GABAergic nerve terminals decrease in the substantia nigra following hemitransections of the striatonigral and pallidonigral pathways.

Glutamic acid decarboxylase (GAD), the enzyme that synthesizes the neurotransmitter, GABA, was immunocytochemically localized in axon terminals as well as in small and medium-sized neurons of the rat substantia nigra. The pattern formed by GAD-containing axon terminals with the dendrites and somata of neurons in the substantia nigra was altered following ipsilateral hemitransections of the striatonigral and pallidonigral pathways. A marked reduction of GAD-positive terminals occurred throughout this brain region, but the ventral fifth of the pars reticulata showed a nearly normal pattern of GAD-positive axon terminals. The results of this investigation are consistent with results from biochemical studies which have indicated that the striatonigral and/or pallidonigral pathways are GABAergic. In addition, these results suggest that the residual GABAergic terminals remaining after hemitransection are derived from intrinsic neurons of the substantia nigra

Immunocytochemical localization of glutamic acid decarboxylase in neuronal somata following colchicine inhibition of axonal transport.

The enzyme that synthesizes the neurotransmitter γ-aminobutyric acid (GABA), glutamic acid decarboxylase (GAD), has been immunocytochemically localized in the somata and dendrites of certain neurons in rat cerebellum and Ammom's horn following colchicine injections into these two brain regions. In the cerebellum. GAD-positive reaction product was observed in the somata and proximal dendrites of Purkinje, Golgi II, basket and stellate neurons. Occasional staining of the proximal portions of axons was also observed in these colchicine-injected preparations. None of the somata or dendrites of these same cell types exhibited reaction product in preparations that were not pretreated with colchicine, although the axon terminals of these neurons were GAD-positive. In Ammon's horn, the somata of a few cells that are classified as probable basket and other short-axon neurons contained detectable concentrations of GAD in preparations that were not pretreated with colchicine. However, following colchicine injections into the Ammon's horn, there was approximately a five-fold increase in the number of GAD-positive somata of basket and other short-axon neurons. There was also a substantial increase in the extent of dendritic staining exhibited by these neurons. Control injections of saline and lumicolchicine produced the same results as those observed in preparations which were not pretreated with colchicine. Thus, the results from the control injections indicate that the increases in somal and dendritic staining are due to a colchicine-mediated inhibition of the somatofugal transport of GAD rather than to a non-specific effect of the drug and/or the injection procedure. The results of the present study permit the direct identification of the neuronal somata in the cerebellum and Ammon's horn whose synaptic terminals probably use GABA as their neurotransmitter. On the basis of the present findings, a reasonable explanation for the failure of earlier immunocytological studies to detect somal GAD in certain GABAergic neurons is that the axonal transport of GAD appears to occur at a sufficiently rapid rate to limit the somal concentration of GAD to low, undetectable levels. © 1978

Inhibitory, GABAergic nerve terminals decrease at sites of focal epilepsy.

Using an immunocytochemical method for the localization of the gamma-aminobutyric acid (GABA) synthesizing enzyme, glutamic acid decarboxylase (GAD), we have observed GABAergic nerve terminals distributed throughout all layers of normal monkey sensorimotor cortex. These terminals displayed ultrastructural characteristics that suggested that they arose from aspinous and sparsely spinous stellate neurons. In monkeys (Macaca mulatta and M. fascicularis) made epileptic by cortical application of alumina gel, a highly significant numerical decrease of GAD-positive nerve terminals occurred at sites of seizure foci indicating a functional loss of GABAergic inhibitory synapses. A loss of such inhibition at seizure foci could lead to epileptic activity of cortical pyramidal neurons

Immunocytochemical localization of glutamate decarboxylase in rat substantia nigra

l-Glutamate decarboxylase (GAD, EC 4.1.1.15), the enzyme which catalyzes the α-decarboxylase of l-glutamate to form γ-aminobutyric acid (GABA), was localized both light and electron microscopically in rat substantia nigra by an immunoperoxidase method. Large amounts of GAD-positive reaction product were seen throughout the substantia nigra in light microscopic preparations, and it appeared to be localized in punctate structures that were apposed to dendrites and somata. Electron microscopic studies revealed that most of the axon terminals in the substantia nigra were filled with GAD-positive reaction product and formed both axodendritic and axosomatic synapses. Many dendrites were extensively surrounded by GAD-positive terminals which most commonly formed symmetric synaptic junctions, although some formed asymmetric synaptic junctions. The results of this investigation are consistent with biochemical, pharmacological and physiological data which have indicated that neurons of the neostriatum and globus pallidus exert a GABA-mediated, postsynaptic inhibition upon the neurons of the substantia nigra. These findings provide another example in the vertebrate central nervous system where Golgi I projection neurons are inhibitory and use GABA as their neurotransmitter. © 1976

Glutamate decarboxylase localization in neurons of the olfactory bulb.

Glutamate decarboxylase (GAD), the enzyme that synthesizes the neurotransmitter gamma-aminobutyric acid (GABA), has been localized in the rat olfactory bulb by immunocytochemical methods with both light and electron microscopy. The light microscopic results demonstrated GAD-positive puncta concentrated in the external plexiform layer and in the glomeruli of the glomerular layer. In addition, GAD-positive reaction product stained the dentrites and somata of granule and periglomerular cells. The electron microscopic observations confirmed the presence of GAD-positive reaction product within granule and periglomerular somata and dendrites. In electron micrographs of the external plexiform layer, the gemmules which arise from the distal dentrites of granule cells were also observed to be filled with reaction product, and these structures corresponded in size and location to the puncta observed in light microscopic preparations. The gemmules were observed to form reciprocal dendrodentritic synaptic junctions with mitral cell dentrites which lacked reaction product. In the glomeruli, GAD-positive reaction product was observed in the dentritic shafts and gemmules of periglomerular cells which also formed reciprocal dendrodentritic synaptic contacts with mitral/tufted cell dentrites. The localization of GAD in known inhibitory neurons of the olfactory bulb supports the case that these local circuit neurons use GABA as their neurotransmitter. The present study demonstrates that GAD molecules located within certain neuronal somata and dentrites can be visualized with antisera prepared against GAD that was purified from synaptosomal fractions of mouse brains. This finding suggests that the lack of GAD staining within somata and dentrites of GABA-ergic neurons noted in previous studies of the cerebellum and spinal cord was probably due to low GAD concentrations, rather than to antigenic differences among GAD molecules located in different portions of the neuron. A striking differences among GAD molecules located in different portions of the neuron. A striking difference between the granule and periglomerular neurons of the olfactory bulb and the neurons of the cerebellum and spinal cord is that the former have presynaptic dentrites while the latter do not. Since GAD-positive reaction product can be detected in the somata and dentrites of GABA-ergic neurons which have presynaptic dentrites, it is suggested that these neurons may differ from other GABA-ergic neurons with respect to either transport or metabolism of GAD

Buttressing staples with cholecyst-derived extracellular matrix (CEM) reinforces staple lines in an ex vivo peristaltic inflation model

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ Springer Science + Business Media, LLC 2008Background - Staple line leakage and bleeding are the most common problems associated with the use of surgical staplers for gastrointestinal resection and anastomotic procedures. These complications can be reduced by reinforcing the staple lines with buttressing materials. The current study reports the potential use of cholecyst-derived extracellular matrix (CEM) in non-crosslinked (NCEM) and crosslinked (XCEM) forms, and compares their mechanical performance with clinically available buttress materials [small intestinal submucosa (SIS) and bovine pericardium (BP)] in an ex vivo small intestine model. Methods - Three crosslinked CEM variants (XCEM0005, XCEM001, and XCEM0033) with different degree of crosslinking were produced. An ex vivo peristaltic inflation model was established. Porcine small intestine segments were stapled on one end, using buttressed or non-buttressed surgical staplers. The opened, non-stapled ends were connected to a peristaltic pump and pressure transducer and sealed. The staple lines were then exposed to increased intraluminal pressure in a peristaltic manner. Both the leak and burst pressures of the test specimens were recorded. Results - The leak pressures observed for non-crosslinked NCEM (137.8 ± 22.3 mmHg), crosslinked XCEM0005 (109.1 ± 14.1 mmHg), XCEM001 (150.1 ± 16.0 mmHg), XCEM0033 (98.8 ± 10.5 mmHg) reinforced staple lines were significantly higher when compared to non-buttressed control (28.3 ± 10.8 mmHg) and SIS (one and four layers) (62.6 ± 11.8 and 57.6 ± 12.3 mmHg, respectively) buttressed staple lines. NCEM and XCEM were comparable to that observed for BP buttressed staple lines (138.8 ± 3.6 mmHg). Only specimens with reinforced staple lines were able to achieve high intraluminal pressures (ruptured at the intestinal mesentery), indicating that buttress reinforcements were able to withstand pressure higher than that of natural tissue (physiological failure). Conclusions - These findings suggest that the use of CEM and XCEM as buttressing materials is associated with reinforced staple lines and increased leak pressures when compared to non-buttressed staple lines. CEM and XCEM were found to perform comparably with clinically available buttress materials in this ex vivo model.Enterprise Irelan

Interpersonal and affective dimensions of psychopathic traits in adolescents : development and validation of a self-report instrument

We report the development and psychometric evaluations of a self-report instrument designed to screen for psychopathic traits among mainstream community adolescents. Tests of item functioning were initially conducted with 26 adolescents. In a second study the new instrument was administered to 150 high school adolescents, 73 of who had school records of suspension for antisocial behavior. Exploratory factor analysis yielded a 4-factor structure (Impulsivity α = .73, Self-Centredness α = .70, Callous-Unemotional α = .69, and Manipulativeness α = .83). In a third study involving 328 high school adolescents, 130 with records of suspension for antisocial behaviour, competing measurement models were evaluated using confirmatory factor analysis. The superiority of a first-order model represented by four correlated factors that was invariant across gender and age was confirmed. The findings provide researchers and clinicians with a psychometrically strong, self-report instrument and a greater understanding of psychopathic traits in mainstream adolescents