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Interanimal variability in preexisting collaterals is a major factor determining outcome in experimental angiogenesis trials.

Despite numerous animal trials reporting that cell therapy promotes collateral flow, clinical trials have not convincingly shown benefit. Patient-related risk factors are often used to explain these discrepancies. However, during the course of our own angiogenesis studies using mice, we noted large anatomical variability in collateral vessels. The purpose of the present investigation was to define how important this factor might be in determining intervention outcomes. Hindlimb ischemia was induced in BALB/c mice by ligating the superficial femoral artery. After 24 h, animals were treated by injecting the adductor muscle with either control media or cultured mesenchymal stem cells (MSCs). Blood flow recovery was measured using laser-Doppler [laser-Doppler perfusion imaging (LDPI) ratio]. In a second experiment, mice were stratified 24 h after arterial ligation before treatment by using a simple clinical score of the ligated leg: 1, able to flex, mild discoloration; 2, no flexion, mild discoloration; 3, severe discoloration; and 4, any necrosis. Without stratification, blood flow recovery significantly increased in the MSC-treated group (P < 0.05, n = 6 MSC group, n = 7 media group). In the experiment employing stratification, all differences between the groups disappeared (n = 11 MSC group, n = 10 media group; P = 0.3). Furthermore, we found a striking inverse correlation between clinical score on day 1 and the LDPI ratio on day 28 (P < 0.0001; n = 79). Anatomical confirmation of the disparity in preexisting collaterals was found in two different mouse strains using microscopic computed tomography. In conclusion, there is substantial interanimal variability in preexisting collateral flow, and this variability can importantly influence outcome. To overcome this, either animals must be stratified before treatment, the number of animals must be increased substantially, or, preferably, both.

Animals↗

Modulation of extracellular pH by glutamate and GABA in rat hippocampal slices.

1. Alkaline extracellular pH transients evoked by afferent stimulation, and local pressure ejection of glutamate and gamma-aminobutyric acid (GABA), were studied in the CA1 region of rat hippocampal slices. Amino acid-evoked responses were obtained by use of a dual micromanipulator, with the tip of a double-barreled pH-sensitive microelectrode positioned 50 microns from a pressure ejection pipette. 2. At 31 degrees C, in Ringer solutions buffered with 26 mM HCO3- and 5% CO2, mean extracellular pH in submerged 300-microns slices was 7.15 +/- 0.12 (n = 27 slices), at a tissue depth of approximately 150 microns. In Ringer buffered with 35 mM HCO3- and 5% CO2, extracellular pH was 7.29 +/- 0.10 (n = 19 slices). 3. Repetitive stimulation of the Schaffer collaterals caused an extracellular alkaline shift in stratum oriens, pyramidale, and radiatum, averaging 0.05 +/- 0.03 pH units among all regions (n = 138), with a maximum response of 0.16 pH units. Alkaline transients of similar appearance were obtained by local ejection of glutamate (0.01-0.12 pH units, n = 110) and GABA (0.01-0.18 pH units, n = 137). Control ejection of these amino acids into dilute agar caused only small acid shifts. 4. Superfusion of 100 microM picrotoxin abolished the GABA-evoked alkaline shift but failed to inhibit the Schaffer collateral- and glutamate-evoked alkalinizations. 5. Superfusion of 10(-5)-10(-3) M acetazolamide acidified the baseline by 0.05-0.10 pH units and amplified the Schaffer collateral- and glutamate-evoked alkaline shifts.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetazolamide↗

M-mode echocardiography in anteroseptal myocardial infarction. Lack of sensitivity.

Eighteen patients with documented anteroseptal myocardial infarction (ASMI) were investigated with both cardiac catheterization and M-mode echocardiography. All had greater than 75% occlusion of the left anterior descending artery (LAD), proximal to the first septal perforator in 12, and distal to it in 6; 17 of 18 had abnormal septal motion by angiography. In contrast, echocardiography revealed abnormal septal motion in only 5 of 18; two others had diminished septal wall thickness in relation to posterior ventricular wall. The presence of these echocardiographic signs was not dependent either on relation of stenosis to septal perforators or on presence of septal collaterals. Although abnormal septal motion by M-mode echocardiography may indicate ASMI, normal motion does not exclude it nor does it help localize stenosis of the LAD.

Adult↗

Early morphological changes of primary afferent neurons and their processes in newborn mice after treatment with capsaicin.

Degenerating figures of dorsal root ganglion (DRG) neurons and their central and peripheral processes (dorsal root and saphenous nerve) and terminals (central terminals in the superficial dorsal horn and cutaneous nerve of the hind paw dorsal skin) of neonatal mice were examined 30 min, 1, 2 and 5 h, and 2, 3, 5, and 10 days after subcutaneous injection of capsaicin on post-natal day 2. Many small DRG neurons showed degeneration 1 h after treatment. Scarcely any features of degeneration were seen in the DRG and dorsal root 10 days after treatment. The degenerating aspects of terminal axons in the marginal layer of the superficial dorsal horn were characterized by enlarged round axons with closely packed osmiophilic materials, lamellar bodies, and loss of axoplasmic organelles. Two types of central terminals (C-terminals) showed degeneration in the substantia gelatinosa from 30 min after treatment onward. One type consisted of small, round, sinuous or slender dark terminals (CI-terminals), and the other of large, pale, round or angular terminals (CII-terminals). Those that degenerated markedly had homogeneously electron-dense axoplasm with dilated synaptic vesicles and inclusion bodies. Extensive degeneration of terminal axons in the marginal layer occurred 5 h after treatment, whereas conspicuous degeneration of C-terminals occurred from 30 min to 10 days after treatment in the substantia gelatinosa. CI-terminals showed marked degeneration during the first 3 days, whereas marked degeneration of CII-terminals occurred between 5 and 10 days after treatment. This time difference between the peaks of degeneration of CI- and CII-terminals indicates an important difference in the origins of these two types of capsaicin-sensitive, nociceptive fibers in the superficial dorsal horn; CI-terminals are derived from small DRG cells, whereas CII-terminals are derived from larger DRG cells. Unmyelinated axons in the dorsal root, saphenous nerve, and dorsal skin of the hind paw showed similar degeneration patterns 2 h after treatment to those of terminal axons in the marginal layer. Thus, the degenerating profiles in the marginal layer suggest that these axons arose from collaterals of unmyelinated primary axons descending or ascending within the marginal layer. Numerous enlarged degenerating axons showing vacuolation were conspicuous in the dorsal skin 3 days after treatment. The synchronous degeneration of the smaller DRG neurons, their central and peripheral processes, and their CI-terminals in the substantia gelatinosa supports the idea that the smaller DRG neurons are directly influenced by capsaicin, and that their degeneration is followed by centrifugal degeneration.

Animals↗

Multifactor evaluation of the determinants of ischemic electrocardiographic response to maximal treadmill testing in coronary disease.

Despite widespread use of treadmill stress in the detection of coronary disease, detailed information relating the important features of coronary pathoanatomy to the ischemic response noted on the electrocardiogram is lacking. Accordingly, 91 consecutive patients undergoing graded maximal exercise tests (MEXT) who were found to have clinical stenosis (larger than or equal to 75 per cent luminal narrowing) of at least one of the three major coronary arteries on coronary arteriography were evaluated. Positive MEXT was defined as larger than or equal to 0.1 mV horizontal or downsloping S-T segment depression larger than or equal to 0.08 second beyond J point. Over-all sensitivity of positive MEXT was 59 of 91 (65 per cent) patients; 11 of 26 (42 per cent) with single vessel stenosis, 20 of 30 (66 per cent) with two vessel disease and 28 of 35 (80 per cent) with three vessel disease. In patients with two vessel disease, the frequency (p less than 0.05) of positive MEXT was greater in those with (15 of 21;71 per cent) than in those without (five of nine; 55 per cent) stenosis of the left anterior descending artery. Concerning the site of intravessel stenosis, the frequency of positive MEXT was greater (p less than 0.05) with stenosis proximal to the left anterior descending artery in patients with one vessel disease. Quantification of total numbers of intra- and intervessel stenoses revealed 2.7 stenoses in the 59 patients with positive MEXT in contrast (p less than 0.01) to 1.9 in 32 patients with negative MEXT. Similarly, graded luminal narrowing index of severity of total stenoses per patient was 9.9 in those with positive MEXT compared (p less than 0.01) to 6.1 in those with negative MEXT. The poststenotic myocardial perfusion index, estimated by graded distal vessel opacification per major vessel disease, was only 1.5 in those with positive MEXT contrasted (p less than 0.01) to 2.4 in those with negative MEXT. These data indicate that sensitivity of positive MEXT in patients with coronary disease is most closely determined by the number of major coronary vessels involved, the total number of major vessels stenosed, the severity of total stenoses and poststenotic distal vessel perfusion. Less important factors are the precise site of intravessesl stenosis and the specific major coronary artery involved, although stenosis proximal to the left anterior descending artery favored positive MEXT. Unimportant variables were the quality of collateral vessels, ventricular function and prior inferior infarction. Angina occurred more frequently in those with positive MEXT, and marked degree of positive MEXT indicated stenosis proximal to the left anterior descending artery.

Adult↗

The potassium channel modulator flupirtine shifts the frequency-response function of hippocampal synapses to favour LTD in mice.

Flupirtine is a centrally acting nonopioid analgesic with muscle-relaxant properties. Flupirtine has been found to activate inwardly rectifying potassium conductances and hence to indirectly inhibit the activation of NMDA receptors. NMDA receptor activation is crucial for the induction of long-term potentiation (LTP) of synaptic transmission, which is considered as cellular correlate of learning and memory and of central sensitization in chronic pain states. Although flupirtine has been widely used for the management of pain, its effects on synaptic plasticity have not yet been investigated. We, therefore, performed extracellular and whole-cell patch-clamp recordings in hippocampal slices of mice to examine the effects of flupirtine on synaptic plasticity and neuronal membrane properties. Excitatory postsynaptic potentials (EPSPs) in the CA1 region were evoked alternately by stimulating two independent Schaffer collateral-commissural inputs. LTP and long-term depression (LTD) were induced by different stimulation paradigms (100 Hz, 10 Hz, 5 Hz, and 1 Hz). Flupirtine (30 microM) diminished the degree of LTP and enhanced LTD. This effect is most likely due to the hyperpolarization of CA1 pyramidal neurons and the reduction of their input resistance found after application of flupirtine. The observed effects on synaptic strength could underly the beneficial effects of flupirtine on different types of chronic pain.

Aminopyridines↗

Memory performance used to detect radiation effects on cognitive functioning.

Although radiotherapy remains a necessary and frequently used treatmentfor brain tumors, uncertainty remains about the nature and severity of neurocognitive morbidity. We show that verbal-semantic memory (free recall of word list) is sensitive to damaging radiation effects in 20 patients with low-grade, supratentorial, primary brain tumors who received moderate doses of partial-brain irradiation. We previously reported that verbal-semantic memory is dissociated from visual memory (acquisition and recall) during the same phase ofradiation effects, indicating that memory is differentially affected by radiation. In this study, we provide evidence of the nature of the iatrogenic radiation effect on memory by testing collateral cognitive functions that might explain the specific memory impairment. We found that the verbal-semantic recall impairment was not associated with impairments in auditory attention, auditory processing speed, auditory-verbal working memory, or in the temporal coding or subjective organization of word-list recall. These findings focus damaging radiation effects on primary retrievalprocesses, rather than on earlier cognitive processes or executive processes affecting recall. Knowledge of the specific patterns of change in cognition would guide the differential diagnosis and rehabilitation of survivors of brain tumors whose conditions are complicated by tumors with multiple treatments.

Adult↗

Periaqueductal grey matter stimulation produces naloxone sensitive inhibition of reticular neurones in rat caudal medulla.

Neurones in the caudal medulla reticular formation (CRF) are excited by peripheral noxious stimuli and thus may have a role in nociceptive information processing. Stimulation of sites within the dorsal periaqueductal grey matter (PAG) produced a prolonged inhibition of CRF neurones. On 11 of 16 neurones tested microiontophoretic application of naloxone was found to attenuate these inhibitions suggesting that the neurotransmitter involved may have been an endogenous opioid. Histochemical localization of beta endorphin-like immunoreactivity (beta ELI) showed fibres containing beta ELI in the vicinity of PAG stimulation sites and scattered individual fibres with short collateral branches in the vicinity of recording sites in CRF.

Analgesia↗

Deformable organisms for automatic medical image analysis.

We introduce a new approach to medical image analysis that combines deformable model methodologies with concepts from the field of artificial life. In particular, we propose "deformable organisms", autonomous agents whose task is the automatic segmentation, labeling, and quantitative analysis of anatomical structures in medical images. Analogous to natural organisms capable of voluntary movement, our artificial organisms possess deformable bodies with distributed sensors, as well as (rudimentary) brains with motor, perception, behavior, and cognition centers. Deformable organisms are perceptually aware of the image analysis process. Their behaviors, which manifest themselves in voluntary movement and alteration of body shape, are based upon sensed image features, pre-stored anatomical knowledge, and a deliberate cognitive plan. We demonstrate several prototype deformable organisms based on a multiscale axisymmetric body morphology, including a "corpus callosum worm" that can overcome noise, incomplete edges, considerable anatomical variation, and interference from collateral structures to segment and label the corpus callosum in 2D mid-sagittal MR brain images.

Algorithms↗

Myocardial infarction in patients aged 40 years and below: an angiographic review.

Over a period of 27 months, 32 patients aged 40 and below were admitted for acute myocardial infarction. Twenty-nine had coronary angiography with a mean of 15.7 +/- 10.0 days following infarction. Fourteen patients had single vessel, 10 multi-vessel and 5 had only minor coronary disease. Disease in the left anterior descending (LAD) artery was more common than in the circumflex or right coronary artery (RCA), but myocardial infarction occurred with near equal frequency in both the LAD and RCA territories. Only 2 infarct-related vessels were collateralized. Spontaneous coronary dissection was detected in 2 patients. The left ventricular function was significantly impaired in about half of the patients.

Adult↗

Sleep deprivation-induced alterations in excitatory synaptic transmission in the CA1 region of the rat hippocampus.

Although the function of sleep remains elusive, there is compelling evidence to suggest that sleep plays an important role in learning and memory. A number of studies have now shown that sleep deprivation (SD) results in significant impairment of long-term potentiation (LTP) in the hippocampus. In this study, we have attempted to determine the mechanisms responsible for this impairment. After 72 h SD using the multiple-platform technique, we observed a reduction in the whole-cell recorded NMDA/AMPA ratio of CA1 pyramidal cells in response to Schaffer collateral stimulation. This impairment was specific to sleep deprivation as rats placed over a single large platform, which allowed sleep, had a normal NMDA/AMPA ratio. mEPSCs evoked by local application of a high osmolarity solution revealed no differences in the AMPA receptor function. NMDA currents recorded from outside-out patches excised from the distal dendrites of CA1 cells displayed a reduction in amplitude after SD. While there were no alterations in the glutamate sensitivity, channel open probability or the single channel conductance of the receptor, a crosslinking assay demonstrated that the NR1 and NR2A subunits of NMDA receptors were preferentially retained in the cytoplasm after SD, indicating that SD alters NMDAR surface expression. In summary, we have identified a potential mechanism underlying SD-induced LTP impairment. This synaptic alteration may underlie the cognitive deficits seen following sleep deprivation and could represent a target for future intervention studies.

Animals↗

Modification of non-conservative double-strand break (DSB) rejoining activity after the induction of cisplatin resistance in human tumour cells.

The induction of collateral radioresistance after the development of cisplatin resistance is a well-documented phenomenon; however, the exact processes that are responsible for the cisplatin-induced radioresistance remain to be elucidated. There was no obvious difference in the level of radiation-induced DNA double strand breaks (DSBs), in DSB rejoining rates, or the level of the catalytic subunit of the DNA-dependent protein kinase (DNA-PKcs) in the cisplatin- and radiation-sensitive 2780/WT and cisplatin-resistant 2780/CP cell lines. However, there was a significantly (P < 0.01) lower level of DSB misrejoining activity within nuclear protein extracts derived from the cisplatin- and radiation-sensitive 2780/WT and OAW42/WT tumour cell lines than in similar extracts from their cisplatin- (and radiation-) resistant 2780/CP and OAW42/CP counterparts. All of the DSB misrejoining events involved deletions of between 134 and 444 bp that arose through illegitimate recombination at short repetitive sequences, such as those that arise through non-homologous repair (NHR). These data further support the notion that the radiosensitivity of DSB repair proficient human tumour cell lines may be partly determined by the predisposition of these cell lines to activate non-conservative DSB rejoining pathways. Furthermore, our data suggest that the induction of acquired cisplatin resistance is associated with a two- to threefold decrease in the activity of a non-conservative DSB rejoining mechanism that appears to be a manifestation of NHR.

Chromosome Inversion↗

Gadolinium-enhanced 3-dimensional magnetic resonance angiography of pulmonary blood supply in patients with complex pulmonary stenosis or atresia: comparison with x-ray angiography.

BACKGROUND: In patients with complex pulmonary stenosis or atresia, a detailed delineation of all sources of pulmonary blood supply is necessary for planning surgical and transcatheter procedures and usually requires diagnostic cardiac catheterization. The goals of this study were to determine whether gadolinium-enhanced 3D magnetic resonance angiography (MRA) can provide a noninvasive alternative to diagnostic catheterization and to compare MRA and x-ray angiography measurements of pulmonary arteries and aortopulmonary collaterals (APCs). METHODS AND RESULTS: Thirty-two patients with pulmonary stenosis or atresia (median age: 4.7 years, range: 1 day to 46.9 years) underwent both MRA and cardiac catheterization (median time: 1 month). Diagnoses included tetralogy of Fallot (TOF) with pulmonary atresia (n=13), TOF with pulmonary stenosis (n=4), post-Fontan palliation (n=5), and other complex congenital heart disease (n=10). Compared with catheterization and surgical observations, MRA had a 100% sensitivity and specificity for the diagnosis of main (n=10) and branch pulmonary artery (PA) stenosis or hypoplasia (n=38), as well as absent (n=5) or discontinuous (n=4) branch PAs. All 48 major APCs diagnosed by catheterization were correctly diagnosed by MRA. Three additional APCs were diagnosed by MRA but not by catheterization. The mean difference between MRA and catheterization measurements of 33 pulmonary vessel diameters was 0.5+/-1.5 mm, with a mean interobserver difference of 0.4+/-1.5 mm. CONCLUSIONS: Gadolinium-enhanced 3D MRA is a fast and accurate technique for delineation of all sources of pulmonary blood supply in patients with complex pulmonary stenosis and atresia and can be considered a noninvasive alternative to diagnostic catheterization with x-ray angiography.

Adolescent↗

[Clinical response to inhalation and oral antibiotics in patients with bronchiectasis].

INTRODUCTION: The aim of this technique was to achieve high concentration of the antibiotic that excedeed the minimal inhibitory concentration (MIC) of the microbial load present in the sputum. METHOD: To evaluate the bronchiectasis patients with pictures of infectious exacerbations response to the treatment with antibiotic by oral way (roxitromicin 300 mg/day for 21 days) and in cases of failure of this schema the use of antibiotic by inhalatory way (gentamicin 80 mg/2 times day for 21 days), 28 patients were evaluated a special ambulatory, some signs and respiratory symptoms according to the "Cotes modified scale" (sputum, cough, bronchospasm and dyspnea). STATISTICAL ANALYSIS: We used: Kappa concordant test and McNemar test for discordation in the evaluation of the degree of signal and respiratory symptoms, Wilcoxon test for periods without infection, Fisher test for the collaterals effects presented, G of Cochran test for the personal history analysis. RESULTS: The personal history did not influence the evolution of bronchopulmonary infeccion, the evaluated signs and symptoms had significant improvement except dyspnea that stayed the same in 80% of the cases. DISCUSSION: The group that had used the antibiotics schema by inhalatory way after oral scheme failure had a significant longer period without bronchopulmonary infection but with superior collateral effects without clinicals repercussions. CONCLUSION: The use of inhalatory antibiotic in infectious exacerbations in patients with bronchiectasis was better than the oral way.

Administration, Inhalation↗

Electrophysiological and morphological properties of layers V-VI principal pyramidal cells in rat prefrontal cortex in vitro.

This study examined the electrophysiological and morphological characteristics of layers V-VI pyramidal prefrontal cortex (PFC) neurons. In vitro intracellular recordings coupled with biocytin injections that preserved some of the PFC efferents to the nucleus accumbens (NAc) were made in brain slices. Four principal pyramidal cell types were identified and classified as regular spiking (RS) (19%), intrinsic bursting (IB) (64%), repetitive oscillatory bursting (ROB) (13%), and intermediate (IM) (4%) types. All PFC cells exhibited either subthreshold oscillation in membrane voltage or pacemaker-like rhythmic firing. IB neurons were demonstrated electrophysiologically and cytochemically to be PFC-->NAc neurons. In all IB and some RS neurons, a tetrodotoxin-sensitive, slowly inactivating Na+ current and a transient Ni(2+)-sensitive, low-threshold Ca2+ current mediated subthreshold inward rectification. During sustained membrane depolarization, the Na+ current was opposed by a 4-aminopyridine-sensitive, outwardly rectifying, slowly inactivating K+ current. Together, these three currents controlled the firing threshold of the PFC neurons. All IB and ROB cells also had postspike Ca(2+)-mediated depolarizing afterpotentials, postburst Ca(2+)-dependent after hyperpolarizations, and low- and high-threshold Ca2+ spikes. In addition, ROB cells had a hyperpolarizing "sag" mediated by the cationic conductance, Ih. IB and ROB neurons had extensive dendritic trees and radially ascending or tangentially projecting axon collaterals. RS and IM cells had comparatively simpler morphological profiles. These electrophysiological and morphological properties of the four principal pyramidal PFC cell types have provided valuable details for understanding further how PFC processes input and transmit outputs to regions such as the NAc.

Animals↗

Ultrasound findings in carotid artery dissection: analysis of 43 patients.

BACKGROUND AND PURPOSE: To analyze the value of ultrasound for early diagnosis and follow-up of internal carotid artery dissection. METHODS: The carotid arteries were evaluated in 43 consecutive patients using extracranial and transcranial pulsed-wave Doppler and duplex sonography. RESULTS: Ultrasound examination was performed, on average, 7.7 days after the first symptoms. The dissections subsequently were verified by MRI (16 patients), angiography (13 patients), or both (14 patients) on average 4.4 days later. The overall sensitivity of the combined examination was 95% (93% for extracranial Doppler, 86% for transcranial Doppler, and 79% for duplex sonography). All three methods detected occlusions or high-grade stenoses in 100% of patients and moderate- or low-grade stenoses in 80% (combined methods), 70% (extracranial Doppler), 40% (transcranial Doppler), and 20% (duplex) of the patients. The findings in 33 patients with an occlusion or high-grade stenosis according to neuroradiology were as follows: absent flow signal in the internal carotid artery (100%) and biphasic (stump) flow in its bulb (86%), high-resistance flow pattern of the ipsilateral common carotid artery (91%), signs of collateral flow across the circle of Willis (97%), and low flow in the middle cerebral artery (79%) on transcranial insonation. In seven patients, a moderate stenosis of the high cervical carotid segment was found because of a retromandibular high-velocity signal. In five of them this was the only abnormal finding. Duplex examination was helpful because it confirmed absent internal carotid artery flow or stump flow in the case of occlusion or high-grade stenosis (100%) and excluded an atherosclerotic origin by demonstrating a patent bulb (100%) and the absence of plaques (95%). Follow-up studies showed recanalization in 63% of patients, occurring at variable intervals. Occlusion persisted in 37%. CONCLUSIONS: Ultrasound performed within the first weeks can corroborate a clinically suspected carotid dissection in up to 95% of patients. Repetitive follow-up studies in most cases are sufficient to monitor evolution.

Adult↗

Structure-function relationships in rat brainstem subnucleus interpolaris. XI. Effects of chronic whisker trimming from birth.

Whisker trimming from birth reduces activity and alters receptive fields (RFs) in the barrel cortex and thalamus. To assess whether or not this reflects deprivation effects on trigeminal (V) first- and second-order neurons, 59 primary afferents and 343 cells in V brainstem subnucleus interpolaris (SpVi) were studied in rats whose whiskers were trimmed daily for 6-9 weeks from birth. Deprivation did not effect brainstem somatotopy or primary afferent RFs. However, many SpVi cells had abnormal RFs and higher-order inputs, resembling the changes caused by infraorbital nerve injury. For example, in controls, only 3% of whisker-sensitive local circuit neurons responded to more than one whisker, whereas 35% of the deprived and 41% of the infraorbital nerve cut samples had multiwhisker. RFs. Deprived rats also had higher than normal incidences of cells with split or absent RFs, RFs spanning more than one V division, intermodality convergence, and directional or high-velocity sensitivity. Because these changes mimic those caused by nerve section, deprivation may underlie some nerve injury effects on V brainstem RF size and character. Insofar as cytochrome oxidase, anterograde labeling, and unit recordings revealed normal topography in deprived primary afferents and SpVi cells, RF changes in SpVi cells may reflect altered SpVi circuitry. To test this hypothesis, we assessed the morphology of 32 similarly deprived V primary afferents. In SpVi, deprived fibers had normal numbers of collaterals with normal shapes, transverse arbor areas, and topography. However, the total number of boutons per collateral was significantly reduced. Thus, deprivation effects on V higher-order RFs reflect quantitative changes in V afferent terminals.

Afferent Pathways↗

Autoradiographic study of the cellular localization of [3H]glibenclamide binding sites in the rat hippocampus.

[3H]Glibenclamide, a potent ATP-sensitive K+ channel blocker, is a specific ligand for the identification of the sulfonylureas receptors which are closely related to ATP-sensitive K+ channels. In order to determine the pre- or postsynaptic localization of these receptors in the rat hippocampus, we studied the effects of selective kainate or colchicine-induced lesions on the regional distribution of [3H]glibenclamide binding. A decreased binding was found in the following conditions: in CA3, after destruction of the mossy fiber terminals but not of the CA3 cells; in CA1, after destruction of the CA1 cells but not of the Schaffer collaterals; in the fascia dentata, after destruction of the granule cells. These results suggest that glibenclamide binding sites are mainly localized on the mossy fibers in CA3, and on the granular and pyramidal neurons in the fascia dentata and CA1, respectively.

Animals↗