Characteristics of MRI Findings after Subarachnoid Hemorrhage and D-Dimer as a Predictive Value for Early Brain Injury.

BACKGROUND: The pathological mechanisms of early brain injury (EBI) have remained obscure. Several studies have reported on the neuroradiological findings of EBI. However, to our knowledge, no study has attempted to explore the mechanism of EBI after subarachnoid hemorrhage (SAH). Therefore, this study evaluates whether the initial plasma D-dimer levels were associated with EBI, classifies magnetic resonance imaging (MRI) findings, and speculates about the mechanism of EBI. METHODS: This study included 97 patients hospitalized within 24 h from the onset of nontraumatic SAH. The patients underwent MRI within 0-5 days from onset (before vasospasm) to detect EBI. EBI was radiologically defined as diffusion-weighted imaging (DWI)-positive lesions that appear dark on apparent diffusion coefficient maps, excluding procedure-related lesions. EBI, plasma D-dimer levels, and clinical features were retrospectively investigated. RESULTS: Elevated D-dimer levels were associated with poor outcomes. Patients with EBI had significantly higher D-dimer levels than those without EBI. EBI was detected in 24 patients (27.3%) of all, and in 22 (45%) of 49 patients with World Federation of Neurosurgical Societies (WFNS) grade 4-5 SAH. EBI was frequently observed in the paramedian frontal lobe. There were several types of the pathology in EBI, including widespread symmetrical cerebral cortex lesions, focal cortex lesions, periventricular injury, and other lesions impossible to classify due to unknown mechanisms such as thrombotic complication and microcirculatory disturbance, ultra-early spasm, and spreading depolarization. CONCLUSIONS: This study suggests that D-dimer levels predict poor outcomes in patients with SAH and that EBI was associated high D-dimer levels.

Ligand-Enabled Copper-Catalyzed N-Alkynylation of Sulfonamide with Alkynyl Benziodoxolone: Synthesis of Amino Acid-Derived Ynamide.

Ynamides are versatile building blocks in organic synthesis. However, the synthesis of amino acid-derived ynamides is difficult but in high demand. Herein, we disclose the copper-catalyzed Csp-N coupling of sulfonamide, including amino acid and peptide derivatives, to give ynamides by using alkynyl benziodoxolones with broad functional group tolerance under mild reaction conditions. The electron-rich bipyridine as a ligand and ethanol as solvent were used for the success of this reaction. The usefulness of the obtained amino acid-derived ynamide as building block was showcased by further derivatization to unique amino acid derivatives. A control experiment to elucidate the mechanistic insight was also described.

N-Alkenylation of hydroxamic acid derivatives with ethynyl benziodoxolone to synthesize cis-enamides through vinyl benziodoxolones.

The stereoselective synthesis of cis-ß-N-alkoxyamidevinyl benziodoxolones (cis-ß-N-RO-amide-VBXs) from O-alkyl hydroxamic acids in the presence of an ethynyl benziodoxolone-acetonitrile complex (EBX-MeCN) is reported herein. The reaction was performed under mild conditions including an aqueous solvent, a mild base, and room temperature. The reaction tolerated various O-alkyl hydroxamic acids derived from carboxylic acids, such as amino acids, pharmaceuticals, and natural products. Vinyl dideuterated cis-ß-N-MeO-amide-VBXs were also synthesized using deuterium oxide as the deuterium source. Valine-derived cis-ß-N-MeO-amide-VBX was stereospecifically derivatized to hydroxamic acid-derived cis-enamides without the loss of stereoselectivity or reduction in the deuterium/hydrogen ratio.

Spontaneous Cervical Epidural Hematoma Treated with rt-PA: A Pitfall in Stroke Practice.

Although hemorrhagic complications may arise with thrombolytic therapy using recombinant tissue plasminogen activator (rt-PA), deterioration following administration of rt-PA for hemorrhagic disease is an iatrogenic complication. Caution has recently been raised regarding aortic dissection. A case of cervical epidural hematoma treated with rt-PA is reported herein. The patient was an 87-year-old woman with a history of hemodialysis, brainstem infarction, and stenosis of bilateral internal carotid arteries treated with ticlopidine. She was transferred to our hospital with severe occipital and neck pain. Diffusion-weighted imaging revealed patchy signal hyperintensity in the left cerebellar hemisphere. Right hemiparesis appeared 2 h later, but repeat magnetic resonance imaging (MRI) revealed no new lesions. Administration of rt-PA was performed under a diagnosis of hyper-acute cerebral infarction. Irregular hemodialysis was initiated for pulmonary edema. Complete tetraplegia appeared after hemodialysis, 10 h after rt-PA administration. Repeat MRI revealed cervical epidural hematoma, and hematoma removal was performed. After 10 days, hemiparesis recovered to manual muscle testing (MMT) 2 in the left extremities but remained at MMT0 in the right extremities. Cervical epidural hematoma is a rare complication in stroke practice. Although rt-PA should be administered as soon as possible, since "time is brain," spending a few minutes on spinal MRI is preferable to prevent iatrogenic deterioration. For atypical cases of cerebral infarction, the possibility of cervical epidural hematoma should be considered.

Complication rate, cure rate, and long-term outcomes of microsurgery for intracranial dural arteriovenous fistulae: a multicenter series and systematic review.

Although microsurgery is an established treatment modality for intracranial dural arteriovenous fistula (dAVF), data regarding the perioperative complication rate, cure rate, and long-term outcomes remain scarce. The aims of this study were to describe our original experience with microsurgery, including the surgical complications and pitfalls, and conduct a systematic review of the relevant literature. A multicenter cohort of patients with dAVF treated by microsurgery was retrospectively assessed. In addition, the PubMed database was searched for published studies involving microsurgery for dAVF, and the complication rate, cure rate, and long-term outcomes were estimated. The total number of patients in our multicenter series and published articles was 553 (593 surgeries). The overall rates of transient complications, permanent complications, death, and incomplete treatment were 11.4, 4.0, 1.2, and 6.5%, respectively. A favorable outcome was achieved for 90.1% patients, even though almost half of the patients presented with intracranial hemorrhage. Of note, the incidence of recurrence was only one per 8241 patient-months of postoperative follow-up. Surgeries for anterior cranial fossa dAVF were associated with a lower complication rate, whereas those for tentorial dAVF were associated with higher complication and incomplete treatment rates. The complication and incomplete treatment rates were lower with simple disconnection of cortical venous drainage than with radical occlusion/resection of dural shunts. Our findings suggest that the cure rate, complication rates, and outcomes of microsurgery for dAVF are acceptable; thus, it could be a feasible second-line treatment option for dAVF. However, surgeons should be aware of the specific adverse events of microsurgery.

Long-Term Clinical Outcome and Prognosis After Thrombectomy in Patients With Concomitant Malignancy.

Endovascular thrombectomy (EVT) is the preferred treatment strategy for patients with acute ischemic stroke (AIS). However, clinical outcome and prognosis in patients who undergo EVT in response to AIS with concomitant malignancy have not been fully elucidated. Data of patients with malignancy who underwent EVT at participating institutions between January 2015 and April 2019 were retrospectively analyzed. Patient characteristics, treatment methods, posttreatment strategy, and long-term prognosis were evaluated in 12 patients with prediagnoses of malignancy. Good revascularization (TICI 2b or higher) was achieved in 10 of 12 patients. Among the eight patients who survived more than 2 weeks from onset, four patients showed good clinical outcome [modified Rankin Scale (mRS) <2] at 60 days posttreatment and were able to continue treatment for malignancy. However, seven of eight patients died within a year of EVT (median survival, 83 days) due to progression of malignancy. One-year survival was achieved in only one patient whose etiology of stroke was determined as infectious endocarditis and not Trousseau syndrome. Even after successful revascularization and good short-term clinical outcome, the long-term prognosis after thrombectomy in patients with malignancy was poor. Thrombectomy for concomitant malignancy requires judicious decision, and further studies are necessary to fully elucidate its efficacy.

Synthesis of Phenol-Derived cis-Vinyl Ethers Using Ethynyl Benziodoxolone.

The stereoselective synthesis of cis-ß-phenoxyvinyl benziodoxolones (cis-ß-phenol-VBXs) from an ethynyl benziodoxolone-acetonitrile complex (EBX-MeCN) and various phenols is reported herein. The reaction tolerates different phenol derivatives, including complex natural products, and can be conducted under mild conditions. The synthesis was performed in an aqueous solvent in the absence and presence of a catalytic amount of a base. Selectively mono- and di-deuterated cis-ß-phenol-VBXs were also prepared. cis-ß-Phenol-VBXs were stereospecifically derivatized to cis-alkynylvinyl ethers and cis-iodovinyl ethers without loss of stereoselectivity or reduction in the deuterium/hydrogen ratio.

Acute systematic inflammatory response syndrome and serum biomarkers predict outcomes after subarachnoid hemorrhage.

Subarachnoid hemorrhage (SAH) can trigger immune activation sufficient to induce systematic inflammatory response syndrome (SIRS). Serum inflammatory biomarkers and SIRS can predict a poor outcome. The relationship between surgical stress and inflammatory response is well known but described in few reports in the neurosurgical population. We aimed to ascertain whether postoperative SIRS and initial serum biomarkers were associated with outcomes and evaluate whether the postoperative SIRS score differed between those with clipping and coil embolization. We evaluated 87 patients hospitalized within 24 h from onset of nontraumatic SAH. Serum biomarkers, such as levels of C-reactive protein (CRP), white blood cells (WBC), and D-dimer, as well as stress index (SI: blood sugar/K ratio) were obtained at admission. SIRS scores 3 days after admission were derived by adding the number of variables meeting the standard criteria (heart rate [HR] >90, respiratory rate [RR] >20, temperature >38 °C or <36 °C, and WBC count <4000 or >12,000). Clinical variables were compared according to whether they were associated with poor outcomes. Coil embolization was performed in 30 patients and clipping in 57. WBC, SI, D-dimer levels, and SIRS scores were significantly higher in patients with poor-grade SAH and were associated with poor outcomes. SIRS scores were significantly higher with clipping than with coil embolization among patients with good-grade SAH without intracerebral hemorrhage. Acute SIRS and serum biomarkers predict outcomes after SAH. Moreover, our study suggests the influence of surgical invasion via clipping on SIRS after SAH.

Synthesis of cis-ß-Amidevinyl Benziodoxolones from the Ethynyl Benziodoxolone-Chloroform Complex and Sulfonamides.

The synthesis of cis-ß-amidevinyl benziodoxolones from the ethynyl benziodoxolone-chloroform complex and sulfonamides is reported. Evidence indicates that highly reactive unsubstituted ethynyl benziodoxolone undergoes Michael addition of sulfonamides, including sterically demanding acyclic amino acid derivatives. The synthesis of selectively deuterated cis-ß-amidevinyl benziodoxolones and investigation of ethynyl-λ3-iodane reactivity are also described.

Synthesis, Characterization, and Reactivity of an Ethynyl Benziodoxolone (EBX)-Acetonitrile Complex.

The synthesis of a crystalline ethynyl-1,2-benziodoxol-3(1 H)-one (EBX)-acetonitrile complex is described. EBX has been widely used as an active species for a variety of reactions; however, its high instability has so far prevented its isolation. The EBX-acetonitrile is self-assembled into a double-layered honeycomb structure through weak hypervalent iodine secondary interactions and hydrogen bonding. The N-ethynylation of a variety of sulfonamides using the EBX-acetonitrile complex as a substrate under mild conditions is also described.

[Dural Arteriovenous Fistulae in the Tentorium Manifesting as Dementia].

BACKGROUND: Tentorial dural arteriovenous fistula(dAVF)is a relatively rare disease which accounts for about 4.8% of all types of dAVF reported in Japan. Approximately 12.5% of intracranial dAVFs manifest with dementia-like symptoms. However, a tentorial dAVF typically presents more aggressively and rarely manifests as dementia. Here, we report the case of a patient with a tentorial dAVF manifesting as dementia, who was successfully treated with surgical interruption of the draining vein using indocyanine green video angiography(ICG-VA). CASE PRESENTATION: A case of a 69-year-old man with a history of colon cancer, hypertension, and previous stroke presenting with cognitive impairment. CT showed multiple intracranial hemorrhages in the left parietal and occipital lobes, and MRI demonstrated flow void in the left cerebellopontine angle. DSA revealed left tentorial dAVF with venous reflux. We performed surgical interruption of the draining vein. The patient's mental status immediately returned to baseline. Serial MRIs showed decreasing edema in the left occipital lobe and thalamus. CONCLUSIONS: Cognitive impairment is an uncommon but curable symptom of tentorial dAVF. Surgical interruption of the draining vein using ICG-VA is a relatively simple and safe procedure to perform in such a case.

Novel Hemoglobin-Based Oxygen Carrier Bound With Albumin Shows Neuroprotection With Possible Antioxidant Effects.

Background and Purpose- A hemoglobin-albumin cluster, 1 core of hemoglobin covalently bound with 3 shell albumins, designated as HemoAct was developed as a hemoglobin-based oxygen carrier. We aim to investigate neuroprotection by HemoAct in transient cerebral ischemia and elucidate its underlying mechanisms. Methods- Male rats were subjected to 2-hour transient middle cerebral artery occlusion and were then administered HemoAct transarterially at the onset of reperfusion. Neurological and pathological findings were examined after 24 hours of reperfusion to identify neuroprotection by HemoAct. Intermittent measurements of cortical blood flow and oxygen content were performed, and a histopathologic analysis was conducted on rats during the early phase of reperfusion to assess the therapeutic mechanism of HemoAct. In addition, the antioxidant effects of HemoAct were examined in hypoxia/reoxygenation-treated rat brain microvascular endothelial cells. Results- Neurological deterioration, infarct and edema development, and the activation of MMP-9 (matrix metalloprotease-9) and lipid peroxidation after 24 hours of reperfusion were significantly ameliorated by the HemoAct treatment. Reductions in blood flow and tissue partial oxygen pressure in the cortical penumbra after 6 hours of reperfusion were significantly ameliorated by the HemoAct treatment. The histopathologic analysis of the cortical penumbra revealed that HemoAct in HemoAct-treated rats showed superior microvascular perfusion with the mitigation of microvascular narrowing changes than autologous erythrocytes in nontreated rats. Although HemoAct extravasated into the ischemic core with serum protein, it did not induce an increase in serum extravasation or reactive oxygen species production in the ischemic core. In vitro experiments with rat brain microvascular endothelial cells revealed that HemoAct significantly suppressed cellular reactive oxygen species production in hypoxia/reoxygenation-treated cells, similar to albumin. Conclusions- HemoAct exerted robust neuroprotection in transient cerebral ischemia. Superior microvascular perfusion with an oxygen delivery capability and possible antioxidant effects appear to be the underlying neuroprotective mechanisms.

Superficial Temporal Artery-Superior Cerebellar Artery Bypass with Anterior Petrosectomy.

BACKGROUND: Superficial temporal artery (STA) to superior cerebellar artery (SCA) bypass is associated with a relatively high risk of surgical complications, such as hematoma and/or edema caused by temporal lobe retraction. Therefore, the right side is typically used to avoid retraction of the left temporal lobe. In this report, we present a case of left STA-SCA bypass with anterior petrosectomy to avoid retraction of dominant-side temporal lobe and describe the surgical technique in detail. CASE DESCRIPTION: A 69-year-old man presented with gradual worsening of dysarthria and gait disturbance. Magnetic resonance imaging showed no signs of acute infarction, but digital subtraction angiography showed severe stenosis of basilar artery and faint flow in the distal basilar artery. On 3-dimensional computed tomography angiography, posterior communicating arteries were not visualized; we could identify the left SCA, but not the right SCA. Despite dual antiplatelet therapy, a small fresh brainstem infarct was detected 10 days after admission. To avert fatal brainstem infarction and further enlargement of the infarct, we performed left STA-SCA bypass with anterior petrosectomy to avoid retraction of the dominant-side temporal lobe. Postoperative imaging revealed no new lesions, such as infarction or temporal lobe contusional hematoma, and confirmed the patency of the bypass. Postoperative single-photon emission computed tomography demonstrated improved cerebral blood flow in the posterior circulation. The patient was transferred to another hospital for rehabilitation. CONCLUSIONS: This method helps minimize the risk of injury to the temporal lobe, especially that of the dominant side.

Impact of Antiplatelets and Anticoagulants on the Prognosis of Intracerebral Hemorrhage.

BACKGROUND: Intracerebral hemorrhage (ICH) associated with antithrombotic therapy (AT) is becoming more common as the use of those medications increases in the aging population. METHODS: This study included 490 consecutive patients hospitalized for nontraumatic ICH in a single center during an 8-year period, which was subdivided into former (2008-2011) and latter (2012-2015). Patients were classified into those with no antithrombotic drugs (NATs) and those with AT. The AT group was divided into 4 subgroups according to medications: antiplatelet (AP1), multiple antiplatelets (AP2), anticoagulant (AC), and antiplatelet and anticoagulant (APC). We evaluated the clinical characteristics and prognosis and compared the number of patients on AT between the former and latter groups. RESULTS: There were 125 patients treated with AT (25.5%), including 50 (10.2%) on AP1, 14 (2.9%) on AP2, 32 (6.5%) on ACs, and 29 (5.9%) on APCs. Compared with the former group, the latter group had a higher number of patients on AT (19.3% versus 31.7%), AP1 (9.8% versus 10.6%), AP2 (1.6% versus 4.1%), ACs (4.9% versus 8.1%), and APCs (2.90% versus 8.9%). Compared with the NAT group, the patients in the AT group had a larger ICH volume, more frequent hematoma expansion, and higher rate of poor outcome, particularly for those on APCs. CONCLUSION: The number of ICH patients on AT has increased; these patients were more likely to have a poor prognosis than those who were not on AT. Care should be taken when giving a combination of antiplatelets and anticoagulants in ICH.

Superior Microvascular Perfusion of Infused Liposome-Encapsulated Hemoglobin Prior to Reductions in Infarctions after Transient Focal Cerebral Ischemia.

BACKGROUND: The development of cerebral infarction after transient ischemia is attributed to postischemic delayed hypoperfusion in the microvascular region. In the present study, we assessed the microvascular perfusion capacity of infused liposome-encapsulated hemoglobin (LEH) in a therapeutic approach for transient middle cerebral artery occlusion (tMCAO). METHODS: Two-hour middle cerebral artery occlusion rats were immediately subjected to intra-arterial infusion of LEH (LEH group) or saline (vehicle group) or no treatment (control group), and then to recanalization. Neurological findings, infarct and edema progression, microvascular endothelial dysfunction, and inflammatory reactions were compared between the 3 groups after 24 hours of reperfusion. Microvascular perfusion in the early phase of reperfusion was evaluated by hemoglobin immunohistochemistry and transmission electron microscopy. RESULTS: The LEH group achieved significantly better results in all items evaluated than the other groups. Hemoglobin immunohistochemistry revealed that the number of hemoglobin-positive microvessels was significantly greater in the LEH group than in the other groups (P < .01), with microvascular perfusion being more likely in narrow microvessels (≤5 µm in diameter). An electron microscopic examination revealed that microvessels in the control group were compressed and narrowed by swollen astrocyte end-feet, whereas those in the LEH group had a less deformed appearance and contained LEH particles and erythrocytes. CONCLUSION: The results of the present study demonstrated that the infusion of LEH reduced infarctions after tMCAO with more hemoglobin-positive and less deformed microvessels at the early phase of reperfusion, suggesting that the superiority of the microvascular perfusion of LEH mediates its neuroprotective effects.

Treatment of Recurrent Intracranial Aneurysms After Clipping: A Report of 23 Cases and a Review of the Literature.

OBJECTIVE: There are no established treatment strategies for aneurysms that recur after clipping. In this study, we present cases of patients who experienced recurrent aneurysms after clipping and subsequently underwent surgical intervention. METHODS: Between 2004 and 2015, we surgically treated 23 aneurysms that recurred at a previously clipped site. Patient characteristics and clinical history were retrospectively reviewed. RESULTS: Patients included 19 women and 4 men 45-81 years old. Aneurysms recurred 3-31 years (mean, 15.4 years) after the initial operation. For 18 cases, the first clinical presentation was a subarachnoid hemorrhage; aneurysms were incidentally diagnosed in 5 patients. Aneurysm locations were as follows: 9 on the internal carotid artery; 4 on the middle cerebral artery; 7 on the anterior communicating artery; 2 on the distal anterior cerebral artery; and 1 on the basilar artery. The reasons for retreatment included subarachnoid hemorrhage (n = 9) and aneurysm regrowth detected on follow-up examinations (n = 14). Endovascular treatment was performed in 10 cases, and direct surgery was performed in 13 cases (clipping in 8, clipping or trapping with bypass in 5). Various complex vascular reconstructions, including high-flow bypass and intracranial-intracranial in situ bypass, were performed for recurrent aneurysms. CONCLUSIONS: In our experience, coil embolization is a safe and effective procedure for treating recurrent aneurysms. When cases are unsuitable for coil embolization, surgical treatment often requires neurosurgeons not only to overcome the general technical difficulty of reoperative clipping but also to perform challenging vascular reconstruction.

Transarterial Regional Brain Hypothermia Inhibits Acute Aquaporin-4 Surge and Sequential Microvascular Events in Ischemia/Reperfusion Injury.

BACKGROUND: Although transarterial regional hypothermia is an attractive alternative to general hypothermia, its efficacy and underlying mechanisms remain unclear. OBJECTIVE: To confirm transarterial regional hypothermia therapeutic effects on ischemia/reperfusion (I/R) injury and to elucidate the mechanisms responsible. METHODS: The therapeutic effects of transarterial regional hypothermia were initially investigated in 2-hour middle cerebral artery occlusion rats regionally infused with 10°C saline (cold saline group) or 37°C saline (warm saline group) and untreated rats (control group) just before the onset of 24 hours of reperfusion. The time course of infarct and edema progression, inflammatory reactions, microvascular morphological changes, and aquaporin-4 (AQP4) expression was analyzed after 0, 2, 6, and 24 hours of reperfusion. RESULTS: Cold saline infusion only lowered brain temperatures for 30 minutes but mediated strong neuroprotective effects with infarct volume reductions of less than one-third. The time-course analysis revealed the following sequence of ischemia/reperfusion injury-related events in the control group: upregulated expression of AQP4 (2 hours); microvascular narrowing resulting from swollen astrocytic end-feet (2-6 hours); infarct and edema progression, blood-brain barrier disruption, and upregulated expression of intracellular adhesion molecule-1 (6-24 hours); and the activation of other inflammatory reactions (24 hours). These sequential events were inhibited in the cold saline group. CONCLUSION: Transarterial regional hypothermia initially inhibited the acute AQP4 surge and then attenuated microvascular narrowing, blood-brain barrier disruption, and activation of other inflammatory reactions, leading to strong neuroprotective effects. More direct and intensive cooling of the endothelium and its surroundings may contribute to these effects. ABBREVIATIONS: AQP4, aquaporin-4BBB, blood-brain barrierIba1, ionized calcium-binding adapter molecule 1ICA, internal carotid arteryICAM-1, intracellular adhesion molecule-1I/R, ischemia/reperfusionMCAO, middle cerebral artery occlusionMMP-9, matrix metalloproteinase-9.

[Metronidazole-Induced Encephalopathy during Brain Abscess Treatment:Two Case Reports].

Metronidazole is a widely used antibiotic against anaerobic bacteria and protozoa. We report two cases of metronidazole-induced encephalopathy(MIE)during treatment of a brain abscess with metronidazole. The patients developed mental disturbance, and brain MRI showed reversible signals on DWI, FLAIR, and T2. Case 1: A 48-year-old woman was admitted to our hospital with a cerebellar abscess. We initiated treatment with oral metronidazole. After taking the medication, she developed mental disturbance, and her brain MRI showed a hyperintensity within the corpus callosum. We suspected metronidazole toxicity and discontinued metronidazole treatment. The symptoms resolved rapidly within a week, and the hyperintensity on the MRI disappeared. Case 2: A 22-year-old man was admitted to our hospital with a brain abscess. We initiated treatment with oral metronidazole. On day 38, he developed mental disturbance, and his MRI showed hyperintensities within the bilateral dentate nuclei and corpus callosum. These symptoms were consistent with MIE. After cessation of metronidazole, his symptoms and abnormal MRI signals completely disappeared.

Reappraisal of Microsurgical Revascularization for Anterior Circulation Ischemia in Patients with Progressive Stroke.

BACKGROUND: Intravenous thrombolysis using tissue plasminogen activator and endovascular treatment for acute ischemic stroke is becoming an established standard therapy. However, there is no consensus in the treatment of patients who are suffering from progressive neurologic symptoms in the later stages. The purpose of this study was to evaluate the safety and efficacy of microsurgical revascularization in such patients with progressive stroke. METHODS: We retrospectively reviewed the clinical and radiological records of 14 consecutive patients with progressive stroke who underwent emergency open surgery for anterior circulation occlusion within 7 days after onset. Surgical candidates were carefully selected on the basis of symptom severity, diffusion-weighted imaging, and perfusion study. Superficial temporal artery to middle cerebral artery bypass was applied for atherosclerotic occlusion, and microsurgical embolectomy was applied for embolic occlusion. RESULTS: Superficial temporal artery to middle cerebral artery bypass was performed in 12 patients, microsurgical embolectomy in 1, and the combination of these modalities in 1. As a result, complete revascularization was achieved in all patients. The National Institutes of Health Stroke Scale scores significantly improved after surgery (at third postoperative day, P < 0.05; at 14th postoperative day, P < 0.01). A favorable outcome (modified Rankin Scale 0-2) was achieved in 12 of the 14 (85.7%) patients. Minor intracerebral hemorrhage occurred in 1 patient and hyperperfusion syndrome occurred in 1 patients; however, the patients subsequently recovered without additional treatment. CONCLUSIONS: Microsurgical revascularization is a feasible treatment option for patients with progressive stroke due to anterior circulation major vessel occlusion.

Post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin can reduce ischemia reperfusion injury.

Despite successful revascularization, reperfusion after prolonged ischemia causes ischemia reperfusion (I/R) injury. Recruitment and activation of neutrophils is thought to be a key event causing I/R injury. We examined whether post-ischemic intra-arterial infusion of liposome-encapsulated hemoglobin (LEH), an artificial oxygen carrier without neutrophils, could reduce I/R injury in a rat transient middle cerebral artery occlusion (MCAO) model. Male Sprague-Dawley rats were subjected to 2-h MCAO and then were divided into three groups: (1) LEH group (n=7) infused with LEH (Hb concentration of 6g/dl, 10ml/kg/h) through the recanalized internal carotid artery for 2h, (2) vehicle group (n=8) infused with saline (10ml/kg/h) in the same manner as the LEH group, and (3) control group (n=9) subjected to recanalization only. After 24-h reperfusion, all rats were tested for neurological score and then sacrificed to examine infarct and edema volumes, myeloperoxidase (MPO) expression, matrix metalloproteinase-9 (MMP-9) expression and activity, and reactive oxygen species (ROS) production. Compared with the control group and the vehicle group, the LEH group showed a significantly better neurological score and significantly smaller infarct and edema volumes. MPO expression, MMP-9 expression and activity, and ROS production in the LEH group were also significantly lower than those in the control and vehicle groups. The results in the present study suggest that post-ischemic intra-arterial infusion of LEH can reduce I/R injury through reducing the effect of MMP-9, most likely produced by neutrophils. This therapeutic strategy may be a promising candidate to prevent I/R injury after thrombolysis and/or thromboectomy.