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Results for “selective vulnerability”

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PubMed1996

Regional reductions of transketolase in thiamine-deficient rat brain.

Thiamine deficiency impairs oxidative metabolism and causes metabolic encephalopathy. An early reduction in transketolase (TK) activity may be an important pathogenic event. To assess the role of TK, we have delineated the regional/cellular distribution of TK protein and mRNA in adult rat brain in pyrithiamine-induced thiamine deficiency. TK activity declined in both vulnerable and spared regions. Immunoblots showed a parallel reduction of TK protein. With a few exceptions, immunocytochemistry indicated an overall decline of TK immunoreactivity and the decrease was not specific to vulnerable areas. In contrast to the pronounced, general decline of TK protein, in situ hybridization revealed a regional decrease of 0-25% of TK mRNA in thiamine deficiency. Northern blots indicated a similar level of TK mRNA in whole brain in thiamine deficiency. These results show that the decline of TK activity results from a proportional decrease of TK protein, and the deficiency may be due to an instability of TK protein or an inhibition of TK mRNA translation. The lack of correlation of the distribution, and the absence of specific alteration, of TK in affected regions suggest that the reduced TK may not be linked directly to selective vulnerability in thiamine deficiency.

Animals↗

PubMed1998

Electrophysiology of the neuroprotective agent riluzole on striatal spiny neurons.

Striatal spiny neurons are selectively vulnerable in Huntington's disease (HD). No effective treatment is available to limit neuronal death in this pathological condition. In an experimental model of HD, a beneficial effect has recently been reported by the neuroprotective agent riluzole. We performed intracellular recordings in order to characterize the electrophysiological effects of this compound on striatal spiny neurons. Riluzole (0.1-100 microM) affected neither the resting membrane potential nor the input resistance/membrane conductance of the recorded cells. Bath application of this pharmacological agent produced a dose-dependent reduction of the number of spikes evoked by long-lasting depolarizing pulses. The EC50 value for this effect was 0.5 microM. Low doses of riluzole selectively reduced the firing frequency in the last part of the depolarizing pulse suggesting a use-dependent action at low concentrations of this compound. Riluzole produced a dose-dependent reduction of the amplitude of the corticostriatal glutamatergic excitatory post-synaptic potentials (EPSPs) with an extrapolated EC50 value of 6 microM. This effect was reversible and maximal at a concentration of 100 microM. Paired-pulse facilitation (PPF) was not affected by riluzole suggesting that the reduction of excitatory transmission was not only caused by a decrease of presynaptic release. Accordingly, riluzole also reduced the amplitude of membrane depolarization induced by exogenous glutamate. The modulatory action of riluzole on the activity of striatal spiny neurons might support the use of this drug in experimental models of excitotoxicity and in the neurodegenerative disorders involving the striatum.

Animals↗

PubMed2000

Neuroimaging: applications in disorders of early brain development.

Neuroimaging techniques have established new connections between etiological factors and disorders of early brain development. Neuroimaging has also strengthened the link between patterns of selective vulnerability in the developing brain and clinical syndromes, especially cerebral palsy. Both computed tomography (CT) and magnetic resonance imaging (MRI) identify early developmental malformations, including neural tube defects, callosal dysgenesis, neuronal migration disorders, posterior fossa malformations, and hydrocephalus. Periventricular white matter damage, most commonly seen in premature infants, is best visualized by cranial ultrasonography in the neonatal period and on MRI later in childhood. In term infants and children with genetic metabolic diseases, various applications of nuclear magnetic resonance, including MRI, have important diagnostic roles. The utility of diffusion-weighted imaging, MR spectroscopy, and functional MRI to further understanding of brain injury, biochemistry, and function is under active investigation. In summary, selecting the appropriate neuroimaging technique can improve diagnosis and management of childhood neurodevelopmental disorders.

Brain↗

PubMed1998

Light and electron microscopic distribution of the AMPA receptor subunit, GluR2, in the spinal cord of control and G86R mutant superoxide dismutase transgenic mice.

Excitotoxicity has been hypothesized to contribute to amyotrophic lateral sclerosis (ALS) neurodegeneration. The similar pattern of vulnerability in the spinal cord of mutant superoxide dismutase (SOD-1) transgenic mice and mice treated with excitotoxins supports a role for excitotoxicity in the mechanism of degeneration. The distribution of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) class of glutamate receptors (GluRs) with different calcium permeabilities has been proposed as an explanation for this differential vulnerability. GluR2 appears to be the dominant determinant of calcium permeability for AMPA receptors; thus, it is critical for their contribution to excitotoxic mechanisms. In this study, we investigate the distribution of GluR2 immunoreactivity in the spinal cord of control and SOD-1 transgenic mice. GluR2 immunoreactivity is present equally within vulnerable neurons (i.e., motor neurons and calretinin-immunoreactive neurons) as well as nonvulnerable neurons (i.e., calbindin-immunoreactive neurons and dorsal horn neurons). In addition, postembedding immunoelectron microscopy reveals that GluR2 is present in synapses of dorsal and ventral horn neurons and that the percentage of labeled synapses and numbers of immunogold particles per synapse do not vary between these spinal cord regions. Comparing control mice with SOD-1 transgenic mice, at both the light and the electron microscopic levels, the distribution and intensity of GluR2-immunoreactivity do not appear to be altered. These results suggest that the cellular and synaptic distribution of GluR2 is not a determinant of the selective vulnerability observed in SOD-1 transgenic mice or in ALS patients.

Amyotrophic Lateral Sclerosis↗

PubMed1994

Differential expression of the immediate early genes c-fos, c-jun, junB, and NGFI-B in the rat brain following transient forebrain ischemia.

The temporospatial expression pattern of four immediate early genes (IEGs) (c-fos, c-jun, junB, NGFI-B) following 30 min of global ischemia was investigated in rat brains by in situ hybridization and immunohistochemistry (c-fos). All examined IEG mRNAs, as well as Fos-like immunoreactivity, increased transiently in vulnerable and resistant brain regions following ischemia, but the induction profiles were distinct. Ischemia caused a post-ischemic early-onset, transient c-fos induction in wide-spread regions, as well as a late-onset induction restricted to vulnerable regions. Late-onset c-fos induction was observed in the CA1 region and the ventral thalamus but not in the striatum or neocortex, where neurons degenerate at a quicker pace. After recirculation, c-jun mRNA appeared to be initially coinduced with c-fos mRNA, but c-jun mRNA levels remained elevated or increased in various regions, including all vulnerable regions, when c-fos mRNA had already declined to near basal levels. Compared to c-fos and c-jun, junB induction was less pronounced and confined largely to the dentate gyrus. NGFI-B mRNA increased moderately and only in brain regions exhibiting the most dramatic c-fos increases and with similar kinetics. The differential activation of the investigated IEGs suggests that rather complex long-term adaptive processes may be initiated at the genomic level after global ischemia. The present findings provide further evidence that the activation of IEGs forms part of the brain's metabolic response to ischemia, but no simple correlation appears to exist between the induction of the investigated IEGs and the phenomenon of selective vulnerability.

Animals↗

PubMed2006

Cerebral palsy.

Cerebral palsy (CP) is a group of disorders of movement and posture resulting from nonprogressive disturbances of the fetal or neonatal brain. More than 80% of cases of CP in term infants originate in the prenatal period; in premature infants, both prenatal or postnatal causes contribute. The most prevalent pathological lesion seen in CP is periventricular white matter injury (PWMI) resulting from vulnerability of the immature oligodendrocytes (pre-OLs) before 32 wk of gestation. PWMI is responsible for the spastic diplegia form of CP and a spectrum of cognitive and behavioral disorders. Oxidative stress and excitotoxicity resulting from excessive stimulation of ionotropic glutamate receptors on preOLs are the most prominent molecular mechanisms for PWMI. Asphyxia around the time of birth in term infants accounts for less than 15% of CP in developed countries but the incidence is higher in underdeveloped areas. Asphyxia causes a different pattern of brain injury and CP than is seen after preterm injuries. This type of CP is associated with the clinical syndrome of hypoxic-ischemic encephalopathy shortly after the insult, and the cortex, basal ganglia, and brainstem are selectively vulnerable to injury. Experimental models indicate that neurons in the neonatal brain are more likely to die by delayed apoptosis extending over days to weeks than those in the adult brain. Neurons die by glutamate-mediated excitotoxicity involving downstream caspase-dependent and caspase-independent cell death pathways. Recent reports indicate that males and females preferentially utilize different pathways. Clinical trials indicate that mild hypothermia reduces death or disability in term infants following asphyxia and basic research suggests that this approach might be combined with pharmacological strategies in the future.

Asphyxia Neonatorum↗

PubMed1991

A crosslinguistic study of grammaticality judgments in Broca's aphasia.

Crosslinguistic studies of sentence comprehension and production in Broca's aphasia have yielded two complementary findings: (1) grammatical morphology appears to be more impaired than word order principles in every language studied, but (2) the degree to which grammatical morphology is retained by aphasic patients depends upon the "strength" or importance of those morphemes in the patient's premorbid language. In an earlier study comparing violations of word order and agreement, we found that English-speaking Broca's aphasics showed greater sensitivity to errors of ordering than to errors of agreement, providing further evidence for the selective vulnerability of morphology. However, because English is a rigid word order language with a relatively weak inflectional system, it could be argued that word order is resilient to brain damage because it is the strongest source of information in this language. The present study compared the performance of English-speaking Broca's aphasics and normal controls with their Italian counterparts in the same grammaticality judgment experiment. Four predictions relating to our previous work were confirmed. (1) Italian aphasics, like their English-speaking counterparts, showed general preservation of grammatical knowledge and (2) they were able to use this knowledge in an "on-line" fashion. (3) Within each language, Broca's aphasics showed greater impairment in their ability to recognize errors of morphological selection (i.e., agreement) compared with errors made by moving the same words to an incorrect position downstream. Nevertheless (4), crosslinguistic differences observed in previous studies of comprehension and production were also observed in this grammaticality judgment task: a processing advantage for agreement errors in Italian normals and aphasics, and a processing advantage for ordering errors in English normals and aphasics.

Adult↗

PubMed1998

Upregulation of the enzyme chain hydrolyzing extracellular ATP after transient forebrain ischemia in the rat.

A short ischemic period induced by the transient occlusion of major brain arteries induces neuronal damage in selectively vulnerable regions of the hippocampus. Adenosine is considered to be one of the major neuroprotective substances produced in the ischemic brain. It can be released from damaged cells, but it also could be generated extracellularly from released ATP via a surface-located enzyme chain. Using the rat model of global forebrain ischemia, we applied a short (10 min) transient interruption of blood flow and studied the distribution of ectonucleotidase activities in the hippocampus. Northern hybridization of mRNA isolated from hippocampi of sham-operated and ischemic animals revealed an upregulation of ectoapyrase (capable of hydrolyzing nucleoside 5'-tri- and diphosphates) and ecto-5'-nucleotidase (capable of hydrolyzing nucleoside 5'-monophosphates). A histochemical analysis that used ATP, UTP, ADP, or AMP as substrates revealed a strong and selective increase in enzyme activity in the injured areas of the hippocampus. Enhanced staining could be observed first at 2 d. Staining increased within the next days and persisted at 28 d after ischemia. The spatiotemporal development of catalytic activities was identical for all substrates. It was most pronounced in the CA1 subfield and also could be detected in the dentate hilus and to a marginal extent in CA3. The histochemical staining corresponded closely to the development of markers for reactive glia, in particular of microglia. The upregulation of ectonucleotidase activities implies increased nucleotide release from the damaged tissue and could play a role in the postischemic control of nucleotide-mediated cellular responses.

Actins↗

PubMed2003

Idiopathic Parkinson's disease: possible routes by which vulnerable neuronal types may be subject to neuroinvasion by an unknown pathogen.

The progressive, neurodegenerative process underlying idiopathic Parkinson's disease is associated with the formation of proteinaceous inclusion bodies that involve a few susceptible neuronal types of the human nervous system. In the lower brain stem, the process begins in the dorsal motor nucleus of the vagus nerve and advances from there essentially upwards through susceptible regions of the medulla oblongata, pontine tegmentum, midbrain, and basal forebrain until it reaches the cerebral cortex. With time, multiple components of the autonomic, limbic, and motor systems become severely impaired. All of the vulnerable subcortical grays and cortical areas are closely interconnected. Incidental cases of idiopathic Parkinson's disease may show involvement of both the enteric nervous system and the dorsal motor nucleus of the vagus nerve. This observation, combined with the working hypothesis that the stereotypic topographic expansion pattern of the lesions may resemble that of a falling row of dominos, prompts the question whether the disorder might originate outside of the central nervous system, caused by a yet unidentified pathogen that is capable of passing the mucosal barrier of the gastrointestinal tract and, via postganglionic enteric neurons, entering the central nervous system along unmyelinated praeganglionic fibers generated from the visceromotor projection cells of the vagus nerve. By way of retrograde axonal and transneuronal transport, such a causative pathogen could reach selectively vulnerable subcortical nuclei and, unimpeded, gain access to the cerebral cortex. The here hypothesized mechanism offers one possible explanation for the sequential and apparently uninterrupted manner in which vulnerable brain regions, subcortical grays and cortical areas become involved in idiopathic Parkinson's disease.

Brain↗

PubMed2003

Pro-brain-derived neurotrophic factor is decreased in parietal cortex in Alzheimer's disease.

Brain-derived neurotrophic factor (BDNF) promotes the function and survival of the major neuronal types affected in Alzheimer disease, such as hippocampal, cortical and basal forebrain cholinergic neurons. We and others have demonstrated a reduction in BDNF mRNA expression in Alzheimer's disease hippocampus and cortex, which may help to explain the selective vulnerability of these neurons. Several studies have also shown decreased BDNF protein in Alzheimer's disease. BDNF protein is synthesized as a precursor, proBDNF, which is cleaved to the mature 14-kDa form. We demonstrate here that BDNF exists as a mixture of proBDNF and mature BDNF in all regions tested of human brain. Using Western blotting, we observe a 40% reduction in proBDNF levels in Alzheimer's disease parietal cortex compared to controls. Thus, decreased BDNF protein measured by ELISA and immunohistochemistry likely represents a mixture of the two BDNF forms, and previously reported decreases in BDNF protein may be due, at least in part, to a significant reduction in proBDNF levels. Although the biological activity of proBDNF is unknown, reduced proBDNF may have functional consequences for the selective neuronal degeneration in Alzheimer's disease brain.

Aged↗

PubMed2000

Psychophysical evidence for rod vulnerability in age-related macular degeneration.

PURPOSE: To determine whether there is rod system dysfunction in the central retina of patients with age-related macular degeneration (AMD). METHODS: Dark-adapted sensitivity (500-nm stimulus) and light-adapted sensitivity (600 nm) were measured psychophysically at 52 loci in the central 38 degrees (diameter) of retina in 80 patients with AMD, and results were compared with those from older adult normal controls. All dark-adapted data were corrected for preretinal absorption. RESULTS: Mean field dark-adapted sensitivity was significantly lower in AMD patients as a group than in normal subjects. Within the AMD group were subsets of patients with normal mean dark- and light-adapted sensitivities; reduced dark-adapted sensitivities without detectable light-adapted losses; both types of losses; and, least commonly, only light-adapted losses. Regional retinal analyses of the dark-adapted deficit indicated the greatest severity was 2 degrees to 4 degrees or approximately 1 mm from the fovea, and the deficit decreased with increasing eccentricity. CONCLUSIONS: These psychophysical results are consistent with histopathologic findings of a selective vulnerability for parafoveal rod photoreceptors in AMD. The different patterns of rod and cone system losses among patients at similar clinical stages reinforces the notion that AMD is a group of disorders with underlying heterogeneity of mechanism of visual loss. Dark-adapted macula-wide testing may be a useful complement to the more traditional outcome measures of fundus pathology and foveal cone-based psychophysics in future AMD trials.

Aged↗

PubMed1993

The high sensitivity to rotenone of striatal dopamine uptake suggests the existence of a constitutive metabolic deficiency in dopaminergic neurons from the substantia nigra.

The toxicity of the 1-methyl-4-phenylpyridinium ion (MPP+), an inhibitor of complex I of the respiratory chain, on nigrostriatal dopaminergic neurons contrasts with its relative inefficiency towards other catecholaminergic cell populations in spite of their ability to accumulate this neurotoxin through their high-affinity uptake system. A constitutive metabolic deficiency of the nigrostriatal dopaminergic neurons could account for their particular vulnerability to MPP+. In order to substantiate this hypothesis, we compared the inhibitory effects of rotenone, an inhibitor of mitochondrial oxidative phosphorylation, on the uptake of dopamine, serotonin, noradrenaline and GABA in mouse striatal synaptosomes, and of dopamine, serotonin and GABA in cultured mesencephalic neurons. In both preparations, the uptake of dopamine was much more affected than that of other neurotransmitters by rotenone. This result was confirmed using two other unrelated inhibitors of oxidative phosphorylation. Moreover, dopamine uptake in synaptosomes from the dorsolateral striatum was more sensitive to rotenone than uptake in synaptosomes from the nucleus accumbens. This indicates that intrinsic metabolic properties of the nigrostriatal dopaminergic neurons may explain the strong inhibition by rotenone of striatal dopamine uptake. Altogether, these results suggest that a constitutive metabolic deficiency could account, at least in part, for the selective vulnerability of the nigrostriatal dopaminergic pathway to the action of the neurotoxin MPP+.

Animals↗

PubMed1993

Ischemia-mediated neuronal injury.

Resuscitation of the brain after a period of global ischemia is limited by two classes of post-ischemic pathologies: hemodynamic disturbances which prevent the adequate re-oxygenation of the ischemic brain, and metabolic disturbances which may lead to delayed neuronal death in so-called selectively vulnerable brain regions. The hemodynamic disturbances can be classified into the no-reflow phenomenon and the post-ischemic hypoperfusion syndrome. The no-reflow phenomenon results from a combination of increased blood viscosity and perivascular edema; the severity increases with the duration of ischemia, and the treatment is by combining arterial hypertension with dehydration and anticoagulation. The post-ischemic hypoperfusion syndrome is independent of the duration of ischemia, it develops after a delay and is due to an impairment of the metabolic/hemodynamic coupling mechanisms; there is no specific treatment at the present. The most important metabolic disturbance leading to delayed neuronal death is prolonged inhibition of protein synthesis. The injury is manifested already after 5 min ischemia but it progresses little if ischemia is prolonged to 1 h. Inhibition occurs at the translation level due to selective inhibition of polypeptide chain initiation. After brief periods of ischemia, the disturbance can be reversed by various anesthetics and hypothermia but there is no treatment if ischemia is prolonged. Exitotoxity, free radical-mediated reactions, disturbances of polyamine metabolism, acidosis and selective disturbances of gene expression may also be involved but are probably of lesser importance.

Animals↗

PubMed1995

Up-regulation of bax and down-regulation of bcl-2 is associated with kainate-induced apoptosis in mouse brain.

Systemic administration of kainate induces cell death in vulnerable regions of the rodent brain. Neuronal degeneration is associated with internucleosomal DNA fragmentation and induction of presumptive cell death effector genes (e.g. p53, c-fos) suggesting that kainate activates an apoptotic pathway. In the present study, kainate-induced DNA damage has been demonstrated at the cellular level by in situ nick translation in the mouse hippocampus and neocortex at 24 h and 48 h after intraperitoneal injections. In the same regions, the intensity of Bcl-2 immunoreactivity decreased by about 45% as measured by digital image analysis. Most important, kainate treatment evoked a nearly 3-fold increase in bax mRNA levels within the mouse brain. The down-regulation of bcl-2, which promotes cell survival, and the up-regulation of bax, which promotes programmed cell death, may have functional significance in kainate-mediated excitotoxicity and in the selective vulnerability of specific brain regions.

Animals↗

PubMed2005

Susceptibility of striatal neurons to excitotoxic injury correlates with basal levels of Bcl-2 and the induction of P53 and c-Myc immunoreactivity.

The present studies evaluated the potential contribution of Bcl-2, p53, and c-Myc to the differential vulnerability of striatal neurons to the excitotoxin quinolinic acid (QA). In normal rat striatum, Bcl-2 immunoreactivity (Bcl-2-i) was most intense in large aspiny interneurons including choline acetyltransferase positive (CAT+) and parvalbumin positive (PARV+) neurons, but low in a majority of medium-sized neurons. In human brain, intense Bcl-2-i was seen in large striatal neurons but not in medium-sized spiny projection neurons. QA produced degeneration of numerous medium-sized neurons, but not those enriched in Bcl-2-i. Many Bcl-2-i-enriched interneurons including those with CAT+ and PARV+ survived QA injection, while medium-sized neurons labeled for calbindin D-28K (CAL D-28+) did not. In addition, proapoptotic proteins p53-i and c-Myc-i were robustly induced in medium-sized neurons, but not in most large neurons. The selective vulnerability of striatal medium spiny neurons to degeneration in a rodent model of Huntington's disease appears to correlate with their low levels of Bcl-2-i and high levels of induced p53-i and c-Myc-i.

Adult↗

PubMed1998

Vulnerable neuronal subsets in Alzheimer's and Pick's disease are distinguished by their tau isoform distribution and phosphorylation.

Aggregated tau proteins constitute the basic matrix of neuronal inclusions specific to numerous neurodegenerative disorders. Monodimensional and two-dimensional Western blot analyses performed on cortical brain homogenates allowed discrimination between disease-specific tau protein profiles. These observations raised the issue of the physiopathological significance of such specificities. Alzheimer's disease (AD) pathological tau proteins (PTPs) (tau 74, 69, 64, 55) were compared with those of Pick's disease (PiD) (tau 64, 55) using a panel of antibodies against peptidic sequences of tau isoforms corresponding to exons 2, 3, and 10. AD and PiD could then be critically differentiated by the absence of translated tau isoforms with exon 10 in PiD PTPs, along with the absence of the phosphorylation site on Ser262. Immunohistochemical studies corroborate these findings. Indeed, Pick bodies were strongly immunostained by an anti-"exon 2" antibody but failed to reveal any anti-exon 10 reactive epitope. Tangles in AD contained exon 2, 3, and 10 epitopes. Altogether, our results demonstrated that Pick bodies develop within specific neuronal subsets that express specific patterns of 7 isoforms lacking exon 10 peptidic sequence. We conclude that neurodegenerative disorders imply attrition of selectively vulnerable neuronal subsets, a process revealed, and may be sustained by specific tau isoform patterns.

Alzheimer Disease↗

PubMed1992

Immunocytochemical study of an early microglial activation in ischemia.

Transient arrest of the cerebral blood circulation results in neuronal cell death in selectively vulnerable regions of the rat brain. To elucidate further the involvement of glial cells in this pathology, we have studied the temporal and spatial distribution pattern of activated microglial cells in several regions of the ischemic rat brain. Transient global ischemia was produced in rats by 30 min of a four-vessel occlusion. Survival times were 1, 3, and 7 days after the ischemic injury. The microglial reaction was studied immunocytochemically using several monoclonal antibodies, e.g., against CR3 complement receptor and major histocompatibility complex (MHC) antigens. Two recently produced monoclonal antibodies against rat microglial cells, designated MUC 101 and 102, were also used to identify microglial cells. Following ischemia, the microglial reaction was correlated with the development of neuronal damage. The earliest presence of activated microglial cells was observed in the dorsolateral striatum, the CA1 area, and the dentate hilus of the dorsal hippocampus. However, the microglial reaction was not confined to areas showing selective neuronal damage, but also occurred in regions that are rather resistant to ischemia, such as the CA3 area. Particularly in the frontoparietal cortex, the appearance of MHC class II-positive microglial cells provided an early indication of the subsequent distribution pattern of neuronal damage. The microglial reaction would thus seem to be an early, sensitive, and reliable marker for the occurrence of neuronal damage in ischemia.

Animals↗

PubMed2005

Excitotoxicity and ALS: what is unique about the AMPA receptors expressed on spinal motor neurons?

It has been repeatedly reported that spinal motor neurons are selectively vulnerable to AMPA receptor-mediated excitotoxicity. Therefore, identifying the uniqueness of AMPA receptors that are expressed on motor neurons, especially in individuals affected with sporadic amyotrophic lateral sclerosis (ALS) is essential for elucidating the etiology of this disorder. The mechanism that initiates motor neuronal death appears to be an exaggerated influx of Ca(2+) through AMPA receptors. The determinants that affect this Ca(2+) influx are Ca(2+) permeability, which is regulated by the presence of the GluR2 subunit and by RNA editing at the Q/R site of GluR2; channel desensitization, which is regulated by alternative splicing at the flip/flop site and by RNA editing at the R/G site of GluR subunits; and receptor density on the cell surface, which is controlled by many factors including regulatory proteins, direct phosphorylation and RNA editing at the Q/R site. This review focuses on recent progress on the molecular dynamics of AMPA receptors and discusses the pathophysiology of selective motor neuron death mediated by AMPA receptors in individuals affected with sporadic ALS.

Amyotrophic Lateral Sclerosis↗