Investigation of cavitation as a possible damage mechanism in blast-induced traumatic brain injury

Cavitation was investigated as a possible damage mechanism for war-related traumatic brain injury (TBI) due to an improvised explosive device (IED) blast. When a frontal blast wave encounters the head, a shock wave is transmitted through the skull, cerebrospinal fluid (CSF), and tissue, causing negative pressure at the contrecoup that may result in cavitation. Numerical simulations and shock tube experiments were conducted to determine the possibility of cranial cavitation from realistic IED non-impact blast loading. Simplified surrogate models of the head consisted of a transparent polycarbonate ellipsoid. The first series of tests in the 18-inch-diameter shock tube were conducted on an ellipsoid filled with degassed water to simulate CSF and tissue. In the second series, Sylgard gel, surrounded by a layer of degassed water, was used to represent the tissue and CSF, respectively. Simulated blast overpressure in the shock tube tests ranged from a nominal 10-25 pounds per square inch gauge (psig; 69-170?kPa). Pressure in the simulated CSF was determined by Kulite thin line pressure sensors at the coup, center, and contrecoup positions. Using video taken at 10,000 frames/sec, we verified the presence of cavitation bubbles at the contrecoup in both ellipsoid models. In all tests, cavitation at the contrecoup was observed to coincide temporally with periods of negative pressure. Collapse of the cavitation bubbles caused by the surrounding pressure and elastic rebound of the skull resulted in significant pressure spikes in the simulated CSF. Numerical simulations using the DYSMAS hydrocode to predict onset of cavitation and pressure spikes during cavity collapse were in good agreement with the tests. The numerical simulations and experiments indicate that skull deformation is a significant factor causing cavitation. These results suggest that cavitation may be a damage mechanism contributing to TBI that requires future study.     

Falloposcopic identification of a fimbrio-ovarian mucus connection as a possible mechanism for tubal oocyte capture

Falloposcopy combined with laparoscopy was performed in 11 women during the late follicular phase of spontaneous menstrual cycles, and a preovular follicle was confirmed to be present in each case. The fimbrial end of the tube and the ipsilateral ovary containing the preovular follicle were suspended in a fluid environment of 200 ml of lactated Ringer's solution which acted as a support medium for visualization of tubal mucus and facilitated the endoscopy procedure. As the falloposcope was passed through the fimbrial opening, it was observed to carry clear, elastic and filamentous strands of mucus material from within the distal tubal lumen in 4 of 11 procedures. As these mucus strands were carried on the tip of the falloposcope to touch the surface of the ovary containing the preovular follicle, they attached, on contact, in all cases. The fimbrio-ovarian mucus bridge created was quite strong and could be stretched for up to 7 mm before it detached from the ovarian surface. The mucus attachment appeared to be equally secure over the preovular follicle and adjacent ovarian surfaces. These fimbrio-ovarian mucus connections, which have a high affinity for ovarian surface attachment about the time of ovulation, may play an important role in securing tubal oocyte capture in humans.     

Sex differences in cortical plasticity and behavior following anterior cortical kindling in rats.

This experiment examined the effect of electrical kindling on the morphology of frontal (Fr1) neocortical layer III pyramidal cell dendrites in both male and female rats. Repeated elicitation of afterdischarge resulted in an increase in the severity of the behavioural seizures and an increase in afterdischarge duration, frequency and amplitude in all rats. The late component of the transcallosal evoked responses also increased following both 7 and 25 kindling sessions in male rats and following 25 kindling sessions in female rats. Analysis of the Golgi-Cox impregnated pyramidal cell dendrites indicated a significant decrease in the amount of apical and basilar dendritic spine density, length and branching in female rats following 7 days, but not 25 days, of kindling. Male rats had significantly lower apical and basilar dendritic spine density and branching measures following 25 days, but not 7 days, of kindling, as well as significantly lower apical and basilar dendritic length following 7 days of kindling. The differential gender effect suggests that males and females recruit similar plastic mechanisms although at different times in response to electrical kindling.     

Enhanced renal cortical vascularization in experimental hypercholesterolemia

BACKGROUND: Experimental hypercholesterolemia is associated with pro-inflammatory changes and impaired regulation of tissue perfusion, which may lead to neovascularization. However, it is yet unknown whether such changes take place in the kidney. In this study, using a novel three-dimensional (3-D) micro computed-tomography technique we tested the hypothesis that hypercholesterolemia was associated with increased microvascular density in the renal cortex. METHODS: Kidneys were excised from pigs after 12 weeks of either a normal (N = 6) or high cholesterol (HC; N = 5) diet, histology slides processed, and a segmental renal artery injected with a radio-opaque intravascular silicone polymer. Renal samples were scanned with micro computed-tomography, transverse and three-dimensional images were reconstructed, and microvessels (80 to 360 microm in diameter) counted in situ. RESULTS: Serum cholesterol levels were significantly higher in hypercholesterolemic compared to normal pigs (383 +/- 76 vs. 81 +/- 7 mg/dL, P < 0.01), and microvascular spatial density was significantly higher in their inner and middle renal cortex (189 +/- 7 vs. 126 +/- 6 microvessels/cm2, P < 0.0001). Hypercholesterolemic kidneys also showed mild interstitial mononuclear infiltration and heavier immunostaining of vascular endothelial growth factor, but no other signs of morphological damage. CONCLUSIONS: These results demonstrate that early diet-induced hypercholesterolemia is associated with increased microvascular density in the renal cortex, which precedes signs of overt renal morphological damage. These alterations may potentially affect regulation and/or spatial distribution of intrarenal blood flow in hypercholesterolemia, and may participate in renal disease progression.     

Epidural catheter breakage: a possible mechanism

The breakage of an epidural catheter within a patient is an uncommon but troublesome complication of continuous epidural block, and its cause is rarely discovered. Several possible mechanisms for catheter breakage have been proposed, but few can be reproduced experimentally. Review of two recent medicolegal cases concerning catheters that were severed at the time of insertion led to laboratory studies in an attempt to find an explanation. The results of this work demonstrated that it was possible to break or severely damage an epidural catheter by heavy contact between the tip of the epidural needle and a bony surface, if a length of the catheter was protruding from the tip.     

Chiropractic treatment of cystitis: a possible mechanism

The rationale behind chiropractic treatment of visceral disorders has been based on an original concept by the profession's founder, D.D. Palmer, hypothesis and anecdotal evidence. No research has been done to support the hypothesis. Recent research, however, has identified the presence of neuropeptides being released from the sensory nerve endings. This case report describes the history of a patient who was suffering from the symptoms of cystitis without any demonstrable pathological agent. The report discusses the possible mechanism behind the symptoms, their connection to vertebral subluxation complex and the ole of neuropeptides.     

Dynamics and plasticity of stimulus-selective persistent activity in cortical network models

Persistent neuronal activity is widespread in many areas of the cerebral cortex of monkeys performing cognitive tasks with a working memory component. Modeling studies have helped understanding of the conditions under which persistent activity can be sustained in cortical circuits. Here, we first review several basic models of persistent activity, including bistable models with excitation only and multistable models for working memory of a discrete set of pictures or objects with structured excitation and global inhibition. In many experiments, persistent activity has been shown to be subject to changes due to associative learning. In cortical network models, Hebbian learning shapes the synaptic structure and, in turn, the properties of persistent activity when pictures are associated together in the course of a task. It is shown how the theoretical models can reproduce basic experimental findings of neurophysiological recordings from inferior temporal and perirhinal cortices obtained using the following experimental protocols: (i) the pair-associate task; (ii) the pair-associate task with color switch; and (iii) the delay match to sample task with a fixed sequence of samples.     

Neuroprotective effects of propofol in models of cerebral ischemia: inhibition of mitochondrial swelling as a possible mechanism

BACKGROUND: Propofol (2,6-diisopropylphenol) has been shown to attenuate neuronal injury in a number of experimental conditions, but studies in models of cerebral ischemia have yielded conflicting results. Moreover, the mechanisms involved in its neuroprotective effects are yet unclear. METHODS: The authors evaluated the neuroprotective effects of propofol in rat organotypic hippocampal slices exposed to oxygen-glucose deprivation, an in vitro model of cerebral ischemia. To investigate its possible mechanism of action, the authors then examined whether propofol could reduce Ca2+-induced rat brain mitochondrial swelling, an index of mitochondrial membrane permeability, as well as the mitochondrial swelling evoked by oxygen-glucose deprivation in CA1 pyramidal cells by transmission electron microscopy. Finally, they evaluated whether propofol could attenuate the infarct size and improve the neurobehavioral outcome in rats subjected to permanent middle cerebral artery occlusion in vivo. RESULTS: When present in the incubation medium during oxygen-glucose deprivation and the subsequent 24 h recovery period, propofol (10-100 microM) attenuated CA1 injury in hippocampal slices in vitro. Ca2+-induced brain mitochondrial swelling was prevented by 30-100 microM propofol, and so were the ultrastructural mitochondrial changes in CA1 pyramidal cells exposed to oxygen-glucose deprivation. Twenty-four hours after permanent middle cerebral artery occlusion, propofol (100 mg/kg, intraperitoneal) reduced the infarct size by approximately 30% when administered immediately after and up to 30 min after the occlusion. Finally, propofol administered within 30 min after middle cerebral artery occlusion was unable to affect the global neurobehavioral score but significantly preserved spontaneous activity in ischemic rats. CONCLUSIONS: These results show that propofol, at clinically relevant concentrations, is neuroprotective in models of cerebral ischemia in vitro and in vivo and that it may act by preventing the increase in neuronal mitochondrial swelling.     

Biological motion processing as a hallmark of social cognition

Visual processing of biological motion (BM) produced by living organisms is of immense value for successful daily-life activities and, in particular, for adaptive social behavior and nonverbal communication. Investigation of BM perception in neurodevelopmental disorders related to autism, preterm birth, and genetic conditions substantially contributes to our understanding of the neural mechanisms underpinning the extraordinary tuning to BM. The most prominent research outcome is that patients with daily-life deficits in social cognition are also compromised on visual body motion processing. This raises the question of whether performance on body motion perception tasks may serve a hallmark of social cognition. Overall, the findings highlight the role of structural and functional brain connectivity for proper functioning of the neural circuitry involved in BM processing and visual social cognition that share topographically and dynamically overlapping neural networks.     

Enhanced resistance to the effects of hypothermic ischemia in the preserved canine kidney

Addition of trifluoperazine (TFP), a powerful calmodulin inhibitor to Collins' flush solution has exerted a significant protective effect on the cold-preserved kidney, with successful autotransplantation of 80% of preserved kidneys (4 of 5) after 72 hr of storage. In contrast, use of Collins' solution alone resulted in successful autotransplantation of only 33% (2 of 6) of kidneys after a similar period of preservation. In an attempt to analyze the significance of this result, the microcirculation of preserved kidneys was studied with injections of technetium-labeled microspheres into the kidneys, followed by study with a noninvasive radionuclide scintiphotography (RNS) technique that does not interfere with subsequent transplantation of the kidney. Such studies demonstrate that prolonged cold preservation after flush-cooling with Collins' solution is associated with a progressive deterioration of the integrity of the microcirculation, resulting in poor flow to the renal cortex. In contrast, when TFP is added to the Collins' solution, there are uniform increases in renal cortical flow in kidneys stored for 48 and 72 hr, with preservation of the integrity of the renal microcirculation. Biological testing shows a clear-cut correlation between these observations and the capacity of the tested kidneys to sustain life after retransplantation. Further experiments suggest that the decreases observed in cortical flow in kidneys preserved in the cold for 72 hr are a consequence of cellular swelling, and not of a vasospastic response. The data support the conclusion that TFP exerts its protective effect on the basis of its membrane stabilizing capacity as a calmodulin inhibitor, and not through direct vasodilatation.     

术后认知功能障碍的炎症机制

背景 术后认知功能障碍(postoperative cognitive dysfunction,POCD)是老年患者手术后常见的中枢神经系统并发症.目前POCD的发病机制尚不清楚.POCD的发生影响了患者术后恢复,延长了住院时间,增加了术后并发症的发生率和死亡率;对家庭及社会造成严重的经济负担,POCD将成为一个严重的社会问题.目的 旨在推进POCD的研究,使得这一严重问题得到解决.内容 以往的研究表明,麻醉、手术可能是的POCD主要原因,而老龄则是惟一明确的危险应素,提示中枢神经系统退行性改变与POCD的发生可能有着重要联系,而麻醉和手术加重了这种退行性改变所致的认知功能衰退.趋向 较多研究表明炎症反应在与衰老有关的认知功能减退中起着重要作用,而手术创伤和应激引起的炎症反应是围术期发生的重要病理生理学改变.近年来炎症反应在POCD发生中的作用备受关注,现对POCD发生中炎症反应方面的研究进展进行综述.     

术后认知功能障碍的炎症机制

背景 术后认知功能障碍(postoperative cognitive dysfunction,POCD)是老年患者手术后常见的中枢神经系统并发症.目前POCD的发病机制尚不清楚.POCD的发生影响了患者术后恢复,延长了住院时间,增加了术后并发症的发生率和死亡率;对家庭及社会造成严重的经济负担,POCD将成为一个严重的...     

Abnormal cortical synaptic plasticity in primary motor area in progressive supranuclear palsy

No study has yet investigated whether cortical plasticity in primary motor area (M1) is abnormal in patients with progressive supranuclear palsy (PSP). We studied M1 plasticity in 15 PSP patients and 15 age-matched healthy subjects. We used intermittent theta-burst stimulation (iTBS) to investigate long-term potentiation (LTP) and continuous TBS (cTBS) to investigate long-term depression (LTD)-like cortical plasticity in M1. Ten patients underwent iTBS again 1 year later. We also investigated short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) in M1 with paired-pulse transcranial magnetic stimulation, tested H reflex from upper limb flexor muscles before and after iTBS, and measured motor evoked potential (MEP) input-output (I/O) curves before and after iTBS. iTBS elicited a significantly larger MEP facilitation after iTBS in patients than in healthy subjects. Whereas in healthy subjects, cTBS inhibited MEP, in patients it significantly facilitated MEPs. In patients, SICI was reduced, whereas ICF was normal. H reflex size remained unchanged after iTBS. Patients had steeper MEP I/O slopes than healthy subjects at baseline and became even more steeper after iTBS only in patients. The iTBS-induced abnormal MEP facilitation in PSP persisted at 1-year follow-up. In conclusion, patients with PSP have abnormal M1 LTP/LTD-like plasticity. The enhanced LTP-like cortical synaptic plasticity parallels disease progression.     

Prevention of apoptosis as a possible mechanism behind improved cryoprotection of hematopoietic cells by catalase and trehalose

BACKGROUND: Our previous in vitro work has shown the usefulness of membrane stabilizers and antioxidants as additives in conventional freezing medium to freeze mouse and human hematopoietic cells. The present work was carried out using murine model to test the in vivo engraftment ability of mouse bone marrow frozen with (test cells) or without (control cells) addition of a combination of trehalose and catalase in the medium containing 10% dimethyl sulfoxide (DMSO). METHODS: Viability, nucleated cell recovery, and progenitor content of revived cells were measured. Freezing efficacy was tested by in vivo assays like colony forming unit-spleen (CFU-S), pre-CFU-S, and short-term engraftment of frozen marrow in irradiated mice. Long-term engraftment ability of frozen marrow was assessed using a Ly5.1-Ly 5.2 chimera model. Levels of apoptosis and reactive oxygen species (ROS) generated in revived cells were estimated. The former by Annnexin V, TUNEL, and DNA laddering and the latter by DCFH-DA probe. RESULTS: Our results show that the combination of catalase and trehalose with 10% DMSO improves freezing efficacy not only in terms of viability, cell recovery, and progenitor content but also by in vivo assays like CFU-S, pre-CFU-S, and short- and long-term engraftment. Both the level of apoptosis and ROS generation were considerably reduced in test set as compared to control set. CONCLUSIONS: We conclude that inclusion of a combination of trehalose and catalase in conventional freezing medium leads to enhanced engraftment potential of cryopreserved mouse bone marrow cells probably by preventing apoptotic cell death. Our observation using animal model may have significant clinical implications.     

Warfarin as a possible teratogen.

A case of congenital stippled epiphyses is presented, and attention is drawn to the possibility that this condition was caused by maternal ingestion of warfarin during early pregnancy.     

Monozygotic twins non-concordant for oligomeganephronic renal hypoplasia: artery-vein placental shunting as a possible pathogenetic mechanism

The etiology and pathogenesis of oligomeganephronic renal hypoplasia (OMN) are not known. In the present paper a second case of monozygotic twins non-concordant for OMN is described. It is hypothesized that one of the mechanisms which have been proposed to explain structural defects in monozygotic twins, namely placental artery-vein shunting, may have been involved in the pathogenesis of OMN in these patients. In OMN in general vascular abnormalities may have to be considered as a pathogenetic mechanism.     

Acetylcholine as a possible neurotransmitter in penile erection

We investigated the erectile response to intracavernous injection of increasing doses of acetylcholine (0.5 to 500 micrograms.) in 10 monkeys. To differentiate between nicotinic (ganglionic) and muscarinic (parasympathetic postganglionic) effects, acetylcholine was likewise administered after 1.6 mg. trimethaphan camsylate and 0.1 mg. atropine, alone or sequentially. Erections were induced by cavernous nerve stimulation before and after atropine. Acetylcholine induced a dose-dependent, triphasic erectile response: a first tumescence phase followed by contraction and a subsequent second phase of tumescence. Atropine reduced but did not abolish the erectile response to acetylcholine: attainment of maximal intracavernous pressure after neurostimulation was both delayed and reduced (mean 25 cm. H2O). Only after combined nicotinic and muscarinic blockade was the erectile response to acetylcholine completely abolished. Histologic staining for acetylcholinesterase in five additional monkeys that had not received acetylcholine showed dense staining within the cavernous erectile tissue and around the cavernous arteries. Our data suggest that acetylcholine is a possible neurotransmitter for penile erection in monkeys.     

Intermolecular phosphorylation of insulin receptor as possible mechanism for amplification of binding signal

Clustering of cell-surface insulin receptors has led to the speculation that intermolecular phosphorylation of unoccupied receptors catalyzed by ligand-occupied receptors within the cluster could be a mechanism by which the insulin-binding signal is amplified. We examined whether insulin receptors can be phosphorylated by an intermolecular mechanism. In this study, we used highly purified insulin receptors isolated from rat liver plasma membranes and human placental membranes. Rat liver insulin receptors were "activated" by incubation with 10 nM insulin in the presence of ATP. Subsequent to removal of insulin by immunodepletion, these receptors were used as an enzyme source to study phosphorylation of unphosphorylated "substrate" human receptors. Initially, we found no evidence that the addition of activated rat receptors increased phosphorylation of human receptors, when assessed by immunoprecipitation with a human-specific monoclonal antibody. To examine the possibility that these negative results were due to insufficient receptor concentration, activated human receptors were mixed with unphosphorylated substrate receptors at concentrations up to 60 micrograms/ml. In this study, we found that addition of activated receptors resulted in increased phosphorylation of the substrate receptors at the highest concentrations employed. These are the first data indicating that insulin receptors per se are capable of intermolecular phosphorylation. In vivo, this could be the initial step in amplifying the insulin-binding signal.