Electrical responses and synaptic connections of giant serotonin-immunoreactive neurons in crayfish olfactory and accessory lobes

Five pairs of identified 5HT-IR cells in the deutocerebrum of the crayfish Cherax are known to have their synaptic endings in the accessory and olfactory lobes. Two of these cells, one on each side of the brain, are significantly larger than the others. Dye fills of these “giant” cells reveal each to be an interneuron with its branches confined to, but distributed throughout, the olfactory and accessory lobes on the side of the brain ipsilateral to its cell body and with no branches to the contralateral side. Intracellular recordings from the giant cells were made while stimulating the olfactory afferents and tracts within the brain in an attempt to discover the inputs and outputs to the cells. Electrical stimulation of chemoreceptor sensilla on the outer branch of the antennule does not excite the giant 5HT neurons. Focal extracellular electrical stimulation of the olfactory globular tract containing the axons of projection neurons from the olfactory and accessory lobes produces excitatory synaptic potentials and action potentials in the giant cells. Focal extracellular electrical stimulation of the deutocerebral commissure, the axons of which terminate in the glomeruli of the accessory lobes, also results in excitation of the giant cells. We conclude that the input to the giant cells is via axons in the deutocerebral commissure and collaterals from the projection neurons, ending in the glomeruli of the accessory lobes. The output of the giant cells is to the olfactory lobes, where it may serve to modulate olfactory signals.     

Synaptic connections between identified neuron types in the antennal lobe glomeruli of the cockroach,Periplaneta americana: II. local multiglomerular interneurons

Synapses between three types of antennal lobe neurons, namely, local multiglomerular interneurons, antennal receptor neurons, and γ-aminobutyric acid (GABA)-immunoreactive neurons, were studied by means of a combination of three different markers. The interneurons were labeled by intracellular injection of horseradish peroxidase (HRP) into a single soma or a small group of neurons. Antennal receptor cells were marked by experimentally induced anterograde degeneration, and GABA-containing neurons were identified by postembedding immunogold staining. The following types of connections were found: Local interneurons receive input synapses from 1) degenerated receptor neuron axons, 2) GABA-immunogold-labeled neurites, and 3) non-GABA-immunoreactive neurons. The interneurons form output synapses onto the same three neuron groups. Contacts were also found between HRP-labeled interneurons themselves. The majority of synapses were dyadic. In most cases, only one postsynaptic neuronal process of the dyads was labeled and, thus, was identified. Polysynaptic connections were found between GABA-immunoreactive neurites, HRP-labeled interneuron processes, and nonlabeled neurites or between HRP-labeled interneuron processes and two interconnected GABA-immunoreactive processes. The present findings provide anatomical evidence for an earlier suggested monosynaptic connection between afferent receptor fibers and local, at that time putative, GABAergic interneurons. They further reveal that local multiglomerular interneurons are synaptically interconnected. The interneurons, in addition, form serial connections via more than one GABA-immunoreactive neuron with non-GABA-immunoreactive and putative projection neurons. Such polysynaptic connections would be a substrate for a feed-forward “disinhibition” of projection neurons, which has been suggested on the basis of electrophysiological findings. J. Comp. Neurol. 383:529-540, 1997. © 1997 Wiley-Liss, Inc.     

Nuclear bridges in multinucleated giant cells associated with primary lymphoma of the brain in acquired immune deficiency syndrome (AIDS)

Summary In an autopsied case of a 37-year-old man with acquired immune deficiency syndrome (AIDS), multinucleated giant cell encephalopathy was noted in close proximity to multiple nodules of primary lymphoma of the brain. Some multinucleated giant cells and macrophages contained HTLV-III-like viral particles. Nuclear bridges, thin strands connecting individual nuclei with one another, were observed with both light and electron microscopes within some of the multinucleated giant cells. There were also thin tapering nuclear processes, which were probably part of nuclear bridges. The possibility that the nuclear bridges and processes represent amitotic nuclear division is discussed.     

Activation of microglial and endothelial cells in the rat brain after treatment with interferon-gamma in vivo

Activation of microglial cells occurs during the pathogenesis of various neurologic diseases. However, the mechanisms of activation in vivo are still elusive. We infused adult rats intravenously with interferon-γ and demonstrated microglial cell activation after three days of treatment. We show for the first time that microglial cells proliferate inside the brain in response to a circulating cytokine. Microglial cells were induced to express major histocompatibility (MHC) class I and class II antigens and small amounts of leukocyte function-associated molecule 1 (LFA-1, CD11a). On endothelial cells of the brain, MHC class I and class II antigens and intercellular adhesion molecule 1 (ICAM-1, CD54) were enhanced. GLIA 19:181–189, 1997. © 1997 Wiley-Liss, Inc.     

Comparative localization of serotonin1A, 1C,and 2 receptor subtype mRNAs in rat brain

Serotonin (5-HT) mediates its effects on neurons in the central nervous system through a number of different receptor types. To gain better insight as to the localization of 5-HT responsive cells, the distribution of cells expressing mRNAs encoding the three 5-HT receptor subtypes 1A,1C, and 2 was examined in rat brain with in situ hybridization using cRNA probes. 5-HT1A receptor mRNA labeling was most pronounced in the olfactory bulb, anterior hippocampal rudiment, septum, hippocampus (dentate gyrus and layers CAI-3), entorhinal cortex, interpeduncular nucleus, and medullary raphe nuclei. 5-HT 1C receptor mRNA labeling was the most abundant and widespread of the three 5-HT receptor subtypes examined. Hybridization signal was denset in the choroid plexus, anterior olfactory nucleus, olfactory tubercle piriform cortex, septum, subiculum, entorhinal cortex, claustrum, accumbens nuclues, striatum, lateral amygdala, paratenial and paracentral thalamic nuclei, subthalamic nucleus, substantia nigra, and reticular cell groups. 5-HT2 receptor mRNA was localized to the olfactory bulb, anteriorhippocampal rudiment, frontal cortex, piriform cortex, entorhinal cortex, claustrum, pontine nuclei, and cranial nerve motor nuclei including the oculomotor, trigeminal motor, facial, dorsal motor nucleus of the vagus, and hypoglossal nuclei. The distributions of mRNAs for the three different 5-HT receptor subtypes overlap with regions that bind various 5-HT receptor-selective ligands and are present in nearly all areas known to receive serotonergic innervation. The results of this study demonstrate that nervous which express these 5-HT receptor subtypes are very widespread in the central nervous system, yet possess unique distributions with in the rat brain. Moreover, previously unreported regions of 5-HT receptor subtype expression were observed, particulary with the 5-HT receptor riboprobe in the brainstem. Finally, several brain areas contain multiple 5-HT receptor subtype mRNAs, which leads to the possibility that individual cells may express more than one 5-HT receptor subtype. © 1995 Willy-Liss, Inc.     

Alterations of natural killer cells in traumatic brain injury

To investigate the relationship between natural killer（NK） cells and traumatic brain injury（TBI）, we tracked an established phenotype of circulating NK cells at several time points in patients with different grades of TBI. In serial peripheral blood samples, NK cells were prospectively measured by flow cytometry of CD3-CD56＋ lymphocytes. Compared to healthy controls, TBI patients had reductions in both the percentage and the absolute number of NK cells. Furthermore, the magnitude of NK cell reduction correlated with the degree of TBI severity at several time points. That is, NK cell population size was independently associated with lower Glasgow Coma Scale scores. In addition, at some time points, a positive correlation was found between the NK cell counts and Glasgow Outcome Scale scores. Our results indicate that TBI induces a reduction in the number of NK cells, and the magnitude of the reduction appears to parallel the severity of TBI.     

Synaptic connections between identified neuron types in the antennal lobe glomeruli of the cockroach,Periplaneta americana: I. uniglomerular projection neurons

A combination of three different labels was used to demonstrate synapses between three types of neurons within the glomeruli: 1) antennal receptor cells, 2) γ-aminobutyric acid (GABA)-immunoreactive neurons, and 3) uniglomerular projection neurons. Receptor cell axons were experimentally severed and caused to degenerate; uniglomerular projection neurons, a subgroup of glomerular output neurons, were labeled by intracellular horseradish peroxidase (HRP) injection and GABA-containing neurons by postembedding immunogold staining. The following synaptic connections were identified: 1) Receptor cell axons form monosynaptic contacts in a dyadic fashion onto a dendritic process of a uniglomerular projection neuron and in addition onto a GABA-immunoreactive neuron. 2) Receptor cell axons form polysynaptic connections with dendrites of uniglomerular projection neurons via GABA-immunoreactive neurons. 3) GABA-immunoreactive neurons form dyadic output synapses onto receptor cell axons and in addition onto projection neuron dendrites. These findings provide further evidence that signal transfer from receptor cells onto uniglomerular projection neurons is mediated by two different paths: first, a monosynaptic and presumably excitatory route and, second, an inhibitory polysynaptic route via GABAergic, most likely multiglomerular interneurons. The output synapses of GABA-immunoreactive neurons onto both receptor cells and uniglomerular projection neurons are assumed to exert control functions in regulating the neuronal activity within the glomeruli. J. Comp. Neurol. 378:307–319, 1997. © 1997 Wiley-Liss, Inc.     

Human neural stem cells genetically modified for brain repair in neurological disorders

Existence of multipotent neural stem cells (NSC) has been known in developing or adult mammalian CNS, including humans. NSC have the capacity to grow indefinitely and have multipotent potential to differentiate into three major cell types of CNS, neurons, astrocytes and oligodendrocytes. Stable clonal lines of human NSC have recently been generated from the human fetal telencephalon using a retroviral vector encoding v‐myc. One of the NSC lines, HB1.F3, carries normal human karyotype of 46XX and has the ability to self‐renew, differentiate into cells of neuronal and glial lineages, and integrate into the damaged CNS loci upon transplantation into the brain of animal models of Parkinson disease, HD, stroke and mucopolysaccharidosis. F3 human NSC were genetically engineered to produce L‐dihydroxyphenylalanine (L‐DOPA) by double transfection with cDNA for tyrosine hydroxylase and guanosine triphosphate cylohydrolase‐1, and transplantation of these cells in the brain of Parkinson disease model rats led to L‐DOPA production and functional recovery. Proactively transplanted F3 human NSC in rat striatum, supported the survival of host striatal neurons against neuronal injury caused by 3‐nitropro‐pionic acid in rat model of HD. Intravenously introduced through the tail vein, F3 human NSC were found to migrate into ischemic lesion sites, differentiate into neurons and glial cells, and improve functional deficits in rat stroke models. These results indicate that human NSC should be an ideal vehicle for cell replacement and gene transfer therapy for patients with neurological diseases. In addition to immortalized human NSC, immortalized human bone marrow mesenchymal stem cell lines have been generated from human embryonic bone marrow tissues with retroviral vectors encording v‐myc or teromerase gene. These immortalized cell lines of human bone marrow mesenchymal stem cells differentiated into neurons/glial cells, bone, cartilage and adipose tissue when they were grown in selective inducing media. There is further need for investigation into the neurogenic potential of the human bone marrow stem cell lines and their utility in animal models of neurological diseases.     

Morphology of local "stridulation" interneurons in the metathoracic ganglion of the acridid grasshopper Omocestus viridulus L

The morphological characteristics of five types of local spiking interneurons in the metathoracic ganglion of the acridid grasshopper Omocestus viridulus L. have been revealed by intracellular injection of the fluorescent dye Lucifer Yellow. All these neurons are active during induced stridulation and discharge in the stridulation rhythm. They are structurally unlike any of the metathoracic local interneurons previously described in the Acrididae. Type 1: Unilateral interneurons in the metathoracic neuromere; soma in anterior position; arborization dorsal, in anterolateral, posterolateral, and midline regions. Type 2: Unilateral interneurons in the metathoracic neuromere; neurite with characteristic hairpin bend; soma in lateral position; arborization through the lateral neuropil region. Type 3: Unilateral interneurons in the metathoracic and abdominal neuromeres; soma anterior at the base of the connective; arborization dorsal, in anterolateral, posterolateral, and midline regions, with ladderlike branches into the abdominal neuromeres. Type 4: Symmetrically bilateral neurons; soma in ventral median position; arborization dorsal, in anterolateral, posterolateral, and midline regions. Ipsilateral branches mostly smooth, contralateral mostly varicose. Type 5: Asymmetrically bilateral neurons, soma in ventral median position; ipsilateral branches mostly smooth, contralateral mostly varicose. The ipsilateral branches in particular penetrate all layers of the ganglion. The main arborizations of interneurons of types 1 and 4, and to some extent those of types 3 and 5, occupy the same region, which extends very far dorsally into the vicinity of the median and lateral tracts. There are additional antero- and posterolateral branches in the metathoracic neuromere, in positions where in principle they can overlap with the arborizations of the motoneurons. The interneurons of type 2, and to some extent type 5, arborize mainly in a lateral region that also includes deeper layers of the ganglion and hence encompasses the projections of mechanoreceptive proprioceptors. The interneurons of types 1, 3, and 4 have so-called "sister" neurons, identical to the typical neurons in their metathoracic arborizations but with additional collaterals that pass into the mesothoracic ganglion.     

Regional distribution of iron and iron-regulatory proteins in the brain in aging and Alzheimer's disease.

It is well established that iron, which is of considerable importance for normal neurological function, is highly regulated in all organ systems. However, until recently, iron regulation in the nervous system has received little attention. This study quantitatively compares the levels of the major iron-regulatory proteins, transferrin and ferritin, and iron itself in three cerebral cortical regions of the human brain from material collected at autopsy. Three groups were studied: 1) normal adult (under 65 yr of age), 2) aged (greater than 65), and 3) Alzheimer's disease. Normally, transferrin is more abundant in white matter than in gray matter. Ferritin is approximately 10x more abundant than transferrin throughout the brain regions examined and is evenly distributed, as is iron, in the gray and white matter. In Alzheimer's disease transferrin is consistently decreased particularly in the white matter of the various cerebral cortical regions examined whereas the iron and ferritin changes are inconsistent. The observations in this study are consistent with our general hypothesis that iron homeostasis is disrupted in the aging brain and the alterations in iron-regulatory proteins are exacerbated in Alzheimer's disease. The decrease in transferrin levels could indicate a decreased mobility and subsequent utilization of iron in the brain. Such a decrease in iron availability could play a significant role in neuronal degeneration and increased peroxidative damage known to occur in Alzheimer's disease.     

In vitro evidence for the brain glutamate efflux hypothesis: brain endothelial cells cocultured with astrocytes display a polarized brain-to-blood transport of glutamate

The concentration of the excitotoxic amino acid, L-glutamate, in brain interstitial fluid is tightly regulated by uptake transporters and metabolism in astrocytes and neurons. The aim of this study was to investigate the possible role of the blood-brain barrier endothelium in brain L-glutamate homeostasis. Transendothelial transport- and accumulation studies of ³H-L-glutamate, ³H-L-aspartate, and ³H-D-aspartate in an electrically tight bovine endothelial/rat astrocyte blood-brain barrier coculture model were performed. After 6 days in culture, the endothelium displayed transendothelial resistance values of 1014 ± 70 Ω cm², and ¹⁴C-D-mannitol permeability values of 0.88 ± 0.13 × 10⁻⁶ cm s⁻¹. Unidirectional flux studies showed that L-aspartate and L-glutamate, but not D-aspartate, displayed polarized transport in the brain-to-blood direction, however, all three amino acids accumulated in the cocultures when applied from the abluminal side. The transcellular transport kinetics were characterized with a K_m of 69 ± 15 μM and a J_max of 44 ± 3.1 pmol min⁻¹ cm⁻² for L-aspartate and a K_m of 138 ± 49 μM and J_max of 28 ± 3.1 pmol min⁻¹ cm⁻² for L-glutamate. The EAAT inhibitor, DL-threo-ß-Benzyloxyaspartate, inhibited transendothelial brain-to-blood fluxes of L-glutamate and L-aspartate. Expression of EAAT-1 (Slc1a3), −2 (Slc1a2), and −3 (Slc1a1) mRNA in the endothelial cells was confirmed by conventional PCR and localization of EAAT-1 and −3 in endothelial cells was shown with immunofluorescence. Overall, the findings suggest that the blood-brain barrier itself may participate in regulating brain L-glutamate concentrations. © 2012 Wiley Periodicals, Inc.     

Regional and functional heterogeneity of antigen presenting cells in the mouse brain and meninges

The central nervous system (CNS) is considered to be immune privileged, owing in part to the absence of major histocompatibility (MHC) class II⁺ cells in the healthy brain parenchyma. However, systemic inflammation can activate microglia to express MHC class II, suggesting that systemic inflammation may be sufficient to mature microglia into functional antigen presenting cells (APCs). We examined the effects of systemic lipopolysaccharide (LPS)-induced inflammation on the phenotype and function of putative APCs within the mouse brain parenchyma, as well as its supporting tissues—the choroid plexus and meninges. Microglia isolated from different regions of the brain demonstrated significant heterogeneity in their ability to present antigen to naïve OT-II CD4⁺ T cells following exposure to systemic LPS. Olfactory bulb microglia (but not cortical microglia) intimately interacted with T cells in vivo and stimulated T cell proliferation in vitro, albeit in the absence of co-stimulation. In contrast, myeloid cells within the choroid plexus and meninges were immunogenic and upregulated the co-stimulatory molecule CD80 following systemic inflammation. Dural APCs, which clustered around LYVE-1⁺ lymphatics, were more efficient at stimulating naïve T cell proliferation than choroid plexus APCs, suggesting that the dura may be an under-appreciated site for immune interactions. This study has highlighted the functional diversity of myeloid cells within the sub-compartments of the CNS and its supporting tissues. Furthermore, these findings demonstrate that systemic inflammation can mature selected microglia populations and choroid plexus/meningeal myeloid cells into functional APCs, which may contribute to the pathogenesis of neuroinflammation and neurodegenerative diseases.     

Immunocytochemical localization of luteinizing hormone-releasing hormone (LHRH) in the nervus terminalis and brain of the big brown bat, Eptesicus fuscus.

Little is known about the immunohistochemistry of the nervous system in bats. This is particularly true of the nervus terminalis, which exerts strong influence on the reproductive system during ontogeny and in the adult. Luteinizing hormone-releasing hormone (LHRH) was visualized immunocytochemically in the nervus terminalis and brain of juvenile and adult big brown bats (Eptesicus fuscus). The peripheral LHRH-immunoreactive (ir) cells and fibers (nervus terminalis) are dispersed along the basal surface of the forebrain from the olfactory bulbs to the prepiriform cortex and the interpeduncular fossa. A concentration of peripheral LHRH-ir perikarya and fibers was found at the caudalmost part of the olfactory bulbs, near the medioventral forebrain sulcus; obviously these cells mediate between the bulbs and the remaining forebrain. Within the central nervous system (CNS), LHRH-ir perikarya and fibers were distributed throughout the olfactory tubercle, diagonal band, preoptic area, suprachiasmatic and supraoptic nuclei, the bed nuclei of stria terminalis and stria medullaris, the anterior lateral and posterior hypothalamus, and the tuber cinereum. The highest concentration of cells was found within the arcuate nucleus. Fibers were most concentrated within the median eminence, infundibular stalk, and the medial habenula. The data obtained suggest that this distribution of LHRH immunoreactivity may be characteristic for microchiropteran (insectivorous) bats. The strong projections of LHRH-containing nuclei in the basal forebrain (including the arcuate nucleus) to the habenula, may indicate close functional contact between these brain areas via feedback loops, which could be important for the processing of thermal and other environmental stimuli correlated with hibernation.     

Axonogenesis in the medaka embryonic brain

In order to know the general pattern of axonogenesis in vertebrates, we examined axonogenesis in the embryonic brain of a teleost fish, medaka (Oryzias latipes), and the results were compared with previous studies in zebrafish and mouse. The axons and somata were stained immunocytochemically using antibodies to a cell surface marker (HNK-1) and acetylated tubulin and visualized by retrograde and anterograde labeling with a lipophilic dye. The fiber systems developed correlating with the organization of the longitudinal and transverse subdivisions of the embryonic brain. The first axons extended from the synencephalic tegmentum, forming the first fiber tract (fasciculus longitudinalis medialis) in the ventral longitudinal zone of the neural rod, 38 hours after fertilization. In the neural tube, throughout the entire brain two pairs of longitudinal fiber systems, one ventral series and one dorsal or intermediate series, and four pairs of transverse fiber tracts in the rostral brain were formed sequentially during the first 16 hours of axon production. In one of the dorsal longitudinal tracts, its branch retracted and disappeared at later stages. One of the transverse tracts was found to course in the telencephalon and hypothalamus. The overall pattern of the longitudinal fiber systems in medaka brain is similar to that in mouse, but apparently different from that in zebrafish. We propose that a ventral tract reported in zebrafish partially belongs to the dorsal fiber system, and that the longitudinal fiber systems in all vertebrate brains pass through a common layout defined by conserved genetic and developmental programs.     

Localization of neprilysin (EC 3.4.24.11) mRNA in rat brain by in situ hybridization

The distribution of the messenger RNA (mRNA) coding for neprilysin (EC 3.4.24.11) has been studied by in situ hybridization in the adult rat brain. A markedly heterogeneous distribution among various brain regions was found. A strong signal was observed in the glomerular layer of the olfactory bulb, the olfactory tubercle, the caudate putamen, the habenular, anterior pretectal, interpeduncular, red, dorso tegmental, pontine, and vestibular nuclei, the mammillary bodies, the Purkinje cells, and the choroid plexus of the fourth ventricle. A large number of areas such as the cortex, the dentate gyrus, the hippocampus, the medial terminal nucleus of the accessory tract, the accumbens and the arcuate nuclei, the superior and inferior colliculi, and a few regions in the thalamus at the mesencephalic level exhibited a moderate or low signal of hybridization. The majority of these regions are also known to contain the neprilysin protein. On the other hand, the globus pallidus, the substantia nigra, and the central gray matter, which show a high or a moderate amount of neprilysin, did not contain any neprilysin mRNA. Comparison of the regional distribution of neprilysin mRNA with that of its translation product provides insight into neprilysin neuronal pathways in the central nervous system. © 1993 Wiley-Liss, Inc.     

Phylogeny and expression divergence of metabotropic glutamate receptor genes in the brain of zebrafish (Danio rerio)

Glutamate, the most abundant excitatory neurotransmitter of the central nervous system, modulates synaptic transmission and neuronal excitability via metabotropic glutamate receptors (mGluRs). These receptors are essential components for diverse cognitive functions and they represent potential drug targets for the treatment of a number of neurological and psychiatric disorders. Here we describe the phylogenetic relation and mRNA distribution of zebrafish mGluRs. In comparison to the eight mglurs present in the mammalian genome, we identified 13 different mglur genes in the zebrafish genome. In situ hybridization experiments in zebrafish revealed widespread expression patterns for the different mglurs in the central nervous system, implicating their significance in diverse neuronal functions. Prominent mglur expression is found in the olfactory bulb, the optic tectum, the hypothalamus, the cerebellum, and the retina. We show that expression pattern of paralogs generated by the teleost‐specific whole genome duplication is overlapping in some brain regions but complementary in others, suggesting sub‐ and/or neofunctionalization in the latter. Group I mglurs are similarly expressed in brain areas of both larval and adult zebrafish, suggesting that their functions are comparable during these stages. J. Comp. Neurol. 521:1449–1469, 2013. © 2012 Wiley Periodicals, Inc.     

Elevated expression of B-50 (GAP-43)-mRNA in a subpopulation of olfactory bulb mitral cells following axotomy

Neurons in the central nervous system regenerate poorly or not at all. In contrast neurons of the peripheral nervous system have the ability to regrow their nerve fibers over considerable distances. Previously it has been suggested that the absence of the reinduction of the expression of growth associated proteins such as B-50 (GAP43) may be an important factor in the differential response of CNS and PNS neurons to injury. We studied B-50(GAP43) mRNA expression following lesioning of a class of CNS neurons, the olfactory bulb mitral cells. Expression of B-50 mRNA in approximately 40% of the mitral cells was upregulated in response to transection of their axons in the lateral olfactory tract (LOT). Enhanced expression persisted for 10 days postlesion but had virtually declined to control levels by 4 weeks after the lesion. A large proportion of the mitral cells gradually degenerated subsequent to LOT transection. Thus a subpopulation of mitral cells maintains their ability to upregulate B-50, a protein characteristic of growing axons, but enhanced B-50 expression is not accompanied by regeneration of the severed LOT. © 1993 Wiley-Liss, Inc.     

Interictal cardiovascular autonomic responses in patients with temporal lobe epilepsy

PURPOSE: To measure interictal cardiovascular autonomic functions in patients with either refractory or well-controlled temporal lobe epilepsy (TLE). METHODS: For autonomic assessment, heart rate variation during normal and deep breathing, Valsalva maneuver, and tilting were measured in 19 patients with chronic refractory TLE, 19 patients with well-controlled TLE, and 38 age- and sex-matched healthy control subjects. Blood pressure responses to tilting and isometric work also were evaluated. RESULTS: Heart-rate (HR) variation during normal breathing (p = 0.006) and tilting (p = 0.043) was lower in patients with refractory TLE than in control subjects. Heart-rate response to tilting (p = 0.036) was also lower in patients with well-controlled TLE than in control subjects. Blood-pressure responses showed no differences between the patients and the control subjects. Patients taking carbamazepine (CBZ) medication had decreased HR responses to deep breathing (p = 0.046) and to tilting (p = 0.014) compared with the control subjects. CONCLUSIONS: Refractory TLE seems to be associated with dysfunction of the cardiovascular autonomic regulation, manifesting as impaired HR responses to certain stimuli. Interictal autonomic dysfunction is seen in patients with well-controlled TLE as well, but it may be more evident in patients with refractory epilepsy. CBZ medication may also be associated with altered autonomic cardiac control.     

Fetal brain grafts rescue adult retinal ganglion cells from axotomy-induced cell death

After intraorbital transection of the optic nerve of adult rats, 90% of the retinal ganglion cells die within 30 days. Since fetal brain extracts and cocultured fetal target regions support the survival of retinal ganglion cells in vitro (Nurcombe and Bennett: Exp. Brain Res. 44: 249-258, '81; McCaffery et al.: Exp. Brain Res. 48: 377-386, '82; Armson and Bennett: Neurosci. Lett. 38: 181-186, '83) we investigated whether cell death in the adult retina could be prevented by transplanting fetal (E16) thalamus and tectum to the proximal stump of the optic nerve of adult rats that was completely transected 2-3 mm behind the optic disc. Unoperated eyes contained 119,973 (+/- 939, SEM) retinal ganglion cells, estimated from axon counts of the intact optic nerve. Of these, 11,601 (+/- 1,857) remained in control operated eyes at 30 days postoperation while in the eyes of grafted rats, 35,086 (+/- 2,278) retinal ganglion cells were counted. Thus, 23,485 (= 22% of those normally dying after transection of the optic nerve) ganglion cells were rescued by the fetal grafts from cell death normally following axotomy. These results indicate that fetal target regions of retinal ganglion cells contain and/or produce neurotrophic molecules that promote the survival of adult axotomized retinal ganglion cells.