Microglia regulate blood clearance in subarachnoid hemorrhage by heme oxygenase-1

Subarachnoid hemorrhage (SAH) carries a 50% mortality rate. The extravasated erythrocytes that surround the brain contain heme, which, when released from damaged red blood cells, functions as a potent danger molecule that induces sterile tissue injury and organ dysfunction. Free heme is metabolized by heme oxygenase (HO), resulting in the generation of carbon monoxide (CO), a bioactive gas with potent immunomodulatory capabilities. Here, using a murine model of SAH, we demonstrated that expression of the inducible HO isoform (HO-1, encoded by Hmox1) in microglia is necessary to attenuate neuronal cell death, vasospasm, impaired cognitive function, and clearance of cerebral blood burden. Initiation of CO inhalation after SAH rescued the absence of microglial HO-1 and reduced injury by enhancing erythrophagocytosis. Evaluation of correlative human data revealed that patients with SAH have markedly higher HO-1 activity in cerebrospinal fluid (CSF) compared with that in patients with unruptured cerebral aneurysms. Furthermore, cisternal hematoma volume correlated with HO-1 activity and cytokine expression in the CSF of these patients. Collectively, we found that microglial HO-1 and the generation of CO are essential for effective elimination of blood and heme after SAH that otherwise leads to neuronal injury and cognitive dysfunction. Administration of CO may have potential as a therapeutic modality in patients with ruptured cerebral aneurysms

Graduate entry to medicine in Iran

<p>Abstract</p> <p>Backgrounds</p> <p>In Iran medical students are selected from high school graduates via a very competitive national university entrance exam. New proposals have been seriously considered for admitting students from those with bachelor degrees. We assessed the opinions of different stakeholders on the current situation of admission into medicine in Iran, and their views on positive and negative aspects of admitting graduates into medicine.</p> <p>Methods</p> <p>We conducted five focus group discussions and seven in-depth interviews with stakeholders including medical students, science students, university professors of basic sciences, medical education experts, and policy makers. Main themes were identified from the data and analyzed using content analysis approach.</p> <p>Results</p> <p>Medical students believed "graduate admission" may lead to a more informed choice of medicine. They thought it could result in admission of students with lower levels of academic aptitude. The science students were in favor of "graduate admission". The education experts and the professors of basic science all mentioned the shortcomings of the current system of admission and considered "graduate admission" as an appropriate opportunity for correcting some of the shortcomings. The policy makers pointed out the potential positive influences of "graduate admission" on strengthening basic science research. They thought, however, that "graduate admission" may result in lengthening the overall duration of medical education, which is already long in Iran (over 7 years). On the whole, the participants thought that "graduate admission" is a step in the right direction for improving quality of medical education.</p> <p>Conclusion</p> <p>"Graduate admission" has the potential to correct some of shortcomings of medical education. Unlike other countries where "graduate admission" is used mainly to admit students who are mentally mature, in Iran the main objective seems to be strengthening basic sciences.</p

Pharmacological treatment of delayed cerebral ischemia and vasospasm in subarachnoid hemorrhage

Subarachnoid hemorrhage after the rupture of a cerebral aneurysm is the cause of 6% to 8% of all cerebrovascular accidents involving 10 of 100,000 people each year. Despite effective treatment of the aneurysm, delayed cerebral ischemia (DCI) is observed in 30% of patients, with a peak on the tenth day, resulting in significant infirmity and mortality. Cerebral vasospasm occurs in more than half of all patients and is recognized as the main cause of delayed cerebral ischemia after subarachnoid hemorrhage. Its treatment comprises hemodynamic management and endovascular procedures. To date, the only drug shown to be efficacious on both the incidence of vasospasm and poor outcome is nimodipine. Given its modest effects, new pharmacological treatments are being developed to prevent and treat DCI. We review the different drugs currently being tested