Sexually dimorphic microglia and ischemic stroke.

Ischemic stroke kills more women compared with men thus emphasizing a significant sexual dimorphism in ischemic pathophysiological outcomes. However, the mechanisms behind this sexual dimorphism are yet to be fully understood. It is well established that cerebral ischemia activates a variety of inflammatory cascades and that microglia are the primary immune cells of the brain. After ischemic injury, microglia are activated and play a crucial role in progression and resolution of the neuroinflammatory response. In recent years, research has focused on the role that microglia play in this sexual dimorphism that exists in the response to central nervous system (CNS) injury. Evidence suggests that the molecular mechanisms leading to microglial activation and polarization of phenotypes may be influenced by sex, therefore causing a difference in the pro/anti-inflammatory responses after CNS injury. Here, we review advances highlighting that sex differences in microglia are an important factor in the inflammatory responses that are seen after ischemic injury. We discuss the main differences between microglia in the healthy and diseased developing, adult, and aging brain. We also focus on the dimorphism that exists between males and females in microglial-induced inflammation and energy metabolism after CNS injury. Finally, we describe how all of the current research and literature regarding sex differences in microglia contribute to the differences in poststroke responses between males and females.

Stem cell biology in traumatic brain injury: effects of injury and strategies for repair.

Approximately 350,000 individuals in the US are affected annually by severe and moderate traumatic brain injuries (TBI) that may result in long-term disability. This rate of injury has produced approximately 3.3 million disabled survivors in the US alone. There is currently no specific treatment available for TBI other than supportive care, but aggressive prehospital resuscitation, rapid triage, and intensive care have reduced mortality rates. With the recent demonstration that neurogenesis occurs in all mammals (including man) throughout adult life, albeit at a low rate, the concept of replacing neurons lost after TBI is now becoming a reality. Experimental rodent models have shown that neurogenesis is accelerated after TBI, especially in juveniles. Two approaches have been followed in these rodent models to test possible therapeutic approaches that could enhance neuronal replacement in humans after TBI. The first has been to define and quantify the phenomenon of de novo hippocampal and cortical neurogenesis after TBI and find ways to enhance this (for example by exogenous trophic factor administration). A second approach has been the transplantation of different types of neural progenitor cells after TBI. In this review the authors discuss some of the processes that follow after acute TBI including the changes in the brain microenvironment and the role of trophic factor dynamics with regard to the effects on endogenous neurogenesis and gliagenesis. The authors also discuss strategies to clinically harness the factors influencing these processes and repair strategies using exogenous neural progenitor cell transplantation. Each strategy is discussed with an emphasis on highlighting the progress and limiting factors relevant to the development of clinical trials of cellular replacement therapy for severe TBI in humans.

Mild hypothermia protects auditory function during cochlear implant surgery.

OBJECTIVE/HYPOTHESIS: Loss of auditory function after cochlear implant (CI) electrode insertion occurs in two stages in the laboratory rat. An immediate loss is followed by a progressive loss over 7 days. Similar stages of acute and progressive neuronal loss occur after trauma in the central nervous system where hypothermia has been shown to have a protective effect. We hypothesize that hypothermia has a similar protective effect against loss of auditory function caused by CI electrode insertion trauma. METHODS: Thirty rats underwent surgery in one cochlea; the contralateral ear was an unoperated control. In the normothermia group, CI electrode insertion trauma was generated with rectal temperature maintained at 37 degrees C throughout the experiment. In the mild hypothermia group, electrode trauma was generated with rectal temperature lowered to 34 degrees C. In the surgical control group, mock surgery was performed at 37 degrees C. Multiple frequency auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE) testing of all ears was performed before surgery, immediately afterward, and on postoperative days 3, 5, and 7. RESULTS: Both ABR and DPOAE testing demonstrated partial loss of auditory function after electrode insertion trauma. However, the hypothermia group had significantly less functional loss in the immediate stage and no significant loss in the progressive stage. CONCLUSION: Mild hypothermia protects auditory function during CI electrode insertion.