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Biomedical subjects

T Kawamata

Publications and source records attributed to T Kawamata.

At least 19 recordsLinked to original sources
PubMed1998

Formalin-induced release of excitatory amino acids in the skin of the rat hindpaw.

Application of glutamate to skin evokes pain-related behaviors [S.M. Carlton, G.L. Hargett, R.E. Coggeshall, Localization and activation of glutamate receptors in unmyelinated axons of rat glabrous skin, Neurosci. Lett., 197 (1995) 25-28; D.L. Jackson, C.B. Graff, J.D. Richardson, K.M. Hargreaves, Glutamate participates in the peripheral modulation of thermal hyperalgesia in rats, Eur. J. Pharmacol., 284 (1995) 321-325.] and peripherally-administered glutamate antagonists can prevent the nociception produced by inflammation [E.M. Davidson, R.E. Coggeshall, S.M. Carlton, Peripheral NMDA and non-NMDA glutamate receptors contribute to nociceptive behaviors in the rat formalin test, NeuroReport, 8 (1997) 941-946; Jackson et al., 1995.] In this study, the concentrations of glutamate and aspartate in the plantar of the rat hindpaws were measured before and after the subcutaneous administration of formalin. Increases in glutamate and aspartate concentrations were observed on the ipsilateral side, but not on the contralateral side, to the injection. This shows that nociception and inflammation caused by formalin injection induces the release of peripheral glutamate and aspartate, which would contribute to nociception and inflammatory pain.

Animals↗
PubMed1998

Single-channel activity of the Ca2+-dependent K+ channel is modulated by FK506 and rapamycin.

Single-channel patch clamp recordings were performed in primary cultured neurons from rat dorsal hippocampi. Ca2+-dependent and TEA-sensitive K+ current was recorded from the neurons. Application of immunosuppressants FK506 and rapamycin to the channel inside the plasma membrane of the neurons significantly prolonged the mean open time of the channel. Calcineurin autoinhibitory fragment and W-7 induced no significant alteration in the mean open time of the channel. These results suggest that modulation of the activity of the Ca2+-dependent K+ channel by FK506 and rapamycin is directly through association of immunosuppressants with FKBP12.

Animals↗
PubMed1998

Isoform-specific redistribution of calcineurin A alpha and A beta in the hippocampal CA1 region of gerbils after transient ischemia.

To investigate isoform-specific roles of Ca2+/calmodulin-dependent phosphatase [calcineurin (CaN)] in ischemia-induced cell death, we raised antibodies specific to CaN A alpha and CaN A beta and localized the CaN isoforms in the hippocampal CA1 region of Mongolian gerbils subjected to a 5-min occlusion of carotid arteries. In the nonischemic gerbil, immunoreactions of both isoforms were highly enriched in CA1 regions, especially in the cytoplasm and apical dendrites of CA1 pyramidal neurons. At 4-7 days after the induced ischemia, immunoreactivities of the CaN A alpha isoform in CA1 pyramidal cells were markedly reduced, whereas they were enhanced in the CA1 radiatum and oriens layers. In contrast, CaN A beta immunoreactivities were reduced in all layers of the ischemic CA1 region, whereas they were enhanced in activated astrocytes, colocalizing with glial fibrillary acidic protein. These findings suggest that up-regulation of CaN A alpha in afferent fibers in CA1 and up-regulation of CaN A beta in reactive astrocytes may be involved in neuronal reorganization after ischemic injury.

Animals↗
PubMed1998

Premedication with oral dextromethorphan reduces postoperative pain after tonsillectomy.

UNLABELLED: The aim of the present study was to examine whether premedication with dextromethorphan, a clinically available N-methyl-D-aspartic acid (NMDA) receptor antagonist, could reduce postoperative pain after tonsillectomy. Thirty-six patients scheduled for elective bilateral tonsillectomy were investigated in a double-blinded, randomized study. The patients were randomly assigned to one of three groups: control, dextromethorphan 30 mg (Dex 30), and dextromethorphan 45 mg (Dex 45) groups. In the control group, premedication was with oral placebo and intramuscular (i.m.) midazolam and atropine. In the Dex 30 and Dex 45 groups, patients were premedicated with i.m. midazolam and atropine and oral dextromethorphan 30 mg and 45 mg, respectively. Pain was evaluated repeatedly throughout 7 postoperative days, at rest and on swallowing, using a self-rating visual analog scale (VAS). The total doses of analgesics administered postoperatively were also recorded. The Dex 45 group showed significantly lower VAS scores than the control group both at rest and on swallowing throughout the 7 days. The total doses of postoperative analgesics in the Dex 45 group were significantly less than those in the control group. The Dex 30 group showed significantly lower VAS scores than the control group at rest, but not on swallowing. These results indicate that premedication with Dex 45 reduces postoperative pain after tonsillectomy, not only at rest but on swallowing. IMPLICATIONS: Recently, it has been suggested that central sensitization caused by the activation of N-methyl-D-aspartic acid receptors may contribute to the postoperative pain. We found that premedication with 45 mg of dextromethorphan, a clinically available N-methyl-D-aspartic acid receptor antagonist, reduced postoperative pain after tonsillectomy.

Administration, Oral↗
PubMed1998

Induced hypertension improves regional blood flow and protects against infarction during focal ischemia: time course of changes in blood flow measured by laser Doppler imaging.

OBJECTIVE: To characterize changes in regional blood flow (rCBF) during and after a period of arterial occlusion and determine the effect on rCBF and on the extent of infarction when the mean arterial blood pressure is increased during the period of occlusion. METHODS: rCBF in the middle cerebral artery (MCA) territory of rabbits was monitored using laser Doppler perfusion imaging before, during, and after a 1- or 2-hour period of MCA occlusion, and the size of the infarction was assessed by 2,3,5-triphenyltetrazolamine chloride staining after 2 hours of reperfusion. Test animals, the mean arterial blood pressure of which was increased by 65 mm Hg with intravenous phenylephrine during the ischemia, were compared with control animals that remained normotensive. The laser Doppler perfusion imager (Lisca Developments Co., Linköping, Sweden) scanned a 3-cm2 area of cortex with a resolution of 4 mm2 every 15 minutes. RESULTS: MCA occlusion reduced rCBF to 71 +/- 2% of the control level (n = 24, P < 0.001). Hypertension (HTN) restored rCBF to 84 +/- 3% of the control level (n = 12, P < 0.01), but the HTN-induced improvement diminished with time, so that after 1 hour, there was no longer a significant difference between hypertensive and normotensive animals. HTN during the MCA occlusion caused a 97% reduction in infarct size (P < 0.05) in the animals subjected to 1 hour of occlusion but caused only a 45% reduction (P approximately 0.1) in the animals subjected to 2 hours of occlusion. CONCLUSION: This study supports the use of HTN to minimize ischemic injury from short intervals of major intracranial vessel occlusion but fails to demonstrate protection when HTN is maintained during occlusions of more than 1 hour.

Animals↗
PubMed1998

[Involvement of calcineurin A alpha and A beta in neuronal death in a gerbil model of cerebral ischemia].

Treatment with FK506, an inhibitor of Ca2+/calmodulin dependent phosphatase (calcineurin, CaN), within 1 hr after transient ischemia afforded protection from apoptotic death in CA1 pyramidal neurons. To investigate isoform-specific roles of CaN in the neuronal cell death, we localized CaN A alpha and CaN A beta in the gerbil hippocampus using isoform-specific antibodies. In control gerbils, immunoreactions of both isoforms were highly enriched in hippocampal CA1 pyramidal neurons. Four to seven days after the induced ischemia, immunoreactivities of both isoforms were markedly reduced in the CA1 pyramidal cell and lacunosum-molecular layers. The CaN A alpha immunoreactivity was increased in the CA1 radiatum and oriens layers, whereas that of CaN A beta was enhanced in reactive astrocytes in the CA1 region. These findings suggest that CaN A alpha is involved in sprouting of afferent fibers in CA1 and that CaN A beta is involved in the reaction of astrocytes such as assembly of glial fibril acidic protein.

Animals↗
PubMed1997

A novel missense mutation in the presenilin-1 gene in a familial Alzheimer's disease pedigree with abundant amyloid angiopathy.

A number of missense mutations associated with early-onset familial Alzheimer's disease have been reported in the presenilin-1 gene. The mutations were demonstrated to cluster in specific regions of the the protein. We report here a novel missense mutation at the C-terminus of the third transmembrane domain in the presenilin-1 protein in a family of Japanese origin with early-onset Alzheimer's disease. This mutation is located at a site that is different from the sites at which mutations are known to cluster. Although the clinical phenotype is similar to those of pedigrees associated with other presenilin-1 mutations, postmortem examination of this pedigree revealed heavy amyloid deposits in the walls of small meningeal arteries as well as around small vessels within the brain parenchyma. These results indicate that a mutation at the C-terminus of the third transmembrane domain in the presenilin-1, which is a novel site for mutations, may play a key role in Alzheimer's pathogenesis.

Adult↗
PubMed1997

Intracisternal basic fibroblast growth factor enhances functional recovery and up-regulates the expression of a molecular marker of neuronal sprouting following focal cerebral infarction.

Focal cerebral infarction (stroke) due to unilateral occlusion of the middle cerebral artery in mature rats produces deficits in sensorimotor function of the contralateral limbs that recover partially over time. We found that biweekly intracisternal injection of basic fibroblast growth factor (bFGF; 0.5 microg/injection), a potent neurotrophic polypeptide, markedly enhanced recovery of sensorimotor function of the contralateral limbs during the first month after stroke without apparent adverse side effects. Immunostaining for growth-associated protein 43 (GAP-43), a molecular marker of axonal sprouting, showed a selective increase in GAP-43 immunoreactivity in the intact sensorimotor cortex contralateral to cerebral infarcts following bFGF treatment. These results show that bFGF treatment can enhance functional recovery after stroke, and that the mechanism may include stimulation of neuronal sprouting in the intact brain.

Animals↗
PubMed1997

Cloning of the cDNA encoding rat Presenilin-1.

We isolated rat presenilin-1 (PS-1; also called S182 previously) cDNA from total brain RNA by using a reverse transcription-polymerase chain reaction (RT-PCR) technique with primers homologous to the conserved sequences of human and mouse PS-1. Rat PS-1 cDNA encoded 468 amino acids (aa) and the deduced aa sequence was highly homologous to those of the human (88.4%) and mouse (92.7%). Northern blot analysis of the rat PS-1 cDNA revealed two mRNA species in rat neurotypic pheochromocytoma and glioma cell lines (PC-12 and C6, respectively) that migrated at rates corresponding to approximately 3.0 and 7.5 kb.

Alzheimer Disease↗
PubMed1997

Hemodynamic depression and microthrombosis in the peripheral areas of cortical contusion in the rat: role of platelet activating factor.

Cerebrovascular damages leading to subsequent reductions in regional cerebral blood flow (rCBF) may play an important role in secondary cell damages following traumatic brain injury (TBI). Recent studies have demonstrated that rCBF markedly decrease in experimental model of TBI (e.g. fluid percussion injury, acute subdural hematoma, contusion). However, precise mechanisms underlying post-traumatic CBF reduction remain unclear. In the present study, the rCBF changes and microthrombosis formation were investigated in a cortical contusional model in rats, and the effects of etizolam (platelet activating factor antagonist) on microthrombosis were tested. The rCBF in the peripheral areas increased transiently, and decreased to ischemic level 3 hours post- injury. The histological examinations revealed microthrombosis formation in the contused area, extending from the center to the peripheral areas within 6 hours post-injury. The rCBF decrease and the contusion necrosis volume were significantly attenuated by etizolam administration. These results indicate that platelet activating factor is involved in microthrombosis formation and hemodynamic depression, and resultant ischemic damages within areas surrounding the contusion.

Animals↗
PubMed1997

Antioxidant, OPC-14117, attenuates edema formation and behavioral deficits following cortical contusion in rats.

Oxygen free radicals may contribute to tissue injury processes in the central nervous system following ischemia or trauma. Recent studies have suggested that inhibition of free radicals improves the outcome in experimental models involving such conditions, and antioxidant therapy appears promising. In the present study, behavioral changes and edema formation in rat cortical contusion model were investigated, and the effects of a superoxide radical scavenger, OPC-14117, were tested. Wistar rats were anesthetized with halothane inhalation. Cortical contusion was induced in the parietal cortex employing a controlled cortical impact device. Immediately following injury induction, OPC-14117 was administered (300 mg/kg, p.o.). Edema formation was assessed in the center and peripheral areas of the contusion by the specific gravity method. Behavioral changes were evaluated by the Morris water maze test and the habituation of exploratory activity. The results revealed that the vehicle-administered control showed progressive edema formation and behavioral deficits following the injury. These changes were significantly attenuated by the OPC-14117 treatment (p < 0.05). Further, OPC-14117 reduced the size of contusional necrosis (p < 0.05). These findings suggest that superoxide free radicals are involved in contusion-induced edema formation, necrosis formation, and behavioral deficits, and that OPC-14117 has a therapeutic potential to prevent secondary cell damage following traumatic brain injury.

Animals↗
PubMed1997

Antinociceptive interaction of intrathecal alpha2-adrenergic agonists, tizanidine and clonidine, with lidocaine in rats.

BACKGROUND: The intrathecal alpha2-adrenergic agonist, clonidine, has been shown to have considerable antinociceptive effect, although clonidine causes hypotension and bradycardia. The combination of intrathecal clonidine and local anesthetics enhances analgesic effects, whereas the combination may cause marked hypotension and motor blockade, which may limit the clinical application of the combination. Tizanidine, another alpha2-adrenergic agonist, has also provided antinociception without producing pronounced hemodynamic changes. This study was designed to evaluate the antinociceptive and hemodynamic interactions of tizanidine and clonidine with lidocaine. METHODS: Male Sprague Dawley rats were chronically implanted with lumbar intrathecal catheters. The tail-flick test was used to assess the thermal nociceptive threshold. The ability of intrathecal tizanidine, clonidine, lidocaine, or the combinations of alpha2-adrenergic agonist and lidocaine to alter the tail-flick latency was examined. To characterize the antinociceptive interaction, the isobolographic analysis was applied. Additionally, the motor function, blood pressure and heart rate after intrathecal administration of drugs and combinations were also monitored. RESULTS: Intrathecal tizanidine, clonidine, or the combinations increased the tail-flick latency in dose- and time-dependent fashion without affecting motor function. The order potencies (dose producing a 50% of peak effect, in microg) of tizanidine and clonidine were 1.8 and 0.75, respectively. With isobolographic analysis, tizanidine with lidocaine and clonidine with lidocaine showed significantly synergistic antinociceptive interaction. Potency ratio analysis and fractional analysis also confirmed the synergistic interaction. At the doses in the combinations showing comparable antinociception, tizanidine with lidocaine, unlike clonidine with lidocaine, did not affect motor function or blood pressure. CONCLUSION: The authors' results show that intrathecal tizanidine and clonidine synergistically interact with lidocaine so that the degree of antinociception to somatic noxious stimuli are enhanced. The antinociceptive synergistic interaction between tizanidine and lidocaine may be useful in clinical practice without affecting blood pressure, heart rate, or motor function.

Adrenergic alpha-2 Receptor Agonists↗
PubMed1997

Establishment of a murine model for metastasis of cytokine-producing tumor to the brain.

The A375 cell line, derived from human malignant melanoma, has characteristics of interleukin-6 (IL-6) production. By using this cell line, we have investigated a murine metastasis model of IL-6-producing tumors to the brain by injecting A375 cells directly into the left cardiac ventricle. Nude mice were anesthetized with intraperitoneal injection of pentobarbital sodium. Next, A375 cells suspended in phosphate-buffered saline (PBS) were injected into the left cardiac ventricle of mice. An intracardiac injection of 10(5) cells developed tumor colonies in the brain after 4 to 6 weeks. Metastatic cells were found in every lobe of the brain. An immunocytochemical study revealed IL-6 production by A375 cells at the metastatic sites in the brain. By the transfection of genes encoding proteins into A375 cells, a novel model of protein expression in the brain in vivo could be constructed. Our system does not require great skill. Our experimental model will facilitate future studies of the local effects of proteins in the brain.

Animals↗
PubMed1997

Possible different mechanism between amyloid-beta (25-35)-and substance P-induced chemotaxis of murine microglia.

The mechanism of murine microglial chemotaxis induced by amyloid-beta protein (A beta (25-35)) was investigated. A beta (25-35) dose-dependently stimulated microglial chemotaxis at concentrations between 100 pM and 10 nM. Substance P, a NK-1 agonist, stimulated chemotaxis at concentrations of 10 nM or more. GR-64349, a NK-2 agonist, and senktide, a NK-3 agonist, did not stimulate microglial chemotaxis. We examined whether homologous desensitization of chemotaxis would occur by A beta (25-35). The chemotactic effect of microglia was homologously desensitized by 10 nM A beta (25-35). On the other hand, substance P at 10 nM did not desensitize the A beta (25-35)-induced chemotaxis. These data show that A beta (25-35) induces the chemotaxis of microglia probably through a receptor other than the NK-1 receptor.

Amyloid beta-Peptides↗
PubMed1997

Augmentation of both hemolysate-induced contraction and activation of protein kinase C by submaximum activation in canine cerebral arteries in vitro.

Although phorbol esters, synthetic activators of protein kinase C (PKC), can stimulate large increases in the binding of cytosolic PKC to form membrane-bound PKC (PKCm, an indicator of PKC activation), the authors report that even small increases in PKCm induced by phorbol esters (8-12% of total PKC content) can be associated with significant PKC-mediated contractions in vitro (50-85% of maximum) in normal canine cerebral arteries. Increases in PKCm of similarly small magnitude were found in vitro when control artery segments were exposed to hemolysate, but only if the arterial smooth-muscle cells were first slightly depolarized by increased extracellular potassium to values of membrane potential similar to those observed in canine cerebral arteries during chronic cerebral vasospasm. These increases in PKCm (6-8% of total PKC content) coincided with a greatly augmented contractile response to hemolysate. These results show that the previous observation of only a small increase in PKCm (approximately 7% of total PKC content) after experimental subarachnoid hemorrhage in the canine model does not preclude a potentially important role for PKC-mediated contraction in the pathogenesis of cerebral vasospasm.

Animals↗
PubMed1997

The role of polypeptide growth factors in recovery from stroke.

In recent studies we have examined the potential role of one trophic growth factor, bFGF, in the processes of wound healing and functional recovery following experimental stroke. In studies of the endogenous expression of bFGF after focal cerebral infarction in rats, we found that bFGF gene expression was induced within 1 day and that bFGF protein levels were increased within 3 days in tissue surrounding focal infarcts. Increased bFGF expression was localized to reactive astroglia. Increased endogenous bFGF expression may contribute to neuronal survival and sprouting, glial proliferation, and new blood vessel growth (angiogenesis) in the poststroke brain. In studies of the exogenous administration of bFGF after infarction, we found that the early administration of bFGF reduces infarct size, whereas the later administration of bFGF, while not affecting infarct size, enhances functional recovery. The mechanism of this enhancement may include protection against the late retrograde death of distant neurons and/or the promotion of new neuronal sprouting and synapse formation. Basic FGF represents only one of many trophic growth factors and cytokines that are likely to act as important signaling molecules directing processes of tissue repair and functional reorganization following stroke. Our challenge in future studies is to understand the role of each of these factors singly, and in combination. One consequence of such studies should be the development of new molecular treatments to enhance recovery from stroke.

Animals↗
PubMed1997

[Two cases of severe metabolic acidosis after monitoring of evoked spinal cord potential].

Evoked spinal cord potential (ESCP) elicited by direct spinal cord stimulation has been applied to monitor the spinal cord function during spinal surgery. We report here two patients who showed excessive muscle contraction and developed severe metabolic acidosis as a result of the stimulation of spinal cord to measure ESCP. These changes were prevented by vecuronium administration prior to ESCP monitoring. These results suggest that excessive muscle contraction by direct spinal cord stimulation may lead to metabolic acidosis. In conclusion, the use of a non-depolarizing muscle relaxant is recommended to prevent the adverse effects of ESCP monitoring.

Acidosis↗