Background and Purpose-The role of interleukin (IL)-1␤ remains unknown in early brain injury (EBI) after subarachnoid hemorrhage (SAH), although IL-1␤ has been repeatedly reported to increase in the brain and cerebrospinal fluid. The aim of this study is to examine the effects of IL-1␤ inactivation on EBI after SAH in mice. Methods-The endovascular perforation model of SAH was produced and 112 mice were assigned to sham, SAHϩ vehicle, and SAHϩ N-Ac-Tyr-Val-Ala-Asp-chloromethyl ketone (Ac-YVAD-CMK, 6 and 10 mg/kg) groups. Ac-YVAD-CMK, a selective inhibitor of IL-1␤ converting enzyme, or vehicle was administered intraperitoneally 1 hour post-SAH. EBI was assessed in terms of mortality within 24 hours, neurological scores, brain water content at 24 and 72 hours, Evans blue dye extravasation and Western blot for IL-1␤, c-Jun N-Terminal kinase (JNK), matrix metalloproteinase (MMP)-9, and zonula occludens (ZO)-1 at 24 hours after SAH. Results-High-dose (10 mg/kg) but not low-dose (6 mg/kg) treatment group significantly improved neurological scores, mortality, brain water content, and Evans blue dye extravasation compared with the vehicle group. Although both dosages of Ac-YVAD-CMK attenuated the mature IL-1␤ induction, only high-dose treatment group significantly inhibited the phosphorylation of JNK, MMP-9 induction, and ZO-1 degradation. Conclusion-IL-1␤

It has been reported that gap junction contributes to ischemic brain injury and gap junction inhibitors improve neurological outcome in ischemic brain injury models. In the present study, we investigated the effects of gap junction inhibitor, carbenoxolone, on mortality, neurological deficits and brain edema in mice with intracerebral hemorrhage. A total of 80 male CD-1 mice were divided into two parts with two end-points for this study. In part one, animals were divided into four groups: sham, vehicle treatment following intracerebral hemorrhage induction, low-dose carbenoxolone (33 mg/kg) treatment 1 hour after intracerebral hemorrhage induction and high-dose carbenoxolone (100 mg/kg) treatment 1 hour after intracerebral hemorrhage induction groups. Animals were euthanized after 24 hours. In part two, animals were divided into four groups: sham, vehicle treatment 1 hour after intracerebral hemorrhage induction, single high-dose of carbenoxolone treatment at 1 hour after intracerebral hemorrhage induction and three high-doses of carbenoxolone treatment 1, 24 and 48 hours respectively after intracerebral hemorrhage induction. Animals were euthanized after 72 hours. Intracerebral hemorrhage was induced by collagenase injection. Neurological deficits were evaluated using modified Garcia's neurological test, wire hanging and beam balance tests. Brain edema was measured by brain water content. Our results showed that intracerebral hemorrhage produced brain edema and neurological deficits in mice. Carbenoxolone treatment failed to reduce brain edema and neurological deficits. In fact, the high dose of carbenoxolone aggravated neurological deficits and increased mortality 72 hours after the treatment. In conclusion, inhibition of gap junction has no short-term neuroprotective effect on intracerebral hemorrhage-induced brain injury. Further studies are required to assess the long-term effects of gap junction inhibitors in intracerebral hemorrhage models.

The continuation of a review of delayed vasospasm after aneurysmal subarachnoid haemorrhage, originally published in 1994 and partially updated at the ninth vasospasm conference in Turkey, is presented. Further online and physical searches have been made of the relevant literature. The incidence of delayed ischaemic deficit (DID) or symptomatic vasospasm reported in 1994 was 32.5% in over 30,000 reported cases. In recent years, 1994-2009, it was 6,775/23,806, or 28.5%. Many of the recent reports did not specify whether a calcium antagonist was used routinely, and when this was stated (usually nimodipine or nicardipine), DID was noted in 22.0% of 10,739 reported patients. The outcome of delayed ischaemia in the earlier survey was a death rate of 31.6%, with favourable outcomes in 36.2%. In recent reports, though with fewer than 1,000 patients, the outcome is possibly better, with death in 25.6% and good outcome in 54.1%. It thus appears likely that delayed vasospasm is still common but less so, and that the overall outcome has improved. This may be due to the more widespread use of calcium antagonists and more effective fluid management. A number of other mechanical and drug treatments are also mentioned.

This study summarized the role of inflammation in the early brain injury after subarachnoid hemorrhage. Elevation of cytokines, activation of MMPs and phosphorylation of MAPK contributes to neuronal apoptosis and brain edema. Anti-inflammation may be potential strategy for the prevention and suppression of early brain injury after subarachnoid hemorrhage.

In the present study, we investigated whether the administration of nicotinamide adenine dinucleotide (NAD+) provides brain protection in a mouse model of intracerebral hemorrhage (ICH). Male CD-1 mice were divided into sham, ICH treated with vehicle and ICH treated with NAD+ (10 or 20 mg/kg, intranasal) groups. Intranasal delivery of NAD+ resulted in an increase in NAD+ contents in the brains. ICH was induced by collagenase injection. Neurological function, hemorrhage volume and brain edema were measured 24 hours after injection. ICH caused significant neurological deficit with associated brain edema. NAD+ (10 and 20 mg/kg) failed to reduce brain injury after ICH. These results suggest that NAD+ has no neuroprotective effect at 24 hours after ICH.

A tracheobronchial stent insertion was scheduled under general anesthesia in a 67-year-old man with a gastric tube-bronchial fistula after esophagectomy for cancer. Because the duration of apnea was expected to be long, we decided to use percutaneous cardiopulmonary support (PCPS) for gas exchange. The catheter insertion for PCPS was done under spinal anesthesia to eliminate pain during the procedure. Total intravenous anesthesia was performed after PCPS started, and the patient was intubated orally. When the Y-stent was inserted through a rigid bronchoscope, the patient had to be extubated. After extubation, oxygen saturation in his right hand dropped temporarily, whereas that in his left hand remained at 100%. This discrepancy occurred because arterial blood that was not fully oxygenated circulated in his right limb due to cardiac output rather than PCPS. We could minimize this desaturation in the right limb by ventilating the right lung through intubation into the right main trachea. We were able to manage this patient without critical accidents through detailed planning and special attention under PCPS.

Tetrahydrobiopterin (BH4) is an essential cofactor for nitric oxide synthase (NOS) and is presently used clinically to treat forms of phenylketonuria. BH4 has been reported to restrain superoxide generation of NOS and chemically reduce superoxide. However, there has been no report concerning the effects of BH4 in intracerebral hemorrhage (ICH). In the present study, we investigated the neuroprotective effect of BH4 against ICH-induced brain injury in a mouse model.A total of 26 male CD1 mice (31-39 g) were divided into sham, ICH-vehicle, and ICH-treated with BH4 groups (n = 8 in each group). ICH was induced by collagenase injection into the right basal ganglia. BH4 (20 mg/kg) was administrated intraperitoneally at 1 h after ICH. The effect of BH4 was measured by neurological score and brain water content at 24 h after ICH.Our data demonstrates that ICH caused significant neurological deficit that is associated with brain edema. Treatment with BH4 did not reduce brain edema and neurological deficits at 24 h after ICH in mice. Further study is required to investigate the long-term effect of BH4 in ICH-induced brain injury.

Immediate pretreatment with either hyperbaric (2.5ATM, 1 h) or normobaric oxygen (100% FIO2, 1 h) increased brain edema and worsened neurological function at 24 h following SBI.