Biomedical subjects

Shinichiro Mizumatsu

Publications and source records attributed to Shinichiro Mizumatsu.

6 recordsLinked to original sources

PubMed2006

Alterations in hippocampal neurogenesis following traumatic brain injury in mice.

Clinical and experimental data show that traumatic brain injury (TBI)-induced cognitive changes are often manifest as deficits in hippocampal-dependent functions of spatial information processing. The underlying mechanisms for these effects have remained elusive, although recent studies have suggested that the changes in neuronal precursor cells in the dentate subgranular zone (SGZ) of the hippocampus might be involved. Here, we assessed the effects of unilateral controlled cortical impact on neurogenic cell populations in the SGZ in 2-month-old male C57BL6 mice by quantifying numbers of dying cells (TUNEL), proliferating cells (Ki-67) and immature neurons (Doublecortin, Dcx) up to 14 days after TBI. Dying cells were seen 6 h after injury, peaked at 24 h and returned to control levels at 14 days. Proliferating cells were decreased on the ipsilateral and contralateral sides at all the time points studied except 48 h after injury when a transient increase was seen. Simultaneously, immature neurons were reduced up to 84% relative to controls on the ipsilateral side. In the first week post-TBI, reduced numbers of Dcx-positive cells were also seen in the contralateral side; a return to control levels occurred at 14 days. To determine if these changes translated into longer-term effects, BrdU was administered 1 week post-injury and 3 weeks later the phenotypes of the newly born cells were assessed. TBI induced decreases in the numbers of BrdU-positive cells and new neurons (BrdU/NeuN) on the ipsilateral side without apparent changes on the contralateral side, whereas astrocytes (BrdU/GFAP) were increased on the ipsilateral side and activated microglia (BrdU/CD68) were increased on both ipsi- and contralateral sides. No differences were noted in oligodendrocytes (BrdU/NG2). Taken together, these data demonstrate that TBI alters both neurogenesis and gliogenesis. Such alterations may play a contributory role in TBI-induced cognitive impairment.

Animals↗

PubMed2006

[A case of brain metastasis from gastric cancer involving bilateral middle cerebellar peduncles].

A case with brain metastasis involving bilateral middle cerebellar peduncles (bMCP) was reported. A 71-year-old male with gastric cancer was treated for multiple brain metastasis by gamma knife radiosurgery (GKR) in September, 2004. Two months after the initial GKR, MRI showed asymmetrical enhanced lesions involving bMCP. A few months later, MRI revealed an expansional infiltration of bMCP lesions. The patient had presented with headache loss of appetite, cerebellar ataxia, diplopia and slight dysmetria. PET showed 2-deoxy-2- [18F] fluoro-D-glucose (FDG) uptake of the bMCP lesions. The lesions were diagnosed as brain metastasis of gastric cancer. The patient underwent his second GKR (marginal dose : 19Gy, maximum dose 38Gy) MRI revealed the disappearance of the tumors 3 months after the second GKR. One year later, the patient showed no evidence of recurrence. For the last time, our case was diagnosed as brain metastasis from gastric cancer without meningeal carcinomatosis. It was suggested that FDG-PET can provide additional information about the lesion of bMCP. GKR may be useful to treat the tumor in bMCP.

Adenocarcinoma↗

PubMed2005

Surgical treatment of a lenticulostriate artery aneurysm. Case report.

A previously healthy 61-year-old man presented with basal ganglia hemorrhage caused by rupture of a small aneurysm arising from the distal lenticulostriate artery associated with moyamoya-like disease and manifesting as left hemiparesis and dysarthria. The patient underwent frontotemporal craniotomy. Neck clipping of the aneurysm was performed through the hematoma cavity. He was transferred for rehabilitation with left hemiparesis. Three-dimensional computed tomography angiography was very useful for preoperative planning and evaluation of the anatomical correlation between the aneurysm and the hemorrhage.

Basal Ganglia Cerebrovascular Disease↗

PubMed2004

Radiation-induced cognitive impairments are associated with changes in indicators of hippocampal neurogenesis.

During treatment of brain tumors, some head and neck tumors, and other diseases, like arteriovenous malformations, the normal brain is exposed to ionizing radiation. While high radiation doses can cause severe tissue destruction, lower doses can induce cognitive impairments without signs of overt tissue damage. The underlying pathogenesis of these impairments is not well understood but may involve the neural precursor cells in the dentate gyrus of the hippocampus. To assess the effects of radiation on cognitive function, 2-month-old mice received either sham treatment (controls) or localized X irradiation (10 Gy) to the hippocampus/cortex and were tested behaviorally 3 months later. Compared to controls, X-irradiated mice showed hippocampal-dependent spatial learning and memory impairments in the Barnes maze but not the Morris water maze. No nonspatial learning and memory impairments were detected. The cognitive impairments were associated with reductions in proliferating Ki-67-positive cells and Doublecortin-positive immature neurons in the subgranular zone (SGZ) of the dentate gyrus. This study shows significant cognitive impairments after a modest dose of radiation and demonstrates that the Barnes maze is particularly sensitive for the detection of radiation-induced cognitive deficits in young adult mice. The significant loss of proliferating SGZ cells and their progeny suggests a contributory role of reduced neurogenesis in the pathogenesis of radiation-induced cognitive impairments.

Animals↗

PubMed2003

Extreme sensitivity of adult neurogenesis to low doses of X-irradiation.

Therapeutic irradiation of the brain is associated with a number of adverse effects, including cognitive impairment. Although the pathogenesis of radiation-induced cognitive injury is unknown, it may involve loss of neural precursor cells from the subgranular zone (SGZ) of the hippocampal dentate gyrus and alterations in new cell production (neurogenesis). Young adult male C57BL mice received whole brain irradiation, and 6-48 h later, hippocampal tissue was assessed using immunohistochemistry for detection of apoptosis and numbers of proliferating cells and immature neurons. Apoptosis peaked 12 h after irradiation, and its extent was dose dependent. Forty-eight h after irradiation, proliferating SGZ cells were reduced by 93-96%; immature neurons were decreased from 40 to 60% in a dose-dependent fashion. To determine whether acute cell sensitivity translated into long-term changes, we quantified neurogenesis 2 months after irradiation with 0, 2, 5, or 10 Gy. Multiple injections of BrdUrd were given to label proliferating cells, and 3 weeks later, confocal microscopy was used to determine the percentage of BrdUrd-labeled cells that showed mature cell phenotypes. The production of new neurons was significantly reduced by X-rays; that change was dose dependent. In contrast, there were no apparent effects on the production of new astrocytes or oligodendrocytes. Measures of activated microglia indicated that changes in neurogenesis were associated with a significant inflammatory response. Given the known effects of radiation on cognitive function and the relationship between hippocampal neurogenesis and associated memory formation, our data suggest that precursor cell radiation response and altered neurogenesis may play a contributory if not causative role in radiation-induced cognitive impairment.

Animals↗

PubMed2002

Irradiation induces neural precursor-cell dysfunction.

In both pediatric and adult patients, cranial radiation therapy causes a debilitating cognitive decline that is poorly understood and currently untreatable. This decline is characterized by hippocampal dysfunction, and seems to involve a radiation-induced decrease in postnatal hippocampal neurogenesis. Here we show that the deficit in neurogenesis reflects alterations in the microenvironment that regulates progenitor-cell fate, as well as a defect in the proliferative capacity of the neural progenitor-cell population. Not only is hippocampal neurogenesis ablated, but the remaining neural precursors adopt glial fates and transplants of non-irradiated neural precursor cells fail to differentiate into neurons in the irradiated hippocampus. The inhibition of neurogenesis is accompanied by marked alterations in the neurogenic microenvironment, including disruption of the microvascular angiogenesis associated with adult neurogenesis and a marked increase in the number and activation status of microglia within the neurogenic zone. These findings provide clear targets for future therapeutic interventions.

Animals↗