Background and Purpose-The potential neuroprotective effect of the granulocyte colony-stimulating factor (G-CSF) after glutamate-induced excitotoxicity in cell culture and after focal cerebral ischemia in rats was studied. We hypothesized the existence of the G-CSF receptor (G-CSFR) as a main G-CSF effector on neurons, and immunohistochemistry, immunoblotting, and polymerase chain reaction were performed. The G-CSFR-mediated action was studied by activation of signal transducer(s) and activator(s) of transcription-3 (STAT3) in the periphery of the infarction. Methods-Neuroprotection of various G-CSF concentrations on glutamate-induced excitotoxicity was studied in cell culture. In vivo, ischemia was induced by use of a suture occlusion model of the middle cerebral artery (90-minute occlusion) in the rat. Thirty minutes after the induction of ischemia, the animals (nϭ12 per group) received G-CSF at 60 g/kg body wt IV for 90 minutes or vehicle (saline). Infarct volume was calculated on the basis of 2,3,5-triphenyltetrazolium chloride staining 24 hours after ischemia. Expression of the G-CSFR was studied by immunohistochemistry and verified by reverse transcription-polymerase chain reaction and immunoblotting. Expression of STAT3 was determined by immunohistochemistry. Results-In cell culture, G-CSF exhibited a significant neuroprotective effect after glutamate-induced excitotoxicity (PϽ0.05). A G-CSF concentration of 10 ng/mL was maximally effective, resulting in a nearly complete protection. In vivo, G-CSF reduced infarct volume to 47% (132.0Ϯ112.7 mm 3 versus 278.9Ϯ91.6 mm 3 [PϽ0.05] in the control group). Immunohistochemistry, Western blotting, and reverse transcription-polymerase chain reaction revealed the existence of G-CSFRs in neurons and glial cells. Animals treated with G-CSF significantly upregulated STAT3 in the periphery of the infarction compared with control animals (PϽ0.05). Conclusions-G-CSF

Background and Purpose-There is only limited knowledge on the time course of perihemorrhagic edema (PHE) after intracerebral hemorrhage (ICH). We aimed to investigate the chronological PHE course and its relation to in-hospital mortality in a large retrospective ICH cohort. Methods-Patients with supratentorial ICH treated at our institution between 2006 and 2009, who had received at least 3 CT scans in the course of conservative treatment, were included in the present analysis. PHE at Days 1, 2, 3, 4 to 6, 7 to 11, 12 to 16, 17 to 21, and Ͼ22 was assessed using a threshold based semiautomatic volumetric algorithm. A chart review was performed to achieve data on duration of stay, ventilation, treatment with external ventricular drains, and in-hospital mortality. Results-Two

Abstract-Life-threatening, space-occupying brain edema occurs in up to 10% of patients with supratentorial infarcts and is traditionally associated with a high mortality rate of up to 80%. Management of these patients is currently being changed to an earlier and more aggressive treatment regimen. Early surgical decompression has recently been proven effective to reduce mortality and increase the number of patients with a favorable outcome in randomized controlled trials and is now the "antiedema" therapy of first choice for patients with large middle cerebral artery infarction aged 60 years or younger. Several medical treatment strategies have been proposed to control brain edema and reduce intracranial pressure, including different osmotherapeutics, hyperventilation, tromethamine, hypothermia, and barbiturate coma. None of these treatments is supported by level 1 evidence of efficacy in clinical trials, and some of them may even be detrimental. Preliminary results on hypothermia for space-occupying hemispheric infarction are encouraging, but far from definitive. (Stroke. 2007;38:3084-3094.)

Background and Purpose-Both intraventricular fibrinolysis (IVF) and lumbar drainage (LD) may reduce the need for exchange of external ventricular drainage (EVD) and shunt surgery in patients with intracerebral hemorrhage and severe intraventricular hemorrhage. We investigated the feasibility and safety of IVF followed by early LD for the treatment of posthemorrhagic hydrocephalus. Methods-This prospective study included patients with spontaneous ganglionic intracerebral hemorrhage and severe intraventricular hemorrhage with acute obstructive posthemorrhagic hydrocephalus who received an EVD (nϭ32). The treatment algorithm started with IVF (4 mg recombinant tissue plasminogen activator every 12 hours) until clearance of the third and fourth ventricles from blood. Thereupon, EVD was clamped and if clamping was unsuccessful, communicating posthemorrhagic hydrocephalus was assumed and LD placed. EVD was removed if there was neither an increase of intracranial pressure nor ventricle enlargement on CT. A ventriculoperitoneal shunt was indicated if "LD weaning" was unsuccessful for Ͼ10 days. Outcome was assessed at 90 and 180 days using the modified Rankin Scale. Results-IVF resulted in fast clearance of the third and fourth ventricles (73Ϯ50 hours). However, early EVD removal was only possible in 4 patients. The remaining 28 patients developed communicating posthemorrhagic hydrocephalus. In all of these patients, early LD was capable to replace EVD. EVD exchange was not necessary and EVD duration was 105Ϯ59 hours. Only one patient required a ventriculoperitoneal shunt. At 180 days, 20 (62.5%) patients had a good (modified Rankin Scale 0 to 3) outcome and 5 (15.6%) patients had died. One patient had asymptomatic ventricular rebleeding. Conclusions-In patients with secondary intraventricular hemorrhage and posthemorrhagic hydrocephalus, the combined treatment approach of IVF and early LD is safe and feasible, avoids EVD exchange, and may markedly reduce the need for shunt surgery.