Collateral Pathway Research Articles

Pelvic collateral pathway during endovascular aortoiliac aneurysm repair with internal iliac artery interruption: a retrospective observational study

BackgroundIpsilateral branches of the deep femoral artery (DFA) are qualitatively identified as collateral arteries based on angiography after internal iliac artery (IIA) interruption. The purpose of this study was to quantitatively identify the major collateral pathway after unilateral IIA interruption during endovascular aortoiliac aneurysm repair to preserve the pelvic circulation and reduce the risk of ischemic complications.MethodsThe study population included 28 patients (mean age 76.3 years) with aortoiliac aneurysm who underwent endovascular aneurysm repair with unilateral IIA interruption from August 2012 to January 2020. The diameters of the bilateral preoperative and postoperative DFA, lateral femoral circumflex artery (LFCA), medial femoral circumflex artery (MFCA) and obturator artery (ObA) were measured on contrast-enhanced computed tomography using a 3-dimensional image analysis system. The measured values were evaluated and analyzed with a repeated measures two-way analysis of variance and Dunnett’s test.ResultsThe postoperative diameters of the MFCA (P = 0.051) and ObA (P = 0.016) were observed to be larger than the preoperative diameters. Such increases in the MFCA (P < 0.001) and ObA (P < 0.001) diameters were only found to be significant on the unilateral side of the IIA interruption, and the diameter of the ipsilateral LFCA (P < 0.001) was also found to have significantly increased in size. However, no significant arterial extension was found on the contralateral side.ConclusionsThe ipsilateral MFCA-ObA pathway might therefore be a major collateral pathway arising from the DFA to preserve pelvic circulation after unilateral IIA interruption.

Assessment of collateral venous flow using temporary clip placement at ICG videoangiography.

As there are many collateral pathways between venous systems, intraoperative venous injury rarely induces venous infarction. In some patients, however, venous injury during microsurgical manipulation may cause acute and/or delayed serious complications. Although intraoperative evaluation using indocyanine green (ICG) videoangiography is very useful, it is difficult to assess the flow direction using this technique. A simple technique using temporary clips and ICG videoangiography was applied to assess the collateral venous pathway in 4 cases of surgical manipulation-related injury or occlusion of the main superficial Sylvian vein in patients with aneurysm. The flow direction and collateral pathway can be easily visualized after release of temporary occlusion. A collateral venous pathway can be evaluated with the present simple technique described here.

Efficacy of intraoperative cine-portogram for complicated portal vein reconstruction in pediatric living donor liver transplantation.

Sufficient PV flow is necessary to achieve successful PV reconstruction in pediatric LDLT. IOCP can be used to assess the severity of PV stenosis and to identify potential portosystemic collateral pathways. The present study reviewed the utility of IOCP and the outcomes of patients who underwent assessment with an IOCP. Consecutive primary LDLTs were performed in 488 pediatric recipients between November 2005 and October 2019. IOCP was used in patients who were unable to achieve sufficient PV flow after the ligation of collaterals. In total, 11 patients underwent IOCP to assess potential portosystemic collateral pathways. The median age and body weight was 8months (IQR, 6-11months) and 6.6kg (IQR, 5.7-8.9kg), respectively. The reasons for using the IOCP were recurrent PV thrombus in seven patients and insufficient PV flow in four patients. IOCP revealed remaining collaterals in six patients and residual hypoplastic PV in eight patients. Two patients required additional interruption of the potential collaterals under IOCP, which were unable to be recognized as a dominant portosystemic collateral pathway on preoperative imaging. All eight patients with residual hypoplastic PV required vein graft interposition for the complete removal of the hypoplastic PV. All the patients are currently doing well with a median follow-up period of 4.9years (IQR, 2.2-5.6years). IOCP can be an effective tool for precisely detecting occult portosystemic collateral pathways and for assessing the patency of the PV anastomosis in pediatric LDLT.

Noradrenaline Release from Locus Coeruleus Terminals in the Hippocampus Enhances Excitation-Spike Coupling in CA1 Pyramidal Neurons Via β-Adrenoceptors.

Release of the neuromodulator noradrenaline signals salience during wakefulness, flagging novel or important experiences to reconfigure information processing and memory representations in the hippocampus. Noradrenaline is therefore expected to enhance hippocampal responses to synaptic input; however, noradrenergic agonists have been found to have mixed and sometimes contradictory effects on Schaffer collateral synapses and the resulting CA1 output. Here, we examine the effects of endogenous, optogenetically driven noradrenaline release on synaptic transmission and spike output in mouse hippocampal CA1 pyramidal neurons. We show that endogenous noradrenaline release enhances the probability of CA1 pyramidal neuron spiking without altering feedforward excitatory or inhibitory synaptic inputs in the Schaffer collateral pathway. β-adrenoceptors mediate this enhancement of excitation-spike coupling by reducing the charge required to initiate action potentials, consistent with noradrenergic modulation of voltage-gated potassium channels. Furthermore, we find the likely effective concentration of endogenously released noradrenaline is sub-micromolar. Surprisingly, although comparable concentrations of exogenous noradrenaline cause robust depression of slow afterhyperpolarization currents, endogenous release of noradrenaline does not, indicating that endogenous noradrenaline release is targeted to specific cellular locations. These findings provide a mechanism by which targeted endogenous release of noradrenaline can enhance information transfer in the hippocampus in response to salient events.

Collateral circulation of the femoral and genicular systems in human lower limbs is highly uncommon.

The descending branch of the lateral circumflex artery is a septocutaneous vessel that is vital for free and pedicle thigh flap transfer surgeries when repairing tissue defects. It also forms an anastomosis with the superior lateral genicular artery to create a collateral pathway for circumventing occlusions in the superficial femoral artery (SFA). Many anatomical texts and atlases imply the persistence of this anastomosis. However, previous studies indicate variability in the source of the arteries that form the anastomosis, and have reported cases where an anastomosis does not exist. We hypothesized that variations from the conventional accepted pattern can be predicted by comparisons of arterial diameters, and that unconventional anastomoses may be present to facilitate collateral circulation to the limb. Fifty-one limbs were dissected and analyzed to establish the source of the descending branch of the lateral circumflex artery, classify the types of anastomoses, and compare the diameters of the descending branch of the lateral circumflex artery, the SFA and the profunda femoris artery to the common femoral artery (CFA). Vessel diameters were normalized to the diameter of the CFA to allow comparison of limbs from both sexes and to minimize the effects of cadaver size on correlating vessel size to the presence or absence of collateral circuits. We report that 62.7% of limbs (32/51) had typical branching patterns; however, only 27.4% of limbs (14/51) had any anastomosis to connect the proximal and distal regions of the thigh. Importantly, the SFA had a wider relative diameter in limbs without anastomoses than in limbs that had normal anastomoses, perhaps precluding the formation of a collateral pathway. Overall, collateral circulation of the lower limb was highly uncommon, in contrast to information inferred from anatomical texts. This study suggests the need for more thorough procedures for determining viable anastomoses prior to thigh flap surgeries to ensure flap survival.

A Review of the Circle of Willis: Investigative Methods, Anatomical Variations and Correlated Ischemic Brain Diseases

The Circle of Willis (CoW) is the most important collateral pathway communicating between the bilateral carotid system and the posterior circulation. Many techniques have been used to investigate the configuration and function of the CoW and their advantages and disadvantages are reviewed here. In previous studies, morphometric variation in CoW has been widely detected; however, the frequency of variation ranges largely, between 10% and 85%. Some differences in reported frequency may reflect differences in: the definition of CoW variation, the methods used to examine variation and study populations. Two conclusions, however, are clear: (i) the prevalence of variation in the posterior circle is higher than in that of the anterior circle; and (ii) variations in the CoW are correlated with cerebral or carotid vessel diseases. Although the cause of the variants remains unclear, both genetic background and hemodynamics could play important roles. Lastly, the correlation between the CoW and ischemic brain diseases is discussed. In future, artificial intelligence will be helpful for evaluating the CoW.

Microtubule‐associated protein 2 mediates induction of long‐term potentiation in hippocampal neurons

Microtubule-associated protein (MAP) 2 has been perceived as a static cytoskeletal protein enriched in neuronal dendritic shafts. Emerging evidence indicates dynamic functions for various MAPs in activity-dependent synaptic plasticity. However, it is unclear how MAP2 is associated with synaptic plasticity mechanisms. Here, we demonstrate that specific silencing of high-molecular-weight MAP2 in vivo abolished induction of long-term potentiation (LTP) in the Schaffer collateral pathway of CA1 pyramidal neurons and in vitro blocked LTP-induced surface delivery of AMPA receptors and spine enlargement. In mature hippocampal neurons, we observed rapid translocation of a subpopulation of MAP2, present in dendritic shafts, to spines following LTP stimulation. Time-lapse confocal imaging showed that spine translocation of MAP2 was coupled with LTP-induced spine enlargement. Consistently, immunogold electron microscopy revealed that LTP stimulation of the Schaffer collateral pathway promoted MAP2 labeling in spine heads of CA1 neurons. This translocation depended on NMDA receptor activation and Ras-MAPK signaling. Furthermore, LTP stimulation led to an increase in surface-expressed AMPA receptors specifically in the neurons with MAP2 spine translocation. Altogether, this study indicates a novel role for MAP2 in LTP mechanisms and suggests that MAP2 participates in activity-dependent synaptic plasticity in mature hippocampal networks.

Prenatal Cannabinoid Exposure Mediated Cognitive Deficits in the Offspring: Elucidation of the Mechanism and Identifying Therapeutic Targets

Cannabinoid is currently one of the most commonly used recreational drugs in the world with an approximate user of 22.2 million. As more and more states in the US are legalizing the use of cannabinoid, the rate of cannabinoid use is increasing specially in pregnant women. The active ingredient of cannabis is delta‐9‐tetrahydrocannabinol (THC) which can cross blood placental barrier and may cause enduring alterations in synaptic circuitry of the fetal brain. The aim of our study is to investigate the mechanism of learning and memory deficits in case of prenatal cannabinoid exposure (PCE) in the adolescent offspring. An osmotic pump filled with either vehicle or the cannabinoid receptor full agonist WIN55,212‐2 (2 mg/kg body weight/day) was implanted subcutaneously in Gestational Day‐3 to deliver the drug at a constant rate until the pups were born. Open field test was performed to see the effect of PCE on locomotor activity which revealed no abnormality in the general motor activity. Contextual fear conditioning test indicated a significantly reduced freezing behavior in the PCE group compared to the vehicle exposed group. Hippocampus based spatial memory test Morris water maze showed that during the trial period, PCE animals exhibit no preference for any particular quadrant while control animals had an increased preference for the quadrant where the hidden platform was present during the training period. Electrophysiological experiments were performed on the Schaffer collateral pathway of acute hippocampal slices to measure synaptic plasticity. Impairment in both long term potentiation (LTP) and long‐term depression (LTD), which are important parameters of synaptic plasticity, were observed. These impairments were associated with downstream changes in the glutamatergic signaling. An increase in cannabinoid receptor type 1(CB1) expression followed by reduced neural cell adhesion molecule (NCAM) and its active form polysialylated NCAM (PSA‐NCAM) expression have been observed in the hippocampus of PCE animals. Interestingly, restoration of PSA‐NCAM activity restored the LTP deficits observed in PCE animals. Thus, based on the previous studies and our current data, it can be postulated that, the observed cognitive deficits in the PCE animals might be partly due to an imbalance in glutamate receptors mediated neurotransmission influenced by NCAM/PSA NCAM. Understanding this specific NCAM/PSA‐NCAM interdependent signaling cascade will lead to an identification of a specific therapeutic target to improve gestational cannabinoid exposure mediated memory deficits.

Right inferior phrenic artery; Don't miss on MDCT before chemoembolization of hepatic dome HCC

BackgroundTransarterial chemoembolization (TACE) is considered a standard local-regional treatment for intermediate-stage hepatocellular carcinoma (HCC) and the most common bridging therapy. HCC typically receives its blood supply from the hepatic artery; however, it can recruit a parasitic supply from extrahepatic collateral arteries. The right inferior phrenic artery (RIPA) is considered the most common extrahepatic collateral pathway supplying HCC and so interfere with the therapeutic efficacy of TACE resulting in treatment failure and poor outcome. Imaging by MDCT with angiography has an essential role in depicting the presence or absence of an EHC arterial supply during the pre-TACE evaluation. We analyzed MDCT studies with CT angiography of patients with hepatic dome HCC retrospectively to confirm the diagnosis of HCC and to assess its blood supply. All patients were subjected to a proper assessment by history, clinical examination, as well as routine laboratory investigationsResultsOur study includes 58 cases with hepatic dome HCC. On CT angiography, the extrahepatic collateral from the RIPA supplying hepatic dome HCC was detected in about 33 out of 58 cases (56.9%). The RIPA arose directly from the aorta in 30 cases (90.9%) with only three cases (9.1%) from the celiac trunk. All cases were managed with TACE with about 25 out of 33 cases (75.8%) with extrahepatic RIPA were undergone concomitant embolisation of both RIPA and hepatic artery during TACE procedure.ConclusionMDCT assesses well the HCC arterial supply which is fundamental for planning subsequent cannulation and embolization of extrahepatic RIPA supply to hepatic dome HCC.

A unique temporary collateral pathway between carotid-vertebrobasilar arteries in a carotid dissection patient

BackgroundIn adults, the anastomosis between carotid and vertebrobasilar arteries is usually the posterior communicating artery, sometimes the primitive trigeminal artery. In this case, the basilar artery fed the internal carotid artery through the pontine-to-tentorial artery anastomosis after severe stenosis from traumatic carotid dissection.Case presentationA 32-year-old female was diagnosed with ischemic stroke caused by traumatic carotid artery dissection. Aspirin (100 mg/day) and clopidogrel (75 mg/day) were prescribed. Digital subtraction angiography performed 6 days after stroke onset showed a dissection in the cervical segment of left internal carotid artery with severe local stenosis, and a collateral pathway from BA to the cavernous segment of internal carotid artery through the lateral pontine and tentorial artery. Without interventional therapy, clinical symptoms improved significantly within 10 days after onset. At 3-month follow-up, left common carotid artery angiography showed the stenosis had been significantly improved with a residual aneurysm. There was no collateral pathway between carotid-vertebrobasilar arteries, and a residual small artery originated from the posterior vertical segment of cavernous internal carotid artery. The small artery was clearly visualized by 3-dimensional rotational angiography and identified the tentorial artery.ConclusionTo the author’s knowledge, this is the first report of a collateral pathway between carotid vertebrobasilar arteries through the pontine-to-tentorial artery anastomosis. Meanwhile, tentorial artery origination directly from the cavernous segment of internal carotid artery is rare and easily mistaken for persistent primitive trigeminal artery. 3-dimensional rotational angiography can provide sensitive and accurate diagnostic assessment of the small artery, and may be a useful tool for screening of abnormal small arteries.

Arterial communication around the pancreatic tail enabled division of the gastroduodenal artery during pancreaticoduodenectomy in patient with complete celiac artery occlusion: a case report

BackgroundStenosis or obstruction of the celiac artery (CA) is known as celiac artery stenosis (CAS) and is usually accompanied by the formation of arterial anastomosis between the superior mesenteric artery (SMA) system and the CA system. Arterial bypass is mainly achieved through the gastroduodenal artery (GDA); therefore, the division of the GDA during pancreaticoduodenectomy (PD) could pose a problem in patients with CAS.Case presentationWe reported a case of PD presenting complete occlusion of the CA, in which perfusion to organs in the CA system was maintained via peri-pancreatic arterial communication. There were complicated arterial anastomoses around the pancreas, which were clearly visualized on a three-dimensional reconstruction of the arterial system using multi-detector computed tomography. Among these complicated anastomoses, one well-developed anastomosis between the SMA and the splenic artery through the dorsal pancreatic artery (DPA) was identified. The DPA was considered to work as a potential collateral pathway from the SMA to organs in the CA system after division of the GDA. During surgery, Doppler ultrasonography detected hepatopetal arterial flow even after the GDA clamping; therefore, we performed typical PD with division of the GDA. The postoperative course of the patient was uneventful, and there was no sign of ischemic complications in the CA system organs including the liver, stomach or spleen.ConclusionsThree-dimensional reconstruction of the arterial system using multi-detector computed tomography and the intraoperative GDA clamping test were useful to determine whether it was possible to divide the GDA in PD, in the case of CAS.

Collateral Development and Arteriogenesis in Hindlimbs of Swine After Ligation of Arterial Inflow

BackgroundDevelopment of collateral vasculature is key in compensating for arterial occlusions in patients with peripheral artery disease (PAD). We aimed to examine the development of collateral pathways after ligation of native vessels in a porcine model of PAD. MethodsRight hindlimb ischemia was induced in domestic swine (n = 11) using two versions of arterial ligation. Version 1 (n = 6) consisted of ligation with division of the right external iliac, profunda femoral, and superficial femoral arteries. Version 2 (n = 5) consisted of the ligation of version 1 with additional ligation with division of the right internal iliac artery. Development of collateral pathways was evaluated with standard angiography before arterial ligation and at termination (30 days later). Relative luminal diameter of the arteries supplying the ischemic right hind limb were determined by two-dimensional angiography. ResultsThe dominant collateral pathway that developed after version 1 ligation connected the right internal iliac artery to the right profunda femoral and then to the right superficial femoral and popliteal artery. Mean luminal diameter of the right internal iliac artery at termination increased by 38% compared with baseline. Two codominant collateral pathways developed in version 2 ligation: (i) from the left profunda femoral artery to the reconstituted right profunda femoral artery and (ii) from the common internal iliac trunk and the left internal iliac artery to the reconstituted right internal iliac artery, which then supplied the right profunda femoral and then the right superficial femoral and popliteal artery. The mean diameter of the left profunda and the left internal iliac artery increased at termination by 26% and 21%, respectively (P < 0.05). ConclusionsTwo versions of hindlimb ischemia induction (right ilio-femoral artery ligation with and without right internal iliac artery ligation) in swine produced differing collateral pathways, along with changes to the diameter of the inflow vessels (i.e., arteriogenesis).

Peak systolic velocity and color aliasing are important in the development of duplex ultrasound criteria for external carotid artery stenosis

ObjectiveThe external carotid artery (ECA) serves as a major collateral pathway for ophthalmic and cerebral artery blood supply. It is routinely examined as part of carotid duplex ultrasound, but criteria for determining ECA stenosis are poorly characterized and typically extrapolated from internal carotid artery data. This is despite the fact that the ECA is smaller in diameter, with a higher resistance and lower volume flow pattern. We hypothesized that using the cutoff of a peak systolic velocity (PSV) ≥125 cm/s, extrapolated from internal carotid artery data, will overestimate the prevalence of ≥50% ECA stenosis and aimed to determine a more appropriate criterion. MethodsFrom December 2016 to July 2017, consecutive carotid duplex ultrasound studies performed in our university hospital Intersocietal Accreditation Commission-accredited vascular laboratory were prospectively identified and categorized with respect to prevalence and distribution of ECA PSVs and color aliasing, an indication of turbulent flow or flow acceleration. Presence of color aliasing was determined by two individual reviewers and agreement assessed by Cohen κ coefficient. ECA stenosis was calculated by the North American Symptomatic Carotid Endarterectomy Trial (NASCET) method in patients with computed tomography angiography (CTA) performed within 3 months of carotid duplex ultrasound without an intervening intervention. Receiver operating characteristic analysis was performed to identify best criteria for determining ≥50% ECA stenosis. ResultsThere were 1324 ECAs from 662 patients analyzed; 174 patients had a total of 252 ECAs with PSV ≥125 cm/s (19% of the total sample). Of those ECAs with PSVs ≥125 cm/s, 30.5% were between 125 and 149 cm/s, 22.2% were between 150 and 174 cm/s, 13.1% were between 175 and 199 cm/s, and 34.1% were ≥200 cm/s. There were 341 ECAs that were analyzed for the presence of color aliasing. In 86 ECAs with PSV ≥200 cm/s, 58.1% had color aliasing, whereas in 255 ECAs with PSV <200 cm/s, only 19.2% had color aliasing (P = .0001). There were 325 CTA studies reviewed and assessed for the presence of a ≥50% ECA stenosis as determined by CTA. Overall, the combination of an ECA PSV ≥200 cm/s with the presence of color aliasing provided the highest combination of sensitivity (90%), specificity (96%), positive predictive value (83%), and negative predictive value (98%) and the greatest area under the curve of 0.971 for determining the presence of a ≥50% ECA stenosis based on CTA. ConclusionsA PSV ≥125 cm/s alone probably overestimates the prevalence of ≥50% ECA stenosis. A PSV ≥200 cm/s combined with color aliasing is highly predictive of >50% ECA stenosis based on correlation with CTA.

The importance of the Moskowitz artery as a lesser-known collateral pathway in the medial laparoscopic approach to splenic flexure mobilisation and its evaluation with preoperative computed tomography.

IntroductionThe collateral pathways between the superior mesenteric artery (SMA) and inferior mesenteric artery (IMA) play an important role in colonic surgery. The most well-known are the Drummond marginal artery and Riolan’s arch. The Moskowitz artery, also known as the meandering mesenteric artery, is a lesser-known collateral pathway and represents another link between SMA and IMA. The Moskowitz artery runs along the colonic mesentery floor and represents the link between the proximal segment of the middle colic artery and the ascending branch of the left colic artery.AimTo comprehend the presence and importance of the Moskowitz artery (meandering mesenteric artery) in preoperative patients by using computed tomography (CT) studies.Material and methodsWe retrospectively reviewed all abdominal CT images performed using intravenous contrast for any reason at the Radiology Department of Yeditepe University Hospital between April 2015 and September 2018. Patients older than 18 years with intravenous contrast (arterial and venous phases with a cross-section thickness of 0.625 mm), who underwent abdominal CT scan, and patients without any abdominal surgery were included in the study. As a result of the screening, 109 CT scans with eligibility criteria were included in this study.ResultsThere were 109 cases in this study; 50 (45.9%) of them were male and 59 (54.1%) were female. Moskowitz artery was found in 18 (16.5%) cases; 8 were males and 10 were females. Riolan’s arch was present in 30 cases, of whom 15 were male and 15 were female. In our study Moskowitz artery and Riolan’s arch were monitored as separate vascular structures, and in all cases with Moskowitz artery, Riolan’s arch was also present. There was a statistically significant difference (p < 0.05) between the combined MCA emerging type and the presence of MA, and 12 cases with combined branch and 6 cases with single branch had Moskowitz artery. There was a statistically significant difference (p < 0.05) between LCA types and the presence of MA, and the Moskowitz artery was the most common seen at type 1 LCA.ConclusionsKnowledge of the relationship between Riolan’s arch and the Moskowitz artery is valuable, and preoperative evaluation of this artery may be beneficial in the presence of Riolan’s arch. In addition, preoperative radiological evaluation and its importance are prominent in minimising intraoperative bleeding during splenic flexure mobilisation with a medial laparoscopic approach and reducing the risk of colorectal anastomosis leakage.

A Review of the Circle of Willis: Investigative Methods, Anatomical Variations and Correlated Ischemic Brain Diseases

The Circle of Willis (CoW) is the most important collateral pathway communicating between the bilateral carotid system and the posterior circulation. Many techniques have been used to investigate the configuration and function of the CoW and their advantages and disadvantages are reviewed here. In previous studies, morphometric variation in CoW has been widely detected; however, the frequency of variation ranges largely, between 10% and 85%. Some differences in reported frequency may reflect differences in: the definition of CoW variation, the methods used to examine variation and study populations. Two conclusions, however, are clear: (i) the prevalence of variation in the posterior circle is higher than in that of the anterior circle; and (ii) variations in the CoW are correlated with cerebral or carotid vessel diseases. Although the cause of the variants remains unclear, both genetic background and hemodynamics could play important roles. Lastly, the correlation between the CoW and ischemic brain diseases is discussed. In future, artificial intelligence will be helpful for evaluating the CoW.

Adiponectin Knockout Mice Display Cognitive and Synaptic Deficits.

Adiponectin is an adipokine that has recently been under investigation for potential neuroprotective effects in various brain disorders including Alzheimer's disease, stroke, and depression. Adiponectin receptors (AdipoR1 and AdipoR2) are found throughout various brain regions, including the hippocampus. However, the role of these receptors in synaptic and cognitive function is not clear. Therefore, the goal of the current study was to evaluate synaptic and cognitive function in the absence of adiponectin. The current study utilized 12-month-old adiponectin knockout (APN-KO) mice and age-matched controls to study cognitive and hippocampal synaptic alterations. We determined that AdipoR1 and AdipoR2 are present in the synaptosome, with AdipoR2 displaying increased presynaptic vs. postsynaptic localization, whereas AdipoR1 was enriched in both the presynaptic and postsynaptic fractions. APN-KO mice displayed cognitive deficits in the novel object recognition (NOR) and Y-maze tests. This was mirrored by deficits in long-term potentiation (LTP) of the hippocampal Schaefer collateral pathway in APN-KO mice. APN-KO mice also displayed a reduction in basal synaptic transmission and an increase in presynaptic release probability. Deficits in LTP were rescued through hippocampal slice incubation with the adiponectin receptor agonist, AdipoRon, indicating that acute alterations in adiponectin receptor signaling influence synaptic function. Along with the deficits in LTP, altered levels of key presynaptic and postsynaptic proteins involved in glutamatergic neurotransmission were observed in APN-KO mice. Taken together, these results indicate that adiponectin is an important regulator of cognition and synaptic function in the hippocampus. Future studies should examine the role of specific adiponectin receptors in synaptic processes.

Effects of uninterrupted sinusoidal LF-EMF stimulation on LTP induced by different combinations of TBS/HFS at the Schaffer collateral-CA1 of synapses

Long-term potentiation (LTP) is an important aspect of synaptic plasticity and is one of the main mechanisms involved in memory. Low-frequency electromagnetic fields (LF-EMFs) such as transcranial magnetic stimulation are emerging neuromodulation tools for the regulation of LTP. However, whether LF-EMFs have different effects on different types of LTP has not yet been verified. Herein, we studied the regulatory effects of 15 Hz/2 mT sinusoidal magnetic field as pre-magnetic stimulation on several types of LTP, which were induced by theta-burst(TBS) or high-frequency stimulation (HFS) or some combination of them, and applied N-methyl-D-aspartate receptor(NMDAR) antagonists to observe the relationship between the regulation of LTP by LF-EMFs and NMDAR in the Schaffer collateral pathway of rat brain slices in vitro. The results presented in this paper are the performance of TBS and HFS was not exactly the same and the recovery speed of TBS-LTP was faster than HFS-LTP after receiving the regulation of LF-EMFs; moreover, the LTP level was affected by the order of combination and the effect of pre-magnetic stimulation could maintain the entire process of the combined induction experiment, while NMDAR antagonists could not completely offset the influence of LF-EMFs. The memory patterns are diverse, and this study has shown LF-EMFs can regulate LTP such as TBS-LTP and HFS-LTP and can continuously affect multiple LTP induction processes. However, different memory processes may have different performance in the face of LF-EMFs regulation. In terms of the mechanism of LF-EMFs-induced LTP regulation, NMDARs may be involved in the process of LF-EMF regulation of LTP, but are not the only factor.

Regulation of Hippocampal Memory by mTORC1 in Somatostatin Interneurons.

Translational control of long-term synaptic plasticity via Mechanistic Target Of Rapamycin Complex 1 (mTORC1) is crucial for hippocampal learning and memory. The role of mTORC1 is well characterized in excitatory principal cells but remains largely unaddressed in inhibitory interneurons. Here, we used cell-type-specific conditional knock-out strategies to alter mTORC1 function selectively in somatostatin (SOM) inhibitory interneurons (SOM-INs). We found that, in male mice, upregulation and downregulation of SOM-IN mTORC1 activity bidirectionally regulates contextual fear and spatial memory consolidation. Moreover, contextual fear learning induced a metabotropic glutamate receptor type 1 (mGluR1)-mediated late long-term potentiation (LTP) of excitatory input synapses onto hippocampal SOM-INs that was dependent on mTORC1. Finally, the induction protocol for mTORC1-mediated late-LTP in SOM-INs regulated Schaffer collateral pathway LTP in pyramidal neurons. Therefore, mTORC1 activity in somatostatin interneurons contributes to learning-induced persistent plasticity of their excitatory synaptic inputs and hippocampal memory consolidation, uncovering a role of mTORC1 in inhibitory circuits for memory.SIGNIFICANCE STATEMENT Memory consolidation necessitates synthesis of new proteins. Mechanistic Target Of Rapamycin Complex 1 (mTORC1) signaling is crucial for translational control involved in long-term memory and in late long-term potentiation (LTP). This is well described in principal glutamatergic pyramidal cells but poorly understood in GABAergic inhibitory interneurons. Here, we show that mTORC1 activity in somatostatin interneurons, a major subclass of GABAergic cells, is important to modulate long-term memory strength and precision. Furthermore, mTORC1 was necessary for learning-induced persistent LTP at excitatory inputs of somatostatin interneurons that depends on type I metabotropic glutamatergic receptors in the hippocampus. This effect was consistent with a newly described role of these interneurons in the modulation of LTP at Schaffer collateral synapses onto pyramidal cells.

Collateral vein dynamics in mouse models of venous thrombosis: Pathways consistent with humans

IntroductionProlific collateralization in the venous system has been associated with more severe disease. However, there is a scarcity of information on venogenesis and collateral vessel progression over time. Further, little is understood regarding the relevance of the most common preclinical model—the mouse—for studying venous collateralization. The purpose of this work was to non-invasively and quantitatively characterize collateral vein development and progression in two murine models of deep vein thrombosis using magnetic resonance imaging (MRI). MethodsVenous thrombosis (VT) was induced in 12–14-week-old male C57BL/6 mice using either the inferior vena cava (IVC) ligation model (n = 5) or the electrolytic IVC model (n = 5). Magnetic Resonance Imaging (MRI) methods optimized for small venous imaging were used on days 2, 6, 14, and 21 following venous thrombosis induction to quantify collateral development and thrombus volume. ResultsCollateral veins ~150–200 μm in diameter could be tracked in three dimensions. Collateral pathways were influenced by pre-existing anatomy; mice with bilateral IVC branches showed a predominant superficial collateral pathway (superficial and internal epigastric veins), whereas mice with no lateral branches exhibited a strong intermediate collateral pathway (gonadal and periureteric veins) and were less likely to develop ascending lumbar collaterals. The degree of venogenesis showed a positive correlation with thrombus volume in both models (combined R2 = 0.64, p < 0.0001). ConclusionsVenous collateral pathways in C57BL/6 mice are consistent with those described in humans. Collateral pathways are influenced by pre-existing anatomy, and the degree of collateralization correlates with thrombus volume.

Angiographic Findings in Patients with Hepatocellular Carcinoma Previously Treated Using Proton Beam Therapy.

Given the growing interest in using proton beam therapy (PBT) for hepatocellular carcinoma (HCC), it is possible that transarterial chemoembolization (TACE) could be used for selected patients who have previously undergone PBT. However, these cases can be technically challenging to treat and require appropriate preparation. Thus, we aimed to identify angiographic findings in this setting. We retrospectively identified 31 patients (28 men and 3 women, mean age: 69 years, range: 43–84 years) who underwent hepatic angiography plus TACE or transarterial infusion chemotherapy (TAI) for HCC that recurred after PBT (July 2007 to June 2018). We discovered four angiographic findings, which we speculate were related to the previous PBT. 18 patients experienced recurrence in the irradiated field, and 13 patients experienced recurrence outside the irradiated field. 29 patients underwent TACE and only 2 patients underwent TAI. The mean number of previous PBT treatments was 1.3 ± 0.6 (range: 1–4). The median interval from the earliest PBT treatment to hepatic angiography was 559 days (range: 34–5,383 days), and the median interval from the latest PBT treatment to hepatic angiography was 464 days (range: 34–5,383 days). Abnormal staining of the irradiated liver parenchyma was observed in 22 patients, which obscured the angiographic tumor staining in 4 patients. Development of a tortuous tumor feeder vessel was observed in 13 patients. Development of an extrahepatic collateral pathway was observed in 7 patients. Development of an arterioportal or arteriovenous shunt was observed in 4 patients. Based on these findings, we conclude that PBT was associated with various angiographic findings during subsequent transarterial chemotherapy for recurrent HCC, and familiarity with these findings will be important in developing appropriate treatment plans.