Bradykinin postconditioning protects rat hippocampal neurons after restoration of spontaneous circulation following cardiac arrest via activation of the AMPK/mTOR signaling pathway

Bradykinin(BK)is an active component of the kallikrein-kinin system that has been shown to have cardioprotective and neuroprotective effects.We previously showed that BK postconditioning strongly protects rat hippocampal neurons upon restoration of spontaneous circulation(ROSC)after cardiac arrest.However,the precise mechanism underlying this process remains poorly understood.In this study,we treated a rat model of ROSC after cardiac arrest(induced by asphyxiation)with 150μg/kg BK via intraperitoneal injection 48 hours after ROSC following cardiac arrest.We found that BK postconditioning effectively promoted the recovery of rat neurological function after ROSC following cardiac arrest,increased the amount of autophagosomes in the hippocampal tissue,inhibited neuronal cell apoptosis,up-regulated the expression of autophagy-related proteins LC3 and NBR1 and down-regulated p62,inhibited the expression of the brain injury marker S100βand apoptosis-related protein caspase-3,and affected the expression of adenosine monophosphate-activated protein kinase/mechanistic target of rapamycin pathway-related proteins.Adenosine monophosphate-activated protein kinase inhibitor compound C clearly inhibited BK-mediated activation of autophagy in rats after ROSC following cardiac arrest,which aggravated the injury caused by ROSC.The mechanistic target of rapamycin inhibitor rapamycin enhanced the protective effects of BK by stimulating autophagy.Our findings suggest that BK postconditioning protects against injury caused by ROSC through activating the adenosine monophosphate-activated protein kinase/mechanistic target of the rapamycin pathway.

Glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor regulate the interaction between astrocytes and Schwann cells at the trigeminal root entry zone

The trigeminal root entry zone is the zone at which the myelination switches from peripheral Schwann cells to central oligodendrocytes.Its special anatomical and physiological structure renders it susceptible to nerve injury.The etiology of most primary trigeminal neuralgia is closely related to microvascular compression of the trigeminal root entry zone.This study aimed to develop an efficient in vitro model mimicking the glial environment of trigeminal root entry zone as a tool to investigate the effects of glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor on the structural and functional integrity of trigeminal root entry zone and modulation of cellular interactions.Primary astrocytes and Schwann cells isolated from trigeminal root entry zone of postnatal rats were inoculated into a two-well silicon culture insert to mimic the trigeminal root entry zone microenvironment and treated with glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor.In monoculture,glial cell line-derived neurotrophic factor promoted the migration of Schwann cells,but it did not have effects on the migration of astrocytes.In the co-culture system,glial cell line-derived neurotrophic factor promoted the bidirectional migration of astrocytes and Schwann cells.Brain-derived neurotrophic factor markedly promoted the activation and migration of astrocytes.However,in the co-culture system,brain-derived neurotrophic factor inhibited the migration of astrocytes and Schwann cells to a certain degree.These findings suggest that glial cell line-derived neurotrophic factor and brain-derived neurotrophic factor are involved in the regulation of the astrocyte-Schwann cell interaction in the co-culture system derived from the trigeminal root entry zone.This system can be used as a cell model to study the mechanism of glial dysregulation associated with trigeminal nerve injury and possible therapeutic interventions.

Anatomy of the perirectal fascia at the level of rectosacral fascia revisited

Background:The relative anatomical understanding of the perirectal fasciae is of paramount importance for the proper performance of total mesorectal excision(TME).This study was to demonstrate the planes of TME and validates the intraoperative findings using cadaveric observations.Methods:In this combined retrospective and prospective study,bilateral attachment of the rectosacral fascia(RSF)was observed in 28 cadaveric specimens(male,n=14;female,n=14).From January 2018 to December 2019,surgical videos of 67 patients who underwent laparoscopic TME at the Affiliated Union Hospital of Fujian Medical University(Fuzhou,China)were reviewed and interpreted with the cadaveric findings.Results:The RSF(synonym:Waldeyer’s fascia)is the end of the pre-hypogastric fascia at the level of S4 and comprises two layers(upper and lower).These two layers provide double fascial protection for the venous sacral plexus.It inserts into the fascia propria of the rectum along a broad horizontal arc that merges anterolaterally in an oblique downward direction until it meets the posterolateral merge of Denonvilliers’fascia at the lateral rectal ligament(LRL).This ligament does not look like a true ligament but is more likely to be a fascial combination that cushions the rectal innervation and middle rectal vessels.Conclusions:Understanding the lateral attachment of RSF and its contribution to LRL provides invaluable surgical guidance to dissect this critical area.Therefore,lateral dissection is proposed from the anterior to the posterior direction to find the correct plane that guarantees an intact mesorectal envelope to protect the important nearby nerve structures.

The“terminal line”:a novel sign for the identification of distal mesorectum end during TME for rectal cancer

Background:Although the clinical importance of complete,intact total mesorectal excision(TME)is the widely accepted standard for decreasing local recurrence of rectal cancer,the residual mesorectum still represents a significant component of resection margin involvement.This study aimed to use a visible intraoperative sign to detect the distal mesorectal end to ensure complete inclusion of the mesorectum and avoid unnecessary over-dissection.Methods:The distal mesorectum end was investigated retrospectively through a review of 124 operative videos at the Union Hospital of Fujian Medical University(Fujian,China)and Cleveland Clinic(Ohio,USA)by two independent surgeons who were blinded to each other.Furthermore,28 cadavers and 44 post-operative specimens were prospectively examined by hematoxylin and eosin(H&E)staining and Masson’s staining to validate and confirm the findings of the retrospective part.Univariate and multivariate analyses were carried out to detect the independent factors that can affect the visualization of the distal mesorectal end.Results:The terminal line(TL)is the distal mesorectal end of the transabdominal and transanal TME(taTME)and appears as a remarkable pearly white fascial structure extending posteriorly from 2 to 10 o’clock.Histopathological examination revealed that the fascia propria of the rectum merges with the presacral fascia at the TL,beyond which the mesorectum ends,with no further downward extension.In the retrospective observation,the TL was seen in 56.6%of transabdominal TME and 56.0%of taTME operations.Surgical approach and tumor distance from the anal verge were the independent variables that directly influenced the detection of the TL(P=0.03 and P=0.01).Conclusion: The TL is a visible sign where the transabdominal TME should end and the taTME should begin. Recognitionof the mesorectal end may impact the certainty of complete mesorectum inclusion. Further clinical trials are needed toconfirm the preliminary findings.

MMP-9 deficiency accelerates the progress of periodontitis

Periodontitis is a chronic inflammatory disease caused by periodontopathic bacteria that affects periodontal support tissues.1 If left untreated,it results in loss of periodontal attachment and alveolar bone resorption.Approximately one-half of adults in the United States older than 30 years have periodontal disease.2 Though the disease is initiated by bacterial infection,it activates host defense systems that eventually lead to the degradation of the periodontium.During periodontitis,the disease progress involves further production of pro-inflammatory mediators such as cytokines,proteolytic enzymes like matrix metalloproteinases(MMPs),and their inhibitors.