Stacey Q Wolfe

Spontaneous intracerebral hemorrhage (ICH) is a catastrophic illness causing significant morbidity and mortality. Despite advances in surgical technique addressing primary brain injury caused by ICH, little progress has been made treating the subsequent inflammatory cascade. Pre-clinical studies have made advancements identifying components of neuroinflammation, including microglia, astrocytes, and T lymphocytes. After cerebral insult, inflammation is initially driven by the M1 microglia, secreting cytokines (e.g., interleukin-1β [IL-1β] and tumor necrosis factor-α) that are involved in the breakdown of the extracellular matrix, cellular integrity, and the blood brain barrier. Additionally, inflammatory factors recruit and induce differentiation of A1 reactive astrocytes and T helper 1 (Th1) cells, which contribute to the secretion of inflammatory cytokines, augmenting M1 polarization and potentiating inflammation. Within 7 days of ICH ictus, the M1 phenotype coverts to a M2 phenotype, key for hematoma removal, tissue healing, and overall resolution of inflammation. The secretion of anti-inflammatory cytokines (e.g., IL-4, IL-10) can drive Th2 cell differentiation. M2 polarization is maintained by the secretion of additional anti-inflammatory cytokines by the Th2 cells, suppressing M1 and Th1 phenotypes. Elucidating the timing and trigger of the anti-inflammatory phenotype may be integral in improving clinical outcomes. A challenge in current translational research is the absence of an equivalent disease animal model mirroring the patient population and comorbid pathophysiologic state. We review existing data and describe potential therapeutic targets around which we are creating a bench to bedside translational research model that better reflects the pathophysiology of ICH patients.

Background and Purpose- Successful reperfusion can be achieved in more than two-thirds of patients treated with mechanical thrombectomy. Therefore, it is important to understand the effect of blood pressure (BP) on clinical outcomes after successful reperfusion. In this study, we investigated the relationship between BP on admission and during the first 24 hours after successful reperfusion with clinical outcomes. Methods- This was a multicenter study from 10 comprehensive stroke centers. To ensure homogeneity of the studied cohort, we included only patients with anterior circulation who achieved successful recanalization at the end of procedure. Clinical outcomes included 90-day modified Rankin Scale, symptomatic intracerebral hemorrhage (sICH), mortality, and hemicraniectomy. Results- A total of 1245 patients were included in the study. Mean age was 69±14 years, and 51% of patients were female. Forty-nine percent of patients had good functional outcome at 90-days, and 4.7% suffered sICH. Admission systolic BP (SBP), mean SBP, maximum SBP, SBP SD, and SBP range were associated with higher risk of sICH. In addition, patients in the higher mean SBP groups had higher rates of sICH. Similar results were found for hemicraniectomy. With respect to functional outcome, mean SBP, maximum SBP, and SBP range were inversely associated with the good outcome (modified Rankin Scale score, 0-2). However, the difference in SBP parameters between the poor and good outcome groups was modest. Conclusions- Higher BP within the first 24 hours after successful mechanical thrombectomy was associated with a higher likelihood of sICH, mortality, and requiring hemicraniectomy.

The spontaneously hypertensive rat (SHR) exhibits alterations in the renin-angiotensin-aldosterone system which are similar to those that characterize patients with "nonmodulating" hypertension, a common and highly heritable form of essential hypertension. Accordingly, we determined whether the inheritance of a DNA restriction fragment length polymorphism (RFLP) marking the renin gene of the SHR was associated with greater blood pressure than inheritance of a RFLP marking the renin gene of a normotensive control rat. In an F2 population derived from inbred SHR and inbred normotensive Lewis rats, we found the blood pressure in rats that inherited a single SHR renin allele to be significantly greater than that in rats that inherited only the Lewis renin allele. To the extent that the SHR provides a suitable model of "nonmodulating" hypertension, these findings raise the possibility that a structural alteration in the renin gene, or a closely linked gene, may be a pathogenetic determinant of increased blood pressure in one of the most common forms of essential hypertension in humans.

OBJECTIVE: Women compose a minority of neurosurgery residents, averaging just over 10% of matched applicants per year during this decade. A recent review by Lynch et al. raises the concern that women may be at a higher risk than men for attrition, based on analysis of a cohort matched between 1990 and 1999. This manuscript aims to characterize the trends in enrollment, attrition, and postattrition careers for women who matched in neurosurgery between 2000 and 2009. METHODS: Databases from the American Association of Neurological Surgeons (AANS) and the American Board of Neurological Surgery (ABNS) were analyzed for all residents who matched into neurosurgery during the years 2000-2009. Residents were sorted by female gender, matched against graduation records, and if graduation was not reported from neurosurgery residency programs, an Internet search was used to determine the residents' alternative path. The primary outcome was to determine the number of women residents who did not complete neurosurgery training programs during 2000-2009. Secondary outcomes included the total number of women who matched into neurosurgery per year, year in training in which attrition occurred, and alternative career paths that these women chose to pursue. RESULTS: Women comprised 240 of 1992 (12%) matched neurosurgery residents during 2000-2009. Among female residents there was a 17% attrition rate, compared with a 5.3% male attrition rate, with an overall attrition rate of 6.7%. The majority who left the field did so within the first 3 years of neurosurgical training and stayed in medicine--pursuing anesthesia, neurology, and radiology. CONCLUSIONS: Although the percentage of women entering neurosurgical residency has continued to increase, this number is still disproportionate to the overall number of women in medicine. The female attrition rate in neurosurgery in the 2000-2009 cohort is comparable to that of the other surgical specialties, but for neurosurgery, there is disparity between the male and female attrition rates. Women who left the field tended to stay within medicine and usually pursued a neuroscience-related career. Given the need for talented women to pursue neurosurgery and the increasing numbers of women matching annually, the recruitment and retention of women in neurosurgery should be benchmarked and assessed.