Cervical juxtafacet cysts: case report and literature review.

BACKGROUND: Juxtafacet cysts of the cervical and thoracic spine are rare and often present with myelopathy. Juxtafacet cysts are well recognized entities found commonly in the lumbar spine but are unusual in the cervical and thoracic spine. We present a case of a patient with gait disturbance and early myelopathy who was found to have a juxtafacet cyst at the cervico-thoracic junction. We further review the literature. PURPOSE: To describe a case of a cervico-thoracic juxtafacet cyst and review the literature. STUDY DESIGN: Case report and subject review. METHODS: One patient presenting with early myelopathy and pain underwent surgery for resection of the lesion. Pathologic analysis revealed a juxtafacet cyst. RESULTS: The patient recovered uneventfully with relief of his pain. Pubmed review revealed less than 30 similar cases in the literature. CONCLUSION: Juxtafacet cysts of the cervical spine are rare entities. These lesions comprise both synovial cysts and ganglion cysts. The benign lesions present with myelopathy and should be considered in patients with cystic lesions in the cervical spinal canal.

Regional differences in the expression of corticostriatal synaptic plasticity.

Field recordings of responses to activation of corticostriatal afferents were made in coronally sectioned rat brain slices. Each recording site was categorized according to its medial to lateral and rostral to caudal position to investigate anatomical differences in synaptic plasticity. Individual responses were highly variable exhibiting extremes of tetanus induced depression and potentiation. Consequently, averaging masked the capacity of these synapses to express long-term forms of plasticity. Block of GABA(A) inhibition and elimination of dopaminergic input with 6-hydroxydopamine lesions both acted to increase the expression of potentiation, but again considerable variability was observed. Separation of recordings into medial and lateral groups revealed clear anatomical trends which contributed to the variability observed in the total sample. Paired-pulse, post-tetanic and long-term potentiation was greater in medial than in lateral groups in normal artificial cerebral spinal fluid. Similar tendencies were seen after block of GABA(A) receptors with bicuculline. 6-Hydroxydopamine lesions in combination with bicuculline treatment reduced medial to lateral differences. Factoring in medial to lateral trends revealed block of GABA(A) receptor mediated inhibition had its greatest effect on medial corticostriatal responses and 6-hydroxydopamine lesions had their greatest effect on lateral responses. From these data we suggest anatomical variation in striatal circuitry may underlie regional differences in synaptic plasticity evoked by corticostriatal activation.

Functional state of corticostriatal synapses determines their expression of short- and long-term plasticity.

Relationships between presynaptic function and short- and long-term plasticity were investigated at adult corticostriatal synapses. Wide variability was observed in the expression of short- and long-term synaptic plasticity. Intracellular records from 47 cells produced 17 examples of LTD (<90% of control), 10 examples of no long-term change (between 90-110% of control), and 20 examples of LTP (>110% of control). Similar variation existed in paired-pulse and posttetanic plasticities. The variability expressed in all three forms of plasticity appears to be related, based on correlations found between the paired-pulse ratio (PPR) and tetanus-induced short- (3 min posttetanus) and long-term plasticities (16-20 min posttetanus). These data suggest that tetanus-induced changes in synaptic strength are related to the intrinsic, preconditioned behavior of synapses. Every cell showing paired-pulse depression also expressed LTD in response to high-frequency activation of its afferents. Those synapses showing paired-pulse potentiation tended to express LTP, although exceptions did exist. Similar relationships were found in a parallel analysis of population spikes. PPR also changed in association with the expression of posttetanic and long-term depression. Greater paired-pulse potentiation was observed in medial intracellular recordings, but no medial to lateral differences were seen in posttetanic plasticities. Field recordings also showed a medial bias toward paired-pulse and posttetanic potentiation, but not in long-term plasticity. Block of postsynaptic L-type Ca(2+) channels with nifedipine eliminated LTD expression, but overall no differences were found between nifedipine and control cells.

Time-dependent blockade of STP and LTP in hippocampal slices following acute stress in mice.

The characteristics of short-term potentiation (STP) and long-term potentiation (LTP) in the CA1 region of hippocampal slices were determined at various times following exposure to acute stress produced by restraint and tail-shock in mice. In slices prepared from control animals, theta-burst stimulation resulted in a large increase in evoked field excitatory postsynaptic potentials (EPSPs) amplitude and slope that remained stable at least up to 30 min after stimulation. Slices prepared 1 h after stress exhibited a marked decrease in the extent of both STP and LTP. STP and LTP magnitude were still significantly decreased 24 h after stress exposure and were completely restored to control levels by 48 h. These results provide evidence for a reversible impairment of STP and LTP in CA1 following an acute episode of stress, and suggest that stress activates processes different from those activated by LTP-inducing stimuli.

Complement and glutamate neurotoxicity. Genotypic influences of C5 in a mouse model of hippocampal neurodegeneration.

Using mice genetically deficient in the complement (C)-system component C5, this study explored a potential novel role of the C-system in Ca(2+)-mediated control of glutamate AMPA receptor functions. We found that Ca2+ preincubation of frozen brain tissue sections enhances AMPA binding capacity more dynamically in C5 deficient (C5-) than congenic C5 sufficient (C5+) mice. The Ca(2+)-mediated response was mostly localized to the CA3 and CA1 subdivisions of the pyramidal layers of the hippocampal formation. In C5- mice, kainic acid (KA) excitotoxicity that models hippocampal neurodegeneration abolished the Ca(2+)-mediated induction of hippocampal AMPA binding. The changes in AMPA binding preceded temporally and overlapped anatomically the appearance of apoptotic features in the same hippocampal neuron layers. C5- mice showed greater hippocampal neurodegeneration then C5+ mice. NMDA binding controlled for specificity of glutamate-mediated changes and found no C5 genotypic influences. The study gives further credence to the role of the C-system in modifying the intensity and outcome during response to conditions leading to hippocampal neurodegeneration.

Glycine-induced long-term potentiation is associated with structural and functional modifications of alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid receptors.

Global long-term potentiation (LTP) was induced in organotypic hippocampal slice cultures by a brief application of 10 mM glycine. Glycine-induced LTP was occluded by previous theta burst stimulation-induced potentiation, indicating that both phenomena share similar cellular processes. Glycine-induced LTP was associated with increased [3H]alpha-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) binding in membrane fractions as well as increased amount of a selective spectrin breakdown product generated by calpain-mediated spectrin proteolysis. Antibodies against the C-terminal (C-Ab) and N-terminal (N-Ab) domains of GluR1 subunits were used to evaluate structural changes in AMPA receptor properties resulting from glycine-induced LTP. No quantitative or qualitative changes were observed in Western blots from membrane fractions prepared from glycine-treated slices with C-Ab. In contrast, Western blots stained with N-Ab revealed the formation of a 98-kDa species of GluR1 subunits as well as an increased amount of immunoreactivity after glycine-induced LTP. The amount of spectrin breakdown product was positively correlated with the amount of the 98-kDa species of GluR1 after glycine treatment. Functional modifications of AMPA receptors were evaluated by determining changes in the effect of pressure-applied AMPA on synaptic responses before and after glycine-induced LTP. Glycine treatment produced a significant increase in AMPA receptor function after potentiation that correlated with the degree of potentiation. The results indicate that LTP induction produces calpain activation, truncation of the C-Ab domain of GluR1 subunits of AMPA receptors, and increased AMPA receptor function. They also suggest that insertion of new receptors takes place after LTP induction.

Effects of a nitric oxide synthase inhibitor on NMDA receptor function in organotypic hippocampal cultures.

Nitric oxide (NO) has been proposed to trigger long-term potentiation (LTP) at CA3 to CA1 synapses. We previously reported that NO synthesis inhibitors and blockers reduce an electrophysiological index of NMDA receptor activation in acute hippocampal slices. We now show that the NOS inhibitor, NG-methyl-L-arginine (MLA), also reversibly prevents LTP induction in organotypic hippocampal slices and significantly reduces a biochemical index of NMDA receptor function. These results results further indicate that MLA inhibits LTP induction by interfering with NMDA receptor functions.

Effects of ethanol and temperature on NMDA receptor function in different mouse genotypes.

The present study investigated whether temperature-related changes in NMDA receptor sensitivity to ethanol might play a role in mediating the effects of body temperature on behavioral sensitivity to ethanol or in determining genotypic differences in sensitivity to ethanol. We accomplished this by determining the effects of ethanol on three different mouse genotypes (C57, LS, and SS) on two types of NMDA receptor-mediated responses at 30 degrees and 35 degrees C: (i) extracellularly recorded synaptic potentials elicited in the CA1 region of the in vitro hippocampal slice preparation by stimulation of the Schaffer-commisural pathway in the presence of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor blocker, 6,7-dinitroquinoxaline-2,3-dione, and low magnesium concentration; and (ii) increase in [3H]MK-801 binding elicited by glutamate in telencephalic membrane preparations. Ethanol significantly decreased NMDA receptor-mediated excitatory postsynaptic potential (EPSP) amplitude and area in the three genotypes. In C57, the effect of ethanol on NMDA receptor-mediated EPSP amplitude and area was more pronounced at 30 degrees C, compared with that at 35 degrees C. In most cases, there was a good correlation between the effects of ethanol on EPSP amplitude and area. The order of sensitivity between the three genotypes was C57 = LS > SS at 35 degrees C and C57 > LS = SS at 30 degrees C. Similarly, ethanol significantly decreased glutamate-stimulated [3H]MK-801 binding in membrane fractions. The effect of ethanol was temperature-dependent, because ethanol produced more inhibition at 30 degrees C than at 35 degrees C in all genotypes. The effect of ethanol on MK-801 binding was concentration-dependent, and the sensitivity to 100 mM ethanol of the genotypes at 35 degrees C was LS > SS = C57, whereas it was SS > LS = C57 at 30 degrees C. Collectively, the results demonstrate that temperature is an important variable that can influence NMDA receptor sensitivity to ethanol measured via electrophysiological and binding techniques, and that temperature can influence relative sensitivity of NMDA receptors to ethanol between mouse genotypes. Furthermore, the findings indicate that temperature-induced changes in sensitivity of NMDA receptors to ethanol may play a role in mediating the effects of body temperature on behavioral sensitivity to ethanol in LS, but not C57 and SS mice.

Hereditary deficiencies in complement C5 are associated with intensified neurodegenerative responses that implicate new roles for the C-system in neuronal and astrocytic functions.

Possible roles of the complement (C) system in the normal and injured brain were explored with inbred mice that carried a frameshift mutation in the C5 gene. A congenic pair was used: the C5-sufficient (C5+) B10.D2/nSnJ strain with the functional allele (Hc1) from the C57BL/10J donor strain was compared with the C5-deficient (C5-) B10.D2/oSnJ with the Hc0 allele from the C5-deficient DBA/2J donor strain. In response to the excitotoxin kainic acid (KA), C5- mice had more hippocampal pyramidal neuron death and greater induction of astrocyte mRNAs (GFAP, apoE, apoJ). In primary astrocyte cultures from unlesioned mice, an inflammatory stimulus (LPS) caused greater production of IL-6 and TNF production in C5- mice. These enhanced responses to KA and LPS suggest that hereditary C5 deficits modify responses to neurodegenerative stimuli of neurons and astrocytes. Moreover, unlesioned C5- mice had smaller input-output slopes for the NMDA component of the EPSP amplitude, but enhanced the Ca(+2)-dependent AMPA binding. Thus, C5 deficits also modify basal properties of glutamatergic neurotransmission that pertain to synaptic plasticity. These findings are also discussed in relation to roles of the C-system in Alzheimer disease (AD). C5 deficiencies may also be considered in the choice of strains as transgene hosts and for genetic analysis of normal and pathological brain functions. In recent transgenic studies for AD, C5- hosts showed greater neurodegeneration, consistent with the present data. These pleiotropic associations of C5 deficiency indicate roles for the C-system in neurodegeneration, but also in normal neural functions.

Effects of EUK-8, a synthetic catalytic superoxide scavenger, on hypoxia- and acidosis-induced damage in hippocampal slices.

Anoxia produces deleterious effects on synaptic transmission in the hippocampal slice preparation. A proposed source of damage is the superoxide radical (.O2-) produced during the earlier period of reoxygenation. The present study tested the effects of a synthetic, catalytic superoxide radical scavenger (EUK-8) on CA1 pyramidal cell responses elicited by electrical stimulation of the Schaffer-commissural pathway after severe anoxic episodes. Following reoxygenation, slices incubated with EUK-8 (50 microM) exhibited significantly better recovery of excitatory postsynaptic potentials (EPSPs) than control slices. In addition, repeated episodes of anoxia produced irreversible loss of synaptic transmission in the majority of control slices (93 +/- 7%, n = 15), compared to a small fraction in EUK-8-incubated slices (27 +/- 12%, n = 15). A thiobarbituric acid (TBA) test was used to assess the effect of EUK-8 on lipid peroxidation elicited in hippocampal slices by acidosis and lactic acid (pH 5.0 and 30 mM lactic acid). Incubation in the presence of EUK-8 totally prevented the increase in lipid peroxidation produced by acidosis and lactic acid in both the incubation medium and the slice homogenates. These results indicate that a superoxide scavenger like EUK-8 prevents damage produced by acidosis and anoxia in hippocampal slices and suggest the possibility of using this type of molecule under various pathological conditions.

Further studies concerning the role of nitric oxide in LTP induction and maintenance.

Nitric oxide (NO) has recently been proposed to act as a retrograde messenger to produce long-term potentiation (LTP) in hippocampal area CA1. This notion is based largely on the absence of LTP when hippocampal slices are incubated in the presence of inhibitors of NO synthase (NOS) or of NO scavengers. In the present study, we tested the effects of such compounds on both the induction and maintenance of LTP in field CA1 of hippocampal slices. Incubation of slices in the presence of N-methyl-L-arginine (MLA) or L-nitro-arginine (LNA), two inhibitors of NOS, or in the presence of hemoglobin (Hb), a NO scavenger, produced a large reduction in the magnitude of LTP induced by a theta burst stimulation (TBS) paradigm. These compounds had no effect on the degree of paired-pulse facilitation but produced a significant reduction of the facilitation of postsynaptic responses occurring during TBS. On the other hand, MLA did not prevent the potentiation induced by application of tetraethylammonium (TEA). These results suggest that the inhibition of LTP produced by these agents could be due to an effect on a physiological mechanism that triggers LTP and not necessarily on an event that follows the triggering step.