Townsendgrossman5577

Rationale Neurofibromatosis type 1 (NF1) is associated with higher rates of epilepsy compared to the general population. Some NF1 patients with epilepsy do not have intracranial lesions, suggesting the genetic mutation itself may contribute to higher rates of epilepsy in these patients. We have recently demonstrated increased seizure susceptibility in the Nf1+/- mouse, but it is unknown whether this model displays altered epileptogenicity, as has been reported in patients with NF1. The aim of this study was to determine whether the Nf1+/- mouse is more susceptible to electrical kindling-induced epileptogenesis. Methods Young male or female adult Nf1+/- or Nf1+/+ (wild-type; WT) mice were implanted with electrodes for neocortical or hippocampal kindling paradigms. Neocortical kindling was performed for 40 stimulation sessions followed by baseline EEG monitoring to detect possible SRSs. Hippocampal kindling was performed with a modified extended kindling paradigm, completed to a maximum of 80 sessions to try toof the Racine seizure score over the kindling sessions, mainly due to a faster increase in seizures severity early during the kindling process. However, SRSs were seen in 50% of Nf1+/- mice after modified extended kindling and in no WT mice. Western blots showed hippocampal kindling increased the ratio of phosphorylated/total Akt in both the WT and Nf1+/- mice, while neocortical kindling led to increased ratios of phosphorylated/total Akt and MAPK in Nf1+/- mice only. SHR-3162 Conclusions We have demonstrated for the first time an increased rate of epileptogenesis in an animal model of NF1 with no known macroscopic/neoplastic brain lesions. This work provides evidence for the genetic mutation itself playing a role in seizures and epilepsy in patients with NF1, and supports the use of the Nf1+/- mouse model in future mechanistic studies.Receptor-interacting protein kinase 3 (RIPK3) regulates a newly discovered cell death form called necroptosis. RIPK3 nuclear translocation and inflammatory factor release are involved in necroptosis after rat global cerebral ischemia/reperfusion (I/R) injury. link2 The purpose of this study was to investigate the effects of interactions between the RIPK3 and apoptosis-inducing factor (AIF) necroptosis pathway and the JNK-mediated inflammatory pathway. Rats were subjected to 4-vessel occlusion and reperfusion injury. RIPK3 inhibitor GSK872, RIPk3 recombinant adeno-associated virus (rAAV) and JNK-specific inhibitor SP600125 were intracerebroventricular injected before I/R. Hippocampus CA1 tissue were obtained and RIPK3, AIF, p-JNK, IL-6 were determined by western blot analysis. The RIPK3 and AIF interaction were also analyzed by immunofluorescence and immunoprecipitation. The expression of endogenous RIPK3, AIF, p-JNK and IL-6 was increased in hippocampus CA1 in I/R group. In addition, RIPK3 was increased in both theregulated inflammatory mediators may promote the necroptosis initiation.Introduction Cumulative disease burden may be associated with survival chances after out-of-hospital cardiac arrest (OHCA). The relative contributions of cumulative disease burden on survival rates at the pre-hospital and in-hospital phases of post-resuscitation care are unknown. Methods The association between cumulative comorbidity burden as measured by the Charlson Comorbidity Index (CCI) and pre-hospital and in-hospital survival rates was studied using data (2010-2014) from a prospective OHCA registry in the Netherlands. The association between CCI and survival rate (overall survival [OHCA-hospital discharge], pre-hospital survival [OHCA-hospital admission] and in-hospital survival [hospital admission-hospital discharge]) was assessed using logistic regression analyses. The relative contributions of CCI on pre-hospital and in-hospital survival rates were determined using the Nagelkerke test. Results We included 2510 OHCA patients aged ≥18y. CCI was significantly associated with overall survival rate (OR 0.71; 95%CI 0.61-0.83; P less then 0.01). CCI was not associated with pre-hospital survival rate (OR 0.96; 95%CI 0.76-1.23; P = 0.92) whereas high CCI was significantly associated with low in-hospital survival rate (OR 0.41; 95%CI 0.27-0.62; P = 0.01). The relative contributions of CCI on pre-hospital and in-hospital survival were 1.1% and 8.1%, respectively. Conclusion Pre-existing high comorbidity burden plays a modest role in reducing survival rate after OHCA, and only in the in-hospital phase. The present study offers data that may guide clinicians in discussing resuscitation options during advance care planning with patients with high comorbidity burden. This may be helpful in creating a patients' informed choice.Aim of study In hospital cardiac arrests occur at a rate of 1-5 per 1000 admissions and are associated with significant morbidity and mortality. We aimed to investigate the association between deviations from ACLS protocol and patient outcomes. Methods This retrospective review was conducted at a single academic medical center. Data was collected on patients who suffered cardiac arrest from December 2015-November 2019. Our primary endpoint was return of spontaneous circulation. Secondary endpoints included survival to discharge and discharge with favorable neurological outcomes. Results 108 patients were included, 74 obtained return of spontaneous circulation, and 23 survived to discharge. The median number of deviations from the ACLS protocol per event in ROSC group was 1 (IQR 0-3) compared to 6.5 (IQR 4-12) in non-ROSC group (p less then .0001). The probability of obtaining ROSC was 96% with 0-2 deviations per event, 59% with 2-5 deviations per event, and 11% with greater than 6 deviations per event (p less then .0001). The median deviation per event in patients who survived to discharge was 0 (IQR 0-1) vs. 3 (IQR 1-6, p less then .0001) in those who did not. Lastly, survival to discharge with a favorable neurological outcome may be associated we less deviations per event (p less then .006). Conclusion Our findings highlight the importance of adherence to the ACLS protocol. link3 We found that deviations from the algorithm are associated with decreased rates of ROSC and survival to discharge. Additionally, higher rates of protocol deviations may be associated with higher rates of neurological impairments after cardiac arrest.Objectives Cardiac arrest recognition, ambulance dispatch and dispatcher-assisted cardiopulmonary resuscitation (DA-CPR) by emergency medical dispatch (EMD) are crucial for an optimal outcome of out-of-hospital cardiac arrest (OHCA). In EMD, crowding is caused by a mismatch between the number of emergency calls and the number of dispatchers available per shift. Crowding in the emergency department has been shown to decrease performance and outcomes; however, little is known about the effect of crowding in EMD. We aimed to evaluate the incidence of crowding in the EMD and the effect of emergency call crowding on dispatcher-assisted CPR instruction performance in OHCA calls. Methods We used a nationwide OHCA database from 2013 to 2016 consisting of patients with the presumed cardiac origin who were dispatched by Seoul EMD. The main exposure was an hourly number of total incoming emergency calls to EMD. The number of hourly calls was categorized into quartiles (≤40 calls, 41-51 calls, 52-61 calls and ≥62 calls).strategic approach to addressing crowding in EMD according to the crowding distribution.The cerebellum is involved in motor learning, and long-term depression (LTD) at parallel fiber-to-Purkinje cell (PF-PC) synapses has been considered to be a primary cellular mechanism for motor learning. In addition, the contribution of norepinephrine (NE) to cerebellum-dependent learning paradigms has been reported. Thus, the roles of LTD and of NE in motor learning have been studied separately, and the relationship between the effects of NE and LTD remains unclear. Here, we examined effects of β-adrenergic receptor (β-AR) activity on the synaptic transmission and LTD at PF-PC synapses in the cerebellar flocculus. The flocculus regulates adaptation of oculomotor reflexes, and we previously reported the involvement of both LTD and β-AR in adaptation of an oculomotor reflex. Here we found that specific agonists for β-AR or NE did not directly change synaptic transmission, but lowered the threshold for LTD induction at PF-PC synapses in the flocculus. In addition, protein kinase A (PKA), which is activated downstream of β-AR, facilitated the LTD induction. Altogether, these results suggest that NE facilitates LTD induction at PF-PC synapses in the flocculus by activating PKA through β-AR.The present study examined if repeated bouts of micro- and hypergravity during parabolic flight (PF) alter structural integrity of the neurovascular unit (NVU) subsequent to free radical-mediated changes in regional cerebral perfusion. Six participants (5♂, 1♀) aged 29 ± 11 years were examined before, during and after a 3 h PF and compared to six sex and age-matched (27 ± 6 years) normogravity controls. Blood flow was measured in the anterior (middle cerebral artery, MCA; internal carotid artery, ICA) and posterior (vertebral artery, VA) circulation (duplex ultrasound) in-flight over the course of 15 parabolas. Venous blood was assayed for free radicals (electron paramagnetic resonance spectroscopy), nitric oxide (NO, ozone-based chemiluminescence) and NVU integrity (chemiluminescence/ELISA) in normogravity before and after exposure to 31 parabolas. While MCA velocity did not change (P > 0.05), a selective increase in VA flow was observed during the most marked gravitational transition from micro- to hypergravity (P 0.05). Collectively, these findings suggest that the cumulative effects of repeated gravitational transitions may promote minor blood-brain barrier disruption, potentially related to the combined effects of haemodynamic (posterior cerebral hyperperfusion) and molecular (systemic oxidative-nitrosative) stress.Vascular endothelial cells were activated during acute ischemic brain injury, which could induce neural progenitor cell proliferation and migration. However, the mechanism was still unknown. In the current study, we explored whether vascular endothelial cells promoted neural progenitor cell proliferation and whether migration occurs via exosome communication. The acute middle cerebral artery occlusion (MCAO) model was prepared, and exosomes were isolated from bEnd.3 cells by ultracentrifugation. In the exosome injection (Exos) group and PBS injection (control) group, exosomes or PBS were injected intraventricularly into rats' brains 2 h after MCAO surgery, respectively. Sham group rats received the same surgical but did not cause middle cerebral artery occlusion. The infarct volume was reduced on day 21 after ischemic brain injury by MRI, and neurobehavioral outcomes were improved on day 7, 14, and 21 by exosome injection compared with the control (p less then 0.05). On the 21st day after MCAO, the animals were euthanized, and the number of BrdU/nestin-positive cells was measured by immunofluorescence. BrdU/nestin-positive cells in Exos group rats were significantly increased (p less then 0.05) in the peri infarct area, the ipsilateral DG zone of the hippocampus, and the ventral sub-regions of SVZ when compared with the rats in the control group. Further, in vitro study demonstrated that neural progenitor cell proliferation and migration were activated after exosomes treatment, and cell apoptosis was attenuated compared to the control (p less then 0.05). Our study suggested that exosomes should be essential for the reconstruction of neuronal vascular units and brain protection in an acute ischemic injured brain.