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PubMed2001

A new method for detecting pedicular wall perforation during pedicle screw insertion.

STUDY DESIGN: Sensitivity, specificity, and predictive value analyses of a method that can be used to detect pedicular wall perforation during pedicle screw insertion were assessed. OBJECTIVE: To determine the accuracy of observing the fatty material expelled during pedicle screw insertion for detecting pedicular wall perforations. SUMMARY OF BACKGROUND DATA: Although many methods for safe and accurate insertion of a pedicle screw are described, the rates of misplacement still are high, and complications may occur from improper placement of pedicle screws. Computer-assisted insertion techniques are reported to be very accurate, but these techniques are not yet commonly available. METHODS: In this study, 74 pedicle screw insertions were observed for the material expelled after drilling for the pedicle screw. The outflows of blood and fatty particles were recorded separately. The position of the pedicle screws after surgery was verified by computed tomography. The specificity, sensitivity, positive and negative predictive values, and kappa statistics were assessed. RESULTS: Visible fatty particles were observed during 51 pedicle screw insertions. The histologic analysis showed that the fatty particles were coming from the bone marrow of the corpus. For the observation of fatty particles in detecting perforations along the pedicle screw pathway, the specificity was 98%, the sensitivity 73%, the positive predictive value 84%, the negative predictive value 95%, and the kappa statistic 0.74. CONCLUSIONS: The observation of fatty particles in the blood that comes out after drilling for the pedicle screw may indicate that there is no perforation along the pedicle screw pathway. The observation is easy to perform and does not require any special instruments. Therefore, it can be used alone or in combination with other methods to improve the accuracy of pedicle screw insertion.

Adipose Tissue↗
PubMed1999

Age-related changes in synaptic function: analysis of the effect of dietary supplementation with omega-3 fatty acids.

Depolarization-induced transmitter release in synaptosomes prepared from the hippocampus of aged rats is decreased compared with release from young animals. Although the underlying cause of this deficit is not known, some evidence suggests that increased membrane rigidity may contribute to these age-related synaptic changes. One possible consequence of the decreased transmitter release in the hippocampus of aged rats is a reduced ability to sustain long-term potentiation in perforant path-granule cell synapses, a pathway in which maintenance of long-term potentiation and increased glutamate release have been coupled. The observation that there is an age-dependent impairment in long-term potentiation is consistent with this view. If the age-related deficits in release and long-term potentiation are a consequence of increased membrane rigidity, it must be predicted that any manoeuvre which reverses membrane rigidity should reverse these functional deficits. In the present study, we investigated the effect of dietary manipulation of aged rats with omega-3 fatty acids on synaptic function. The data obtained indicate that an eight-week modified feeding schedule reversed the age-related impairments in long-term potentiation and depolarization-induced glutamate transmitter release. We also report that the concentrations of both docosahexanoic acid and arachidonic acid, two main polyunsaturated fatty acids in neuronal membranes, were decreased in the hippocampus of aged rats, and were restored by dietary manipulation. The data are consistent with the hypothesis that these deficits results from a change in membrane composition.

Aging↗
PubMed1977

Granuloma annulare with transfollicular perforation.

In recent years the phenomenon of transepithelial elimination has been found to be the underlying mechanism in a variety of skin disorders. "Perforating dermatoses" may show transepidermal or transfollicular elimination or a combination of the two. A case of papular granuloma annulare is reported, where in one lesion the pilary apparatus actively participated in the elimination of necrobiotic collagen from the dermis. To our knowledge, perforating granuloma annulare with a transfollicular pathway has not previously been described. Also, a classification of perforating dermatoses is presented.

Aged↗
PubMed1999

Activation of mGluRII induces LTD via activation of protein kinase A and protein kinase C in the dentate gyrus of the hippocampus in vitro.

The involvement of metabotropic glutamate receptor group II (mGluRII) in the induction of long-term depression (LTD) was investigated in the medial perforant path of the rat dentate gyrus, a region with a very high density of mGluRII. Perfusion of either of two potent mGluRII agonists, (2S,1R,2R,3R)-2-(2S, 1'R, 2'R, 3'R)-2 (2' 3'-dicarboxycyclopropyl)glycine (DCG-IV) or (+)-2- aminobicyclo[3.1.0]hexane-2-6-dicarboxylic acid (LY354740) induced a reversible inhibition of the field EPSP followed, upon washout of the agonist, by LTD. The reversible inhibition was associated with a change in paired pulse depression, indicating an underlying presynaptic reduction in the probability of transmitter release, whereas the LTD was not associated with a change in paired pulse depression, indicating either a presynaptic reduction in the number of active release sites, or a postsynaptic change. Further evidence that the DCG-IV-induced LTD was generated by activation of mGluRII was the finding that the mGluRII antagonist (RS)-alpha-methylserine-O-phosphate monophenylphosphoryl ester (MSOPPE) prevented the induction of the LTD induced by DCG-IV. The DCG-IV-induced LTD showed mutual occlusion with LFS-induced LTD. The generation of the agonist-induced LTD required, in part, activation of N-methyl-D-aspartate receptors (NMDAR), as LTD induction was partially blocked in the presence of the NMDAR antagonist D-2-amino-5-phosphonopentanoate (AP5). Evidence for involvement of protein kinase C (PKC) and protein kinase (PKA) in the induction of LTD by activation of mGluRII was obtained by showing an inhibition of the DCG-IV-induced LTD by the PKC inhibitors Ro-31-8220 and bisindolylmaleimide I, and also by the PKA inhibitor H-89. The study demonstrates that activation of mGluRII induces LTD via activation the PKA and PKC pathways in the medial perforant path of the dentate gyrus.

Animals↗
PubMed2006

Acute ethanol administration decreases GAP-43 and phosphorylated-GAP-43 in the rat hippocampus.

Acute alcohol ingestion is well known to have deleterious effects on memory and also known to inhibit long-term potentiation, a putative cellular substrate of memory. In this study, we for the first time revealed that growth-associated protein 43 (GAP-43), which is well known as a presynaptic substrate of protein kinase C and one of the major synaptic plasticity-related genes, was down regulated by single ethanol administration (2.5 g/kg, 15% in saline, i.p.) in the rat hippocampus. Using real-time PCR, we confirmed that GAP-43 mRNA level is significantly decreased 2 h after ethanol administration. GAP-43 and p-GAP-43 (Ser41) immunoreactivities in the hippocampus were also reduced 4 h after ethanol administration. Immunohistochemical study showed that the reduction of GAP-43 and p-GAP-43 expression was associated with the perforant and mossy fibers pathways. These results suggest that the reduction of GAP-43 in the hippocampus might be, at least in part, a cause of memory impairment after acute ethanol ingestion.

Analysis of Variance↗
PubMedDate not supplied

On the integration of subthreshold inputs from Perforant Path and Schaffer Collaterals in hippocampal CA1 pyramidal neurons.

Using a realistic model of a CA1 hippocampal pyramidal neuron, we make experimentally testable predictions on the roles of the non-specific cation current, I(h), and the A-type Potassium current, I(A), in modulating the temporal window for the integration of the two main excitatory afferent pathways of a CA1 neuron, the Schaffer Collaterals and the Perforant Path. The model shows that the experimentally observed increase in the dendritic density of I(h) and I(A) could have a major role in constraining the temporal integration window for these inputs, in such a way that a somatic action potential (AP) is elicited only when they are activated with a relative latency consistent with the anatomical arrangement of the hippocampal circuitry.

Action Potentials↗
PubMed1997

Heterosynaptic LTD and depotentiation in the medial perforant path of the dentate gyrus in the freely moving rat.

We examined the characteristics of heterosynaptic long-term depression (LTD) and depotentiation of previously established long-term potentiation (LTP) in the medial and lateral entorhinal afferents to the dentate gyrus in the awake rat. Rats were prepared for chronic recording of dentate gyrus evoked potentials to activation of the medial and lateral perforant paths. This study in awake rats confirms that heterosynaptic LTD can be induced at inactive medial perforant path synapses in conjunction with the induction of LTP produced by high-frequency stimulation of the lateral perforant path. This form of LTD was long lasting and reversible by tetanic stimulation delivered to the depressed pathway. In contrast, tetanic stimulation of the medial perforant path had only a small heterosynaptic effect on the lateral pathway, suggesting that the two input pathways to the dentate gyrus are not symmetrical in their ability to induce heterosynaptic LTD. We also examined the ability of high-frequency stimulation of one pathway to produce depotentiation of the other pathway. We found that when LTP was first induced in the medial perforant path, depotentiation was induced heterosynaptically by tetanization of the lateral pathway. Both newly established LTP (30 min) and LTP induced and saturated by repeated tetanic stimulation over several days can be depotentiated heterosynaptically. Moreover, depotentiation of the medial perforant path synapses was found to be linearly correlated with the magnitude of LTP induced in the lateral perforant path synapses, and subsequent tetanic stimulation of the depotentiated medial perforant path restored LTP to an extent that counterbalanced depotentiation. The saturation and repotentiation experiments provide clear support for the conclusion that the rapid reversal of LTP reflects true depotentiation of the medial input. Again, as with heterosynaptic LTD, tetanization of the medial perforant path had little effect on previously induced LTP in the lateral path. These results provide evidence that medial perforant path synapses can be depressed and depotentiated heterosynaptically. They suggest that in the intact rat synaptic changes in the afferents to the dentate gyrus from the lateral entorhinal cortex exert powerful control over ongoing or recent synaptic plasticity in the medial entorhinal afferents.

Animals↗
PubMed1988

Synaptic reorganization in the hippocampus induced by abnormal functional activity.

Abnormal functional activity induces long-lasting physiological alterations in neural pathways that may play a role in the development of epilepsy. The cellular mechanisms of these alterations are not well understood. One hypothesis is that abnormal activity causes structural reorganization of neural pathways and promotes epileptogenesis. This report provides morphological evidence that synchronous perforant path activation and kindling of limbic pathways induce axonal growth and synaptic reorganization in the hippocampus, in the absence of overt morphological damage. The results show a previously unrecognized anatomic plasticity associated with synchronous activity and development of epileptic seizures in neural pathways.

Animals↗
PubMed1985

The cutaneous blood supply of the neck: relevance to incision planning and surgical reconstruction.

Previous descriptions of the blood supply of the neck have been contradictory. Neck dissections were performed on 17 adult cadavers after perfusion with radio-opaque microfil silicone rubber compound. In four cadavers cervical incisions were created and flaps elevated prior to perfusion to help demonstrate vascular pathways. In all cadavers myocutaneous perforators were seen passing from the sternocleidomastoid, strap muscles, and trapezius to supply the dermal-subdermal plexus. Also, there were consistently identifiable branches of the superior thyroid, posterior auricular, occipital, facial and transverse cervical arteries, which supply both the platysmal vascular plexus and the overlying dermal-subdermal plexus. The dermal-subdermal plexus is continuous across the midline and this contralateral pathway is supplied chiefly from branches of the superior thyroid artery, facial artery, and myocutaneous perforators of the strap muscles. This information may be useful in the planning of cervical incisions and the design of platysma myocutaneous flaps.

Adult↗
PubMed2006

Long-term depression in identified stellate neurons of juvenile rat entorhinal cortex.

The entorhinal cortex (EC) serves as a gateway to the hippocampus and plays a pivotal role in memory processing in the brain. Superficial layers of the EC convey the cortical input projections to the hippocampus, whereas deep layers of the EC relay hippocampal output projections back to the superficial layers of the EC or to other cortical regions. Whereas the EC expresses long-term potentiation (LTP) and depression (LTD), the underlying cellular and molecular mechanisms have not been determined. Because the axons of the stellate neurons in layer II of the EC form the perforant path that innervates the dentate gyrus granule cells of the hippocampus, we studied the mechanisms underlying the long-term plasticity in identified stellate neurons. Application of high-frequency stimulation (100 Hz for 1 s, repeated 3 times at an interval of 10 s) or forskolin (50 microM) failed to induce significant changes in synaptic strength, whereas application of pairing (presynaptic stimulation at 0.33 Hz paired with postsynaptic depolarization from -60 to -10 mV for 5 min) or low-frequency stimulation (LFS, 1 Hz for 15 min) paradigm-induced LTD. Pairing- or LFS-induced LTDs were N-methyl-D-aspartate receptor-dependent and occluded each other suggesting that they have the similar cellular mechanism. Pairing-induced LTD required the activity of calcineurin and involved AMPA receptor endocytosis that required the function of ubiquitin-proteasome system. Our study provides a cellular mechanism that might in part explain the role of the EC in memory.

Aging↗
PubMed1987

The effects of knife cuts of hippocampal pathways on epileptic activity in the seizure-sensitive gerbil.

Previous studies have shown morphological differences in the hippocampal formation of seizure-sensitive gerbils as compared to seizure-resistant gerbils. To determine the significance of these differences, lesions were made of hippocampal afferents and efferents. Seizure-sensitive gerbils with bilateral knife cuts of the perforant path, including those with bilateral fornix lesions, showed no seizure activity following surgery. However, bilateral transections of the fimbria of the fornix, unilateral lesions of the perforant path and sham surgeries had no significant effect on seizure activity. The termination of seizure activity with bilateral lesions of the perforant path suggests that this pathway, as opposed to the fornix, is required for motor seizures in this strain of gerbils.

Animals↗
PubMed1998

An evidenced-based clinical pathway for acute appendicitis decreases hospital duration and cost.

BACKGROUND/PURPOSE: In the pediatric population, appendicitis remains the most common surgical emergency encountered. The purpose of this study was to determine the impact of an evidence-based clinical pathway for acute appendicitis on patient care as well as hospital and home care costs at the authors' pediatric institution. METHODS: A prospective evaluation was conducted of an appendicitis clinical pathway (June 1996 through November 1996) compared with historical control patients (June 1994 through November 1994) not cared for by the pathway. RESULTS: Data (average +/- SD) for 120 pathway (P) patients were compared with 122 control (C) patients. Age (11.5 +/- 3.6 years for C v 11.2 +/- 3.9 years for P), rates of negative appendectomy (12.3% for C v 9.2% for P) and perforation (26.2% for C v 18.3% for P) were similar. Pathway patients with nonperforated appendicitis were more often discharged from the hospital within 24 hours (48% for C v 67% for P; P = .014) with lower hospital costs ($4,095 +/- $1,280 for C v $3,638 +/- $1,633 for P; P = .001). Pathway patients with perforated appendicitis had shorter hospitalization (185.2 +/- 59 hours for C v 113 +/- 44 hours for P; P = .0001) and lower hospital costs ($11,175 +/- $3,893 for C v $7,823 +/- $2,366 for P; P = .0001). CONCLUSION: An evidence-based appendicitis pathway decreased duration of hospitalization and cost without adversely affecting diagnosis or therapy. Clinical pathways for surgical diagnoses may prove useful as a means to minimize costs without compromising patient care.

Acute Disease↗
PubMed1985

Evidence for amelioration of ischaemic neuronal damage in the hippocampal formation by lesions of the perforant path.

The effect of lesions of two excitatory afferent pathways on the cellular damage in the hippocampus following complete cerebral ischaemia was investigated in the rat. Lesions transecting the perforant path led to a significant decrease in cellular damage in the hippocampal CA1 region ipsilateral to the lesion as compared to the contalateral side and to control. Lesions of the fimbria-fornix, on the other hand, had no significant effects. We propose that the protective effect of the perforant path lesions is due to removal of glutamatergic/aspartergic pathways and that release of these excitatory amino acids might be a critical factor for neuronal necrosis following cerebral ischaemia.

Animals↗
PubMed2001

Glycinergic/GABAergic synapses in the lateral superior olive are excitatory in neonatal C57Bl/6J mice.

The lateral superior olive (LSO), a nucleus involved in sound localization, receives tonotopically organized, inhibitory input from the medial nucleus of the trapezoid body (MNTB). To better understand the development of this glycinergic/GABAergic pathway, we used Gramicidin-perforated patch clamp recordings to characterize MNTB-evoked postsynaptic potentials in LSO neurons of neonatal C57Bl/6J mice. We found that during the first postnatal week, MNTB-evoked responses change from being depolarizing to being hyperpolarizing. Most interestingly, depolarizing glycinergic/GABAergic synaptic potentials were able to trigger action potentials, demonstrating that the MNTB-LSO pathway can act as a true excitatory pathway. This transient excitatory action of immature MNTB-LSO synapses might play an important role in activity-dependent sharpening of the tonotopic organization of inhibitory connections in the LSO.

Animals↗
PubMed1991

Electrophysiological characterization of associational pathway terminating on dentate gyrus granule cells in the rat.

The functional topography and parameters of excitation and inhibition were determined in the in situ associational pathway of the rat dentate gyrus. The functional topography was found to be consistent with previous anatomical studies. The greatest amplitude population spikes and the strongest paired-pulse inhibition were generated with the stimulating electrode placed in the hilus at least 1.5 mm caudal to the ipsilateral dentate gyrus recording electrode. With this standard electrode configuration, neither long-term potentiation of the population spike nor of the population excitatory postsynaptic potential occurred. Hilar associational pathway activation of dentate gyrus granule cells elicited paired-pulse responses similar to those produced in granule cells by perforant path stimulation. Thus, the associational pathway provides another way to assess dentate granule cell function electrophysiologically.

Animals↗
PubMed1992

Bilateral knife cuts to the perforant path disrupt spatial learning in the Morris water maze.

Both the hippocampus and the entorhinal cortex are known to be crucial for spatial learning, but the contribution of the pathway linking the two structures, the perforant path (PP), has never been tested in a spatial learning paradigm. The present study examined the role of the PP in spatial learning using the Morris water maze. Seven days after bilateral transection of the PP with a fine-bladed knife, rats were habituated to the pool, then trained to swim from varying start locations to a platform submerged in a fixed location. After 28 training trials over 5 days, probe trials (without any platform present) were given to assess spatial memory for the location. Compared to sham-operated controls, lesioned rats showed slower learning and poorer asymptotic performance in terms of both swim path distance and escape latency, and less preference for the correct quadrant during probe trials. When the platform location was "reversed" to the opposite quadrant, the lesioned rats again showed poorer learning, poorer asymptotic performance, and reduced preference for the correct quadrant on the probe trial. When tested with a visible platform whose position varied from trial to trial, lesioned rats performed as well as controls. These results are congruent with previous analyses of the contributions of the entorhinal cortex and hippocampus to spatial learning and suggest that for spatial learning, the PP is a critical functional link between these two structures.

Animals↗
PubMed2002

Pathway-specific properties of AMPA and NMDA-mediated transmission in CA1 hippocampal pyramidal cells.

CA1 pyramidal cells receive glutamatergic input from the entorhinal cortex through the perforant path (PP) and from CA3 through Schaffer collaterals (SC). The PP input terminates in the stratum lacunosum molecular approximately 300 microm from the cell body, whereas SC synapses have a more proximal location in the stratum radiatum. We compared the properties of AMPA- and NMDA-mediated transmission at these two inputs. The AMPA-mediated components have linear voltage dependence in both inputs. The reversal potential in the PP is only slightly more positive than in the SC, indicating that distal membrane voltage could be effectively set. The NMDA-mediated responses in the two pathways, however, are very different. The PP exhibits inward rectification, as evidenced by very low outward currents. The rectification persists in the absence of extracellular Mg2+. It cannot be attributed to clamping problems, because large outward AMPA currents can be observed even when conditions are modified to have the AMPA currents kinetically match the NMDA currents. Thus, it appears that the PP NMDA channels have novel properties. A second difference between the PP and SC pathways is that the PP has a larger NMDA/AMPA charge ratio. This difference could be observed under many conditions, including block of all voltage-dependent conductances and elimination of the negative resistance of NMDA channels by removing extracellular Mg2+. The difference in ratio thus cannot be attributed to regenerative currents. The higher NMDA component of the distal PP synapses could help to make these synapses more powerful under depolarizing conditions.

Animals↗
PubMed1999

Theory of electrical creation of aqueous pathways across skin transport barriers.

Experimental studies have shown that application of electrical pulses to human skin that result in U(skin)>30 V for durations of about 1 ms or longer causes a large decrease in electrical resistance within microseconds, followed in seconds by an increase in molecular transport of water-soluble molecules. Local transport regions (LTRs), within which molecular transport is concentrated, mostly form away from the skin's appendages and rete pegs. Theoretical attempts to explain this behavior involve electrically created aqueous pathways ("pores"). For short (about 1 ms) "high voltage" (HV) pulses leading to about U(skin)>50 V, it was hypothesized that such pulses cause electroporation of the multilamellar lipid bilayer membranes of the skin's stratum corneum (SC). Much of the present experimental evidence supports the more specific hypothesis that such pulses create "straight through aqueous pathways", mostly within LTRs, that perforate the SC lipid bilayers and pass through the interiors of hydrated corneocytes. Theoretical estimates of the localized heating within LTRs predict relatively small temperature rises. The theory of LTR formation is incomplete, with both stochastic and deterministic models under consideration. Moderate voltage (MV) pulses leading to about 5<U(skin)<50 V, are consistent with appendageal activation and electroporation. The largest molecular fluxes occur for HV pulses, for which theory predicts large numbers of straight-through aqueous pathways. Both appendageal and stratum corneum electroporation are different from iontophoresis, which occurs at U(skin)<5 V.

Journal Article↗