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ABSTRACT: We documented an interesting case of adult "unilateral (probable)" moyamoya disease displaying familial occurrence in two "definite" cases. A 55-year-old female presented with motor aphasia, involuntary movement of the right hand and right homonymous hemianopia due to cerebral infarction. Cerebral angiography revealed typical angiographic findings on the left side and normal findings on the right side; consequently, the patient was diagnosed with probable moyamoya disease. Previously, her mother and nephew had been diagnosed with definite moyamoya disease with bilateral involvement. The patient continued to exhibit unilateral involvement on angiography for more than 4 years. Clinical features such as absence of familial occurrence suggest that most cases of probable moyamoya disease are distinct from definite cases, especially in adults. To the best of our knowledge, this report appears to be the first involving an adult probable case characterized by familial occurrence. The literature pertaining to adult probable moyamoya disease was reviewed and the etiology of this disease was discussed.
Neurosurgical Review 02/2006; 29(1):82-7. · 2.04 Impact Factor
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ABSTRACT: We examined the radiological and histological features of, and the influences of the expression of VEGF and its two major receptors, Flt-1 and Flk-1, on the development of peritumoral brain edema (PTBE) in patients with intracranial meningiomas. The expressions of VEGF and VEGF receptors in the immunohistochemical study were analyzed in relation to several factors, including tumor size, location, vascularity, and blood supply, as seen on digital subtraction angiographic studies. The edema volume (P = 0.0003) and edema index (P < 0.0001) had a significantly positive relation to VEGF expression. The positivity of Flt-1 and Flk-1 was mainly observed in tumor vessels; 44 cases (37.2%) were positive for the Flt-1 antibody and 37 cases (31.4%) for the Flk-1 antibody. The mean value of the edema index of the positive-Flt-1 group (5.220 +/- 11.586) was significantly higher than that of the negative-Flt-1 group (1.782 +/- 2.559) (P < 0.0001). The mean value of the edema index of the positive-Flk-1 group (3.925 +/- 5.870) was slightly higher than that of the negative-Flk-1 group (2.671 +/- 8.136) (P < 0.0001). Our data suggest that the expressions of VEGF and VEGF receptors positively relate to each other and to the formation of PTBE in patients with meningiomas.
Journal of Neuro-Oncology 01/2005; 70(3):349-57. · 3.21 Impact Factor
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ABSTRACT: Certain tumor suppressor genes (TSG) residing on human chromosome 10q are implicated in astrocytic tumors. We thoroughly examined loss of heterozygosity (LOH) on chromosome 10q in astrocytic tumors to determine the extent of deletion and their relation to prognostic variables of patients. We analyzed 63 astrocytic tumors, including 9 diffuse astrocytomas, 36 anaplastic astrocytomas, and 18 glioblastomas. DNAs from tumors and leukocytes were analyzed for LOH at 18 microsatellite loci by polymerase chain reaction using fluorescence-labeled primers. Then correlation between LOH and clinicopathological variables was examined statistically. Twenty-four (66.7%) anaplastic astrocytomas and 15 (83.3%) glioblastomas had at least one LOH on chromosome 10q. However, diffuse astrocytomas exhibited no LOH. Nineteen tumors (10 anaplastic astrocytomas and 9 glioblastomas) were believed to have a total loss of one chromosome 10. Analyses on 20 tumors with interstitial LOH revealed that most of the high LOH regions matched the location of known TSGs, while some novel LOH regions were found preferentially in anaplastic astrocytoma. The median survivals of the total, partial, and no loss groups were 10.1, 14.8, and 46.8 months, respectively, indicating a significant difference in the survivals of these groups (P=0.0289). Thus, analyzing chromosome 10q loss is helpful for diagnosing malignancy in astrocytic tumors and for predicting patients' survival. Our data also suggested that there are novel TSGs for anaplastic astrocytoma at 10q24 and 10q26.
Oncology Reports 11/2004; 12(4):789-95. · 1.84 Impact Factor
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ABSTRACT: The authors report a case of convulsion during intra-arterial selective infusion of fasudil hydrochloride (FSD) for treatment of vasospasm following subarachnoid hemorrhage (SAH). A 47-year-old man (Hunt and Kosnik grade I) presented with sudden onset of headache and was diagnosed with SAH on CT, and admitted to our hospital. Digital subtraction angiography (DSA) performed on admission revealed an anterior communicating artery aneurysm. Neck clipping of the aneurysm was performed on the same day and no neurological deficits were noted postoperatively. Motor aphasia appeared on day 11 after the operation, and emergency DSA revealed vasospasm of the left middle cerebral artery and its branches. Emergency percutaneous transluminal angioplasty was performed with successful dilation of the left M1 artery, and 25 milligrams of FSD was injected into the left M1 artery selectively. During this injection, right hemifacial convulsion appeared, and three minutes later disappeared. No treatment was needed for the seizure. Additional injection of 30 milligrams of FSD into the left internal carotid artery resulted in vasodilatation of the left M1 artery and its branches, improvement of their blood flow on angiography, and recovery from motor aphasia. The patient was discharged 1 month later with no neurological deficits. Intra-arterial selective infusion of FSD plays an important role in treatment for vasospasm following SAH, however, we must be aware of risks of complications such as convulsion.
No shinkei geka. Neurological surgery 06/2004; 32(5):487-91. · 0.13 Impact Factor
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ABSTRACT: The combined use of Guglielmi detachable coils (GDCs) and newly developed mechanically detachable platinum coils (Detach Coil System: DCS) was evaluated for the endovascular treatment of 10 patients with cerebral aneurysms. The number and total length of detachable coils placed into the aneurysms, the detaching time for each coil, and any technical problems were recorded and evaluated. Sixty GDCs and 60 DCSs were used. The detachment time for the DCS (mean 21 seconds) was faster than that for the GDC (mean 2 minutes 35 seconds). One DCS moved inside the aneurysm during the mechanical detachment maneuver, but was successfully placed. Neither detachment system influenced the behavior of the other system during coil implantation. The DCS includes a useful J-shape coil, whereas the GDC can be detached safely in fragile aneurysms. The DCS is also cheaper. The coil systems complemented one another and the combination optimized cost and operating time.
Neurologia medico-chirurgica 06/2004; 44(5):269-73; discussion 274. · 0.61 Impact Factor
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ABSTRACT: A stent-assisted coil embolization has been applied as a novel choice of treatment for vertebral artery dissecting aneurysms (VADAs).
A 45-year-old man suffered from subarachnoid hemorrhage three times within 2 hours. The left vertebral angiogram showed a VADA at the distal origin of the posterior inferior cerebellar artery. The right vertebral artery was hypoplastic, and collateral circulation to the posterior fossa was poor.
Stent-assisted coil embolization was performed under general anesthesia. The aneurysm was excluded from the circulation with good patency of the vertebral artery, although the fourth coil caused rebleeding from the aneurysmal dome during the procedure.
This is the first case report that demonstrates rebleeding from VADA during stent-assisted coil embolization in the acute stage of its rupture. We have to be aware of the risks and be ready to prevent fatal complications with this novel technique.
Surgical Neurology 05/2004; 61(4):365-70; discussion 370. · 1.67 Impact Factor
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ABSTRACT: Previously, we evaluated the therapeutic efficacy of the adenovirus-mediated transduction of the cytosine deaminase (CD) gene and 5-fluorocytosine (5-FC) for malignant gliomas. However, the molecular pathways that mediate the 5-FC/CD gene therapy-induced cell death remains to be elucidated. In this study, we examined the induction of apoptosis and the role of caspases in 5-FC/CD gene therapy using human malignant glioma cells [Gli36delta5 (mutated p53) and U87MG (wild p53)]. The treatment with 5-FC/CD gene-therapy-induced apoptosis both in Gli36delta5 cells and in U87MG cells according to flow cytometric analysis. Immunoblot analysis revealed that caspases 3 and 9 were processed in response to 5-FC/CD in a concentration- and time-dependent manner, but caspase 8 was not. Each caspase 3 and 9 inhibitor significantly reduced apoptosis triggered by 5-FC/CD, but the caspase 8 inhibitor did not affect apoptosis induction. 5-FC/CD significantly promoted the release of cytochorme c from mitochondria in a concentration-dependent manner. These results indicate that 5-FC/CD gene therapy induces apoptosis in human malignant glioma cells and that the apoptotic cell death is mediated by the activation of mitochondrial caspase cascades involving caspases 3 and 9. This is the first report concerning the apoptotic mechanism of 5-FC/CD gene therapy, and these findings could be used to increase the efficacy of suicide gene therapy systems for the treatment of malignant glioma.
Journal of Neuro-Oncology 02/2004; 66(1-2):117-27. · 3.21 Impact Factor
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Hiroaki Terada,
Masayuki Matsushita,
Yun-Fei Lu,
Takeshi Shirai,
Sheng-Tian Li,
Kazuhito Tomizawa,
Akiyoshi Moriwaki,
Shinsaku Nishio,
Isao Date, Takashi Ohmoto,
Hideki Matsui
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ABSTRACT: In glutamate-mediated excitatory neuronal cell death, immunosuppressants (FK506, Cys-A) are powerful agents that protect neurons from apoptosis. Immunosuppressants inhibit two types of enzyme, calcium/calmodulin-dependent protein phosphatase (calcineurin: CaN), and peptidyl-prolyl cis-trans-isomerase (PPIase) activity such as the FKBP family. In this study, we used a protein transduction approach to determine the functional role of CaN and to produce a potential therapeutic agent for glutamate-mediated neuronal cell death. We created a novel cell-permeable CaN autoinhibitory peptide using the 11 arginine protein transduction domain. This peptide was highly efficient at transducing into primary culture neurons, potently inhibited CaN phosphatase activities, and inhibited glutamate-mediated neuronal cell death. These results showed that CaN plays an important role in excitatory neuronal cell death and cell-permeable CaN autoinhibitory peptide could be a new drug to protect neurons from excitatory neuronal death.
Journal of Neurochemistry 01/2004; 87(5):1145-51. · 4.06 Impact Factor
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ABSTRACT: This study was conducted to evaluate the effects of grafting encapsulated basic fibroblast growth factor (bFGF)-secreting cells in rat brains subjected to ischemic injury.
Two cell lines were used for encapsulated grafting in this experiment, namely, a bFGF-secreting cell line established by genetic manipulation of baby hamster kidney (BHK) cells, and a naive BHK cell line. Forty-seven Sprague-Dawley rats were used in this experiment. The animals were divided into the following three groups: those receiving grafts of encapsulated bFGF-secreting cells (BHK-bFGF group); those with grafts of encapsulated naive BHK cells (naive BHK group); and those with no grafts (control group). The authors implanted encapsulated cells into the right striatum of host rats in the BHK-bFGF and naive BHK groups. Six days after grafting, the host and control animals underwent permanent right middle cerebral artery occlusion (MCAO) with an intraluminal suture procedure. The infarct volume was evaluated using 2,3,5-triphenyltetrazolium chloride staining and computerized image analysis 24 hours after MCAO. Fragmentations of DNA in the host brains were analyzed using terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling 12 hours after MCAO. The authors found that the infarct volume in the BHK-bFGF group was reduced by approximately 30% compared with that in the naive BHK and control groups. In the ischemic penumbral area, the number of apoptotic cells in the BHK-bFGF group was significantly decreased compared with that in the other groups.
The grafting of encapsulated BHK bFGF-secreting cells protected the brain from ischemic injury. Encapsulation and grafting of genetically engineered cells such as bFGF-secreting cells is thus thought to be a useful method for protection against cerebral ischemia.
Journal of Neurosurgery 01/2004; 99(6):1053-62. · 2.96 Impact Factor
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ABSTRACT: Moyamoya disease is a progressive vascular disorder of unknown etiology. Theories of inflammatory and immunologic mechanisms have been proposed as the pathogeneses. We have designed a new method of administering N-acetylmuramyl-L-alanyl-D-isoglutamine (MDP) for experimental induction of moyamoya disease using an intravascular interventional technique combined with rod-shaped embolic materials made from lactic acid-glycolic acid copolymer. The embolic materials containing MDP were repeatedly injected into the right internal carotid artery of monkeys in the embolic group. Intravenous injections of MDP solution alone were performed in the intravenous group. Histological examination of the arteries demonstrated reduplication and lamination of the internal elastic laminae, which corresponded with findings of moyamoya disease in both groups. These histological changes occurred not only in the intracranial arteries on the embolization side, but also in the contralateral intracranial and even extracranial arteries. The changes were more prominent in the intravenous group than in the embolic group. We conclude that the systemic humoral factors induced by MDP in this study may be important in the pathogeneses of moyamoya disease. Our observations suggest that moyamoya disease is a systemic vascular disease and has an etiologic factor affecting both intracranial and extracranial arteries
Acta medica Okayama 11/2003; 57(5):241-8. · 0.84 Impact Factor
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ABSTRACT: A 47-year-old woman presented with headache and left homonymous hemianopsia. T1-weighted magnetic resonance (MR) imaging with contrast medium showed a mass lesion with ring-like enhancement in the right temporo-occipital lobe. The patient underwent surgery, focal irradiation, and chemotherapy. The histological diagnosis was glioblastoma. Four months after the operation, the patient again developed headache and left homonymous hemianopsia in addition to vomiting and mild left hemiparesis. MR imaging showed recurrence of the tumor and hydrocephalus. The patient underwent a second craniotomy and placement of a ventriculoperitoneal shunt. Intraoperative findings revealed that the transverse-sigmoid sinus was occluded by tumor invasion. The patient died of intraventricular dissemination 2 months after the second operation. Autopsy revealed metastases in the spleen and lungs. Glioblastoma with metastases to the spleen is very rare. The prognosis for patients is poor. Excessive therapy should not be used for patients with extracranial metastases from glioblastoma.
Neurologia medico-chirurgica 10/2003; 43(9):452-6. · 0.61 Impact Factor
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ABSTRACT: Radiation damage to normal brain tissue induced by interstitial irradiation with iridium-192 seeds was sequentially evaluated by computed tomography (CT), magnetic resonance imaging (MRI), and histological examination. This study was carried out in 14 mature Japanese monkeys. The experimental area received more than 200-260 Gy of irradiation developed coagulative necrosis. Infiltration of macrophages to the periphery of the necrotic area was seen. In addition, neovascularization, hyalinization of vascular walls, and gliosis were found in the periphery of the area invaded by the macrophages. All sites at which the vascular walls were found to have acute stage fibrinoid necrosis eventually developed coagulative necrosis. The focus of necrosis was detected by MRI starting 1 week after the end of radiation treatment, and the size of the necrotic area did not change for 6 months. The peripheral areas showed clear ring enhancement with contrast material. Edema surrounding the lesions was the most significant 1 week after radiation and was reduced to a minimum level 1 month later. However, the edema then expanded once again and was sustained for as long as 6 months. CT did not provide as clear of a presentation as MRI, but it did reveal similar findings for the most part, and depicted calcification in the necrotic area. This experimental model is considered useful for conducting basic research on brachytherapy, as well as for achieving a better understanding of delayed radiation necrosis.
Acta medica Okayama 07/2003; 57(3):123-31. · 0.84 Impact Factor
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ABSTRACT: In this study, we investigated the relationship between intimal thickening of the internal carotid artery (ICA) and immunological reaction, and between occlusion of the ICA and development of basal collateral vessels in moyamoya disease. Rod-shaped lactic acid-glycolic acid copolymer (LGA-50) and N-acetylmuramyl-L-alanyl-D-isoglutamine (muramyl dipeptide: MDP), and immuno-embolic material, were injected into cats unilaterally via the common carotid artery. Histological changes of duplication of the internal elastic lamina could be seen mainly in the terminal portion of the ICA in the animals injected with rod-shaped LGA-50 containing MDP. No angiographic changes were seen in any of the animals. These findings suggest that the immunological reaction induced by MDP caused histological changes in the intima of the ICA similar to those observed in moyamoya disease. This experimental study, however, could not clarify the development of the basal collateral vessels.
Acta medica Okayama 07/2003; 57(3):143-50. · 0.84 Impact Factor
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ABSTRACT: In this report, we examined whether corrosion cast method is also applicable for the measurement and estimation of the rat major arteries in which subarachnoid hemorrhage (SAH) is produced. Additionally, we have examined the diameters of the rat major arteries following SAH. A total of 0.3 ml autologous blood was injected into the cisterna magna of male Sprague-Dawley rats for the SAH model. A perfusion of a semi-polymerized casting medium was performed, 10 min, 30 min, 1 h, 4 h, 8 h, 1 day, 2 days, 3 days, 5 days, and 7 days after SAH. The brains were corroded in a 10% NaOH solution. The BA and the other major arteries were then measured using scanning electron microscopy (SEM). Macroscopic observation and hematoxylin-eosin (HE) staining were also performed. Using the corrosion cast method, the biphasic contractile response was observed in the BA; 8.3% and 11.6% contractions were observed 30 min and 1 day after SAH, respectively. In addition, there was almost no smooth muscle or adventitial thickening in the chronic stage. In contrast, the dilative response was observed in the internal carotid artery and middle cerebral artery 10 min after SAH. Macroscopic findings and HE staining revealed that the extensive basal subarachnoid hematoma had almost disappeared by day 2. These results indicate that in this model, the minimal spasm, which occurs one day after SAH, can be explained by the small capacity of the rat subarachnoid space and the rapid cerebrospinal fluid washout around major vessels at the cerebral base. Moreover, the present data also show the compensatory dilatation in the ICA and MCA in the early stage after SAH.
Neurological Research 07/2003; 25(4):383-9. · 1.52 Impact Factor
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ABSTRACT: Treating a ruptured cerebral aneurysm during symptomatic vasospasm is very difficult. We describe the successful endovascular treatment of such a case and discuss its efficacy.
A 34-year-old man had a sudden onset of severe headache. One week later, he was referred to our institute with gradually progressing right hemiparesis and global aphasia. Cerebral angiography demonstrated severe vasospasm of the left internal carotid artery system and an anterior communicating artery aneurysm. With the patient under general anesthesia, 90% occlusion of the aneurysm was achieved with detachable coils after successful dilatation of the spastic vessels. The patient had an uneventful postoperative course and his neurologic symptoms were improved. Seven months after the endovascular treatment, the enlarged neck remnant of the aneurysm was successfully clipped without difficulty.
The simultaneous treatment of a ruptured aneurysm and vasospasm with percutaneous transluminal angioplasty and coils can produce a better outcome for the patient.
Surgical Neurology 06/2003; 59(5):413-7; discussion 417. · 1.67 Impact Factor
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ABSTRACT: The PC12 cells are well known for their ability to secrete dopamine and levodopa. In multiple animal mode encapsulated PC12 cells have been shown to ameliorate parkinsonian symptoms when transplanted into the striatum; technique is expected to be effective clinically as well. The present study was performed using nonhuman primates to ensure that the transplantation of encapsulated PC12 cells is likely to be both safe and effective in human clinical trials.
Unencapsulated or encapsulated PC12 cells were implanted into the brains of Japanese monkeys (Macaca fuscata). Histological and immunocytochemical analyses were performed 1, 2, 4, and 8 weeks posttransplantation on the unencapsulated cells and 2, 4, and 8 weeks after transplantation on the encapsulated cells. The survival of the PC12 cells inside the capsule was determined by measuring the amounts of dopamine and levodopa released from the capsules a removal from the striatum. Magnetic resonance imaging was performed in both unencapsulated and encapsulated PC12 cell-grafted groups. Due to the immunological reaction of the host brain no unencapsulated PC12 cells remained in the grafted area 8 weeks after transplantation. On the contrary, encapsulated PC12 cells retrieved from the host brain continued to release dopamine and levodopa even 8 weeks after implantation. The host's reaction to the PC12-loaded capsule was much weaker than that to the unencapsulated PC12 cells.
These results suggest that the transplantation of encapsulated PC12 cells could be a safe and effective treatment modality for Parkinson disease in human patients.
Journal of Neurosurgery 05/2003; 98(4):874-81. · 2.96 Impact Factor
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ABSTRACT: The protective effect of excitatory amino acid antagonists for CA3 hippocampal neuronal loss has been well documentated. From a clinical point of view, however, alternative therapies should also be explored because excitatory amino acid antagonists have relatively deleterious side effects. Administration of lecithinized superoxide dismutase (PC-SOD) has recently been demonstrated to reduce brain edema after traumatic brain injury (TBI) in the cerebral cortex. In this study, we investigated the effectiveness of PC-SOD on CA3 hippocampal cell loss by examining hematoxylin and eosin-stained sections.
Rats were divided at random into three groups. The first group received 1 mL of saline (contusion + saline group, n = 5). Rats of the second group were treated with 3000 IU/kg of PC-SOD (contusion + SOD 1 group, n = 5), while the third group received 5000 IU/kg of PC-SOD (contusion + SOD 2 group, n = 5). All agents were administered intraperitoneally 1 minute after traumatic insult and every 24 hours until 2 or 3 days post-TBI. Animals were sacrificed 3 or 7 days after contusion injury.
PC-SOD prevented CA3 neuronal loss 3 days after TBI, and increased the number of surviving CA3 neurons 7 days after TBI.
Our findings suggest that PC-SOD may serve as a pharmacological agent in the treatment of neuronal loss after TBI.
Surgical Neurology 04/2003; 59(3):156-60; discussion 160-1. · 1.67 Impact Factor
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ABSTRACT: A 58-year-old woman complaining of a mild headache was admitted to our hospital. MRI 3 months before admission revealed a round lesion at the right quadrigeminal cistern. Cerebral angiograms demonstrated a fusiform aneurysm arising from the parietooccipital artery, which is the distal branch of the right posterior cerebral artery. Repeated MRI and cerebral angiograms performed on admission demonstrated complete thrombosis of an aneurysm and the parent artery without any clinical symptoms. This is the first case of complete spontaneous thrombosis of an aneurysm of the distal posterior cerebral artery. The mechanism of its development and spontaneous thrombosis in a fusiform aneurysm is discussed.
No shinkei geka. Neurological surgery 03/2003; 31(2):189-93. · 0.13 Impact Factor
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No shinkei geka. Neurological surgery 02/2003; 31(1):7-14. · 0.13 Impact Factor
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ABSTRACT: In this study, we tested brain surface cooling as a new method of inducing selective brain hypothermia, and evaluated its effects on focal cerebral ischemia using a cat model of transient middle cerebral artery (MCA) occlusion. Cats underwent 1 h of MCA occlusion followed by 5 h of reperfusion. Brain surface cooling was induced for 4 h during and after MCA occlusion in the hypothermia group, but not in the normothermia group. Brain surface cooling was performed using saline perfusion into the subdural space. Rectal temperature, brain surface temperature, and deep brain temperature were monitored, and regional cerebral blood flow (rCBF) and somatosensory evoked potential (SEP) were serially measured. After 5 h of reperfusion, water content was also measured. Although the rectal temperature was maintained at about 37 degrees C, the brain surface temperature decreased rapidly to 33 degrees C and was maintained at that temperature. For 3 h following reperfusion, the rCBF was lower in the hypothermia group than in the normothermia group. At 4 and 5 h after reperfusion, the recovery of SEP amplitude was significantly more enhanced in the hypothermia group than in the normothermia group. In the gray matter, the water content was significantly more diminished in the hypothermia group than in the normothermia group. These results demonstrate that our method is useful for protecting the ischemic brain from a transient MCA occlusion. This method may be adapted for neurological surgery.
Acta medica Okayama 01/2003; 56(6):279-86. · 0.84 Impact Factor