Influence of Research Continuity on Physician-Scientists' Career Success.

OBJECTIVE: To determine if maintaining continuity in research topic and method from early to late career yields a greater likelihood of physician-scientists' research career success; that is, achieving research independence and producing impactful publications. METHODS: To explore the effect of maintaining continuity in research, 108 neurology residency graduates (2000-2010) from former medical scientist training programs at the highest National Institute of Neurological Disorders and Stroke- and NIH-funded institutions were identified. Through comparison of PhD dissertations with postgraduate work, research continuity was deemed present if there was evidence of continuity in research topic and method. With publicly available SCOPUS, PubMed, and NIH RePORT data, the correlation that degree of continuity had with h-indices, number of grants awarded, and R01 acquisition was examined. RESULTS: Nearly half of the graduates were classified as noncontinuous (45%), fewer than a quarter as somewhat continuous (22%), and roughly a third as very continuous (32%). The data demonstrated that research continuity increased the ability to acquire a R01, with 83% of R01 or R21 recipients having very continuous research. Very continuous graduates also had higher median number of grants received (2 [interquartile range (IQR) 1-3]) and a higher median h-index (17 [IQR 10.5-20]) compared to the somewhat continuous and noncontinuous groups. CONCLUSIONS: This study highlights research continuity as an important and modifiable variable during the training period of physician-scientists and one that may improve their career success and promote greater retention within the workforce.

Neuroinflammation and neurosteroidogenesis: Reciprocal modulation during injury to the adult zebra finch brain.

Estrogens like estradiol (E2) via their receptors are pluripotent steroid hormones that exert a profound influence on the developing and adult brain in many vertebrates. In songbirds and mammals, acute brain injury resulting from mechanical damage, anoxia and ischemia rapidly upregulates aromatase and E2 synthesis. Interestingly, this E2 provision occurs due to the induction of aromatase expression in reactive astrocytes in areas surrounding brain injury. The resultant increase in E2 is neuroprotective with established influences on apoptosis, gliosis, cytogenesis, neurogenesis and neuroinflammation. Correspondingly, E2 decreases secondary damage following acute brain trauma and may improve recovery. Until very recently however, the signals responsible for the induction of astrocytic aromatase expression in reactive astrocytes were unknown. In the current review, we discuss what is known about the role of astrocytic E2 in neuroprotection with a particular emphasis on a recently discovered interaction between neuroinflammatory and steroidogenic signaling in the zebra finch. We first describe the role of acute inflammatory signaling in the regulation of astrocytic aromatase and central E2 levels. Next, we discuss the emerging role of central E2 in the control of chronic neuroinflammation. Finally, we provide a framework for further work investigating the important role of the interaction between inflammatory and steroidogenic signaling in the protection of neural circuits and behavior following traumatic brain injury (TBI). We also highlight dimorphisms that point to important aspects of sex-specific pathways that underlie the interactions of neuroinflammation and neurosteroidogenesis.

Central Administration of Indomethacin Mitigates the Injury-Induced Upregulation of Aromatase Expression and Estradiol Content in the Zebra Finch Brain.

Injury to the vertebrate brain causes neuroinflammation, characterized in part by increases in prostaglandins. In rodents and songbirds, brain injury also induces the transcription and translation of aromatase in reactive astrocytes around the site of damage. Interestingly, this induction is more rapid in female zebra finches relative to males. Induced aromatization is neuroprotective, as inhibition of aromatase and estrogen replacement, increases and decreases the extent of damage, respectively. Although the consequences of induced astrocytic aromatization are intensely studied, little is known about what factors induce aromatase. Inflammation is sufficient to induce astrocytic aromatase suggesting that the link between inflammation and aromatase expression may be causal. To test this hypothesis, adult male and female zebra finches received bilateral mechanical injuries through which either the cyclooxygenase (COX)-1/2 inhibitor indomethacin or vehicle was administered into contralateral hemispheres. Subjects were killed either 6 or 24 hours after injury. In both sexes, an enzyme immunoassay for prostaglandin E2 (PGE2) revealed that indomethacin decreased PGE2 relative to the contralateral hemisphere at both time points, suggesting that the dose and mode of administration used were successful in affecting neuroinflammation locally. Indomethacin reduced aromatase expression and 17ß-estradiol (E2) content at 6 hours but not 24 hours following injury in females. However, in males, the inhibitory effect of indomethacin on aromatase and E2 was apparent at 24 but not 6 hours after treatment. These data suggest that COX activity, perhaps via consequent prostaglandin secretion, may induce aromatase expression and central E2, an effect that is detectable in temporally distinct patterns between sexes.