OBJECTIVE: The precise incidence and prevalence of idiopathic normal-pressure hydrocephalus (INPH) is not known, and evidence-based clinical diagnostic criteria have not been developed previously. This report contains evidence-based guidelines for clinical diagnosis of INPH that are intended to facilitate future epidemiological studies of INPH, promote earlier and more accurate diagnosis, and ultimately improve treatment outcome. METHODS: The criteria for the diagnosis of INPH are based on evidence from the medical literature, supplemented as necessary by expert opinion. From 1966 to 2003, 653 publications on “normal-pressure hydrocephalus” were cited in MEDLINE, including 29 articles that met the more stringent criteria of including “idiopathic normalpressure hydrocephalus” in their title. Additional studies were considered that explicitly identified INPH cases and/or specified the criteria for a diagnosis of INPH. Studies were graded according to the class of evidence and results summarized in evidentiary tables. For issues of clinical relevance that lacked substantive evidence from the medical literature, the opinions of consulting experts were considered and contributed to “Options.” RESULTS: Evidence-based guidelines for the clinical diagnosis of INPH have been developed. A detailed understanding of the range of clinical manifestations of this disorder and adherence to practice guidelines should improve the timely and accurate recognition of this disorder. CONCLUSION: It is recommended that INPH be classified into probable, possible, and unlikely categories. We hope that these criteria will be widely applied in clinical practice and will promote greater consistency in patient selection in future clinical investigations involving INPH.

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Diagnosing idiopathic normal-pressure hydrocephalus.

https://www.cell.com/trends/cell-biology/pdf/S0962-8924(11)00177-2.pdf

Sphingosine-1-phosphate signaling and its role in disease

Rupture of an intracranial aneurysm is the leading cause of subarachnoid hemorrhage not due to trauma. This review summarizes both the approach to establishing the diagnosis and treatment options, including the placement of intravascular coils to arrest the bleeding. Common management problems include vasospasm, hydrocephalus, and rebleeding.

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Aneurysmal subarachnoid hemorrhage.

Immune and inflammatory mechanisms in neuropathic pain.

Subarachnoid haemorrhage (SAH) causes early brain injury (EBI) that is mediated by effects of transient cerebral ischaemia during bleeding plus effects of the subarachnoid blood. Secondary effects of SAH include increased intracranial pressure, destruction of brain tissue by intracerebral haemorrhage, brain shift, and herniation, all of which contribute to pathology. Many patients survive these phenomena, but deteriorate days later from delayed cerebral ischaemia (DCI), which causes poor outcome or death in up to 30% of patients with SAH. DCI is thought to be caused by the combined effects of angiographic vasospasm, arteriolar constriction and thrombosis, cortical spreading ischaemia, and processes triggered by EBI. Treatment for DCI includes prophylactic administration of nimodipine, and current neurointensive care. Prompt recognition of DCI and immediate treatment by means of induced hypertension and balloon or pharmacological angioplasty are considered important by many physicians, although the evidence to support such approaches is limited. This Review summarizes the pathophysiology of DCI after SAH and discusses established treatments for this condition. Novel strategies--including drugs such as statins, sodium nitrite, albumin, dantrolene, cilostazol, and intracranial delivery of nimodipine or magnesium--are also discussed.

Delayed neurological deterioration after subarachnoid haemorrhage

Background and Purpose—FTY720 is a known sphingosine 1–phosphate receptor agonist. In the present study, we investigated the neuroprotective effect of postischemic administration of FTY720 in rats with 2 hours transient middle cerebral artery occlusion (MCAO). Methods—One hundred eleven male rats were randomly assigned to sham-operated and MCAO treated with vehicle, 0.25 mg/kg and 1 mg/kg of FTY720, another selective sphingosine 1–phosphate receptor-1 agonist SEW2871 (5 mg/kg), or 0.25 mg/kg of FTY720 plus a sphingosine 1–phosphate antagonist, VPC23019 (0.5 mg/kg). Drugs were injected intraperitoneally immediately after reperfusion. Neurological score and infarct volume were assessed at 24 and 72 hours after MCAO. Western blotting, immunohistochemistry, and terminal deoxynucleotidyl transferase-mediated uridine 5′-triphosphate-biotin nick end-labeling were conducted at 24 hours after MCAO. Results—FTY720 significantly reduced infarct volume and improved neurological score at 24 and 72 hours after MCAO com...

Activation of Sphingosine 1-Phosphate Receptor-1 by FTY720 Is Neuroprotective After Ischemic Stroke in Rats

Background and Purpose— The role of interleukin (IL)-1β remains unknown in early brain injury (EBI) after subarachnoid hemorrhage (SAH), although IL-1β has been repeatedly reported to increase in the brain and cerebrospinal fluid. The aim of this study is to examine the effects of IL-1β inactivation on EBI after SAH in mice. Methods— The endovascular perforation model of SAH was produced and 112 mice were assigned to sham, SAH+ vehicle, and SAH+ 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-1β 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-1β, 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 si...

Role of Interleukin-1β in Early Brain Injury after Subarachnoid Hemorrhage in Mice

Background and Purpose—We determined which hemodynamic parameter independently characterizes the rupture status of middle cerebral artery (MCA) aneurysms using computational fluid dynamics analysis. Methods—In 106 patient-specific geometries of MCA aneurysms (43 ruptured, 63 unruptured), morphological and hemodynamic parameters were compared between the ruptured and unruptured groups. Multivariate logistic regression analysis was performed to determine parameters that independently characterized the rupture status of MCA aneurysms. Results—Univariate analyses showed that the aspect ratio, wall shear stress (WSS), normalized WSS, oscillatory shear index, WSS gradient, and aneurysm-formation index were significant parameters. The size of the aneurysmal dome and the gradient oscillatory number were not significantly different between the 2 groups. With multivariate analyses, only lower WSS was significantly associated with the rupture status of MCA aneurysms. Conclusions—WSS may be the most reliable paramete...

Low Wall Shear Stress Is Independently Associated With the Rupture Status of Middle Cerebral Artery Aneurysms

Delayed cerebral vasospasm after aneurysmal subarachnoid hemorrhage (SAH) causes cerebral ischemia and infarction. To date, the pathogenesis and gene expression associated with vasospasm remain poorly understood. The present study used fluorescent differential display to identify differentially expressed genes in a rat model of SAH. By using quantitative RT-PCR, we found that heme oxygenase-1 (HO-1) mRNA was prominently induced in the basilar artery and modestly in brain tissue in a rat vasospasm model. A significant correlation was observed between the degree of vasospasm and HO-1 mRNA levels in the basilar arteries exhibiting vasospasm. Intracisternal injection of antisense HO-1 oligodeoxynucleotide (ODN) significantly delayed the clearance of oxyhemoglobin and deoxyhemoglobin from the subarachnoid space and aggravated angiographic vasospasm. Antisense HO-1 ODN inhibited HO-1 induction in the basilar arteries but not in the whole brain tissue. This phenomenon was not observed in the nontreated, sense HO-1 ODN-treated, or scrambled ODN-treated arteries. We report the protective effects of HO-1 gene induction in cerebral vasospasm after SAH, a finding that should provide a novel therapeutic approach for cerebral vasospasm.

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Heme oxygenase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in rats.

Background and Purpose— Osteopontin (OPN) is an inducible, multifunctional, extracellular matrix protein that may be protective against blood-brain barrier (BBB) disruption after subarachnoid hemorrhage (SAH). However, the protective mechanisms remain unclear. Methods— We produced the endovascular perforation model of SAH in rats and studied the time course of OPN induction in brains by Western blotting and immunofluorescence (n=50). Then, 34 rats were randomly assigned to sham (n=3), sham+OPN small interfering RNA (siRNA, n=3), SAH+negative control siRNA (n=14), and SAH+OPN siRNA (n=14) groups, and 109 rats were allocated to sham+vehicle (n=17), sham+recombinant OPN (n=17), SAH+vehicle (n=33), SAH+recombinant OPN (n=31), and SAH+recombinant OPN+l-arginyl-glycyl-l-aspartate motif–containing hexapeptide (n=11) groups. The effects of OPN siRNA or recombinant OPN on BBB disruption and related proteins were studied. Results— OPN was significantly induced in reactive astrocytes and capillary endothelial cells,...

Hidenori Suzuki

Papers

Activation of Sphingosine 1-Phosphate Receptor-1 by FTY720 Is Neuroprotective After Ischemic Stroke in Rats

Role of Interleukin-1β in Early Brain Injury after Subarachnoid Hemorrhage in Mice

Low Wall Shear Stress Is Independently Associated With the Rupture Status of Middle Cerebral Artery Aneurysms

Heme oxygenase-1 gene induction as an intrinsic regulation against delayed cerebral vasospasm in rats.

Mechanisms of Osteopontin-Induced Stabilization of Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in Rats