were effective in completely blocking the neurotoxic activity of NMA: phencyclidine, ketamine, (+/-)-SKF 10,047, pentazocine, D-aminophosphonovalerate, D-amino-phosphonoheptanoate, D-alpha-aminoadipate, OH-quinoxaline carboxylate, kynurenate, (+/-)-cis-2,3-piperidine dicarboxylate, secobarbital, amobarbital and pentobarbital. The latter 6 agents also protected against KA toxicity but complete protection was observed only from relatively high concentrations. At 20 mM, Mg2+ blocked NMA toxicity but at concentrations up to 30 mM did not block KA toxicity. Compounds that failed to block either NMA or KA toxicity include D- and L-aminophosphonobutyrate, L-glutamic acid diethyl ester, xanthurenate, GABA and taurine. The chick embryo retina is a useful preparation for identifying agents that have either excitotoxic or anti-excitotoxic activity.

Carbon dioxide laser scleral dissection and filtering procedure for glaucoma.

A comparison of eye bank eyes using continuous wave or rapid superpulsed carbon dioxide laser energy indicated that rapid superpulsed was the superior modality for scleral dissection, because there is less charring and puckering of tissue. The results of filtering procedures in five glaucomatous eyes by using rapid superpulsed carbon dioxide energy to perform the scleral dissection revealed the possible advantages of performing the procedure this way might be: (1) the technical ease by which the microdissection is performed under direct microscopic observation with the absence of blood or instruments in the field; (2) the safety factor of never having penetrated into the anterior chamber with a sharp instrument; (3) the possible advantage of the inhibition of healing at the wound margin because of coagulation of tissue at the wound edge by the laser beam; and (4) the bacteriocidal effect of thermal cutting.

The laser in neurological surgery.

The use of lasers in neurosurgical procedures has received a great deal of attention recently. Surgical use of lasers has been viewed with suspicion and skepticism, probably because of (justified) apprehensions about the misuse of lasers in early work and about the ways in which laser light affects tissues, and a lack of understanding of the basic physics and practical operation of lasers. The authors review the physics, biophysics, experimental findings, and operative use of lasers in current neurosurgical practice, and discuss briefly their experience gained in over 150 neurosurgical procedures using the carbon dioxide and argon surgical lasers.

Naloxone blocks morphine enhancement of kainic acid neurotoxicity.

Kainic acid (KA) is a potent convulsant which, when administered subcutaneously, induces sustained limbic seizures and a pattern of limbic brain damage that is thought to be seizure-mediated. Diazepam suppresses and morphine enhances both the seizures and brain damage induced by KA. Here we show that morphine enhancement of KA neurotoxicity is blocked in a dose-dependent manner by subcutaneous pretreatment with naloxone. Theses and related findings support the hypothesis that morphine enhances the seizure-linked neurotoxicity of KA by an opiate specific action at certain limbic receptor sites where opiates suppress GABAergic activity, thereby lowering the threshold for propagation of seizure activity in limbic circuits.

The characteristics in operation of surgical lasers.

The three separate laser applications involved in laser surgery--laser surgery, photocoagulation, and photoradiation therapy--are explored to provide an understanding of the fundamental physical properties of the laser device. How diseased tissue is selectively treated by matching the absorption characteristics of the tissue to the laser and how the laser equipment functions and is operated are described.

Physical considerations of surgical lasers.

Surgical lasers fulfill a needed niche in the less invasive surgical market. An understanding of the fundamentals of lasers and their interaction with tissues are important prerequisites to the understanding of the clinical effects of these devices. This article provides these requisites.

Mid-infrared fiber optics.

Fiber optics for carbon dioxide laser surgery have been in developmental research for the past ten years. An up-to-date presentation of infrared fiber optics as they pertain to laser surgery is presented. Optical properties such as intrinsic and extrinsic electronic absorption, multiphonon absorption, and scatter mechanisms are discussed. Real-world considerations for materials selection and fabrication techniques for both crystalline and glassy fiber optics give the reader a perspective regarding the stage of development of these devices. Data are presented indicating transmission ranges and absorption coefficients for both bulk materials and fabricated fiber optics. The conclusions are drawn based on the needs of the clinician as they relate to the degree of existing technology.

Only certain anticonvulsants protect against kainate neurotoxicity.

Kainic acid (KA), a heterocyclic structural analog of the putative excitatory neurotransmitter, glutamate (Glu), powerfully mimics many of the neuroexcitatory and neurotoxic properties of Glu. KA differs from Glu and its straight chain "excitotoxic" analogs, however, in inducing a limbic seizure-brain damage syndrome when administered subcutaneously (12 mg/kg) to adult rats. This syndrome consists of sustained seizures, resembling amygdaloid kindled seizures, and acute destruction of neural elements in limbic brain regions (amygdala, olfactory cortex, hippocampus, lateral septum and several thalamic nuclei). Early changes consist of massive edematous swelling of glia and neuronal dendrites and either swelling or dark cell changes in neuronal somata, with subsequent necrosis of many of the neurons involved. Elsewhere we demonstrated that pretreatment with morphine markedly enhances both the convulsant and brain damaging actions of KA. Here we report that pretreatment with 2 anticonvulsants (diazepam or phenobarbital) markedly reduces both athe seizure and brain damaging actions of KA, whereas, two other anticonvulsants (phenytoin or valproic acid) fail to suppress either phenomenon. Our findings suggest that a seizure mechanism underlies much of the limbic brain damage induced by systemic KA and that the toxic mechanism may have two mutually reinforcing components--a glutamergic excitatory component and a GABAergic disinhibitory component.

Laser photovaporization of endometrium for the treatment of menorrhagia.

As an alternative to hysterectomy in patients with excessive bleeding, the endometrium was destroyed by means of the neodymium-YAG laser. The photovaporization was done under direct vision through a hysteroscope. Twenty-two patients have been treated, all but one successfully, i.e., little or no menstrual flow. The human uterus having a thick myometrium was found to be ideal for this modality. To suppress endometrial regeneration further, each patient was placed on a regimen of danazol for 2 to 3 weeks prior to and after the procedure. Hysterograms after laser photovaporization showed variable degrees of uterine contraction, scarring, and adhesion formation. Biopsies of the endometrial surface up to 20 months following the procedure showed no evidence of inflammation other than foreign body giant cell reaction around carbon particles. Minimal endometrial regeneration occurred.

Laser safety in podiatry.

Lasers are being used more often in podiatric medicine than ever before. New modalities have certain characteristics that might endanger either the patient and/or the operator or the supportive staff. "Laser Safety in Podiatry" will outline the safety measures in patient protection, operator protection, and supportive staff protection.

Carbon dioxide laser methodology for ablation of plantar verrucae.

Treatment of plantar verrucae has been discussed frequently in medical literature. The present authors discuss a regimen that combines skin currettement with CO2 laser vaporization. They claim that this method provides predictable, successful results (54.5% to 89%) with additional advantages of diminished pain and reduced healing time.