The Anatomy of the Frontalis Muscle Revisited: A Detailed Anatomic, Clinical, and Physiologic Study.

BACKGROUND: There are differing opinions with regard to the specific mechanical forces related to contraction of the frontalis muscle and how it exerts its effects on eyebrow motion. OBJECTIVES: To perform a detailed anatomic and clinical study of the frontalis muscle in cadavers and patients to better define the movement of the frontalis muscle. METHODS: This study consisted of four arms that included: 1) dynamic ecography to evaluate movement of the frontalis muscle, 2) anatomical study of the relationship between the frontalis muscle and the deep fascia, 3) histological study to define the frontalis muscle attachments and 4) clinical study to evaluate the action of the frontalis muscle in patients undergoing a temporal face lift. RESULTS: The frontalis muscle was attached, inserted, and adhered to the deep layer of the fascia in the superior cephalic and middle third of the forehead. In the superior cephalic third of the forehead, loose areolar tissue was observed deep to the frontalis muscle and the deep layer of the fascia. Within the middle third of the forehead, the deep layer of the galea was fused with the periosteum and firmly adhered. In the inferior caudal third of the forehead, the frontalis muscle was separated from the deep galeal aponeurosis and interdigitated with the orbicularis muscle. When the frontal muscle end was dissected free from the deep fascia by approximately 1 cm and pulled upward, no movement of the eyebrows was observed. Eyebrow elevation was only achieved by pulling on the inferior part of the muscle. CONCLUSIONS: Frontalis muscle movement occurs from the inferior caudal end towards the mid part of the muscle as it contracts centripetally on its superficial layer sliding over the deep part strongly attached to the deep fascia.

Relación entre las ciencias básicas y clínicas en la modulación central del dolor / Relationship between basic and clinical sciences in central pain modulation

Esta revisión busca proporcionar a los profesionales de la salud una mayor comprensión del dolor para su actividad clínica-asistencial. Basados en la hipóte-sis de neuroplasticidad presentada inicialmente por Ramón y Cajal y la teoría de la compuerta en la vía dolorosa presentada por Melzack y Wall, se ha ela-borado una revisión bibliográfica con el objetivo de abordar la modulación de la vía nociceptiva desde un punto de vista fisiopatológico. Asimismo, se presen-tan los principales resultados obtenidos durante los últimos años en nuestro laboratorio usando ratas Wistar hembras como modelo de dolor experimental. Finalmente, se describe un circuito original de modu-lación central a nivel del subnúcleo caudal del trigé-mino con una visión integral de los componentes del sistema nociceptivo orofacial, para ayudar al clínico a comprender situaciones de sensibilización central con perpetuación del dolor y cómo paulatinamente el sistema nervioso central pone en marcha un sistema de modulación para adaptarse y alcanzar un estado similar al basal (AU)

This review aims to provide health professionals with a better understanding of pain for their clinical-care activity. Based on the neuroplasticity hypothesis initially presented by Ramón and Cajal, and the gate theory in the pain pathway presented by Melzack and Wall, a literature review has been carried out with the aim of addressing the modulation of the nociceptive pathway from a pathophysiological point of view. The main results obtained in recent years in our laboratory using female Wistar rats as an experimental pain model are also presented. Finally, an original central modulation circuit at the level of the caudal trigeminal subnucleus is described with a comprehensive view of the components of the orofacial nociceptive system, to help the clinician to understand situations of central sensitization with perpetuation of pain and how the central nervous system gradually sets in motion a modulation system to adapt and reach a state similar to the basal one (AU)

Internal hernia after laparoscopic left colectomy: case series and review of the literature

Objective: Laparoscopic colectomy has gained acceptance as a standard treatment for benign and malignant colorectal disease, such as diverticular disease and cancer, among others. Same as in open surgery, the laparoscopic approach carries a low risk of small bowel obstruction in the postoperative period, but in laparoscopic surgery, internal hernia after laparoscopic left colectomy may be a cause of small bowel obstruction with a significant risk of morbidity and mortality. This rare complication may be prevented with routine closure of the mesenteric defects created during the colectomy. Methods: We present four cases of internal herniation after laparoscopic colectomy. Two cases were after laparoscopic left colectomy and two after laparoscopic low anterior resection. All four cases had full splenic flexure mobilization. Routine closure of the mesenteric defect was not performed in the initial surgery. Results: The four patients were treated by laparoscopic reintervention with closure of the mesenteric defect. In two of them, conversion to open surgery was necessary. One of the patients developed recurrent internal herniation after surgical reintervention with mesenteric closure of the defect. All patients were managed without need for bowel resection, and mortality rate was 0%. Conclusion Internal herniation after laparoscopic colorectal surgery is a highly morbid complication that requires prompt diagnosis and management and should be suspected in the early postoperative period. Additional studies with extended follow-up are required to establish recommendations regarding its prevention and management. (AU)

Double barreled wet colostomy. Case report and description of the surgical technique / Colostomia úmida em dupla-boca. Relato de caso e descrição da técnicacirúrgica

ABSTRACT Pelvic exenteration has showed to be beneficial therapeutically and palliatively in locally advanced colorectal cancer. Reconstruction of urinary transit posterior to a cystectomy has always been challenging with many associated complications. We present a 58-year-old male with locally advanced rectal cancer in which a pelvic exenteration and a double-barreled wet colostomy (DBWC) was created for urinary reconstitution. We present the surgical technique of DBWC. DBWC is a good alternative to other urinary reconstructions because fecal and urinary derivation occurs in only one stoma, the stoma output is easier to manage, and fewer complications are seen compared to other urinary reconstructions. Long-term surveillance is mandatory in patients with a DBWC because there is an increased risk of neoplasm in the reservoir.

RESUMO A exenteração pélvica mostrou-se benéfica, tanto terapêutica quanto paliativamente, em casos de câncer colorretal localmente avançado. A reconstrução do trânsito urinário após uma cistectomia sempre foi desafiadora, com muitas complicações associadas. Os autores apresentam o caso de um homem de 58 anos de idade com câncer retal localmente avançado, submetido a uma exenteração pélvica e uma colostomia úmida em dupla-boca (CUDB) para reconstituição urinária. Os autores apresentam a técnica cirúrgica da CUDB, uma boa alternativa para outras reconstruções urinárias, já que a derivação fecal e urinária ocorre em apenas um estoma, a saída do estoma é mais fácil de gerenciar e o método apresenta menos complicações em comparação com outras reconstruções urinárias. A vigilância a longo prazo é obrigatória em pacientes com CUDB, pois há um risco aumentado de neoplasia no reservatório.

Assessment of quality-of-care indicators for colorectal cancer surgery at a single centre in a developing country.

BACKGROUND: The implementation of quality-of-care indicators aiming to improve colorectal cancer (CRC) outcomes has been previously described by Cancer Care Ontario. The aim of this study was to assess the quality-of-care indicators in CRC at a referral centre in a developing country and to determine whether improvement occurred over time. METHODS: We performed a retrospective study of our prospectively collected database of patients after CRC surgery from 2001 to 2016. We excluded patients who underwent local transanal excision, pelvic exenteration or palliative procedures. We evaluated trends over time using the Cochran-Armitage test for trend. RESULTS: A total of 343 patients underwent surgical resection of CRC over the study period. There was improvement of the following indicators over time: the proportion of patients detected by screening (p = 0.03), the proportion of patients with preoperative liver imaging (p = 0.001), the proportion of patients with stage II or III rectal cancer who received neoadjuvant chemotherapy (p = 0.03), the proportion of patients with pathology reports that indicated the number of lymph nodes examined and the number of positive nodes (p = 0.001), and the proportion of patients with pathology reports describing the details on margin status (p = 0.001). CONCLUSION: This study showed the feasibility of applying the Cancer Care Ontario indicators for evaluating outcomes in CRC treatment at a single centre in a developing country. Although there was an improvement of some of the quality-of-care indicators over time, policies and interventions must be implemented to improve the fulfillment of all indicators.

CONTEXTE: Action Cancer Ontario a déjà décrit l'application d'indicateurs de la qualité des soins dans le but d'améliorer l'issue du cancer colorectal (CCR). Le but de cette étude était d'évaluer les indicateurs de la qualité de soins pour le CCR dans un centre de référence d'un pays en voie de développement et de déterminer si des améliorations ont pu être observées avec le temps. MÉTHODES: Nous avons procédé à une étude rétrospective de notre base de données recueillies prospectivement auprès de patients ayant subi une chirurgie pour CCR entre 2001 et 2016. Nous avons exclu les patients qui ont subi une exérèse transanale locale, une exentération pelvienne ou des traitements palliatifs. Nous avons évalué les tendances au fil du temps à l'aide du test Cochran­Armitage pour dégager les tendances. RÉSULTATS: En tout, 343 patients ont subi une résection chirurgicale de CCR au cours de la période de l'étude. On a noté une amélioration des indicateurs suivants au fil du temps : proportion de patients ayant subi un dépistage (p = 0,03), proportion de patients ayant subi des épreuves d'imagerie hépatique préopératoires (p = 0,001), proportion de patients atteints d'un cancer rectal de stade II ou III ayant reçu une chimiothérapie néoadjuvante (p = 0,03), proportion de patients dont les rapports d'anatomopathologie indiquaient le nombre de ganglions lymphatiques examinés et le nombre de ganglions positifs (p = 0,001) et proportion de patients dont les rapports d'anatomopathologie décrivaient le statut des marges (p = 0,001). CONCLUSION: Cette étude a démontré l'applicabilité des indicateurs d'Action Cancer Ontario pour évaluer les résultats du traitement pour CCR dans un seul centre d'un pays en voie de développement. Même si certains des indicateurs de la qualité des soins se sont améliorés au fil du temps, il faut appliquer des politiques et des interventions pour améliorer tous les indicateurs.

The role of PDLIM1, a PDZ-LIM domain protein, at the ribbon synapses in the chicken retina.

PDLIM's protein family is involved in the rearrangement of the actin cytoskeleton. In the present study, we describe the localization of PDLIM1 in chicken photoreceptors. This study provides evidence that this protein is present at the cone pedicles, as well as in other synapses of the chicken retina. Here, we demonstrate the expression pattern of PDLIM1 through immunofluorescence staining, immunoblots, subcellular fractionation, and immunoprecipitation experiments. Also, we consider the possibility that PDLIM1 may be involved in the synaptic vesicle endocytosis and/or the presynaptic trafficking of synaptic vesicles back to the nonready releasable pool. This endocytotic/exocytotic coupling requires a tight link between exocytic vesicle fusion at defined release sites and endocytic retrieval of synaptic vesicle membranes. In turn, photoreceptor ribbon synaptic structure depends on the cytoskeleton arrangement, both at the active zone-related with exocytosis-as well as at the endocytic zone-periactive zone. To our knowledge, the PDLIM1 protein has not been observed in the pre synapses of the retina. Thus, the present study describes the expression and subcellular localization of PDLIM1 for the first time, as well as its modulation by visual environment in the chicken retina.

Effect of periapical inflammation on calcium binding proteins and ERK in the trigeminal nucleus.

Peripheral inflammation induces plastic changes in neurons and glia which are regulated by free calcium and calcium binding proteins (CaBP). One of the mechanisms associated with the regulation of intracellular calcium is linked to ERK (Extracellular Signal-Regulated Kinase) and its phosphorylated condition (pERK). ERK phosphorylation is important for intracellular signal transduction and participates in regulating neuroplasticity and inflammatory responses. The aim of this study is to analyse the expression of two CaBPs and pERK in astrocytes and neurons in rat trigeminal subnucleus caudalis (Vc) after experimental periapical inflammation on the left mandibular first molar. At seven days post-treatment, the periapical inflammatory stimulus induces an increase in pERK expression both in S100b positive astrocytes and Calbindin D28k positive neurons, in the ipsilateral Vc with respect to the contralateral side and control group. pERK was observed coexpressing with S100b in astrocytes and in fusiform Calbindin D28k neurons in lamina I. These results could indicate that neural plasticity and pain sensitization could be maintained by ERK activation in projection neurons at 7 days after the periapical inflammation.

La inflamación periférica induce cambios plásticos en las neuronas y en la glía, los cuales están regulados por el calcio libre y las proteínas fijadoras calcio (CaBP). Uno de los mecanismos asociados con la regulación del calcio intrace-lular está vinculado con la fosforilación de la pro teína quinasa ERK. Asimismo, ERK fosforilado es importante para la trans-ducción de señales intracelulares y participa en la regulación de la neuroplasticidad y las respuestas inflamatorias. El objetivo de este estudio es analizar la expresión de dos CaBPs y pERK en astrocitos y neuronas del subnúcleo caudal del trigémino (Vc) después de una inflamación periapical experimental en el primer molar inferior izquierdo en ratas. A los siete días posteriores al tratamiento, el estímulo inflamatorio periapical induce un aumento en la expresión de pERK, en el número de astrocitos positivos para la proteína marcadora astroglial S100b y en neuronas positivas para Calbindina D28k, en el Vc ipsilateral respecto del lado contralateral y el grupo de control. Además, se observó coexpresión de pERK tanto en astrocitos S100b positivos, como en neuronas fusiformes Calbindin D28k positivas, de la lámina I. Estas observaciones podrían indicar que la neuroplasticidad y la sensibilización al dolor podrían mantenerse mediante la activación de ERK en las neuronas de proyección a los 7 días de la inflamación periapical.

Effect of periapical inflammation on calcium binding proteins and ERK in the trigeminal nucleus / Efecto de la inflamación periapical sobre las proteínas fijadoras de calcio y ERK en el núcleo trigeminal

Peripheral inflammation induces plastic changes in neurons and glia which are regulated by free calcium and calcium binding proteins (CaBP). One of the mechanisms associated with the regulation of intracellular calcium is linked to ERK (Extracellular Signal-Regulated Kinase) and its phosphorylated condition (pERK). ERK phosphorylation is important for intracellular signal transduction and participates in regulating neuroplasticity and inflammatory responses. The aim of this study is to analyse the expression of two CaBPs and pERK in astrocytes and neurons in rat trigeminal subnucleus caudalis (Vc) after experimental periapical inflammation on the left mandibular first molar. At seven days post-treatment, the periapical inflammatory stimulus induces an increase in pERK expression both in S100b positive astrocytes and Calbindin D28k positive neurons, in the ipsilateral Vc with respect to the contralateral side and control group. pERK was observed coexpressing with S100b in astrocytes and in fusiform Calbindin D28k neurons in lamina I. These results could indicate that neural plasticity and pain sensitization could be maintained by ERK activation in projection neurons at 7 days after the periapical inflammation.

La inflamación periférica induce cambios plásticos en las neuronas y en la glía, los cuales están regulados por el calcio libre y las proteínas fijadoras calcio (CaBP). Uno de los mecanismos asociados con la regulación del calcio intrace-lular está vinculado con la fosforilación de la pro teína quinasa ERK. Asimismo, ERK fosforilado es importante para la trans-ducción de señales intracelulares y participa en la regulación de la neuroplasticidad y las respuestas inflamatorias. El objetivo de este estudio es analizar la expresión de dos CaBPs y pERK en astrocitos y neuronas del subnúcleo caudal del trigémino (Vc) después de una inflamación periapical experimental en el primer molar inferior izquierdo en ratas. A los siete días posteriores al tratamiento, el estímulo inflamatorio periapical induce un aumento en la expresión de pERK, en el número de astrocitos positivos para la proteína marcadora astroglial S100b y en neuronas positivas para Calbindina D28k, en el Vc ipsilateral respecto del lado contralateral y el grupo de control. Además, se observó coexpresión de pERK tanto en astrocitos S100b positivos, como en neuronas fusiformes Calbindin D28k positivas, de la lámina I. Estas observaciones podrían indicar que la neuroplasticidad y la sensibilización al dolor podrían mantenerse mediante la activación de ERK en las neuronas de proyección a los 7 días de la inflamación periapical.

Influence of Visceral Fat in the Outcomes of Colorectal Cancer.

AIM: To determine the relationship of visceral fat (VF) with the surgical outcome of the patients with colorectal cancer (CRC) submitted to curative surgery. METHODS: Retrospective analysis of all patients submitted to CRC surgery during 3 years with a minimum of 5 years of follow-up. We assessed the length of hospital stay, complications, pathologic reports, surgical re-interventions and hospital re-admissions, relapses, survival time and disease-free time. VF was calculated based on patients' pre-operative CT-scan. The patients were divided into quartiles according to the VF area. Linear regression models and logistic regression models were used to establish a relationship between VF and all data collected. RESULTS: The study included 199 patients (129 with colon cancer [CC] and 70 with rectal cancer). The average area of VF was 115.7 cm2. Patients with CRC revealed a direct relationship between VF and postoperative complications (p = 0.043), anastomotic leakage (p = 0.009) and re-operation (p = 0.005). The subgroup of patients with CC had an inverse association between VF and lymph nodes harvested (p = 0.027). Survival analyses did not reveal significant differences. CONCLUSION: VF has an influence on postoperative complications, anastomotic leakage and re-operation. A negative influence of VF on lymph nodes harvested was observed on CC patients.

Oncological Implications of Lymph Nodes Retrieval and Perineural Invasion in Colorectal Cancer: Outcomes from a Referral Center.

BACKGROUND: In colorectal cancer (CRC), regional lymphadenectomy provides prognostic information and guides management. The current consensus states that at least 12 lymph nodes (LN) should be evaluated. The aims of this study were to identify whether the number of LN is a predictor for survival and recurrence, and to reveal the role of LN ratio (LNR) and perineural invasion (PNI) in predicting prognosis after curative resection of CRC. METHODS: We included all patients who underwent surgery for CRC between 2000 and 2016 in an academic medical center in Mexico. The LNR cutoff value was 0.25. We analyzed two groups according to the number of LN retrieved: Group 1 (≥ 12 LN) and Group 2 (< 12 LN). RESULTS: We included 305 patients, 13.8% in Stage I, 45.6% in Stage II, and 40.6% in Stage III. The male: female ratio was 1.1. The mean age was 62.6 ± 14 years (range, 19-92). In 233 patients (76.4%), ≥ 12 LN were obtained. Recurrence rates in Groups 1 and 2 were 20.2% versus 26.4%, respectively (p = 0.16). PNI was present in 34 patients (13.2%). An LN harvest < 10 increased local and distant recurrences (p = 0.03). Stage III patients with an LNR ≥ 0.25 had higher overall recurrence rates (p = 0.012) and mortality (p = 0.029). In a multivariate Cox regression analysis, PNI-negative tumors were an independent prognostic factor for disease-free survival (p = 0.011, hazard ratio = 2.78, 95% confidence interval = 1.26-6.16). CONCLUSIONS: An LN retrieval < 10 increased local and distant recurrence rates. LNR was an independent prognostic factor for survival in Stage III tumors. PNI was the only significant independent prognostic factor affecting disease-free survival in our patients.

Mucinous Carcinomatosis: A Rare Association between an Ovarian Tumor and an E-GIST.

Pseudomyxoma peritonei (PMP) and extragastrointestinal stromal tumors (E-GISTs) are both rare entities. Most of the time, PMP is associated with an appendiceal tumor. An ovarian mucinous tumor can mimic appendiceal metastases. E-GIST is a mesenchymal tumor that can arise from the omentum, retroperitoneum, mesentery, or pleura. We present a case of an 87-year-old woman with mucinous carcinomatosis and acute intestinal occlusion submitted to an emergency laparotomy. She has found to have a borderline mucinous tumor of the ovary from the intestinal type with several lesions of pseudomyxoma peritonei and an E-GIST from the epiploons retrocavity (intermediated risk). In the literature, no relation was found between these two rare tumors. E-GIST was an incidental finding in the context of a mucinous carcinomatosis.

Abdominal Catastrophe in Crohn's Disease Surgery.

INTRODUCTION: Performing surgery on patients with Crohn's disease is a true challenge due to the elevated risk of complications related to the chronic proinflammatory response. Stenosis is the leading cause of intestinal resection in these patients. CASE REPORT: The authors present the case of a 50-year-old woman with inflammatory stenosis of the terminal ileum due to Crohn's disease. The patient underwent a laparoscopic ileocecal resection, which was complicated by a small anastomotic dehiscence with localized peritonitis. Several perforations and dehiscences were observed and necessitated an end ileostomy and an open abdomen treated with negative pressure wound therapy. Multiple surgical interventions in the abdomen were performed and negative pressure was maintained until all fistulas were sealed and granulation tissue formed. Patient was discharged after 134 days of hospitalization with both the abdomen and the ileostomy closed. After several months, a hernia repair was performed with bilateral component separation and polypropylene mesh without complications. CONCLUSIONS: Anastomotic dehiscence after intestinal resection can lead to an abdominal catastrophe. Severe peritonitis with enteric fistulas and an open abdomen demands a multidisciplinary approach. Negative pressure wound therapy and nutritional support are key treatments. In these patients, stoma closure and abdominal wall reconstruction after recovery from the acute event represents another surgical challenge.

Enterocutaneous fistula: a novel video-assisted approach.

Video-assisted anal fistula treatment (VAAFT) is a novel minimally invasive and sphincter-saving technique to treat complex anal fistulas described by Meinero in 2006. An enterocutaneous fistula is an abnormal communication between the bowel and the skin. Most cases are secondary to surgical complications, and managing this condition is a true challenge for surgeons. Postoperative fistulas account for 75-85% of all enterocutaneous fistulas. The aim of paper was to devise a minimally invasive technique to treat enterocutaneous fistulas. We used the same principles of VAAFT applied to other conditions, combining endoluminal vision of the tract with colonoscopy to identify the internal opening. We present a case of a 78-year-old woman who was subjected to a total colectomy for cecum and sigmoid synchronous adenocarcinoma. The postoperative course was complicated with an enterocutaneous fistula, treated with conservative measures, which recurred during follow-up. We performed video-assisted fistula treatment using a fistuloscope combined with a colonoscope. Once we identified the fistula tract, we performed cleansing and destruction of the tract, applied synthetic cyanoacrylate and sealed the internal opening with clips through an endoluminal approach. The patient was discharged 5 days later without complications. Two months later the wound was completely healed without evidence of recurrence. This procedure represents an alternative treatment for enterocutaneous fistula using a minimally invasive technique, especially in selected patients not able to undergo major surgery.

Day and night surgery: is there any influence in the patient postoperative period of urgent colorectal intervention?

BACKGROUND: Medical activity performed outside regular work hours may increase risk for patients and professionals. There is few data with respect to urgent colorectal surgery. The aim of this work was to evaluate the impact of daytime versus nighttime surgery on postoperative period of patients with acute colorectal disease. METHODS: A retrospective study was conducted in a sample of patients with acute colorectal disease who underwent urgent surgery at the General Surgery Unit of Braga Hospital, between January 2005 and March 2013. Patients were stratified by operative time of day into a daytime group (surgery between 8:00 and 20:59) and the nighttime group (21:00-7:59) and compared for clinical and surgical parameters. A questionnaire was distributed to surgeons, covering aspects related to the practice of urgent colorectal surgery and fatigue. RESULTS: A total of 330 patients were included, with 214 (64.8%) in the daytime group and 116 (35.2%) in the nighttime group. Colorectal cancer was the most frequent pathology. Waiting time (p < 0.001) and total length of hospital stay (p = 0.008) were significantly longer in the daytime group. There were no significant differences with respect to early or late complications. However, 100% of surgeons reported that they are less proficient during nighttime. CONCLUSIONS: Among patients with acute colorectal disease subjected to urgent surgery, there was no significant association between nighttime surgery and the presence of postoperative medical and surgical morbidities. Patients who were subjected to daytime surgery had longer length of stay at the hospital.

Calbindin-D28k and calretinin in chicken inner retina during postnatal development and neuroplasticity by dim red light.

Members of the family of calcium binding proteins (CBPs) are involved in the buffering of calcium (Ca2+) by regulating how Ca2+ can operate within synapses or more globally in the entire cytoplasm and they are present in a particular arrangement in all types of retinal neurons. Calbindin D28k and calretinin belong to the family of CBPs and they are mainly co-expressed with other CBPs. Calbindin D28k is expressed in doubles cones, bipolar cells and in a subpopulation of amacrine and ganglion neurons. Calretinin is present in horizontal cells as well as in a subpopulation of amacrine and ganglion neurons. Both proteins fill the soma at the inner nuclear layer and the neuronal projections at the inner plexiform layer. Moreover, calbindin D28k and calretinin have been associated with neuronal plasticity in the central nervous system. During pre and early postnatal visual development, the visual system shows high responsiveness to environmental influences. In this work we observed modifications in the pattern of stratification of calbindin immunoreactive neurons, as well as in the total amount of calbindin through the early postnatal development. In order to test whether or not calbindin is involved in retinal plasticity we analyzed phosphorylated p38 MAPK expression, which showed a decrease in p-p38 MAPK, concomitant to the observed decrease of calbindin D28k. Results showed in this study suggest that calbindin is a molecule related with neuroplasticity, and we suggest that calbindin D28k has significant roles in neuroplastic changes in the retina, when retinas are stimulated with different light conditions.

Nicotinamide adenine dinucleotide phosphate/neuronal nitric oxide synthase-positive neurons in the trigeminal subnucleus caudalis involved in tooth pulp nociception.

Sensory information on facial structures, including teeth pulp, periodontium, and gingiva, is relayed in the trigeminal complex. Tooth pulp inflammation constitutes a common clinical problem, and this peripheral injury can induce neuroplastic changes in trigeminal nociceptive neurons. There is considerable evidence that the trigeminal subnucleus caudalis (Vc) is the principal relay for trigeminal nociceptive information as well as modulation of the painful stimuli. Glutamatergic primary afferents innervating the tooth pulp project to the most superficial laminae of the Vc. N-methyl-D-aspartate receptor stimulation leads to the activation of the enzyme nitric oxide synthase (NOS), which synthesizes the free radical nitric oxide (NO). This enzyme is expressed mainly in lamina II interneurons, and in a small number of cells in lamina I as well as in deep laminae projection neurons of Vc. In the present study, we analyzed the temporal changes in neuronal NOS (nNOS) in Vc local circuitries after unilateral intermediate molar pulp injury. Our results demonstrate that a peripheral dental pulp injury leads to neuroplastic changes in the relative amount and activity of nNOS enzyme. Moreover, after a period of time, the nitrergic system shifts to the initial values, independently of the persistence of inflammation in the pulp tissues.

Partial neuroprotection by 17-ß-estradiol in neonatal γ-irradiated rat cerebellum.

Acute and long-term complications can occur in patients receiving radiation therapy. It has been suggested that cytoprotection might decrease the incidence and severity of therapy-related toxicity in these patients. Developing cerebellum is highly radiosensitive and for that reason it is a useful structure to test potential neuroprotective substances to prevent radiation induced abnormalities. Recent studies have shown that estrogen can rapidly modulate intracellular signalling pathways involved in cell survival. Thus, it has been demonstrated that estrogens mediate neuroprotection by promoting growth, cell survival and by preventing axonal pruning. The aim of this work was to evaluate the effect of the treatment with 17-ß-estradiol on the motor, structural and biochemical changes induced by neonatal ionizing radiation exposure, and to investigate the participation of nitric oxide and protein kinase C, two important intracellular messengers involved in neuronal activity. Our results show that perinatal chronic 17-ß-estradiol treatment partially protects against radiation-induced cerebellar disorganization and motor abnormalities. PKC and NOS activities could be implicated in its neuroprotective mechanisms. These data provide new evidence about the mechanisms underlying estrogen neuroprotection, which could have therapeutic relevance for patients treated with radiotherapy.

Pulpar tooth injury induces plastic changes in S100B positive astroglial cells in the trigeminal subnucleus caudalis.

Pain in humans constitutes a complex perception that involves peripheral tissues, nerves and the central nervous system. The glia is thought to be involved in the propagation and modulation of painful stimuli, as well as for the neurotransmission and plastic changes. In this work, an intermediate inflammatory nociceptive stimulus was generated after the exposure of the pulp in the left mandibular first molar. We analyzed the relationship between this tooth injury and the S100B expression in the trigeminal subnucleus caudalis. A significant difference of S100B immunoreactivity between the ipsilateral and the contralateral side could be observed at the 4th postoperative day. Besides, S100B positive-astrocytes located in the ipsilateral side showed an increase in their arborization, but not in the level of expression of the S100B protein. Our findings suggest that a unilateral peripheral nociceptive stimulus produces modifications in S100B positive-astrocytes in both sides of the trigeminal subnucleus caudalis.

Intermittent hypoxia during sleep induces reactive gliosis and limited neuronal death in rats: implications for sleep apnea.

Sleep apnea (SA) can be effectively managed in humans but it is recognized that when left untreated, SA causes long-lasting changes in neuronal circuitry in the brain. Recent neuroimaging studies gave suggested that these neuronal changes are also present even in patients successfully treated for the acute effects of SA. The cellular mechanisms that account for these changes are not certain but animal models of intermittent hypoxia (IH) during sleep have shown neuronal death and impairment in learning and memory. Reactive gliosis has a drastic effect on neuronal survival and circuitry and in this study we examined the neuro-glial response in brain areas affected by SA. Glial and neuronal alterations were analyzed after 1, 3, 5 and 10 days of exposure to IH (8 h/day during the sleep phase, cycles of 6 min each, 10-21% O2) and observed significant astroglial hyperplasia and hypertrophy in parietal brain cortex and hippocampus by studying gliofibrillary acidic protein, Vimentin, S100B and proliferating cell nuclear antigen expression. In addition, altered morphology, reduced dendrite branching and caspase activation were observed in the CA-1 hippocampal and cortical (layers IV-V) pyramidal neurons at short exposure times (1-3 days). Surprisingly, longer exposure to IH reduced the neuronal death rate and increased neuronal branching in the presence of persistent reactive gliosis. Up-regulation of hypoxia inducible factor 1 alpha (HIF-1alpha) and mdr-1, a HIF-1alpha target gene, were observed and increased expression of receptor for advanced end glycated products and its binding partner S100B were also noted. Our results show that a low number of hypoxic cycles induce reactive gliosis and neuronal death whereas continuous exposure to IH cycles reduced the rate of neuronal death and induced neuronal branching on surviving neurons. We hypothesize that HIF-1alpha and S100B glial factor may improve neuronal survival under hypoxic conditions and propose that the death/survival/re-growth process observed here may underlie brain circuitry changes in humans with SA.

Long-lasting effects of neonatal ionizing radiation exposure on spatial memory and anxiety-like behavior.

Neonatal ionizing radiation exposure has been shown to induce a cerebellar cytoarchitecture disarrangement. Since cerebellar abnormalities have been linked to an impairment of behavioral functions, the aim of the present work was to investigate whether exposure of developing rats to ionizing radiations can produce behavioral deficits in the adult. Male Wistar rats were X-irradiated with 5Gy within 48h after birth and were tested in a radial maze and in an open field at 30 and 90 days post irradiation. Irradiated rats showed significative changes in spatial, exploratory, and procedural parameters in the radial maze, as well as a significative decrease in anxiety-like behavior, assessed in the open field. These results suggest that ionizing radiations can induce long-lasting spatial memory and anxiety-related changes. A relationship with radiation-induced cerebellar cytoarchitecture abnormalities supports the hypothesis that cerebellar integrity seems to be critical to achieve spatial performance and emotional behavior establishment.