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Takehiro Nakamura

Publications and source records attributed to Takehiro Nakamura.

26 records · Page 2Linked to original sources
PubMed2003

Iron and iron-handling proteins in the brain after intracerebral hemorrhage.

BACKGROUND AND PURPOSE: Evidence indicates that brain injury after intracerebral hemorrhage (ICH) is due in part to the release of iron from hemoglobin. Therefore, we examined whether such iron is cleared from the brain and the effects of ICH on proteins that may alter iron release or handling: brain heme oxygenase-1, transferrin, transferrin receptor, and ferritin. METHODS: Male Sprague-Dawley rats received an infusion of 100 microL autologous whole blood into the right basal ganglia and were killed 1, 3, 7, 14, or 28 days later. Enhanced Perl's reaction was used for iron staining, and brain nonheme iron content was determined. Brain heme oxygenase-1, transferrin, transferrin receptor, and ferritin were examined by Western blot analysis and immunohistochemistry. Immunofluorescent double labeling was performed to identify which cell types express ferritin. RESULTS: ICH upregulated heme oxygenase-1 levels and resulted in iron overload in the brain. A marked increase in brain nonheme iron was not cleared within 4 weeks. Brain transferrin and transferrin receptor levels were also increased. In addition, an upregulation of ICH on ferritin was of very long duration. CONCLUSIONS: The iron overload and upregulation of iron-handling proteins, including transferrin, transferrin receptor, and ferritin, in the brain after ICH suggest that iron could be a target for ICH therapy.

Animals↗
PubMed2003

Deferoxamine-induced attenuation of brain edema and neurological deficits in a rat model of intracerebral hemorrhage.

OBJECT: In the authors' previous studies they found that brain iron accumulation and oxidative stress contribute to secondary brain damage after intracerebral hemorrhage (ICH). In the present study they investigated whether deferoxamine, an iron chelator, can reduce ICH-induced brain injury. METHODS: Male Sprague-Dawley rats received an infusion of 100 microl of autologous whole blood into the right basal ganglia and were killed 1, 3, or 7 days thereafter. Iron distribution was examined histochemically (enhanced Perl reaction). The effects of deferoxamine on ICH-induced brain injury were examined by measuring brain edema and neurological deficits. Apurinic/apyrimidinic endonuclease/redox effector factor-1 (APE/Ref-1), a repair mechanism for DNA oxidative damage, was quantitated by Western blot analysis. Iron accumulation was observed in the perihematoma zone beginning 1 day after ICH. Deferoxamine attenuated brain edema, neurological deficits, and ICH-induced changes in APE/Ref-1. CONCLUSIONS: Deferoxamine and other iron chelators may be potential therapeutic agents for treating ICH. They may act by reducing the oxidative stress caused by the release of iron from the hematoma.

Animals↗
PubMed2003

Nestin expression after experimental intracerebral hemorrhage.

The current study examines nestin expression after intracerebral hemorrhage (ICH), the role of different blood components in nestin upregulation, and the possibility that low doses of thrombin that induce tolerance to brain injury (thrombin preconditioning) might also induce nestin expression. Adult male Sprague-Dawley rats received an intracaudate injection of either whole blood, thrombin (1 or 5 U) or red blood cells (RBCs). Animals were sacrificed for single and double labeling immunohistochemistry to identify which cells express nestin, and for Western blotting to quantify nestin expression. By immunohistochemistry, nestin immunoreactivity was present in large numbers of astrocytes, surrounding the hematoma from day 3 to 1 week after ICH. After 2 weeks, nestin immunoreactivity was co-localized with a neuronal marker (neuronal specific enolase). By Western blot analysis, nestin was strongly expressed at day 3 (P<0.01) and 1 week (P<0.01), and expression persisted for at least 1 month (P<0.05). Intracerebral injection of thrombin or lysed RBCs resulted in a marked increase in nestin expression. Interestingly, injection of a low dose of thrombin that induces brain tolerance also upregulated nestin. The ICH-induced nestin expression in astrocytes may reflect an early response of these cells to injury, while the delayed expression in neurons might be a part of the adaptative response to injury perhaps leading to recovery of function. Nestin induction by a low dose of thrombin suggests that specific receptor-mediated pathways are involved in inducing nestin expression and that nestin may play a role in thrombin preconditioning.

Animals↗
PubMed2003

Role of the hippocampal CA2 region following postischemic hypothermia in gerbil.

To investigate the changes in the principal subunit of N-methyl-D-aspartate (NMDA) receptor 1 (NR1) following the transient ischemia and postischemic hypothermia, in situ hybridization was used in the gerbil hippocampus. One of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) receptors, Glutamate receptor 2 (GluR2) was also investigated to compare with NR1. Even at 1 day, NR1 and GluR2 mRNAs in the CA1 region were reduced following ischemia. Although postischemic hypothermia prevented almost all the neuronal cell death by ischemia and inhibited the reduction of NR1 and GluR2 mRNAs in the CA1 region after 7 days, the downregulation of NR1 mRNA in the CA2 region was observed even at 1 day. This change was specific for NR1 and not for GluR2. These results suggest that the changes in NR1 and GluR2 receptors at the mRNA level would occur in spite of postischemic hypothermia. The phenomenon in the CA2 region may play an important role to rescue neuronal cell death by ischemia.

Animals↗
PubMed2002

Effects of mild hypothermia and alkalizing agents on brain injuries in rats with acute subdural hematomas.

Brain ischemia is the leading pathopysiological mechanism in the development of secondary brain damage after acute subdural hematoma (SDH). Hypothermia has been employed as an effective cerebroprotective treatment on brain injuries, but the control of the general condition is very difficult under hypothermia, and various severe complications have been reported. Cerebral acidosis in the ischemic area is one of the important factors augmenting the brain edema formation. Tris-(hydroxymethyl)-aminomethane (THAM) has been used as an alkalizing agent for acidosis on brain injury and is reported to be effective. In the present study, we used a rat acute SDH model to assess the effect of mild (35 degrees C) hypothermia and THAM combined treatment on brain water content, brain ischemia, and blood-brain barrier (BBB) permeability at 4 h after hematoma induction. Mild hypothermia did not significantly reduce the brain water content beneath the hematoma (79.5 +/- 0.2%) compared to normothermia (80.2 +/- 0.2%), but mild hypothermia combined to THAM resulted in a significant reduction (78.7 +/- 0.0%; p < 0.01). Combined with mild hypothermia, THAM treatment significantly reduced the Evan's blue extravasation (35 +/- 7 ng/g wet tissue; p < 0.05) compared to normothermia (63 +/- 7 ng/g wet tissue). Furthermore, the volume of infarction at 24 h after the hematoma induction (54 +/- 3 mm(3); p < 0.01) was significantly smaller by the combined treatment compared with normothermia (70 +/- 2 mm(3)). The present findings indicate that mild hypothermia of 35 degrees C combined with THAM presents a potent cerebroprotective strategy. The protection of the BBB is one of the possible cerebroprotective mechanisms in this rat acute SDH model.

Acidosis↗
PubMed2002

Hyperinsulinemia, glucose intolerance, and dyslipidemia induced by acute inhibition of phosphoinositide 3-kinase signaling in the liver.

The physiological relevance of phosphoinositide 3-kinase (PI 3-K) signaling in the liver to fuel homeostasis was investigated. Systemic infusion of an adenovirus encoding a dominant negative mutant of PI 3-K ((Delta)p85) resulted in liver-specific expression of this protein and in inhibition of the insulin-induced activation of PI 3-K in the liver within 3 days, without affecting insulin signaling in skeletal muscle. Hepatic expression of (Delta)p85 led to hyperinsulinemia and to a marked increase in blood glucose concentration in response to oral glucose intake. The increases in both glycogen and glucose 6-phosphate content, as well as in Akt and glycogen synthase activities in the liver, that were induced by glucose intake were markedly impaired in mice expressing (Delta)p85. Despite an upregulation of mRNAs for gluconeogenic enzymes apparent in the liver of these animals, the fasting blood glucose concentration was increased only slightly, and the serum concentrations of gluconeogenic precursors were reduced. However, administration of pyruvate, a substrate for gluconeogenesis, resulted in an exaggerated increase in blood glucose concentration. In the fasted state, the mass of adipose tissue of the mice was about 1.5 times that in control mice. The mice also exhibited marked decreases in the serum concentrations of FFAs and triglyceride and suppression of insulin-induced PI 3-K activation in adipose tissue, probably due to the associated hyperinsulinemia. PI 3-K activity in the liver is thus essential for normal carbohydrate and lipid metabolism in living animals.

Adenoviridae↗
PubMed2002

Seed Coat Cracking in Soybean Isolines for Pubescence Color and Maturity.

Seed coats of soybean crack under various stress conditions. Cracking of seed coats degrades the external appearance of soybean seeds and reduces their commercial value. Previous studies revealed that the T gene responsible for pubescence color, and the maturity genes, E1 and E5, had inhibitory effects on low-temperature induced seed coat cracking. The objective of this study was to evaluate the effects of the T gene and five maturity genes (E1 to E5) on the intensity of seed coat cracking induced by pod-removal treatments. Soybean cv. Harosoy (te1e2E3E4e5) and its near-isogenic lines for T and E1 to E5 loci were used in the experiment. Cracking was induced by removing the upper 50% of pods on the plant 40 d after anthesis. Frequency and degree of cracking were not different among the isolines in the control group. In contrast, there were significant differences among isolines subjected to the pod-removal treatment. Frequency and degree of cracking was low in Harosoy, Harosoy-E1, e3, and e4, and high in Harosoy-T and E2. The results suggest that genotypes at T and E2 loci were associated with severity of seed coat cracking induced by pod-removal. There was a positive correlation (r = 0.90**) between individual seed weight and frequency of cracking among isolines in the pod-removal treatment. Seed coat cracking was probably exacerbated in part by the genes that allow enlargement of individual seeds in response to pod-removal. The differences among isolines suggest that the mechanism of seed coat cracking induced by pod removal may differ from that induced by low temperature treatment.

Journal Article↗