ABSTRACT
Temporal lobe epilepsy or limbic epilepsy lacks effective therapies due to a void in understanding the cellular and molecular mechanisms that set in motion aberrant neuronal network formations during the course of limbic epileptogenesis (LE). Here we show in in vivo rodent models of LE that the phospholipid mediator platelet-activating factor (PAF) increases in LE and that PAF receptor (PAF-r) ablation mitigates its progression. Synthetic PAF-r antagonists, when administered intraperitoneally in LE, re-establish hippocampal dendritic spine density and prevent formation of dysmorphic dendritic spines. Concomitantly, hippocampal interictal spikes, aberrant oscillations, and neuronal hyper-excitability, evaluated 15-16 weeks after LE using multi-array silicon probe electrodes implanted in the dorsal hippocampus, are reduced in PAF-r antagonist-treated mice. We suggest that over-activation of PAF-r signaling induces aberrant neuronal plasticity in LE and leads to chronic dysfunctional neuronal circuitry that mediates epilepsy.
Subject(s)
Epilepsy, Temporal Lobe/drug therapy , Epilepsy, Temporal Lobe/metabolism , Platelet Activating Factor/metabolism , Platelet Membrane Glycoproteins/metabolism , Receptors, G-Protein-Coupled/metabolism , Animals , Blood Platelets/metabolism , Dendritic Spines/metabolism , Dendritic Spines/pathology , Disease Models, Animal , Epilepsy, Temporal Lobe/genetics , Epilepsy, Temporal Lobe/pathology , Hippocampus/drug effects , Hippocampus/metabolism , Hippocampus/pathology , Humans , Limbic Lobe/metabolism , Limbic Lobe/pathology , Mice , Neuronal Plasticity/drug effects , Neurons/drug effects , Neurons/metabolism , Neurons/pathology , Platelet Activating Factor/genetics , Platelet Membrane Glycoproteins/antagonists & inhibitors , Platelet Membrane Glycoproteins/genetics , Receptors, G-Protein-Coupled/antagonists & inhibitors , Receptors, G-Protein-Coupled/geneticsABSTRACT
Infections remain a serious complication in pediatric oncology patients. To determine if daily bathing with Chlorhexidine gluconate can decrease the rate of nosocomial infection in pediatric oncology patients, we reviewed rates of infections in pediatric oncology patients over a 14-month span. Intervention group received daily bath with Chlorhexidine, while the control group did not receive daily bath. The results showed that daily bath with antiseptic chlorhexidine as daily prophylactic antiseptic topical wash leads to decreased infection density amongst the pediatric oncology patients, especially in patients older than 12 years of age. Furthermore, daily chlorhexidine bathing significantly reduced the rate of hospital acquired infection in patients older than 12 years of age. The findings of this study suggest that daily bathing with chlorhexidine may be an effective measure of reducing nosocomial infection in pediatric oncology patients.