Kanehisa Kohno

Evolution of regional changes in apparent diffusion coefficient during focal ischemia of rat brain: the relationship of quantitative diffusion NMR imaging to reduction in cerebral blood flow and metabolic disturbances.

Middle cerebral artery occlusion was performed in rats while the animals were inside the nuclear magnetic resonance (NMR) tomograph. Successful occlusion was confirmed by the collapse of amplitude on an electrocorticogram. The ultrafast NMR imaging technique UFLARE was used to measure the apparent diffusion coefficient (ADC) immediately after the induction of cerebral ischemia. ADC values of normal cortex and caudate-putamen were 726 ± 22 × 10−6 mm2/s and 659 ± 17 × 10−6 mm2/s, respectively. Within minutes of occlusion, a large territory with reduced ADC became visible in the ipsilateral hemisphere. Over the 2 h observation period, this area grew continuously. Quantitative analysis of the ADC reduction in this region showed a gradual ADC decrease from the periphery to the core, the lowest ADC value amounting to about 60% of control. Two hours after the onset of occlusion, the regional distribution of ATP and tissue pH were determined with bioluminescence and fluorescence techniques, respectively. There was a depletion of ATP in the core of the ischemic territory (32 ± 20% of the hemisphere) and an area of tissue acidosis (57 ± 19% of the hemisphere) spreading beyond that of ATP depletion. Regional CBF (rCBF) was measured autoradiographically with the iodo[14C]antipyrine method. CBF gradually decreased from the periphery to the ischemic core, where it declined to values as low as 5 ml 100 g−1 min−1. When reductions in CBF and in ADC were matched to the corresponding areas of energy breakdown and of tissue acidosis, the region of energy depletion corresponded to a threshold in rCBF of 18 ± 14 ml 100 g−1 min−1 and to an ADC reduction to 77 ± 3% of control. Tissue acidosis corresponded to a flow value below 31 ± 11 ml 100 g−1 min−1 and to an ADC value below 90 ± 4% of control. Thus, the quantification of ADC in the ischemic territory allows the distinction between a core region with total breakdown of energy metabolism and a corona with normal energy balance but severe tissue acidosis.

Evaluation of prognostic factors following expansive laminoplasty for cervical spinal stenotic myelopathy

BACKGROUND Expansive laminoplasty of several types has been proposed for patients with cervical multisegmental stenotic myelopathy to reduce postlaminectomy complications. Its effectiveness has not been fully explored by evaluating long-term results and magnetic resonance imaging (MRI) findings before and after surgery. METHODS We conducted a 5-year follow-up study of 22 patients with cervical spondylotic myelopathy and/or ossification of the posterior longitudinal ligament surgically treated with expansive laminoplasty. The operative results were examined using the Japanese Orthopedic Association (JOA) disability scale, with reference to the findings of MRI, computed tomography, and radiography. RESULTS Postoperative improvement was observed in 18 (81.8%) of the 22 patients. In 11 patients the percentage recovery of the JOA score was higher than 50% (average: 83.1%), while in the remaining 11 patients it was lower than 50% (average: 20.1%). Factors contributing to incomplete recovery appear to be related mainly to cord degeneration with atrophy (depicted as a T2-high intensity area) and to specific factors such as long symptom duration, age higher than 70 years, deterioration due to trauma, severe cord compression, radiculopathy, and kyphotic cervical curvature. CONCLUSIONS In cervical myelopathy, patients with multisegmental stenosis, expansive laminoplasty can be expected to provide a favorable outcome by providing sufficient cord decompression and stabilization of the cervical spine, when the stenotic cervical canal is enlarged to the normal range (over 12 mm residual anteroposterior diameter and 200 mm2 residual canal area). The efficacy can be restricted by various factors, especially irreparable cord degeneration.

Angioplasty after Intra-Arterial Thrombolysis for Acute Occlusion of Intracranial Arteries

BACKGROUND AND PURPOSE The purpose of this study was to report our experience with percutaneous transluminal angioplasty (PTA) of intracranial arteries in acute stroke patients who were resistant to intra-arterial thrombolysis alone. METHODS PTA was performed within 6 hours from symptom onset in 13 acute stroke patients in whom no hypodensity areas were observed on initial CT. PTA was classified into 3 categories: immediate (3 patients), delayed (3 patients), and rescue (7 patients) angioplasty. Treatment results in the PTA group for 9 cases of middle cerebral artery (MCA) occlusion were compared with those in the thrombolysis alone group for 12 cases of thrombotic MCA occlusion. RESULTS Technical success rates for immediate, delayed, and rescue angioplasty were 100%, 100%, and 71%, respectively, and that of angioplasty for the MCA was 100%. Ten patients (77%) showed improvement in the National Institutes of Health (NIH) stroke score after treatment. Improvement in NIH stroke scores in the PTA group for MCA occlusion was greater than that in the thrombolysis alone group (P<0.01). Nine patients (69%) had an excellent, good, or fair outcome 3 months after treatment. In 9 patients who had follow-up angiography 1 month after treatment, no restenosis or reocclusion was demonstrated. There were no symptomatic complications during or after treatment. CONCLUSIONS This limited study demonstrates the technical feasibility of angioplasty for intracranial arteries in acute ischemic stroke and suggests that angioplasty may be an effective option for improving the success rate of recanalization and preventing reocclusion of the MCA. The present results encourage us to perform further clinical trials in a larger number of patients to assess the efficacy of this procedure.

Neuroprotective nitric oxide synthase inhibitor reduces intracellular calcium accumulation following transient global ischemia in the gerbil

By observing the ultrastructural intracellular Ca2+ distribution with Ca(2+)-oxalate-pyroantimonate method, we examined whether the protective mechanism of the nitric oxide (NO) synthase inhibitor, N omega-nitro-L-arginine (LNNA), involves change of the intracellular Ca2+ movement in delayed neuronal death (DND) in gerbil hippocampal CA1 neurons following 5-min forebrain ischemia. In the group intraventricularly administered 5.0 mg/ml LNNA, 15 min after reperfusion the intracellular Ca2+ deposits and the mitochondrial Ca2+ uptake index increased to levels similar to those in the control group administered only artificial cerebro-spinal fluid, but by 180 min after reperfusion they had returned to the preischemic level. By 15 min after reperfusion Ca2+ deposits in the endoplasmic reticulum (ER) had almost disappeared in both groups, but at 180 min of reperfusion, the ER in only the LNNA group showed Ca2+ deposits. It is suggested that the neuronal toxicity of NO involves the dysfunction of the intracellular Ca2+ transport system including the mitochondria and ER.

Impairement of vascular reactivity and changes in intracellular calcium and calmodulin levels of smooth muscle cells in canine basilar arteries after subarachnoid hemorrhage.

We examined vascular reactivity to various vasoconstrictors and dilators, and the changes in calcium-calmodulin levels in canine basilar arteries after subarachnoid hemorrhage (SAH). Contractile responses to noradrenaline, serotonin, and potassium chloride were markedly attenuated at 48 hours (P less than 0.05), and further attenuated at 7 and 14 days after SAH (P less than 0.01). Dilation responses to calcium antagonist were maintained at 48 hours after SAH, but were markedly reduced at 7 and 14 days after SAH (P less than 0.05). Transmission electron micrographs of the basilar artery showed contraction of the media between 48 hours and 7 days and degeneration of smooth muscle cells over the 7 days after SAH. Electron microscopic cytochemical examination for calcium showed that intracellular deposits of calcium pyroantimonate increased in smooth muscle cells of basilar arteries at 1 hour after the first intracisternal injection of blood (early spasm), but decreased in smooth muscle cells at 48 hours after SAH (at the beginning of delayed vasospasm). They decreased further in the vessels 7 days after SAH. The calmodulin contents in the basilar arteries were decreased slightly at 6 hours, and significantly (P less than 0.05) at 48 hours after SAH, as determined by radioimmunoassay and phosphodiesterase assay. Therefore, it is considered that delayed vasospasm is not simply an active contraction of the vessels, but a functional or structural derangement of contractile elements of smooth muscle cells after 48 hours after SAH.

Three-dimensional imaging for presentation of the causative vessels in patients with hemifacial spasm and trigeminal neuralgia.

BACKGROUND In patients with hemifacial spasm and trigeminal neuralgia, preoperative detection of the relationship between the blood vessels and the cranial nerves involved is essential. METHODS We studied the causative vessels in 20 patients with hemifacial spasm and six patients with trigeminal neuralgia by means of magnetic resonance (MR) imaging with spoiled gradient recalled acquisition in the steady state (SPGR), MR angiography, and three-dimensional (3-D) imaging reconstructed from the data of SPGR MR imaging by the surface rendering method at a workstation. RESULTS In all patients, the preoperative SPGR MR images demonstrated that the causative vessels compressed or were in contact with the root exit or root entry zone (REZ) of the facial or trigeminal nerve. These causative vessels were identified by inspection of the MR angiographic and 3-D images. The 3-D images provided clear information as to the anatomic relationship between the causative vessels and the REZ of these nerves. These findings were corroborated by the intraoperative findings. The symptoms were completely relieved after surgery in 18 of the patients with hemifacial spasm and in all six patients with trigeminal neuralgia. In all patients, sufficient decompression was depicted on the postoperative SPGR MR images at the causative vessels and the REZ of the nerve. CONCLUSION SPGR MR images, MR angiography, and 3-D images are useful for the identification of the causative vessels in patients with hemifacial spasm or trigeminal neuralgia. The 3-D images are particularly useful for the simulation planning of the operative procedure.

Cerebral Blood Flow Measurement as an Indicator for an Indirect Revascularization Procedure for Adult Patients with Moyamoya Disease

OBJECTIVE Some adult patients with moyamoya disease have been treated successfully by indirect revascularization alone, although surgical indications and hemodynamic changes for these patients have not been fully explored. To examine surgical indications for this procedure, we studied the regional cerebral blood flow (rCBF) and angiographic findings in adult patients with moyamoya disease preoperatively and postoperatively. METHODS On 17 hemispheric sides of 12 adult patients with moyamoya disease treated surgically with a combination of various indirect procedures, mainly by encephaloduroarteriosynangiosis, we retrospectively evaluated changes in rCBF using xenon-133 single photon emission computed tomography, angiographic collateral formation, and clinical results. RESULTS Preoperatively, the rCBF values in the cortices at the bypass site at rest and after acetazolamide loading were lower than normal. The rCBF values were significantly increased after revascularization, approaching normal, except for incomplete recovery of vascular reactivity. The extent of postoperative neovascularization from implanted tissues fed by the external carotid artery system was more developed, in parallel with the preoperative decrease in resting and loading rCBF values. One-third of the operated sides exhibiting both a low rCBF at rest and impaired vascular reactivity in the noninfarcted cortices achieved good revascularization over two-thirds of the middle cerebral artery territory, accompanied by rCBF improvement and moyamoya vessel regression. Enough potential for neovascularization in the noninfarcted cortices was indicated that the resting rCBF was lower than 50 ml/100 g per minute (below the normal value by 2 standard deviations) and did not increase more than that value after loading, even in a 40-year-old patient who presented with a hemorrhage. Clinically, 11 patients (92%) had good results at the 4-year follow-up, whereas 1 patient (8%) with unsatisfactory neovascularization and a lesser extent of moyamoya vessel reduction experienced rebleeding. CONCLUSION We conclude that for the surgical treatment of adult patients with moyamoya disease, indirect procedures, mainly encephaloduroarteriosynangiosis, are recommended for patients with lower rCBF and no or negative vascular reactivity in the noninfarcted cortices, as well as for those who have no indication for the direct procedure. It is possible to determine these indications by a xenon-133 inhalation single photon emission computed tomographic study including an acetazolamide challenge test.

Outcome in elderly patients with ruptured intracranial aneurysm.

Sixty-nine elderly patients over 65 years old with ruptured aneurysms had a significantly worse outcome than 192 younger patients with respect to overall management results and operative results (p less than 0.01). The results of an early operation were better in the elderly patients with grade I-III than in those receiving a delayed operation. Concomitant diseases significantly influenced the results in elderly patients (p less than 0.05). It is possible that an early operation results in the better outcome in elderly patients by decreasing the incidence of delayed ischemic complications and preventing rebleeding.

Protein synthesis and immunoreactivities of contraction-related proteins in smooth muscle cells of canine basilar artery after experimental subarachnoid hemorrhage

We examined time-dependent changes in protein synthesis and in the immunoreactivities of representative contraction-related structural proteins in smooth muscle cells of canine basilar arteries after experimental subarachnoid hemorrhage (SAH). Protein synthesis was assessed by the percentage of polyribosome-forming ribosomes to total ribosomes (aggregation rate), a morphological index of the activity of protein synthesis. The aggregation rates in prostaglandin F2α- (PGF2α) and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-induced contracted basilar arteries were 70.0 ± 7.0% and 71.4 ± 8.7%, respectively, quite similar to the value in normal basilar artery (73.0 ± 8.0%). In the single-SAH group with little delayed histological changes in the basilar arteries, the aggregation rate was significantly decreased to 30.5 ± 6.4% by 24 h after the SAH, and recovered to 52.3 ± 9.0% and 70.2 ± 7.6% at 7 and 14 days postSAH, respectively, when the vasospasm was moderately and completely ameliorated. In contrast, in the double-SAH group in which the basilar arteries developed delayed smooth muscle cell death and long-lasting arterial contraction, a significant decrease in the aggregation rate (25.0 ± 5.0% on day 4) persisted for 14 days. The in vitro incorporation of [3H]-leucine in the basilar arterial cells was also significantly suppressed 4 and 7 days after the initial SAH (1.2 ± 0.4 and 1.4 ± 0.3 × 103 dpm/mg protein) in the double-SAH group, as opposed to no significant decrease in the basilar artery at 7 days postSAH in the single-SAH group (1.9 ± 0.6 × 103 dpm/mg protein). The immunoreactivity of α-smooth muscle actin, a contractile protein, demonstrated by immunohistochemistry and immunoblots, was not altered for up to 14 days even in the double-SAH group, but that of calponin and of h-caldesmon, contraction-inhibiting proteins, was markedly reduced 4–14 days after the initial SAH. Persistent impairment of protein synthesis and relative reduction of immunoreactivities of the contraction-inhibiting proteins were observed in arteries with severe vasospasm and loss of smooth muscle cells, as noted in the double-SAH subjects. These abnormalities may cooperate to cause cerebral arterial narrowing accompanied by degeneration of smooth muscle cells after SAH.

Nitric oxide synthase inhibitor reduces delayed neuronal death in gerbil hippocampal CA1 neurons after transient global ischemia without reduction of brain temperature or extracellular glutamate concentration

We planned a study to determine whether or not the mechanism of nitric oxide (NO) neurotoxicity involves the elevation of extracellular glutamate or changes of brain temperature in the pathogenesis of delayed neuronal death of gerbil hippocampal CA1 neurons following 5-min transient forebrain ischemia. Intraventricular injection of 5 microliters of 5.0 mg/ml N omega-nitro-L-arginine (LNNA) significantly preserved neuronal density in the central part of the CA1 region examined 7 days after 5-min ischemia [188.5 +/- 8.5/mm: 90.0% of the 209.5 +/- 11.1/mm density in the sham-operated controls vs. 16.7 +/- 6.4/mm in those injected with artificial cerebrospinal fluid (CSF) only]. There was no difference between these two groups in hippocampal temperature before, during or after 5-min ischemia. The glutamate concentration ([Glu]) during 5-min ischemia measured by a microdialysis technique was similar in the two groups (peak [Glu.] = 2.76 +/- 0.62 pmol/microliters dialysate in the artificial CSF group and = 2.93 +/- 0.64 pmol/microliters dialysate in the LNNA group). It was found that the neuronal toxicity of NO does not involve hyperthermia or the increase of extracellular glutamate concentration in the hippocampal CA1 region during 5-min ischemia.