The functions of the complement system to both innate and adaptive immunity through opsonization, cell lysis, and inflammatory activities are well known. In contrast, the role of complement in the central nervous system (CNS) which extends beyond immunity, is only beginning to be recognized as important to neurodevelopment and neurodegeneration. In addition to protecting the brain against invasive pathogens, appropriate activation of the complement system is pivotal to the maintenance of normal brain function. Moreover, overactivation or dysregulation may cause synaptic dysfunction and promote excessive pro-inflammatory responses. Recent studies have provided insights into the various responses of complement components in different neurological diseases and the regulatory mechanisms involved in their pathophysiology, as well as a glimpse into targeting complement factors as a potential therapeutic modality. However, there remain significant knowledge gaps in the relationship between the complement system and different brain disorders. This review summarizes recent key findings regarding the role of different components of the complement system in health and pathology of the CNS and discusses the therapeutic potential of anti-complement strategies for the treatment of neurodegenerative conditions.

Glutamate is the major excitatory neurotransmitter in the central nervous system and is intricately linked to learning and memory. Its activity depends on the expression of AMPA and NMDA receptors and excitatory amino transporters on neurons and glial cells. Glutamate transporters prevent the excess accumulation of glutamate in synapses, which can lead to aberrant synaptic signaling, excitotoxicity, or cell death. Neuroinflammation can occur acutely after surgical trauma and contributes to the development of perioperative neurocognitive disorders, which are characterized by impairment in multiple cognitive domains. In this review, we aim to examine how glutamate handling and glutamatergic function are affected by neuroinflammation and their contribution to cognitive impairment. We will first summarize the current data regarding glutamate in neurotransmission, its receptors, and their regulation and trafficking. We will then examine the impact of inflammation on glutamate handling and neurotransmission, focusing on changes in glial cells and the effect of cytokines. Finally, we will discuss these changes in the context of perioperative neuroinflammation and the implications they have for perioperative neurocognitive disorders.

Background Engaging students in interprofessional education for higher order thinking and collaborative problem-solving skills is challenging. This study reports the development of Virtual ER, a serious game played on a virtual platform, and how it can be an innovative way for delivering interprofessional education to medical and nursing undergraduates. Objective We report the development of a serious online game, Virtual ER, and evaluate its effect on teamwork enhancement and clinical competence. We also explore if Virtual ER can be an effective pedagogical tool to engage medical and nursing students with different learning styles. Methods Virtual ER is a custom-made, learning outcome–driven, case-based web app. We developed a game performance scoring system with specific mechanisms to enhance serious gaming elements. Sixty-two students were recruited from our medical and nursing programs. They played the games in teams of 4 or 5, followed by an instructor-led debriefing for concept consolidation. Teamwork attitudes, as measured by the Human Factors Attitude Survey, were compared before and after the game. Learning style was measured with a modified Honey and Mumford learning style questionnaire. Results Students were satisfied with Virtual ER (mean satisfaction score 5.44, SD 0.95, of a possible 7). Overall, Virtual ER enhanced teamwork attitude by 3.02 points (95% CI 1.15-4.88, P=.002). Students with higher scores as activists (estimate 9.09, 95% CI 5.17-13.02, P<.001) and pragmatists (estimate 5.69, 95% CI 1.18-10.20, P=.01) had a significantly higher degree of teamwork attitude enhancement, while students with higher scores as theorists and reflectors did not demonstrate significant changes. However, there was no difference in game performance scores between students with different learning styles. Conclusions There was considerable teamwork enhancement after playing Virtual ER for interprofessional education, in particular for students who had activist or pragmatist learning styles. Serious online games have potential in interprofessional education for the development of 21st century life skills. Our findings also suggest that Virtual ER for interprofessional education delivery could be expanded locally and globally.