Biomedical subjects

Larry C Schmued

Publications and source records attributed to Larry C Schmued.

6 recordsLinked to original sources

PubMed2006

Fluoro-Ruby labeling prior to an amphetamine neurotoxic insult shows a definitive massive loss of dopaminergic terminals and axons in the caudate-putamen.

Fluoro-Ruby (FR) was injected into the substantia nigra (SNc) to label dopaminergic axons and terminals in the caudate putamen (CPu) of rats 7 days prior to a neurotoxic d-amphetamine (AMPH) exposure. Three days after AMPH exposure, a massive loss in the TH immunoreactive (TH(+)) axons and terminals was seen in the CPu. The FR-labeled (FR(+)) axons and terminals in the CPu were greatly diminished with those remaining being enlarged or swollen after AMPH. Fluoro-Jade C (FJ-C) labeling was used to verify AMPH-induced axonal and terminal degeneration. This study demonstrates that fluorescent anterograde tract tracers can be used to show the subsequent axonal and terminal degeneration after systemic exposures to toxins and provides direct evidence that CPu axons and terminals from SNc dopaminergic neurons can be destroyed after neurotoxic exposure to AMPH.

Amphetamine↗

PubMed2005

Neurohistochemical biomarkers of the marine neurotoxicant, domoic acid.

Domoic acid and its potent excitotoxic analogues glutamic acid and kainic acid, are synthesized by marine algae such as seaweed and phytoplankton. During an algal bloom, domoic acid may enter the food web through its consumption by a variety of marine organisms held in high regard as seafoods by both animals and humans. These seafoods include clams, mussels, oysters, anchovies, sardines, crabs, and scallops, among others. Animals, such as pelicans, cormorants, loons, grebes, sea otters, dolphins, and sea lions, which consume seafood contaminated with domoic acid, suffer disorientation and often death. Humans consuming contaminated seafood may suffer seizures, amnesia and also sometimes death. In addition to analytical measurement of domoic acid exposure levels in algae and/or seafood, it is useful to be able to identify the mode of toxicity through post-mortem evaluation of the intoxicated animal. In the present study, using the rat as an animal model of domoic acid intoxication, we compared histochemical staining of the limbic system and especially the hippocampus with degeneration-selective techniques (Fluoro-Jade and silver), a conventional Nissl stain for cytoplasm (Cresyl violet), a myelin-selective stain (Black-Gold), an astrocyte-specific stain (glial fibrillary acidic protein), early/immediate gene responses (c-Fos and c-Jun), as well as for heat shock protein (HSP-72) and blood-brain barrier integrity (rat IgG). The results demonstrate that the degeneration-selective stains are the biomarkers of domoic acid neurotoxicity that are the most useful and easy to discern when screening brain sections at low magnification. We also observed that an impairment of blood-brain barrier integrity within the piriform cortex accompanied the onset of domoic acid neurotoxicity.

Animals↗

PubMed2005

Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons.

The causes and effects of neuronal degeneration are of major interest to a wide variety of neuroscientists. Paralleling this growing interest is an increasing number of methods applicable to the detection of neuronal degeneration. The earliest methods employing aniline dyes were methodologically simple, but difficult to interpret due to a lack of staining specificity. In an attempt to circumvent this problem, numerous suppressed silver methods have been introduced. However, these methods are labor intensive, incompatible with most other histochemical procedures and notoriously capricious. In an attempt to develop a tracer with the methodological simplicity and reliability of conventional stains but with the specificity of an ideal suppressed silver preparation, the Fluoro-Jade dyes were developed. Fluoro-Jade C, like its predecessors, Fluoro-Jade and Fluoro-Jade B, was found to stain all degenerating neurons, regardless of specific insult or mechanism of cell death. Therefore, the patterns of neuronal degeneration seen following exposure to either the glutamate agonist, kainic acid, or the inhibitor of mitochondrial respiration, 3-NPA, were the same for all of the Fluoro-Jade dyes. However, there was a qualitative difference in the staining characteristics of the three fluorochromes. Specifically, Fluoro-Jade C exhibited the greatest signal to background ratio, as well as the highest resolution. This translates to a stain of maximal contrast and affinity for degenerating neurons. This makes it ideal for localizing not only degenerating nerve cell bodies, but also distal dendrites, axons and terminals. The dye is highly resistant to fading and is compatible with virtually all histological processing and staining protocols. Triple labeling was accomplished by staining degenerating neurons with Fluoro-Jade C, cell nuclei with DAPI and activated astrocytes with GFAP immunofluoresence.

Animals↗

PubMed2003

Demonstration and localization of neuronal degeneration in the rat forebrain following a single exposure to MDMA.

Methylenedioxymethamphetamine (MDMA, Ecstasy) is a powerful releaser of serotonin. Increasing recreational use of this stimulant and hallucinogenic drug has raised concerns about its potential to produce brain damage. The vast majority of previous research studies have focused on the compound's ability to deplete serotonin (5-hydroxytryptamine, 5-HT) from axon terminals. Despite extensive research on this '5-HT terminal neurotoxicity', a much less studied aspect of MDMA toxicity involves its ability to actually kill nerve cells. Only two prior studies mention the existence of MDMA-induced neuronal degeneration, as reflected by a limited number of argyrophylic neurons within the somatosensory cortex, following very high doses of MDMA. The development of Fluoro-Jade B as a simple and reliable marker of neuronal degeneration has allowed us to conduct the first comprehensive localization of MDMA induced neuronal degeneration throughout the entire rat forebrain. In addition to the previously reported neuronal degeneration within parietal cortex, degenerating neurons were also observed in the insular/perirhinal cortex, the ventromedial/ventrolateral thalamus, and the tenia tecta. The extent of neuronal degeneration observed generally correlated with the degree of hyperthermia achieved.

Animals↗

PubMed2002

The progression of neuronal, myelin, astrocytic, and immunological changes in the rat brain following exposure to aurothioglucose.

Aurothioglucose (ATG) is presently employed both by clinicians in the treatment of advanced rheumatoid arthritis and by neuroscience researchers to generate lesions around the circumventricular organs (CVOs) of rodent brains, resulting in obese animals. Although the existence of such lesions is well documented, there is relatively little information concerning the changes over time of the different cell types in the regions surrounding the CVOs. To address this question, specific markers allowing identification of four distinct cellular populations were used to characterize respective changes over time. Generally, regions adjacent to the CVOs were more vulnerable than the CVOs themselves, while more caudal structures were more frequently lesioned than more anterior CVO regions. Vascular and glial cells appeared to be the initial targets of ATG, while neuronal cell death occurred subsequent to the inflammatory response. The results of this study help resolve the mechanism of ATG toxicity as reflected by a cascade of pathologies that is consistent with disparate cell types exhibiting specific changes at specific times.

Animals↗

PubMed2002

Relations between brain pathology and temporal lobe epilepsy.

Temporal lobe epilepsy, the most common type of epilepsy in adult humans, is characterized clinically by the progressive development of spontaneous recurrent seizures of temporal lobe origin and pathologically by hippocampal neuronal loss and mossy fiber sprouting. In this study, we sought to test the prominent hypothesis that neuronal loss and mossy fiber sprouting play a critical role in the genesis and progression of temporal lobe epilepsy. Rats receiving a single kainic acid injection experienced a single sustained episode of epileptic status with massive neuronal loss and mossy fiber sprouting, whereas rats receiving triple kainic acid injections experienced two priming episodes and one sustained episode of epileptic status with no detectable neuronal loss and mossy fiber sprouting. Early in the process of chronic seizure development, primed rats that failed to show detectable neuronal loss and mossy fiber sprouting exhibited a starting date and a frequency of spontaneous recurrent seizures similar to those of nonprimed rats that showed massive neuronal loss and mossy fiber sprouting. However, nonprimed rats displayed significantly prolonged episodes of spontaneous recurrent seizures over the whole process of chronic seizure development and more frequent severe seizures later in the process. Similar results were observed in both Fischer-344 and Wistar rats as well as in the rat pilocarpine preparation of temporal lobe epilepsy. These results fail to reveal a relation between neuronal loss-mossy fiber sprouting and the genesis of temporal lobe epilepsy but suggest that neuronal loss, mossy fiber sprouting, or both contribute to the intensification of chronic seizures.

Animals↗