Anti-HMGB1 mAb may provide a novel and effective therapy for TBI by protecting against BBB disruption and reducing the inflammatory responses induced by HMGB1.
BackgroundMost of the results regarding hydrogen (H2) therapy for acute cerebral ischemia are derived from in vitro studies and animal experiments, with only a few obtained from human trials with a limited number of subjects. Thus, there is a paucity of information regarding both the beneficial therapeutic effects as well as the side effects of H2 on acute cerebral ischemia in humans. We designed a pilot study to investigate single dose intravenous H2-administration in combination with edaravone, aiming to provide an initial estimate of the possible risks and benefits in select patients presenting with acute ischemic stroke.MethodsAn open-label, prospective, non-randomized study of intravenous H2-administration was performed in 38 patients hospitalized for acute ischemic stroke. All patients received an H2-enriched intravenous solution in addition to edaravone immediately after the diagnosis of acute ischemic stroke. Acute stroke patients within 3 h of onset received intravenous tissue plasminogen activator (t-PA) (0.6 mg/kg) treatment, and patients receiving t-PA had to commence the administration of the H2-enriched intravenous solution and edaravone before or at the same time as the t-PA was infused.ResultsComplications were observed in 2 patients (5.3%), which consisted of diarrhea in 1 patient (2.6%) and cardiac failure in 1 patient (2.6%). No deterioration in laboratory tests, urinary tests, ECG, or chest X-ray radiograms occurred in any patient in this study. In all patients, the mean National Institutes of Health Stroke Scale (NIHSS) scores at baseline, and 7, 30, and 90 d after admission were 8.2 ± 7.5, 5.6 ± 7.1, 4.9 ± 6.5, and 4.5 ± 6.3, respectively. The early recanalization was identified in 4 of 11 patients (36.4%) who received intravenous t-PA administration. Hemorrhagic transformation was observed in 2 patients (18.2%). None of the patients in this study that were treated with t-PA developed symptomatic intracranial hemorrhage.ConclusionsData from the current study indicate that an H2-enriched intravenous solution is safe for patients with acute cerebral infarction, including patients treated with t-PA.
Decompressive craniectomy is one therapeutic option for severe traumatic brain injury (TBI), and it has long been used for the treatment of patients with malignant post-traumatic brain edema. A lack of definitive evidence, however, prevents physicians from drawing any conclusions about the effects of decompressive craniectomy for the treatment of TBI. Therefore, the aim of the present study was to investigate the influence of decompressive craniectomy on post-traumatic brain edema formation. The aquaporin-4 (AQP4) water channel is predominantly expressed in astrocytes, and it plays an important role in the regulation of brain water homeostasis. In the present study, we investigated the time course of AQP4 expression and the water content of traumatized cortex following decompressive craniectomy after TBI. Adult male Sprague-Dawley rats (300-400 g) were subjected to lateral fluid percussion injury using the Dragonfly device. The effect of decompressive craniectomy was studied in traumatized rats without craniectomy (closed skull, DC-), and in rats craniectomized immediately after trauma (DC+). AQP4 expression was investigated with a Western blot analysis and immunohistochemistry. Brain edema was measured using the wet weight/dry weight method. At 48 h after TBI, AQP4 expression of the DC- group was significantly increased compared with the DC+ group (p < 0.01). In addition, the cortical water content of the DC- group was significantly increased compared to the DC+ group at the same time point (p < 0.05). The present results suggest that decompressive craniectomy may affect AQP4 expression and reduce brain edema formation after TBI.
OBJECTIVE Advanced age is known to be associated with a poor prognosis after surgical clipping of unruptured intracranial aneurysms (UIAs). Keyhole clipping techniques have been introduced for less invasive treatment of UIAs. In this study, the authors compared the complications and clinical and radiological outcomes after keyhole clipping between nonfrail elderly patients (≥ 70 years) and nonelderly patients. METHODS Keyhole clipping (either supraorbital or pterional) was performed to treat 260 cases of relatively small (≤ 10 mm) anterior circulation UIAs. There were 62 cases in the nonfrail elderly group (mean age 72.9 ± 2.6 years [± SD]) and 198 cases in the nonelderly group (mean age 59.5 ± 7.6 years). The authors evaluated mortality and morbidity (modified Rankin Scale score > 2 or Mini-Mental State Examination [MMSE] score < 24) at 3 months and 1 year after the operation, the general cognitive function by MMSE at 3 months and 1 year, anxiety and depression by the Beck Depression Inventory (BDI) and Hamilton Rating Scale for Depression (HAM-D) at 3 months, and radiological abnormalities and recurrence at 1 year. RESULTS Basic characteristics including comorbidities, frailty, and BDI and HAM-D scores were not significantly different between the 2 groups, whereas the MMSE score was slightly but significantly lower in the elderly group. Aneurysm location, largest diameter, type of keyhole surgery, neck clipping rate, and hospitalization period were not significantly different between the 2 groups. The incidence of chronic subdural hematoma was not significantly higher in the elderly group than in the nonelderly group (8.1% vs 4.5%, p = 0.332); rates of other complications including stroke and epilepsy were not significantly different. Lacunar infarction occurred in 3.2% of the elderly group and 3.0% of the nonelderly group. No patient in the elderly group required re-treatment or demonstrated recurrence of clipped aneurysms. The MMSE score at 3 months significantly improved in the nonelderly group but did not change in the elderly group. The BDI and HAM-D scores at 3 months were significantly improved in both groups. No patient died in either group. The morbidity at 3 months and 1 year in the elderly group (1.6% and 4.8%, respectively) was not significantly different from that in the nonelderly group (2.0% and 1.5%, respectively). CONCLUSIONS Keyhole clipping for nonfrail elderly patients with relatively small anterior circulation UIAs did not significantly increase the complication, mortality, or morbidity rate; hospitalization period; or aneurysm recurrence compared with nonelderly patients, and it was associated with improvement in anxiety and depression. Keyhole clipping to treat UIAs in the nonfrail elderly is an effective and long-lasting treatment.
Lateral supraorbital keyhole approach to clip relatively small unruptured AcomA aneurysm promises less invasive and durable treatment.
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