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Biomedical subjects

E Kohmura

Publications and source records attributed to E Kohmura.

At least 19 recordsLinked to original sources
PubMed2003

Quantitative analysis of hyperosmotic and hypothermic blood-brain barrier opening.

Hyperosmotic opening of the blood-brain barrier (BBB) by mannitol is being used to enhance drug transport in human brains. Recently, cooling of the solution has been reported to have potential to open the BBB. However, the mechanism in barrier opening and closure remains elusive. We studied the rapid changes in cerebrovascular permeability after hyperosmotic and hypothermic BBB opening in rats, and then demonstrated that the Na+/Ca++ exchange blocker (KB-R7943) prolongs opening. BBB opening was attained by using intra-arterial infusion of hyperosmotic mannitol (1.6 M) and 1.1 M mannitol (which is less hyperosmotic than commonly used mannitol) at 4 degrees in Sprague-Dawley (SD) rats. To measure the changes in cerebrovascular permeability, perfusate-containing [14C]-sucrose was infused intra-arterially at different time points following hyperosmotic and hypothermic stress. Cerebrovascular permeability was then measured with the in situ brain perfusion technique. 1.6 M Mannitol produced opening of the BBB but the duration of the opening was less than 30 minutes. Use of 1.1 M Mannitol at 4 degrees indicated the same results. We then investigated the effect of a Na/Ca ion exchange blocker (KB-R7943) in both hyperosmotic and hypothermic BBB opening. KB-R7943 extended BBB opening up to 30 min without affecting the peak level of BBB permeability at 5 minutes. Our findings represent important experimental information regarding pharmacological manipulation of BBB opening. The possibility of prolonging the transient opening of the BBB has major clinical implications.

Animals↗
PubMed2002

Haemodynamic assessment in patients with dural arteriovenous fistulae: dynamic susceptibility contrast-enhanced MRI.

Cerebral haemodynamics in patients with dural arteriovenous fistulae (DAVF) have not been fully investigated and their effects are not clear. Our purpose was to assess impaired haemodynamics in patients with DAVF using dynamic susceptibility contrast-enhanced MRI (DSC-MRI). We used this technique in eight control subjects (group I) and 17 patients with DAVF who were scheduled to undergo or had already undergone endovascular embolisation and/or surgical excision. There were seven patients with cavernous sinus DAVF (CSDAVF) and the other ten had unilateral transverse/sigmoid sinus DAVF. All patients with CSDAVF underwent DSC-MRI preoperatively (group II) and those with transverse/sigmoid sinus DAVF underwent preoperative DSC-MRI (group III) and postoperative (group IV) assessment. The ratios of relative cerebral blood volume (rCBV), cerebral blood flow (rCBF) and mean transit time (rMTT) were calculated relative to contralateral values. Patients in group II had no significant haemodynamic impairment in grey (GM) or white matter (WM), but cerebellar rMTT were significantly prolonged ( P<0.05). Group III showed haemodynamic impairment characterised by significant increase in rCBV, prolongation of rMTT and decrease in rCBF in GM ( P<0.05). Significantly increased rCBV and prolonged rMTT in the GM ( P<0.05) were obvious in group III patients irrespective of retrograde leptomeningeal venous drainage (RLVD). In group IV, rCBV and rCBF returned to normal values, whereas rMTT was still significantly prolonged in GM ( P<0.05). Our study indicates that patients with CSDAVF may have impaired cerebellar perfusion, and that those with transverse/sigmoid sinus DVAF can have disturbed cerebral haemodynamics, even in the absence of RLVD.

Arteriovenous Fistula↗
PubMed2002

PTFE-fascia patch inlay method for the anterior approach for cervical intradural spinal lesion.

STUDY DESIGN: A new method for prevention of cerebrospinal fluid leakage was studied. OBJECTIVE: To prevent cerebrospinal fluid leakage, we developed a polytetrafluoroethylene fascia patch inlay method. BACKGROUND: One of the major risks of the anterior approach for intra-dural spinal cord lesions is the cerebrospinal fluid leakage. METHODS: A small hemangioblastoma located on the ventral side of the cervical cord was resected with an anterior approach. The dural closure was performed using this polytetrafluoroethylene fascia patch inlay method. RESULTS: The patient had a satisfactory clinical course with no cerebrospinal fluid leakage. CONCLUSION: This polytetrafluoroethylene fascia patch inlay method is very effective. This method may provide both prevention of CSF leakage and future spinal cord adhesion to the dura.

Cervical Vertebrae↗
PubMed2001

Nuclear factor-kappa B decoy attenuates neuronal damage after global brain ischemia: a future strategy for brain protection during circulatory arrest.

OBJECTIVES: Recent studies have reported that cis element decoy oligodeoxynucleotides against nuclear factor-kappa B block the activation of genes that mediate ischemic injury. To improve brain protection during circulatory arrest in cardiac surgery, we evaluated the efficacy of nuclear factor-kappa B decoy oligodeoxynucleotides in preventing neuronal damage after global brain ischemia. METHODS: Hemagglutinating virus of Japan-liposome complex with fluorescein isothiocyanate-labeled nuclear factor-kappa B decoy oligodeoxynucleotides was injected through the carotid artery during 20 minutes of global brain ischemia in rats to evaluate the efficacy of transfecting the decoy oligodeoxynucleotides. The messenger RNA levels of several factors related to ischemia-reperfusion injury in the hippocampus were estimated by a real-time polymerase chain reaction method 1 hour after reperfusion. Neuronal damage was evaluated by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and by using immunohistochemical study of microtubule-associated protein 2 in the hippocampus CA-1 region 7 days after ischemia. RESULTS: Introduction of the nuclear factor-kappa B decoy oligodeoxynucleotides into rat brain neurons through the carotid artery during global brain ischemia was markedly successful. The polymerase chain reaction study showed that the transfected nuclear factor-kappa B decoy oligodeoxynucleotides effectively inhibited the expression of tumor necrosis factor alpha interleukin 1 beta and intracellular adhesion molecule 1 messenger RNA 1 hour after global brain ischemia. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling staining and microtubule-associated protein 2 immunohistochemistry showed that the transfected nuclear factor-kappa B decoy oligodeoxynucleotides significantly attenuated the neuronal damage 7 days after global brain ischemia. CONCLUSIONS: Therapeutic transfection of nuclear factor-kappa B decoy oligodeoxynucleotides during brain ischemia may be useful for attenuating neuronal damage, suggesting a strategy for cerebral protection against global ischemia.

Animals↗
PubMed2000

Induction of aquaporin-4 water channel mRNA after focal cerebral ischemia in rat.

Aquaporin-4 (AQP4) is a member of a water-selective channel aquaporin-family and mainly expressed in the several structures of the brain and in the collecting duct of the kidney. Here we show its functional involvement in the water homeostasis of the ischemic brain. The expression of AQP4-mRNA is increased in the peri-infarcted cortex during the observation period ( approximately 7 days) after MCA-occlusion, maximally on day 3. The change corresponds to the generation and resolution of brain edema monitored by MRI. The signals for the mRNA are predominantly observed in glial cells in the molecular and outer granular layer of the peri-infarcted cortex. These results indicate that AQP4 plays a role in post-ischemic edema formation.

Animals↗
PubMed2000

Widespread gene transfection into the central nervous system of primates.

We attempted in vivo gene transfection into the central nervous system (CNS) of non-human primates using the hemagglutinating virus of Japan (HVJ)-AVE liposome, a newly constructed anionic type liposome with a lipid composition similar to that of HIV envelopes and coated by the fusogenic envelope proteins of inactivated HVJ. HVJ-AVE liposomes containing the lacZ gene were applied intrathecally through the cisterna magna of Japanese macaques. Widespread transgene expression was observed mainly in the neurons. The lacZ gene was highly expressed in the medial temporal lobe, brainstem, Purkinje cells of cerebellar vermis and upper cervical cord (29.0 to 59.4% of neurons). Intrastriatal injection of an HVJ-AVE liposome-lacZ complex made a focal transfection around the injection sites up to 15 mm. We conclude that the infusion of HVJ-AVE liposomes into the cerebrospinal fluid (CSF) space is applicable for widespread gene delivery into the CNS of large animals. Gene Therapy (2000) 7, 759-763.

Animals↗
PubMed2000

Spontaneous disappearance and reappearance of a ruptured cerebral aneurysm: one case found in a group of 33 consecutive patients with subarachnoid hemorrhage who underwent repeat angiography.

The spontaneous disappearance and reappearance of a ruptured cerebral aneurysm is generally assumed to be a rare phenomenon although the actual incidence is unknown. Among 39 consecutive cases of acute subarachnoid hemorrhage (SAH), 33 were studied by three-dimensional computed tomographic angiography (CTA) within 6 h after the onset of SAH, followed by digital subtraction angiography (DSA) within 24 h after the ictus. Of those patients, one, a 58-year-old woman, had a saccular aneurysm at the distal anterior cerebral artery; the aneurysm was clearly demonstrated by CTA 2.5 h after the SAH onset, but was not shown by a subsequent DSA performed 8.5 h after the ictus. A follow-up DSA detected the neck of aneurysm on day 11, and the whole aneurysm was visualized on day 19. The observations in this particular case suggest that the spontaneous disappearance of a ruptured cerebral aneurysm may occur during the ultra-early stage of SAH and that reappearance may follow during the next few weeks. The patient did not suffer complications such as vasospasm or systemic hypotension nor was she treated with antifibrinolytic agents. The aneurysmal shape and the surrounding clot are considered as putative factors possibly related to the intermittent appearance of the aneurysm.

Aneurysm, Ruptured↗
PubMed1999

BDNF atelocollagen mini-pellet accelerates facial nerve regeneration.

We investigated the effect of BDNF mini-pellet on the GAP-43 mRNA expression and functional status of facial nerve in a rat model of facial nerve transection and immediate repair. The facial function started to recover at 17 days in the placebo group and 14 days in the BDNF group. BDNF group had shorter period of increased GAP-43 mRNA expression than the placebo group. Topically applied BDNF may accelerate the facial nerve regeneration.

Animals↗
PubMed1999

Kainic acid-induced seizure upregulates Na(+)/myo-inositol cotransporter mRNA in rat brain.

A major organic osmolyte, myo-inositol protects cells from perturbing effects of high intracellular concentrations of electrolytes. Myo-inositol is accumulated into cells through Na(+)/myo-inositol cotransporter (SMIT). In order to investigate the regulation of SMIT in generalized seizure, we employed Northern blot analysis and in situ hybridization to study the changes in SMIT mRNA expression in kainic acid-injected rats. Northern blot analysis demonstrated that SMIT mRNA began to increase in the brain 2 h after onset of seizure, and peaked at 12 h. In situ hybridization revealed rapid increase of SMIT mRNA (2 h of seizure) in the CA3 hippocampal pyramidal cells and in the dentate granular cells. Then, at 4-6 h SMIT mRNA expression was observed in the other limbic structure such as amygdala and piriform cortex. Finally, in neocortex and in CA1 pyramidal cells, SMIT mRNA was slowly increased and peaked at 12 h. Microautoradiogram demonstrated that cells expressed SMIT mRNA were mainly neurons. These results suggest that SMIT mRNA is upregulated by kainic acid-induced seizure primarily in structures involved in seizure activity.

Animals↗
PubMed1999

Decrease in N-acetylaspartate without commensurate accumulation of acetate in focal cerebral ischemia in rat.

N-acetylaspartate (NAA) is a plausible marker of neuronal viability which decreases in a variety of neurodestructive conditions. To elucidate the mechanism that leads to NAA decline in two different types of cerebral ischemia in rats, we simultaneously determined cortical concentrations of NAA and its hydrolytic metabolites, aspartate, and acetate by high-resolution 1H-NMR spectroscopy. NAA decreased almost linearly up to 24 h in both decapitation induced global cerebral ischemia, and in ischemic cortices of focal ischemia. Acetate was increased continuously for up to 24 h of global ischemia, while in focal cerebral ischemia it was increased transiently at 6 h. Aspartate did not show any change in global ischemia, while it was decreased in focal ischemia. Although NAA decreased similarly in the brain with global and focal ischemia, temporal changes of two NAA hydrolytic metabolites were different in each type of ischemia. The present results suggest hydrolytic degradation of NAA may be modified alternatively under each pathophysiologic condition.

Acetates↗
PubMed1999

Rapid infusion of high-dose methotrexate resulting in enhanced penetration into cerebrospinal fluid and intensified tumor response in primary central nervous system lymphomas.

OBJECT: Twenty-nine nonimmunocompromised patients with primary central nervous system (CNS) lymphoma were treated with high-dose methotrexate (MTX) therapy followed by irradiation. The authors investigated the correlation of infusion schedules with MTX penetration into cerebrospinal fluid (CSF), tumor response, and survival to develop a regimen that would lead to better clinical results. METHODS: In this study, 100 mg/kg MTX was administered on either a rapid (3-hour) or regular (6-hour) infusion schedule for two or three cycles. Of 28 assessable patients, a complete or partial response was achieved in 15 (93.8%) of 16 who received rapid and in seven (58.3%) of 12 who received regular infusion therapy (p = 0.034). Rapid infusion significantly increased levels of MTX in the CSF (p < 0.001) and resulted in significant tumor volume reduction (p < 0.001). The mean tumor volume after the first, second, and third cycle of rapid infusion therapy was reduced to 34%, 14%, and 9%, respectively, of the initial volume, whereas the corresponding values were 54%, 42%, and 37% for regular infusion. The reduction between the second and third cycle was small and not significant for either schedule. Despite the longer median survival time in patients who underwent rapid MTX infusion and irradiation (> 60 compared with 20 months), the difference in survival was not significant (p = 0.147) because of the small number of patients enrolled. The median survival time was 39.3 months for all assessable patients who received high-dose MTX and radiation therapy, and the median relapse-free survival time was 35.2 months. CONCLUSIONS: Rapid infusion enhanced both MTX penetration into the CSF and tumor response and may improve patient survival. Administration of three or more cycles of therapy should be carefully weighed in terms of cytoreductive benefits.

Adult↗
PubMed1999

Application of a rigid endoscope to the microsurgical management of 54 cerebral aneurysms: results in 48 patients.

OBJECT: To enhance visual confirmation of regional anatomy, endoscopy was introduced during microsurgery for cerebral aneurysms. The risks and benefits are analyzed in the present study. METHODS: The endoscopic technique was used during microsurgery for 54 aneurysms in 48 patients. Forty-three aneurysms were located in the anterior circulation and 11 were in the posterior circulation. Thirty-eight aneurysms (70.4%) had not ruptured. All ruptured aneurysms in the present series produced Hunt and Hess Grade I or II subarachnoid hemorrhage. After initial exposure achieved with the aid of a microscope, the rigid endoscope was introduced to confirm the regional anatomy, including the aneurysm neck and adjacent structures. The necks of 43 aneurysms were clipped using microscopic control or simultaneous microscopic/endoscopic control. After clipping, the positions of the clip and nearby structures were inspected using the endoscope. Use of the neuroendoscope provided useful information that further clarified the regional anatomy in 44 cases (81.5%) either before or after neck clipping. In nine cases (16.7%), these details were available only with the use of the endoscope. In five cases (9.3%), the surgeons reapplied the clip on the basis of endoscopic information obtained after the initial clipping. There were two cases in which surgical complications were possibly related to the endoscopic procedures (one patient with asymptomatic cerebral contusion and another with transient oculomotor palsy). CONCLUSIONS: It is the authors' impression that the use of the endoscope in the microsurgical management of cerebral aneurysms enhanced the safety and reliability of the surgery. However, there is a prerequisite for the surgeon to be familiar with this instrumentation and fully prepared for the risks and inconveniences of endoscopic procedures.

Adult↗
PubMed1998

Changes in brain organic osmolytes in experimental cerebral ischemia.

The cell volume is regulated not only by inorganic ions, but also by organic osmolytes, such as amino acids, methylamines, and polyhydric alcohols (polyols). Using proton nuclear magnetic resonance spectroscopy (1H-NMR), we measured the tissue concentrations of amino acids (alanine, aspartate, gamma-aminobutyric acid (GABA), glutamate, glutamine, N-acetyl-aspartate (NAA), taurine), methylamines (glycerophosphorylcholine (GPC), creatine+phosphocreatine (total creatine, tCr)), and polyols (myo-inositol) in the rat brain after middle cerebral artery occlusion (incomplete focal ischemia) or after decapitation (complete global ischemia). The total osmolytes expressed as a sum of total amino acids, total methylamines, and total polyols were significantly decreased at 24 h of focal ischemia (58.7% of control value, P=0.0025) whereas they were not changed following decapitation. The water content was increased from control value of 77.9%-84.1% after focal ischemia (P<0.0001) but not after decapitation. These results suggest that the brain organic osmolytes are involved in the process of edema formation following focal cerebral ischemia. Further elucidation of the cellular mechanisms regulating these organic osmolytes in cerebral ischemia may promote greater understanding of the pathophysiology involved in the evolution of brain edema.

Alanine↗
PubMed1998

Increased transcription of glutamate-aspartate transporter (GLAST/GluT-1) mRNA following kainic acid-induced limbic seizure.

Expression of mRNA for glutamate-aspartate transporter (GLAST/GluT-1/EAAT1) was studied in the brain of the rat which presented recurrent limbic seizure following systemic administration of kainic acid (KA) by in situ hybridization and Northern blot analysis. The expression of GLAST mRNA was markedly increased after 12 h and peaked after 48 h in animals which demonstrated limbic seizure. The induction of the mRNA were observed in the small non-neuronal cells in the hippocampus, especially around CA3 region and hilus. In contrast, there was no change in GLAST mRNA levels in KA injected seizure-free animals. These findings suggest that GLAST mRNA is induced by seizure and increased extracellular glutamate levels during seizure may be important for induction of GLAST mRNA.

ATP-Binding Cassette Transporters↗
PubMed1998

Restoration of small bone defects at craniotomy using autologous bone dust and fibrin glue.

BACKGROUND: Bone gaps or burr holes often result in small but undesirable scalp or skin depressions after craniotomy. Whereas a number of reports have discussed cranioplasties to avoid large bone defects, little has been written about the problem of small bone defects which, despite their minor size, could result in bothersome cosmetic problems. METHODS: This study was designed to assess a simple method to repair burr hole defects and bridge bone gaps with autologous bone dust and fibrin glue. Bone dust was collected when burr holes were created or craniectomy was performed. After replacement of the bone flap, the burr holes or bone gap were filled with a mixture of bone dust and fibrin glue. RESULTS AND CONCLUSIONS: The mixture of bone dust and fibrin glue was easily shaped to fit bone defects, resulting in favorable cosmetic outcomes 1 to 5 years after operation.

Bone and Bones↗
PubMed1998

Metastatic meningeal hemangiopericytoma of thoracic spine.

We report a case of metastatic meningeal hemangiopericytoma in thoracic spine. A 49-year-old female having a history of tentorial hemangiopericytoma first found 116 months before was admitted to our hospital with acute onset of paraplegia. Magnetic resonance image revealed a tumor invading the left lamina and pedicle of the 8th thoracic vertebra, and compressing the dural sac severely. After subtotal removal of the tumor, the patient showed rapid neurological improvement. The histological findings were characteristic of hemangiopericytoma. Because extradural metastases of meningeal hemangiopericytoma occur long after previous treatment in unexpected sites especially in skeletal system, repeated bone scintigraphy is essential.

Adult↗
PubMed1998

Restenosis following carotid endarterectomy--clinical profiles and pathological findings.

Restenosis following carotid endarterectomy is not a rare condition. Among 122 endarterectomies we experienced, five restenoses (4.1%) were encountered and treated by the second surgery. The present report clarifies the clinical profiles and pathological findings of restenosis following carotid endarterectomy. Mean age of restenosis group (59 years old) was not significantly different from the group without restenosis (62 years old). Average duration between the first endarterectomy and the second surgery was 17 months (8-30 months). Initial symptoms were transient ischemic attack in three sides, minor stroke in one side, and asymptomatic in one. Degree of stenosis was tight (> or = 90%) in two and moderate (70-89%) in three. It is interesting to note that no ulcer was noted in the first endarterectomy specimen. At surgery for restenosis, two cases had symptoms and another two cases were asymptomatic, though all had neck bruits. Four of five lesions were treated by short venous graft from common carotid artery to distal internal carotid artery and another lesion was treated by second endarterectomy and Dacron patch graft. Pathology was studied in four and all showed myointimal hyperplasia. Three of four restenosis tissues showed mutant form p53 by immunohistochemistry. The present study indicates that restenosis following carotid endarterectomy is not a rare status. Short venous bypass across the stenotic portion is the treatment of choice. Monoclonal growth of smooth muscle with mutant form p53 might be related to the restenosis.

Adult↗