Tissue plasminogen activator, aiming to restore cerebral blood flow (CBF), has been used for acute ischemic strokes in clinics; however, its narrow therapeutic time window remains a serious concern. To develop novel prophylactic drugs to alleviate cerebral ischemia/reperfusion injuries, ferulic acid derivative 012 (FAD012) was synthesized and showed comparable antioxidant properties to ferulic acid (FA) and probably possesses the potent ability to cross the blood–brain barrier. A more potent cytoprotective effect of FAD012 against H₂O₂-induced cytotoxicity in PC12 cells was also observed. In vivo toxicity was not observed in rats given a long-term oral administration of FAD012, indicating its good tolerability. A one-week-course oral administration of FAD012 significantly alleviated middle cerebral artery occlusion (MCAO)-induced cerebral ischemia/reperfusion injuries in rats, accompanied by the restoration of CBF and endothelial nitrogen oxide synthetase (eNOS) expression. Treatment with FAD012 significantly restored the cell viability and eNOS expression damaged by H₂O₂, used to mimic MCAO-triggered oxidative stress, in rat brain microvascular endothelial cells. Our findings suggested that FAD012 protected the viability of vascular endothelium and maintained eNOS expression, ultimately contributing to the restoration of CBF, and may provide a rationale for the development of FAD012 into an effective prophylactic drug for patients at high risk of stroke.

Piccolo, a presynaptic cytomatrix protein, plays a role in synaptic vesicle trafficking in the presynaptic active zone. Certain single-nucleotide polymorphisms of the Piccolo-encoding gene PCLO are reported to be associated with mental disorders. However, a few studies have evaluated the relationship between Piccolo dysfunction and psychotic symptoms. Therefore, we investigated the neurophysiological and behavioral phenotypes in mice with Piccolo suppression in the medial prefrontal cortex (mPFC). Downregulation of Piccolo in the mPFC reduced regional synaptic proteins, accompanied with electrophysiological impairments. The Piccolo-suppressed mice showed an enhanced locomotor activity, impaired auditory prepulse inhibition, and cognitive dysfunction. These abnormal behaviors were partially ameliorated by the antipsychotic drug risperidone. Piccolo-suppressed mice received mild social defeat stress showed additional behavioral despair. Furthermore, the responses of these mice to extracellular glutamate and dopamine levels induced by the optical activation of mPFC projection in the dorsal striatum (dSTR) were inhibited. Similarly, the Piccolo-suppressed mice showed decreased depolarization-evoked glutamate and -aminobutyric acid elevations and increased depolarization-evoked dopamine elevation in the dSTR. These suggest that Piccolo regulates neurotransmission at the synaptic terminal of the projection site. Reduced neuronal connectivity in the mPFC-dSTR pathway via suppression of Piccolo in the mPFC may induce behavioral impairments observed in schizophrenia.

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Cannabis withdrawal syndrome (CWS) in humans is characterized by various somatic symptoms, including sleep disturbances. In the present study, we investigated sleep alterations in mice after the cessation of arachidonylcyclopropylamide (ACPA), a cannabinoid type 1 receptor agonist, administration. ACPA‐administered mice (ACPA mice) displayed an increased number of rearings after the cessation of ACPA administration compared to saline‐administered mice (Saline mice). Moreover, the number of rubbings was also decreased in ACPA mice compared with those of the control mice. Electroencephalography (EEG) and electromyography (EMG) were measured for 3 days after the cessation of ACPA administration. During ACPA administration, there was no difference in the relative amounts of total sleep and wake time between ACPA and Saline mice. However, ACPA‐induced withdrawal decreased total sleep time during the light period in ACPA mice after ACPA cessation. These results suggest that ACPA cessation induces sleep disturbances in the mouse model of CWS.

当院で入院加療を行った突発性難聴の治療成績や予後因子について検討を行った. 2012年1月1日～2017年12月31日の間に当院に突発性難聴として入院した症例423例を対象とし, そのうちステロイド大量療法に PGE₁ を併用しなかった症例や入院後にほかの疾患と診断された症例を除外し324例について検討を行った. 難聴の重症度分類は1998年厚生労働省高度難聴調査研究班に従った. 治療の効果判定は厚生省特定疾患急性高度難聴調査研究班 (1984年) の判定基準を用い, 最終受診時の聴力を用いた. 治癒に至った割合を治癒率, 治癒または著明回復に至った症例を改善率と定義し検討を行った. 全体の治療成績は治癒率39.8%, 改善率52.2%であった. 治癒率および改善率について入院時の年齢, 初診時聴力レベル, 自発眼振の有無, 発症から入院治療開始までの日数, 前医での治療の有無を多項ロジスティック回帰分析で検討した. その結果, 治癒率については発症から入院治療開始までの日数が短いほど, 初診時聴力が良いほど有意に高く, 改善率については入院時年齢が若いほど, 入院治療開始までの日数が短いほど有意に高かった. 発症から入院治療開始までの日数による治療効果の検討に関しては, 7日以内に入院治療を行った場合に有意に改善率が高かった. 入院前のステロイドを含む内服加療の有無や自発眼振の有無は治療成績には影響しないという結果であった.

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