Tomoaki Nakai

Combined metabolic and transcriptional profiling identifies pentose phosphate pathway activation by HSP27 phosphorylation during cerebral ischemia

The metabolic pathophysiology underlying ischemic stroke remains poorly understood. To gain insight into these mechanisms, we performed a comparative metabolic and transcriptional analysis of the effects of cerebral ischemia on the metabolism of the cerebral cortex using middle cerebral artery occlusion (MCAO) rat model. Metabolic profiling by gas-chromatography/mass-spectrometry analysis showed clear separation between the ischemia and control group. The decreases of fructose 6-phosphate and ribulose 5-phosphate suggested enhancement of the pentose phosphate pathway (PPP) during cerebral ischemia (120-min MCAO) without reperfusion. Transcriptional profiling by microarray hybridization indicated that the Toll-like receptor and mitogen-activated protein kinase (MAPK) signaling pathways were upregulated during cerebral ischemia without reperfusion. In relation to the PPP, upregulation of heat shock protein 27 (HSP27) was observed in the MAPK signaling pathway and was confirmed through real-time polymerase chain reaction. Immunoblotting showed a slight increase in HSP27 protein expression and a marked increase in HSP27 phosphorylation at serine 85 after 60-min and 120-min MCAO without reperfusion. Corresponding upregulation of glucose 6-phosphate dehydrogenase (G6PD) activity and an increase in the NADPH/NAD+ ratio were also observed after 120-min MCAO. Furthermore, intracerebroventricular injection of ataxia telangiectasia mutated (ATM) kinase inhibitor (KU-55933) significantly reduced HSP27 phosphorylation and G6PD upregulation after MCAO, but that of protein kinase D inhibitor (CID755673) did not affect HSP27 phosphorylation. Consequently, G6PD activation via ischemia-induced HSP27 phosphorylation by ATM kinase may be part of an endogenous antioxidant defense neuroprotection mechanism during the earliest stages of ischemia. These findings have important therapeutic implications for the treatment of stroke.

Endoscopic endonasal surgery for pituitary adenomas extending to the oculomotor cistern

Extension of a pituitary adenoma to the oculomotor cistern harbors the risk of oculomotor nerve impairment and further extension into the interpeduncular cistern. The role of endoscopic endonasal surgery for those lesions was investigated.

Pentose phosphate pathway activation via HSP27 phosphorylation by ATM kinase: A putative endogenous antioxidant defense mechanism during cerebral ischemia-reperfusion

Molecular mechanism underlying ischemic stroke remains poorly understood. We previously reported glucose 6-phosphate dehydrogenase (G6PD) activity in pentose phosphate pathway (PPP) is activated via heat shock protein 27 (HSP27) phosphorylation at serine 85 (S85) by ataxia telangiectasia mutated (ATM) kinase during cerebral ischemia. This mechanism seems to be endogenous antioxidative system. To determine whether this system also works during reperfusion, we performed comparative metabolic analysis of reperfusion effect on metabolism in rat cortex using middle cerebral artery occlusion (MCAO). Metabolic profiling using gas-chromatography/mass-spectrometry analysis showed changes in metabolic state that depended on reperfusion time. Enrichment analysis showed PPP was significantly upregulated during ischemia-reperfusion. Significant increases in fructose 6-phosphate and ribulose 5-phosphate after reperfusion also suggested enhancement of PPP. In relation to PPP, ischemia-reperfusion induced an increase of up to 69-fold in HSP27 transcripts after 24-h reperfusion. Immunoblotting showed gradual increase in HSP27 protein and marked increase in HSP27 phosphorylation (S85) that were time-dependent (4.5-fold after 24-h reperfusion). G6PD activity was significantly elevated after 1-h MCAO (20%), reduced after 1-h reperfusion, increased gradually thereafter and significantly elevated after 24-h reperfusion. The NADPH/NAD+ ratio displayed similar increasing pattern. Intracerebroventricular injection of ATM kinase inhibitor (KU-55933) significantly reduced HSP27 phosphorylation and G6PD activity, significantly increased protein carbonyl, and resulted in increase in infarct size (100%) 24-h after reperfusion following 90-min MCAO. Consequently, G6PD activation via HSP27 phosphorylation by ATM kinase may be part of endogenous antioxidant defense neuroprotection mechanism that is activated during ischemia-reperfusion. These findings have important implications for treatment of stroke.

Successful cerebral thrombectomy for a nonagenarian with stroke in the subacute phase after transcatheter aortic valve implantation

Background: Thromboembolic events are infrequent but serious complications of transcatheter aortic valve implantation (TAVI), occurring in 2.3–10% of the patients. However, the cause of post-TAVI stroke is unclear. Case Description: A 90-year-old female underwent transfemoral-TAVI for severe aortic stenosis. Ten days later, she presented with an ischemic stroke of the left middle cerebral artery territory due to new-onset atrial fibrillation (NOAF). She underwent emergent endovascular thrombectomy with good reperfusion approximately 6 hours after onset of symptoms. At hospital discharge, her National Institutes of Health Stroke Scale score was 11. Conclusions: Although NOAF is rare during the subacute phase of TAVI, in this patient it might be the cause of her stroke. This finding suggests that dual antiplatelet therapy alone may be insufficient in the prevention of stroke after TAVI. Nonetheless, this case demonstrates the efficacy and safety of endovascular thrombectomy in patients with acute ischemic stroke caused by NOAF after TAVI.

Corrigendum to “Combined metabolic and transcriptional profiling identifies pentose phosphate pathway activation by HSP27 phosphorylation during cerebral ischemia” [Neuroscience 349 (2017) 1–16]

CORRIGENDUM TO ‘‘COMBINED METABOLIC AND TRANSCRIPTIONAL PROFILING IDENTIFIES PENTOSE PHOSPHATE PATHWAY ACTIVATION BY HSP27 PHOSPHORYLATION DURING CEREBRAL ISCHEMIA” [NEUROSCIENCE 349 (2017) 1–16] TAICHIRO IMAHORI, a KOHKICHI HOSODA, * TOMOAKI NAKAI, a YUSUKE YAMAMOTO, a YASUHIRO IRINO, b MASAKAZU SHINOHARA, c,d NAOKO SATO, a TAKASHI SASAYAMA, a KAZUHIRO TANAKA, a HIROAKI NAGASHIMA, a MASAAKI KOHTA a AND EIJI KOHMURA a Department of Neurosurgery, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan Division of Evidence-based Laboratory Medicine, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan The Integrated Center for Mass Spectrometry, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan Division of Epidemiology, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan

Cisterna magna meningiomas without dural attachment: Report of two cases

Meningiomas within the cisterna magna without dural attachment are extremely rare. To the best of our knowledge, only three cases of meningiomas within the cisterna magna have been reported in the literature. The authors present two cases of patient with the cisterna magna meningioma without dural attachment. (Case 1) A 36-year-old female presented with a 10-month history of numbness in the left hand. Magnetic resonance imaging (MRI) disclosed the presence of a contrast-enhanced tumor in the posterior fossa. A suboccipital craniectomy was performed, and the tumor located within the cisterna magna with no attachment to the dura. Diagnosis is made as clear cell meningioma. The postoperative course was uneventful, and a recurrence has not been observed for three years. (Case 2) A 58-year-old man presented with a well-circumscribed mass in the posterior fossa. At surgery, the tumor located within the cisterna magna with a connection to the right tenia. The tumor was totally removed without neurological deficits. At a 7-year follow-up, no evidence of a recurrence was observed. It is quite difficult to preoperatively diagnose as a cisterna magna meningioma without dural attachment. However, complete removal of the tumor should be achieved.