Targeting S100B in Cerebral Ischemia and in Alzheimer's Disease.

S100B is an EF-hand calcium-binding protein that exerts both intracellular and extracellular effects on a variety of cellular processes. The protein is predominantly expressed in the central nervous system by astrocytes, both physiologically and during the course of neurological disease. In the healthy adult brain and during development, constitutive S100B expression acts as a trophic factor to drive neurite extension and to referee neuroplasticity.

Risk and uncertainty in health investment.

Extending the Grossman (J Polit Econ 80:223-255, 1972) model of health capital into a stochastic one, we analyze how the presence of Knightian uncertainty about the efficacy of health care affects the optimal health investment behavior of individuals. Using Gilboa and Schmeidler's (J Math Econ 18:141-153, 1989) model of max/min expected utility (MMEU) with multiple priors, we show that an agent retains the initial level of health capital if the price of health care lies within a certain range. We also show that the no-investment range expands as the degree of Knightian uncertainty rises.

Arundic Acid ameliorates cerebral amyloidosis and gliosis in Alzheimer transgenic mice.

Like microglia, reactive astrocytes produce a myriad of neurotoxic substances in various brain pathologies, such as Alzheimer's disease (AD), trauma, and cerebral ischemia. Among the numerous products of reactive astrocytes, attention has recently been directed toward the possible detrimental role of S100B, because the protein has been shown to be highly expressed along with the progression of brain damage and to exert neurotoxic effects at high concentrations. The present study aimed to examine the possible role of astrocyte-derived S100B in the progression of cerebral amyloidosis and gliosis in transgenic mice overproducing mutant amyloid precursor protein (Tg APP(sw) mice, line 2576).

Modulation of astrocytic activation by arundic acid (ONO-2506) mitigates detrimental effects of the apolipoprotein E4 isoform after permanent focal ischemia in apolipoprotein E knock-in mice.

Using homozygous human apolipoprotein E2 (apoE2) (2/2)-, apoE3 (3/3)-, or apoE4 (4/4)-knock-in (KI) mice, we have shown that delayed infarct expansion and reactive astrocytosis after permanent middle cerebral artery occlusion (pMCAO) were markedly exacerbated in 4/4-KI mice as compared with 2/2- or 3/3-KI mice. Here, we probed the putative causal relationship between enhanced astrocytic activation and exacerbation of brain damage in 4/4-KI mice using arundic acid (ONO-2506, Ono Pharmaceutical Co. Ltd), which is known to oppose astrocytic activation through its inhibitory action on S100B synthesis.

Augmented delayed infarct expansion and reactive astrocytosis after permanent focal ischemia in apolipoprotein E4 knock-in mice.

Using homozygous human apolipoprotein E2 (apoE2) (2/2)-, apoE3 (3/3)-, or apoE4 (4/4)-knock-in (KI) mice, we aimed to examine whether an apoE isoform-specific exacerbation of delayed infarct expansion occurs after permanent middle cerebral artery occlusion (pMCAO). Compared with 2/2- or 3/3-KI mice, 4/4-KI mice exhibited significantly larger infarct volumes and worse neurologic deficits after pMCAO, with no significant differences between the latter two groups. Infarct volume in 4/4-KI mice was significantly increased from 1 to 5 days after pMCAO, whereas that in 2/2- or 3/3-KI mice was not significantly altered.

Attenuation of a delayed increase in the extracellular glutamate level in the peri-infarct area following focal cerebral ischemia by a novel agent ONO-2506.

A novel agent, ONO-2506 [(R)-(-)-2-propyloctanoic acid, ONO Pharmaceutical Co. Ltd.] was previously shown to mitigate delayed infarct expansion through inhibition of the enhanced production of S-100beta, while inducing a prompt symptomatic improvement that attained a significant level as early as 24h after drug administration.

Magnetic resonance imaging shows delayed ischemic striatal neurodegeneration.

Brief focal ischemia leading to temporary neurological deficits induces delayed hyperintensity on T1-weighted magnetic resonance imaging (MRI) in the striatum of humans and rats. The T1 hyperintensity may stem from biochemical alterations including manganese (Mn) accumulation after ischemia. To clarify the significance of this MRI modification, we investigated the changes in the dorsolateral striatum of rats from 4 hours through 16 weeks after a 15-minute period of middle cerebral artery occlusion (MCAO), for MRI changes, Mn concentration, neuronal number, reactivities of astrocytes and microglia/macrophages, mitochondrial Mn-superoxide dismutase (Mn-SOD), glutamine synthetase (GS), and amyloid precursor protein.

Increased vulnerability to focal ischemic brain injury in human apolipoprotein E4 knock-in mice.

Accumulating evidence suggests that among the 3 human apolipoprotein E (apoE) isoforms encoded by the human APOE gene, the e4 allele may act to exacerbate brain damage in humans and animals. This study aimed to compare the isoform-specific vulnerability conferred by human apoE to ischemic brain damage, using mice expressing human apoE isoforms (apoE2, apoE3, or apoE4) in place of mouse apoE, produced by the gene-targeting technique in embryonic stem cells (knock-in, KI). Homozygous human apoE2 (2/2), apoE3 (3/3), or apoE4 (4/4) KI mice were subjected to permanent focal cerebral ischemia by a modified intraluminal suture method.

Large giant cell reparative granuloma of the petrous bone--case report.

A 41-year-old man presented with a large mass bulging over the suprazygomatic temporal region. Neuroradiological examination showed that the huge extra-axial mass with osteolytic character originated from the upper surface of the petrous bone. Preoperative obliteration of the feeding arteries with super-selective intravascular embolization was helpful for the total removal of the tumor.

Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats. Part II: suppression of astrocytic activation by a novel agent (R)-(-)-2-propyloctanoic acid (ONO-2506) leads to mitigation of delayed infarct expansion and early improvement of neurologic deficits.

A novel agent, (R)-(-)-2-propyloctanoic acid (ONO-2506), has a unique property in that it modulates functions of activated cultured astrocytes, including pronounced inhibition of S-100beta synthesis. The present study examined whether administration of this agent would mitigate the delayed expansion of infarct volume and the neurologic deficits after permanent middle cerebral artery occlusion (pMCAO) in rats. Daily intravenous administration of ONO-2506 (10 mg/kg) abolished the delayed infarct expansion between 24 and 168 hours after pMCAO, whereas the acute infarct expansion until 24 hours was unaffected.

Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats. Part I: enhanced astrocytic synthesis of s-100beta in the periinfarct area precedes delayed infarct expansion.

An astrocytic protein S-100beta enhances the expression of inducible nitric oxide synthase in cultured astrocytes at micromolar concentrations, leading to nitric oxide-mediated death of cocultured neurons. The present study examined whether S-100beta production by reactive astrocytes accumulating within the periinfarct area was related to delayed expansion of infarct volume after permanent middle cerebral artery occlusion in the rat. After rapid increases during the initial 24 hours, the increase of infarct volume then decelerated while maintaining the increasing tendency until 168 hours in this model, attaining a significant difference compared with that at 24 hours.

Presigmoid transpetrosal approach for the treatment of a large trochlear nerve schwannoma--case report.

A 61-year-old man presented with a rare, large trochlear nerve schwannoma manifesting as left-sided weakness and hypesthesia, bilateral bulbar pareses, and trochlear nerve paresis persisting for 3 months. T1-weighted magnetic resonance imaging with gadolinium revealed an intensely enhanced, well-circumscribed lesion with multicystic formation occupying the prepontine and interpeduncular cisterns and compressing the pons and midbrain with greater extension to the right. The mass was completely removed through the presigmoid transpetrosal approach with preservation of the posterior cerebral, superior cerebellar, and basilar arteries and their branches.