Delayed Cerebral Ischemia After Subarachnoid Hemorrhage: Is There a Relevant Experimental Model? A Systematic Review of Preclinical Literature

Delayed cerebral ischemia (DCI) is one of the main prognosis factors for disability after aneurysmal subarachnoid hemorrhage (SAH). The lack of a consensual definition for DCI had limited investigation and care in human until 2010, when a multidisciplinary research expert group proposed to define DCI as the occurrence of cerebral infarction (identified on imaging or histology) associated with clinical deterioration. We performed a systematic review to assess whether preclinical models of SAH meet this definition, focusing on the combination of noninvasive imaging and neurological deficits. To this aim, we searched in PUBMED database and included all rodent SAH models that considered cerebral ischemia and/or neurological outcome and/or vasospasm. Seventy-eight publications were included. Eight different methods were performed to induce SAH, with blood injection in the cisterna magna being the most widely used (n = 39, 50%). Vasospasm was the most investigated SAH-related complication (n = 52, 67%) compared to cerebral ischemia (n = 30, 38%), which was never investigated with imaging. Neurological deficits were also explored (n = 19, 24%). This systematic review shows that no preclinical SAH model meets the 2010 clinical definition of DCI, highlighting the inconsistencies between preclinical and clinical standards. In order to enhance research and favor translation to humans, pertinent SAH animal models reproducing DCI are urgently needed.

Recruitment of Regulatory T Cells with rCCL17 Promotes M2 Microglia/Macrophage Polarization Through TGFβ/TGFβR/Smad2/3 Pathway in a Mouse Model of Intracerebral Hemorrhage

Background Intracerebral hemorrhage (ICH) is a devastating neurological disease with high mortality and morbidity. The microglia activation and peripheral inflammatory cells infiltration play an important role in the ICH prognosis. Previous studies have demonstrated that regulatory T cells (Tregs) ameliorated neuroinflammation following experimental ICH. However, the specific molecular mechanism underlying such effects of Tregs remains unclear. In the present study, our aims were to examine the effect of Tregs recruitment induced by recombinant CC chemokine ligand 17(rCCL17) in an intrastriatal autologous blood mouse model of ICH and to determine whether the TGF-β/TGF-βR/Smad2/3 pathway was involved in Tregs promoted M2 microglia/macrophage polarization. Methods A total of 404 adult CD1 mice (male, eight-week-old) were subject to sham surgery or autologous blood injection of ICH. A CD25-specific mouse antibody or isotype control mAb was injected intraperitoneally 48h prior to ICH induction to deplete Tregs. Recombinant CCL17 (rCCL17), a C-C chemokine receptor 4 (CCR4), was delivered intranasally at 1 h post-ICH. SB431542, a specific inhibitor of TGF-β was administered intraperitoneally 1 h before ICH induction. Post-ICH assessments included neuro-behavior evaluation, brain edema, hematoma volume, hemoglobin content, western blotting, double immunofluorescence staining and immunohistochemistry. Results Endogenous brain expressions of CCL17 and Tregs marker Foxp3 as well as the number of Tregs in the perihematomal region were increased following ICH. The Tregs deletion by a CD25 antibody aggravated short-term neurological deficits and brain edema, increased the level of inflammatory cytokines and peripheral inflammatory cells infiltration, exacerbated hematoma expansion and increased M1phenotypes of microglia/macrophage in ICH mice. The rCCL17 treatment increased the number of Tregs in the brain, reduced hematoma expansion and brain edema, promoted microglia/macrophage polarization toward M2 phenotypes. Moreover, the expressions of brain TGF-β/phosphorylated-Smad2/3 were increased. The neuroprotective effects of rCCL17 were abolished by co-administration of the selective TGF-β inhibitor SB431542. Conclusions Our study demonstrated rCCL17 recruited of Tregs to brain in the autologous blood injection model of ICH. Tregs promoted microglia/macrophages polarization toward M2 phenotype and alleviation early brain injury, at least in part, through the TGFβ/TGFβR/Smad2/3 signaling pathway in ICH mice. Thus, rCCL17-mediated Tregs recruitment may provide a promising therapeutic strategy to reduce early brain injury after ICH.

Early Results of a Novel Treatment Technique with Autologous Blood for Chronic Lateral Epicondylitis

Background: Chronic lateral epicondylitis can be a severe disabling condition. There is still lack of consensus on best treatment, as no single intervention has been proven to be superior regarding pain relief and improvement of function. Due to the self-limiting nature of this elbow condition, we are looking for a fast and safe treatment method to break through this pattern of pain and loss of elbow function. Autologous blood injection therapy by means of an automatic injection system, can be a promising new treatment option for this group of patients suffering from chronic lateral epicondylitis. In this study, we evaluated the short-term results of autologous blood injection therapy in a standardized way by using an automatic injection system (=ITEC device) for the treatment of chronic lateral epicondylitis. Methods: A total of 141 patients with chronic lateral epicondylitis (88 female, 53 male) were enrolled in this clinical treatment evaluation being treated with the ITEC device. The mean age of the patients was 50.0 years (19 years-73 years). Numeric rating scale (NRS) and a patient reported outcome measurement tool (Oxford Elbow Score (OES)) were measured at baseline, six weeks and three months follow-up. Results: Pain (NRS, OES) and elbow function / quality of life (OES) were significantly improved within 6 weeks after ITEC treatment. This improvement in NRS and OES sustained during the 3 months follow-up period. Conclusion: Autologous blood injection therapy by means of a new automatic injection system (ITEC device) is a safe and effective treatment method for patients with chronic lateral epicondylitis. More research is necessary to see if this effectiveness sustains in the long-term follow-up.

Señales de amenaza y sesgo atencional en lafobia a la sangre, inyecciones y heridasy en la fobia a las serpientes

El objetivo de esta investigación fue estudiar el efecto de una señal que indica la aparición de una imagen fóbica sobre la actividad electrocortical provocada por el estímulo relevante para el trastorno en la fobia a la sangre por lesión en inyección (BII) y la fobia a las serpientes. Una muestra de 13 participantes con fobia BII, 12 individuos con fobia a las serpientes y 14 controles no fóbicos se sometieron a una tarea S1-S2, donde S1 era una palabra que describía el contenido de una imagen posterior (relacionada con la sangre, serpiente y neutral) que apareció 2 segundos después (S2). Obtuvimos las amplitudes ERP P200 y P300 provocadas por las imágenes. Nuestros resultados revelan que P200 no diferenciaba entre el contenido de las imágenes en la fobia BII mientras que, por el contrario, las imágenes relacionadas con la serpiente y la sangre provocaron las respuestas más grandes en los participantes con fobia a las serpientes. Tanto las imágenes relacionadas con la sangre como las de serpientes provocaron amplitudes de P300 mayores que las imágenes neutrales en todos los grupos. Las señales de amenaza redujeron la reacción electrocortical del BII, posiblemente por la provocación de respuestas anticipatorias o reguladoras. Estos resultados son indicativos de una baja atención automática exógena hacia los estímulos temidos en la fobia BII, como lo revela P200, probablemente relacionado con una falta de sesgo de atención al objeto fóbico. The aim of this research was to study the effect of a cue signalling the upcoming of a phobic picture on the electrocortical activity provoked by the disorder-relevant stimulus in in blood-injection-injury (BII) phobia and snake phobia. A sample of 13 BII phobia participants, 12 snake phobia individuals and 14 non-phobic controls underwent an S1-S2 task, where S1 was a word that described the content of a subsequent picture (blood-related, snake and neutral) that appeared 2 seconds later (S2). We obtained the P200 and P300 ERP amplitudes provoked by the pictures. Our results reveal that P200 did not differentiate between picture contents in BII phobia while, in contrast, snake and blood-related pictures provoked the largest responses in snake phobia participants. Both blood-related and snake pictures provoked greater P300 amplitudes than neutral pictures in all the groups. Threat cues reduced the electrocortical reaction of the BII, possibly by the elicitation of anticipatory or regulatory responses. These results are indicative of a low automatic, exogenous attention towards the feared stimuli in BII phobia, as revealed by P200, probably related to a lack of attentional bias to the phobic object.

I Wanna Hold Your Hand: Handholding is Subjectively Preferred to Stroking in Everyday Situations

Social touch is an important form of interpersonal emotion regulation. Two types of touch, C-touch (Slow stroking of skin with C-tactile afferents, such as the forearm) and handholding, have been extensively studied in the context of comforting touch. C-touch has been found to activate unique neural pathways associated with reward signaling, which suggests that it may be a preferable emotion regulation strategy. Notwithstanding, handholding is widely utilized in people’s everyday lives when seeking to regulate another person’s emotions. Here we sought to directly compare participants’ subjective preferences of touch type, in three studies. The studies involved participants imagining themselves in various positive and negative, physical and emotional situations and rating which type of touch (handholding, stroking, no touch) they would prefer. Study 1 (N=99) examined preferred type of touch to receive; Study 2 (N=101) examined touch reception and provision; and Study 3 (N=51) examined touch reception during injections (e.g., vaccine provision) in participants with blood\injection phobia. In all studies, participants preferred handholding over stroking, especially in intense situations. We propose that this preference, despite the unique neural pathways activated by slow stroking, might be due to handholding’s cultural ubiquity, due to it activating top-down regulation processes, or due to it inducing interpersonal synchrony.

Cognitive Biases in Blood-Injection-Injury Phobia: A Review

Blood-injection-injury (BII) phobia can lead to avoidance of crucial medical procedures and to detrimental health consequences, even among health workers. Yet unlike other specific phobias, BII phobia has been understudied. Specifically, while cognitive biases have been extensively investigated in other anxiety disorders, little is known about the same biases in BII phobia. The current article reviews cognitive biases in BII phobia and suggest future directions for further study and treatment. The reviewed biases include attention, expectancy, memory, perception, and interpretation biases. The investigation of these biases is highly relevant, as cognitive biases have been found to interact with anxiety symptoms. Results showed that attention, expectancy, and memory biases are involved in BII phobia, while no studies were found on interpretation nor perception biases. Mixed results were found for attention bias, as different studies found different components of attention bias, while others found no attention bias at all. Similarly, some studies found a-priori/a-posteriori expectancy biases, while other studies found only one type of bias. A better understanding of the cognitive particularities of BII phobia may lead to better treatments and ultimately reduce avoidance of needles and blood-related situations, thereby enabling individuals with BII phobia to undergo potentially life-saving medical procedures.

AUTOLOGOUS BLOOD INJECTION INTRACORONARY ARTERY FOR TREATING SLOW-FLOW AND NO-REFLOW IN ACUTE CORONARY SYNDROME RELATED TO PRIMARY PCI

Slow flow and no-reflow phenomenon are taken to sudden loss of coronary artery flow, typically after stenting or angioplasty in primary PCI. Otherwise conventional therapy, we report a technique, which autologous blood into intracoronary to supply oxygen and break process thrombosis results in successfully management no-reflow in primary PCI