Flow cytometry for receptor analysis from ex-vivo brain tissue in adult rat.

BACKGROUND: Flow cytometry allows single-cell analysis of peripheral biological samples and is useful in many fields of research and clinical applications, mainly in hematology, immunology, and oncology. In the neurosciences, the flow cytometry separation method was first applied to stem cell extraction from healthy or cerebral tumour tissue and was more recently tested in order to phenotype brain cells, hippocampal neurogenesis, and to detect prion proteins. However, it remains sparsely applied in quantifying membrane receptors in relation to synaptic plasticity. NEW METHOD: We aimed to optimize a flow cytometric procedure for receptor quantification in neurons and non-neurons. A neural dissociation process, myelin separation, fixation, and membrane permeability procedures were optimized to maximize cell survival and analysis in hippocampal tissue obtained from adult rodents. We then aimed to quantify membrane muscarinic acetylcholine receptors (mAChRs) in rats with and without bilateral vestibular loss (BVL). RESULTS: mAChR's were quantified for neuronal and non-neuronal cells in the hippocampus and striatum following BVL. At day 30 but not at day 7 following BVL, there was a significant increase (P ≤ 0.05) in the percentage of neurons expressing M2/4 mAChRs in both the hippocampus and the striatum. CONCLUSION: Here, we showed that flow cytometry appears to be a reliable method of membrane receptor quantification in ex-vivo brain tissue.

Cell proliferation in the cochlear nucleus following acoustic trauma in rat.

Our previous studies have suggested that surgical lesions of the rat cochlea induce cell proliferation in the cochlear nucleus (CN) that may be related to neurogenesis. The aim of the present study was to further investigate the nature of cell proliferation in the CN, following acoustic trauma that has previously been shown to induce tinnitus in rats. Rats were subjected either to a unilateral acoustic trauma (16-kHz pure tone, 115dB for 1h under anesthesia) or a sham procedure. Bromodeoxyuridine (BrdU) immunohistochemistry was used to measure cell proliferation and newborn cell survival; an antibody to interleukin-6 was used to investigate inflammatory responses; and double immunolabeling for BrdU and Ki-67, BrdU and CD-11b, and BrdU and doublecortin (DCX), was used to investigate the origin of the proliferating cells. There was a time-dependent increase in the number of BrdU(+ve) cells in the CN following acoustic trauma; however, the number of BrdU(+ve) cells that survived was comparable to that of control animals at 4 weeks post-trauma. Cell proliferation was unlikely to be due to proliferating inflammatory cells as a result of a trauma-induced inflammatory response as the IL-6 expression level was comparable between sham and exposed groups. Immunolabeling revealed the BrdU(+ve) cells to co-express Ki-67 and DCX, but not CD-11b. However, there was no difference in DCX expression between sham and exposed animals. The results suggest that DCX-expressing cells in the CN may proliferate in response to acoustic trauma; however, the proportion of cells proliferating and the survival rate of the newborn cells may not support functional neurogenesis in the CN.

Effects of thalamic lesions on repeated relearning of a spatial working memory task.

Anterior thalamic (ATN) dysfunction produces memory deficits in rats and humans. The current study shows that, with a substantial delay between post-surgery tests, controls show repeated relearning on a spatial working memory task whereas rats with neurotoxic ATN lesions showed repeated relearning deficits. Rats were pre-trained to criterion, but not over trained, on the spatial task. ATN lesions produced the expected spatial memory and relearning deficits about two weeks post-surgery and again either one or 15 weeks later. Control rats also showed forgetting post-surgery and after a 15 week break, relearning the task on each occasion. Controls with only a 1 week break before their final re-test showed negligible forgetting. Thus, a short break between re-tests replicated previous findings with ATN lesions, but a long break allows repeated comparison of rates of learning from a common starting point in sham and ATN-lesioned animals, providing a useful paradigm for future testing of pro-cognitive treatments.

Epidemiology of injuries due to tropical cyclones in Hong Kong: a retrospective observational study.

BACKGROUND: Tropical cyclones are huge circulating masses of wind which form over tropical and sub-tropical waters. They affect an average of 78 million people each year. Hong Kong is a large urban centre with a population of just over 7 million which is frequently affected by tropical cyclones. We aimed to describe the numbers and types of injuries due to tropical cyclones in Hong Kong, as well as their relation to tropical cyclone characteristics. METHODS: The records of all patients presenting to Hong Kong's public hospital emergency departments from 1st January 2004 to 31st December 2009 with tropical cyclone related injuries were reviewed and information regarding patient and injury characteristics was collected. Meteorological records for the relevant periods were examined and data on wind speed, rainfall and timing of landfall and warning signals was recorded and compared with the timing of tropical cyclone related injuries. RESULTS: A total of 460 tropical cyclone related injuries and one fatality across 15 emergency departments were identified during the study period. The mean age of those injured was 48 years and 48% were female. 25.4% of injuries were work related. The head (33.5%) and upper limb (32.5%) were the most commonly injured regions, with contusions (48.6%) and lacerations (30.2%) being the most common injury types. Falls (42.6%) were the most common mechanism of injury, followed by being hit by a falling or flying object (22.0%). In univariable analysis the relative risk of injury increased with mean hourly wind speed and hourly maximum gust. Multivariable analysis, however, showed that relative risk of injury increased with maximum gust but not average wind speed, with relative risk of injury rising sharply above maximum gusts of greater than 20 m/s. Moderate wind speed with high gust (rather than high average and high gust) appears to be the most risky situation for injuries. Relative risk of injury was not associated with rainfall. The majority of injuries (56%) occurred in the 3h before and after a tropical cyclone's closest proximity to Hong Kong, with relative risk of injury being highest mid-morning. CONCLUSIONS: In tropical cyclone related injuries in Hong Kong the head and upper limb are the most commonly affected sites with falls and being hit by a falling or flying object being the most common mechanisms of injury. Hourly maximum gust appears to be more important that mean hourly wind speed in determining risk of injury. These findings have implications for injury prevention measures and emergency planning in Hong Kong and other regions effected by tropical cyclones.

GP views of nurse-led telephone referral for paediatric assessment.

Following the introduction of a new nurse-led telephone referral service to a dedicated paediatric emergency assessment unit (PEAU), a study was conducted to determine the views of general practitioners (GPs) who use the service. The PEAU operates between 10 am and 10 pm on weekdays and between 10 am and 6 pm at weekends. The unit has four beds and treatment and stabilization areas, plus associated services in a dedicated area of a regional child health unit. The design utilized a faxed questionnaire over a 1-month period to all consenting GPs using the PEAU with a postal questionnaire follow-up. Non-parametric Likert scores and qualitative data were used to determine levels of satisfaction with the service and the subsequent management of the referred children. Sixty-nine GPs referred 80 children to the PEAU via the service over a period of 1 month. All consented to participate and were sent a faxed questionnaire, which generated 39 (57%) responses. A follow-up questionnaire sent to the 39 respondents achieved a return of 25 (64%) responses. Thirty-four GPs agreed that referral via the dedicated nurse service was easier than the previous senior house officer referral system. Of the 25 GP respondents to the follow-up postal survey, the majority (17) agreed that the follow-up morning after discharge telephone call to parents by the PEAU nurses was helpful. Four GPs indicated that the 24-hour open access system, offered by the nursing staff, in which a parent may attend PEAU with a discharged child causing concern without a previous appointment, does not always work. This study has shown that a nurse-led telephone referral system to a PEAU for GPs and the subsequent management of the children has been favourably received.

Self-amplification of coherent spontaneous emission in a cherenkov free-electron maser

Ultrashort pulses of microwave radiation have been produced in a dielectric-lined Cherenkov free-electron maser (FEM) amplifier. An intense initial seed pulse, due to coherent spontaneous emission (CSE), arises at the leading edge of the electron pulse. There is evidence to show that 3-4 cycle spikes are produced through the amplification of these seed pulses. A strong dependence of the start-up power on the rise time of the electron pulse has been found. The experimental results are verified by a theoretical analysis. Our study shows that amplification in a FEM amplifier is always initiated by CSE arising from the edge of the electron pulse when the rise time is comparable to the electromagnetic wave period.

Mitochondrial and intrinsic optical signals imaged during hypoxia and spreading depression in rat hippocampal slices.

During hypoxia in the CA1 region of the rat hippocampus, spreading-depression-like depolarization (hypoxic spreading depression or HSD) is accompanied by both a negative shift of the extracellular DC potential (DeltaV(o)), and a sharp decrease in light transmittance (intrinsic optical signal or IOS). To investigate alterations in mitochondrial function during HSD and normoxic spreading depression (SD), we simultaneously imaged mitochondrial depolarization, using rhodamine-123 (R123) fluorescence, and IOS while monitoring extracellular voltage. Three major phases of the R123 signal were observed during hypoxia: a gradual, diffuse fluorescence increase, a sharp increase in fluorescence coincident with the HSD-related DeltaV(o), primarily in the CA1 region, and a plateau-like phase if reoxygenation is delayed after HSD onset, persisting until reoxygenation occurs. Two phases occurred following re-oxygenation: an abrupt and then slow decrease in fluorescence to near baseline and a slow secondary increase to slightly above baseline and a late recovery. Parallel phases of the IOS response during hypoxia were also observed though delayed compared with the R123 responses: an initial increase, a large decrease coincident with the HSD-related DeltaV(o), and a trough following HSD. After reoxygenation, there occurred a delayed increase in transmittance and then a slow decrease, returning to near baseline. When Ca(2+) was removed from the external medium, resulting in complete synaptic blockade, the mitochondrial response to hypoxia did not significantly differ from control (normal Ca(2+)) conditions. In slices maintained in low-chloride (2.4 mM) medium, a dramatic reversal in the direction of the IOS signal associated with HSD occurred, and the R123 signal during HSD was severely attenuated. Normoxic SD induced by micro-injection of KCl was also associated with a decrease in light transmittance and a sharp increase in R123 fluorescence but both responses were less pronounced than during HSD. Our results show two mitochondrial responses to hypoxia: an initial depolarization that appears to be caused by depressed electron transport due to lack of oxygen and a later, sudden, sharp depolarization linked to HSD. The depression of the second, sharp depolarization and the inversion of the IOS in low-chloride media suggest a role of Cl(-)-dependent mitochondrial swelling. Lack of effect of Ca(2+)-free medium on the R123 and IOS responses suggests that the protection against hypoxic damage by low Ca(2+) is not due to the prevention of mitochondrial depolarization.

Nasolacrimal duct obstruction secondary to ectopic teeth.

OBJECTIVE: To describe two patients with nasolacrimal duct obstruction (NLDO) caused by ectopic eruption of teeth. The literature concerning nasal and other unusual ectopic sites of tooth eruption is reviewed. DESIGN: Two interventional case reports and literature review. PARTICIPANTS: A 3-year-old girl with epiphora and recurrent dacryocystitis of the right eye. Previous medical and surgical management was unsuccessful. A 32-year-old female with a long history of right eye discomfort and epiphora. Previous examinations and workup were negative. INTERVENTION: A computed tomographic (CT) scan of the orbits and sinuses was performed in both patients. The ectopic teeth were surgically removed. MAIN OUTCOME MEASURES: Nasolacrimal system function and response to treatment at the last follow-up were recorded. RESULTS: In the first patient, CT imaging disclosed two teeth within the right inferior meatus compressing the nasolacrimal duct. In the second patient, CT revealed a large dental structure in the maxillary sinus compressing the nasolacrimal duct. Endoscopic tooth extraction and nasolacrimal duct probing in the first patient and surgical removal of the dental structure in the second patient effected complete resolution of symptoms. Both patients were symptom free at last follow-up. CONCLUSIONS: These cases suggest that ectopic eruption of teeth should be added to the differential diagnosis of NLDO. Surgical removal of the ectopic teeth compressing the nasolacrimal duct results in resolution of the lacrimal drainage obstruction.

Block of (Na+,K+)ATPase with ouabain induces spreading depression-like depolarization in hippocampal slices.

We used ouabain (100 microM) to block Na+,K(+)ATPase of in vitro rat hippocampal slices. This treatment was sufficient to cause the sudden depolarization that is the hallmark of both spreading depression (SD) and of the SD-like anoxic depolarization (AD). This depolarization was accompanied by a large and sudden increase in [K](o), also reminiscent of that observed during both SD and AD. Ouabain-induced SD did not require a complete inactivation of Na+,K(+)ATPase, as it occurred when the enzyme was still capable of providing recovery of both V(o) and [K](o). The data indicate that functional inactivation of Na+,K(+)ATPase per se initiates events that lead to an SD-like AD. This ouabain-induced depolarization was not affected by block of synaptic transmission, instead it was abolished by hyperosmolarity of the extracellular space. The possible relevance of these findings to the pathophysiology of AD is discussed.

Use of intrinsic optical signals to monitor physiological changes in brain tissue slices.

Optical imaging techniques have the potential to bring a combination of high spatial and temporal resolution to studies of brain function. Many optical techniques require the addition of a dye or fluorescent marker to the tissue, and such methods have proven extremely valuable. It is also known that the intrinsic optical properties of neural tissue are affected by certain physiological changes and that these intrinsic optical signals can provide information not available by other means. Most authors attribute the intrinsic optical change to alterations in cell volume and concomitant change in the concentration of the cytosol. In this article we review the literature on intrinsic optical signals, covering both the mechanisms of the optical change and its use in various branches of neurophysiology. We also discuss technical aspects of the technique as used with hippocampal slices, including illumination methods, cameras, experimental methods, and data collection and analysis procedures. Finally we present data from investigations in which we used intrinsic optical signals in hippocampal slices to study the extent of spread of synaptic activation, propagation of spreading depression, extent and severity of the response to hypoxia, and tissue response to osmotic challenges. We conclude that (1) at least two processes generate intrinsic optical signals in hippocampal slices, one of which causes light scattering to change inversely with cell volume and is related to dilution of the cytoplasm, while the other, opposite in sign, may be due to mitochondrial swelling; and (2) the intrinsic optical signal can be a useful tool for spatial mapping of relatively slow events, but is not suitable for study of fast physiological processes.

Interpretive reproducibility of stress Tc-99m sestamibi tomographic myocardial perfusion imaging.

BACKGROUND: Observer variability has been shown with interpretation of planar thallium-201 images. The interpretive reproducibility of technetium-99m sestamibi tomographic imaging is unknown. This study evaluated the interpretive reproducibility of interpretable Tc-99m sestamibi tomographic images among nuclear cardiologists with a wide range of training and experience. METHODS: Three experienced readers (EX) and 3 less-experienced readers (LEX) interpreted 138 exercise and rest Tc-99m sestamibi tomographic images (101 were abnormal in patients with coronary artery disease [CAD], 37 were normal in patients with <5% likelihood of CAD) twice in random sequence without clinical data. Images of good to excellent quality were randomly selected from a database at 2 nuclear cardiology laboratories. Intraobserver and interobserver agreement for global, left anterior descending (LAD) territory, non-LAD first (normal/abnormal) and second (normal/fixed/reversible) order, and defect extent (normal/single-vessel CAD/multi-vessel CAD) were assessed with percent agreement and Cohen's kappa (kappa) statistic. RESULTS: With regard to intraobserver agreement, first and second order ranged from 87% to 94% and 80% to 90% for global, 82% to 96% and 78% to 95% for LAD, and 88% to 91% and 80% to 90% for non-LAD, respectively. Defect extent ranged from 75% to 90%. There were no differences between EX and LEX for global and non-LAD first and second order, LAD first order, and defect extent. LAD second order was 93% for EX compared with 88% (P = .015) for LEX. With regard to interobserver agreement, first and second order ranged from 73% to 89% and 64% to 85% for global, 73% to 93% and 69% to 91% for LAD, and 76% to 88% and 68% to 84% for non-LAD, respectively. Defect extent ranged from 61% to 82%. Global first and second order ranged from 85% to 87% and 78% to 82% for EX compared with 73% to 84% and 64% to 79% for LEX. LAD first and second order ranged from 89% to 91% and 88% to 89% for EX compared with 73% to 91% and 69% to 70% for LEX. Non-LAD first and second order ranged from 82% to 86% and 76% to 77% for EX compared with 76% to 86% and 68% to 81% for LEX. Defect extent ranged from 69% to 75% for EX compared with 59% to 77% for LEX. CONCLUSIONS: There is moderate to excellent interpretive reproducibility with stress Tc-99m sestamibi SPECT imaging among nuclear cardiologists with a wide range of training and experience.

Smoking as an aetiological factor in a pedigree with Leber's hereditary optic neuropathy.

BACKGROUND/AIMS: Leber's hereditary optic neuropathy (LHON) is a mitochondrial DNA mediated disease which causes severe visual deficits. Although expressivity of the disease is 100%, penetrance is variable, and environmental factors may influence risk of becoming symptomatic. The causative relation between cigarette smoking and disease penetrance was examined. METHODS: The incidence of smoking in 65 age matched family members of one LHON pedigree was retrospectively obtained. Smoking in groups which expressed disease was compared with those which did not. Male subgroups were analysed separately in addition to combined sex groups. RESULTS: The association between smoking and disease penetrance was significant in all subgroups (p values from p=0.0009 to p=0.0001, 95% confidence intervals). Disease penetrance was higher in males than females. The association was weaker in the male group than combined sex groups (p values from p=0.0146 to p=0.0008, 95% confidence intervals), probably because of elimination of female asymptomatic non-smokers in the comparison groups. The association was strengthened in older age groups and in groups which smoked more heavily. CONCLUSIONS: Smoking is significantly associated with disease penetrance in this LHON pedigree. Degree of smoking and number of years smoked correlate with increased risk of developing symptoms.

Porous polyethylene channel implants: a modified porous polyethylene sheet implant designed for repairs of large and complex orbital wall fractures.

PURPOSE: To evaluate the effectiveness of a modified porous polyethylene implant in orbital fracture repair. A porous polyethylene channel implant (PPCI) has internal channels that accept mini- or microplates from conventional plating systems, facilitating fixation to bone in the reconstruction of large, complex orbital fractures. METHODS: The authors used 29 PPCIs to repair 25 orbits. Seventeen cases involved repair of an acute (less than two weeks after injury) fracture of one or more orbital walls. Eight cases represented delayed reconstruction of orbital walls for late enophthalmos or for residual defects after previous operations. RESULTS: A PPCI provides a stable platform for orbital soft tissue. Excellent results were obtained in all patients with acute orbital fractures, whereas good or excellent corrections of enophthalmos and hypoglobus were achieved in all patients who underwent late repair. There were no instances of orbital infection, implant exposure or migration, worsening diplopia, visual loss, or loss of structural support during 31 months of follow-up. CONCLUSIONS: A PPCI allows controlled placement of a porous polyethylene sheet with secure fixation to stable bone. The implant design allows it to be cantilevered from the orbital rim to serve as a stable platform when fractures are too large to support the implant in the posterior orbit. PPCIs are ideally suited for reconstruction of defects resulting from displacement of orbital walls and for repair of posterior floor fractures, medial wall fractures, and combined floor and medial wall defects.

Incorporating advance care planning into family practice [see comment].

Despite widespread support for the concept of advance care planning, few Americans have a living will or a health care proxy. Advance care planning offers the patient the opportunity to have an ongoing dialog with his or her relatives and family physician regarding choices for care at the end of life. Ultimately, advance care planning is designed to clarify the patient's questions, fears and values, and thus improve the patient's well-being by reducing the frequency and magnitude of overtreatment and undertreatment as defined by the patient. An advance directive consists of oral and written instructions about a person's future medical care in the event he or she becomes unable to communicate. There are two types of advance directives: a living will and a health care power of attorney. Family physicians are in an ideal position to discuss advance care plans with their patients. By introducing the subject during a routine office visit, physicians can facilitate a structured discussion of the patient's wishes for end-of-life care. At the next visit, further discussion can include the patient and his or her proxy. A document that clearly delineates the patient's wishes is then developed. The patient should be assured that the directive can be changed at any time according to the patient's wishes. The advance care plan should be reviewed periodically to make sure the specifications continue to be in line with the patient's wishes.

Effect of submucosal diathermy to the inferior turbinates on unilateral and total nasal airflow in patients with rhinitis.

The efficacy of the controversial treatment of submucosal diathermy to the inferior turbinates (SMDIT) was evaluated objectively. Twenty-seven patients with chronic rhinitis were investigated by hourly posterior rhinomanometry to assess changes in total and minimum (Fmin) and maximum (Fmax) unilateral nasal airflow over 5 h, before and 2-3 months after standardized SMDIT treatment. Nasal airflow was recorded at a sample pressure of 75 Pa and the results are reported as medians with interquartile range. Whilst SMDIT caused a significant 51% increase (p < 0.0001) in total nasal airflow from 246 cm3/s (131) to 371 cm3/s (133) the changes in unilateral airflow provided further evidence which strongly supported the benefits of this operation. Unilateral Fmin significantly increased by 136% (p < 0.0001) from 69 cm3/s (82) to 163 cm3/s (74) and Fmax significantly increased by 23% (p < 0.0001) from 171 cm3/s (74) to 211 cm3/s (59). The effect of surgery was to "splint" to the turbinate in a state of relative vasoconstriction. Our findings therefore provide functional evidence of submucosal fibrosis following SMDIT. The greater percentage change in unilateral Fmin suggests that this parameter is a more sensitive index of the effect of nasal surgery than total nasal airflow measurements. The importance of considering the nose as two separate airways in the evaluation of nasal treatments is emphasized.

Volume changes induced by osmotic stress in freshly isolated rat hippocampal neurons.

The degree to which osmotic stress changes the volume of mammalian central neurons has not previously been determined. We isolated CA1 pyramidal cells and measured cell volume in four different ways. Extracellular osmolarity (pio) was lowered by omitting varying amounts of NaCl and raised by adding mannitol; the extremes of pio tested ranged from 134 to 396 mosm/kg. When pio was reduced, cell swelling varied widely. We distinguished three types of cells according to their response: "yielding cells" whose volume began to increase immediately; "delayed response cells" which swelled after a latent period of 2 min or more; and "resistant cells" whose volume did not change during exposure to hypo-osmotic solution. When pio was raised, most cells shrank slowly, reaching minimal volume in 15-20 min. We observed neither a regulatory volume decrease nor an increase. We conclude that the water permeability of the membrane of hippocampal CA1 pyramidal neurons is low compared to that of other cell types. The mechanical support of the plasma membrane given by the cytoskeleton may contribute to the resistance to swelling and protect neurons against swelling-induced damage.

Similar propagation of SD and hypoxic SD-like depolarization in rat hippocampus recorded optically and electrically.

Neuron membrane changes and ion redistribution during normoxic spreading depression (SD) induced, for example, by potassium injection, closely resemble those that occur during hypoxic SD-like depolarization (HSD) induced by oxygen withdrawal, but the degree to which the two phenomena are related is controversial. We used extracellular electrical recording and imaging of intrinsic optical signals in hippocampal tissue slices to compare 1) initiation and spread of these two phenomena and 2) the effects of putative gap junction blocking agents, heptanol and octanol. Both events arose focally, after which a clear advancing wave front of increased reflectance and DC shift spread along the CA1 stratum radiatum and s. oriens. The rate of spread was similar: conduction velocity of normoxic SD was 8.73 +/- 0.92 mm/min (mean +/- SE) measured electrically and 5.84 +/- 0.63 mm/min measured optically, whereas HSD showed values of 7.22 +/- 1.60 mm/min (electrical) and 6.79 +/- 0.42 mm/min (optical). When initiated in CA1, normoxic SD consistently failed to enter the CA3 region (7/7 slices) and could not be initiated by direct KC1 injection in the CA3 region (n = 3). Likewise, the hypoxic SD-like optical signal showed onset in the CA1 region and halted at the CA1/CA3 boundary (9/9 slices), but in some (4/9) slices the dentate gyrus region showed a separate onset of signal changes. Microinjection into CA1 stratum radiatum of octanol (1 mM), which when bath applied arrests the spread of normoxic SD, created a small focus that appeared to be protected from hypoxic depolarization. However, bath application of heptanol (3 mM) or octanol (2 mM) did not prevent the spread of HSD, although the onset was delayed. This suggests that, although gap junctions may be essential for the spread of normoxic SD, they may play a less important role in the spread of HSD.

Heptanol but not fluoroacetate prevents the propagation of spreading depression in rat hippocampal slices.

We investigated whether heptanol and other long-chain alcohols that are known to block gap junctions interfere with the generation or the propagation of spreading depression (SD). Waves of SD were triggered by micro-injection of concentrated KCl solution in stratum (s.) radiatum of CA1 of rat hippocampal tissue slices. DC-coupled recordings of extracellular potential (V0) were made at the injection and at a second site approximately 1 mm distant in st. radiatum and sometimes also in st. pyramidale. Extracellular excitatory postsynaptic potentials (fEPSPs) were evoked by stimulation of the Schaffer collateral bundle; in some experiments, antidromic population spikes were evoked by stimulation of the alveus. Bath application of 3 mM heptanol or 5 mM hexanol completely and reversibly prevented the propagation of the SD-related potential shift (delta V0) without abolishing the delta V0 at the injection site. Octanol (1 mM) had a similar but less reliably reversible effect. fEPSPs were depressed by approximately 30% by heptanol and octanol, 65% by hexanol. Antidromic population spikes were depressed by 30%. In isolated, patchclamped CA1 pyramidal neurons, heptanol partially and reversibly depressed voltage-dependent Na currents possibly explaining the slight depression of antidromic spikes and, by acting on presynaptic action potentials, also the depression of fEPSPs. Fluoroacetate (FAc), a putative selective blocker of glial metabolism, first induced multiple spike firing in response to single afferent volleys and then severely suppressed synaptic transmission (confirming earlier reports) without depressing the antidromic population spike. FAc did not inhibit SD propagation. The effect of alkyl alcohols is compatible with the idea that the opening of normally closed neuronal gap junctions is required for SD propagation. Alternative possible explanations include interference with the lipid phase of neuron membranes. The absence of SD inhibition by FAc confirms that synaptic transmission is not necessary for the propagation of SD, and it suggests that normally functioning glial cells are not essential for SD generation or propagation.