Implication of GluR2 subunit of AMPA receptor in RGS14(414)-mediated memory enhancement

Ongoing quest for finding treatment against memory loss seen in aging and in many neurological and neurodegenerative diseases, so far has been unsuccessful and memory enhancers are seen as a potential remedy against this brain dysfunction. Recently, we showed that gene corresponding to a protein called regulator of G-protein signaling 14 of 414 amino acids (RGS14414) is a robust memory enhancer (Lopez-Aranda et al. 2009: Science). RGS14414-treatment in area V2 of visual cortex caused memory enhancement to such extent that it converted short-term object recognition memory (ORM) of 45min into long lasting long-term memory that could be traced even after many months. Now, through targeting of multiple receptors and molecules known to be involved in memory processing, we found that GluR2 subunit of AMPA receptor might be key to memory enhancement in RGS-animals. RGS14-animals showed a progressive increase in GluR2 protein expression while processing an object information which reached to highest level after 60min of object exposure, a time period required for conversion of short-term ORM into long-term memory in our laboratory set up. Normal rats could retain an object information in brain for 45min (short-term) and not for 60min. However, RGS-treated rats are able to retain the same information for 24h or longer (long-term). Therefore, highest expression of GluR2 subunit seen at 60min suggests that this protein might be key in memory enhancement and conversion to long-term memory in RGS-animals. In addition, we will also discuss the implication of Hebbian plasticity and interaction of brain circuits in memory enhancement.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech. This work was supported by project BFU2013-43458-R from MINECO, P12-CTS-1694 from JA

A Clinical Audit of blood component transfusion practices in Paediatric intensive care unit of a Tertiary Care Hospital, Rawalpindi

Background: To audit the practices involved in blood component transfusion in the management of patients in paediatric intensive care unit of our hospital and to determine the appropriateness of transfusion after comparing them with clinical practice guidelines recommended by Royal Children Hospital (RCH). Methods: All patients admitted in pediatric intensive care which were managed with blood component transfusions were retrospectively audited for 8 weeks. Management details including indications of transfusion and its appropriateness were recorded. Clinical practice guidelines recommended by Royal Children Hospital (RCH) were used as standards. Results: One hundred and ninety-two transfusions were done during the study period out of which 58 percent were done to males and 41 percent to females. Majority of transfusions were done in infants (44%) and O Positive blood group was found rampant among blood groups of all recipients (33.3%). Red cell concentrates were predominantly (55.7%) and appropriately (72%) transfusion among all blood components. Platelet concentrates were most inappropriately transfused (57%) followed by fresh frozen plasma (54%) and red cell concentrates (27%). There was significant percentage of inappropriate transfusion of all blood components (p=0.00). Conclusion: All blood components were significantly found inappropriately transfused, commonest component being platelet concentrates

Regionally selective requirement for D1-D5 dopaminergic neurotransmisson in the medial prefrontal cortex in object-in-place associative recognition memorty:dopamine and object-in-place memory

Object-in-place (OiP) memory is critical for remembering the location in which an object was last encountered and depends conjointly on the medial prefrontal cortex, perirhinal cortex, and hippocampus. Here we examined the role of dopamine D(1)/D(5) receptor neurotransmission within these brain regions for OiP memory. Bilateral infusion of D(1)/D(5) receptor antagonists SCH23390 or SKF83566 into the medial prefrontal cortex, prior to memory acquisition, impaired OiP performance following a 5 min or 1 h delay. Retrieval was unaffected. Intraperirhinal or intrahippocampal infusions of SCH23390 had no effect. These results reveal a selective role for D(1)/D(5) receptors in the mPFC during OiP memory encoding

Evoked Potentials in Neocortical Focal Epileptogenesis in the Rat

The aims of this work were to investigate some of the mechanisms underlying the development of epileptiform activity by studying the changes in evoked potential characteristics that occurred in the in vivo penicillin model of focal epilepsy and to use any such findings as a means of further investigation into the role of the different excitatory receptors in this abnormal activity. Experiments were performed on 93 male wistar rats anaesthetised with urethane (1.9 g/kg; intraperitoneally) . The electrocorticogram (ECoG) and intracortical activity was continually monitored whilst penicillin was electrophoretically ejected into the neocortex in order to produce epileptiform activity. Investigations into the mechanisms of epileptiform activity, using both in-vitro and in-vivo models of focal epilepsy, have on the whole, concentrated on the established focus and the characteristics of established epileptic activity, whether in the form of the extracellularly recorded epileptic spike or the intracellularly recorded paroxysmal depolarisation shift. (PDS). A disadvantage of such an approach is that it cannot yield any information as to any changes in cortical activity that may be occurring before the appearance of the established epileptic focus; although the processes underlying the gross manifestations of epilepsy can be studied, those that lead to such a state cannot. In this study I have used evoked cortical activity to follow any changes that may be occurring in cortical activity before spontaneous epileptiform activity occurs. Evoked potentials can provide an indication as to the overall state of cortical excitability; any changes in cortical excitability being reflected by appropriate changes in evoked activity. During the development of the acute penicillin epileptiform focus in the rat neocortex two distinct and separable stages were defined by the investigation of the changing characteristics of somatosensory evoked potentials (SEPs) and potentials evoked by direct cortical stimulation (DCS) . The first indication that two separate phases of cortical hyperexcitability might exist arose from the differences between the waveforms of enhanced evoked potentials during the development of the epileptiform focus. Small concentrations of penicillin (ejected by electrophoretic currents less than -100 nA) resulted in the enhancement of the amplitude of evoked potentials (up to three times pre-drug levels) with no change in the waveform (phase I); the enhanced potentials were very similar in appearance to normal evoked potentials. Phase I usually occurred within five to ten minutes after the start of penicillin ejection and occurred before the onset of spontaneous epileptiform spiking. Larger concentrations of penicillin (ejected by electrophoretic currents greater than -150 nA) resulted in an enhancement of duration (up to three times the pre-drug levels) as well as further increases in the amplitude (up to nine times pre-drug levels) of evoked potentials (phase II). Phase II was associated with the onset of spontaneous epileptiform spikes, which were very similar in appearance to the enhanced evoked potentials in phase II. The concept of two phases in penicillin epileptogenesis was further substantiated by the findings that the refractory period of the potentials enhanced by small doses of penicillin (phase I) was the same as the refractory period of normal potentials (less than 100 ms for SEPs and 40 ms for DEPs). However the refractory period of enhanced evoked potentials in phase II was much greater (in excess of 300 ms) than that of both normal potentials and evoked potentials in phase II. The stimulus strength response relationship of normal evoked potentials and evoked potentials in phase I were very similar to one another and both followed a sigmoidal relationship. (Abstract shortened by ProQuest.)

Plasticity in Prefrontal Cortex Induced by Coordinated Synaptic Transmission Arising from Reuniens/Rhomboid Nuclei and Hippocampus

The nucleus reuniens and rhomboid nuclei of the thalamus (ReRh) are reciprocally connected to a range of higher order cortices including hippocampus (HPC) and medial prefrontal cortex (mPFC). The physiological function of ReRh is well predicted by requirement for interactions between mPFC and HPC, including associative recognition memory, spatial navigation, and working memory. Although anatomical and electrophysiological evidence suggests ReRh makes excitatory synapses in mPFC there is little data on the physiological properties of these projections, or whether ReRh and HPC target overlapping cell populations and, if so, how they interact. We demonstrate in ex vivo mPFC slices that ReRh and HPC afferent inputs converge onto more than two-thirds of layer 5 pyramidal neurons, show that ReRh, but not HPC, undergoes marked short-term plasticity during theta frequency transmission, and that HPC, but not ReRh, afferents are subject to neuromodulation by acetylcholine acting via muscarinic receptor M2. Finally, we demonstrate that pairing HPC followed by ReRh (but not pairing ReRh followed by HPC) at theta frequency induces associative, NMDA receptor dependent synaptic plasticity in both inputs to mPFC. These data provide vital physiological phenotypes of the synapses of this circuit and provide a novel mechanism for HPC–ReRh–mPFC encoding

An audit of head trauma care and mortality

Objective: To analyze the factors contributing to deaths from head trauma by using standardized assessment parameters and to provide a peer-review of head injury deaths with focus on identifying deficiencies and analyzing contributory factors.Design: Descriptive study.Place and duration of study: The study was carried out at the Emergency, Aga Khan University Hospital during January 1998 to December 1999.Subjects and method: One hundred and three patients above the age of 15 years presenting alive to the Aga Khan University Hospital (AKUH) emergency with head injury were included in this study. Identified deaths data was reviewed by the Hospital Trauma Peer Review Committee and consensus arrived at for categorization of deaths. The potential deficiencies in care were identified and final recommendations made. The data was computed on CDC Trauma Registry (V 3.0) and SPSS (V 8.0).Results: Mean age was 31.9 years (n=103) with predominant male population (4:1). Severe head injury (GCS\u3c8) accounted for 21.3 % (n=22) of all cases with a total number of deaths being 12.6 % (n=13). Deaths were categorized preventable in 3 cases with non-preventable and potentially preventable in 4 and 6 cases respectively. Road traffic accidents were the predominant mechanism (n=8) in all deaths (n=13). The time interval in relation to mortality was biphasic, most deaths occurring either within 24 hours or between 3-7 days of injury. Inappropriate pre-hospital treatment, pre-hospital delays and inappropriate mode of transportation without inter-hospital communication were the process-related defects in pre-hospital care with major determinant of deaths outside AKUH (n=5). Prolonged emergency stay, delayed intensive care availability were the process-related deficiencies whereas inappropriate initial resuscitation, inappropriate initial head injury management were provider-related deficiencies in in-hospital care.Conclusion: Transfer of inappropriately managed patients, lapses in inter-hospital communications, delayed transfers were identified as the major pre-hospital factors whereas lack of ICU beds, portable ventilators in emergency room, delays in CT scan facilities were the deficiencies in the hospital services. Opportunities for improvement in head trauma care are needed to focus on initial resuscitation and appropriate surgical management