Takeshi Kubo

Neuroprotective and antiamnesic effect of donepezil, a nicotinic acetylcholine-receptor activator, on rats with concussive mild traumatic brain injury.

In this study we evaluated the effect of donepezil on the neurodegeneration and behavioral impairments induced by mild traumatic brain injury (MTBI). Donepezil is an acetylcholinesterase inhibitor that is used to treat Alzheimers disease. Donepezil was given orally to rats subjected to MTBI. Treatment with a single oral dose of donepezil (12mg/kg) immediately after injury significantly attenuated MTBI-induced neuronal death and cognitive impairment as measured by preservation of neurons in the CA1 region of the hippocampus and a water maze test respectively. However, these neuroprotective effects were prevented by concomitant injection of mecamylamine, a nicotinic acetylcholine-receptor (nAChR) antagonist, indicating that protection is mediated by nAChR activation.

The phosphatidylinositol-3 kinase/Akt pathway mediates geranylgeranylacetone-induced neuroprotection against cerebral infarction in rats

Previous studies demonstrated the cytoprotective effect of geranylgeranylacetone (GGA), a heat shock protein inducer, against ischemic insult. Phosphatidylinositol-3 kinase/Akt (PI3K/Akt) is thought to be an important factor that mediates neuroprotection. However, the signaling pathways in the brain in vivo after oral GGA administration remain unclear. We measured and compared infarction volumes to investigate the effect of GGA on cerebral infarction induced by permanent middle cerebral artery occlusion in rats. We evaluated the effects of pretreatment with 5-hydroxydecanoate (5HD), a specific mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel inhibitor; diazoxide (DZX), a selective mitoK(ATP) channel opener and wortmannin (Wort), a specific PI3K inhibitor of GGA-induced neuroprotection against infarction volumes. To clarify the relationship between PI3K/Akt activation and neuroprotection, we used immunoblot analysis to determine the amount of p-Akt proteins present after GGA administration with or without Wort treatment. Neuroprotective effects of GGA (pretreatment with a single oral GGA dose (800 mg/kg) 48 h before ischemia) were prevented by 5HD, DZX and Wort pretreatment, which indicates that the selective mitoK(ATP) channel and the PI3K/Akt pathway may mediate GGA-dependent protection. Oral GGA-induced p-Akt and GGA pretreatment enhanced ischemia-induced p-Akt, both of which were prevented by Wort pretreatment. These results suggest that a single oral dose of GGA induces p-Akt and that GGA plays an important role in neuroprotection against cerebral ischemia through the mitoK(ATP) channel opening.

Electroconvulsive seizure-induced VEGF is correlated with neuroprotective effects against cerebral infarction: Involvement of the phosphatidylinositol-3 kinase/Akt pathway.

The present study demonstrates the cytoprotective effect of electrical convulsive stimulation (ECS) as a potential neuroprotective vascular endothelial growth factor (VEGF) inducer against ischemic insult. Phosphatidylinositol-3 kinase/Akt (PI3K/Akt) is thought to be an important factor that mediates neuroprotection. However, the signaling pathways in the brain in vivo after ECS remain unclear. We measured and compared infarction volumes to investigate the effect of ECS on cerebral infarction induced by permanent middle cerebral artery occlusion in rats. We evaluated the effects of pretreatment with Wortmannin (Wort), a specific PI3K inhibitor of ECS-induced neuroprotection against infarction volumes. To clarify the relationship between PI3K/Akt activation and neuroprotection, we used immunoblot analysis to determine the amounts of p-Akt and VEGF proteins present after ECS with or without Wort treatment. Neuroprotective effects of ECS (pretreatment with a single ECS 6h before ischemia) were prevented by Wort pretreatment, which indicates that the PI3K/Akt pathway may mediate ECS-dependent protection. ECS induced p-Akt and VEGF and ECS pretreatment enhanced ischemia-induced VEGF, both of which were prevented by Wort pretreatment. These results suggest that a single ECS induces p-Akt and that ECS plays an important role in neuroprotection against the cerebral ischemia through VEGF induction.

Cognitive alteration after carotid revascularization is correlated with cortical GABAB-ergic modulations

The present study evaluates the hypotheses that a GABAergic mechanism underlies neurobehavioral sequelae of carotid stenosis and that it can be reversed by carotid revascularization. We used the Rivermead Behavioural Memory Test (RBMT), short interval intracortical inhibition (SICI), intracortical facilitation (ICF), long interval intracortical inhibition (LICI), and cortical silent period (CSP) to evaluate cognitive function and cerebral cortical excitability in 16 carotid artery stenosis patients with cognitive impairment before carotid arterial stenting (CAS) and 1 month later. We compared the pre- and post-CAS results and those of 16 healthy controls. CSP was prolonged in patients compared with controls (195.8±18ms vs. 157.8±13.9ms; p<0.0001, unpaired t-test). Patients tended to a have high resting motor threshold and less pronounced SICI and ICF than controls, but differences were not significant. Decreased RBMT score was correlated with hyperperfusion and CSP increase after CAS. RBMT score increase was correlated with CSP normalization. LICI showed positive correlation with CSP. CSP may provide a means of probing the integrity of GABA(B)-ergic networks in an ischemic human brain. CSP and LICI are potential tools to explore neuronal function for improvement as well as impairment after carotid revascularization.

Superficial Temporal Artery-To-Middle Cerebral Artery Anastomosis with Encephalo-Duro-Myo-Synangiosis as a Modified Operative Procedure for Moyamoya Disease

BACKGROUNDnVarious types of revascularization surgery have been performed for moyamoya disease. Although the efficacies of these operations are well recognized, the optimal operative procedure remains undecided. In this report, we describe our modified surgical revascularization procedure for moyamoya disease and retrospectively analyze the results of such surgeries on six sides in six adult patients.nnnMETHODSnOur operative procedure, combining direct and indirect bypasses, is a superficial temporal artery to middle cerebral artery anastomosis with encephalo-duro-myo-synangiosis. The encephalo-duro-myo-synangiosis is an indirect bypass combining the encephalo-duro- and encephalo-myo-synangioses. This operative procedure has been used routinely in adult patients since 2002.nnnRESULTSnPerioperative complications were noted in one of the six operations. This complication was transient and no attributive lesions were detected on CT or MRI. Revascularization was seen in cerebral blood flow studies in all patients, and the clinical outcomes were excellent or good. Effective neovascularization through the grafts was observed in all patients in follow-up angiographies.nnnCONCLUSIONSnThis operative procedure provides needed revascularization and prevents ischemic deficits. This modified procedure is useful for responding to subsequent additional ischemia in the area of the anterior cerebral artery and should be considered one of the optimal procedures for treating moyamoya disease.

Third nerve palsy caused by compression of the posterior communicating artery aneurysm does not depend on the size of the aneurysm, but on the distance between the ICA and the anterior–posterior clinoid process

OBJECTIVEnThird nerve palsy (TNP) caused by a posterior communicating artery (PCoA) aneurysm is a well-known symptom of the condition, but the characteristics of unruptured PCoA aneurysm-associated third nerve palsy have not been fully evaluated. The aim of this study was to analyze the anatomical features of PCoA aneurysms that caused TNP from the viewpoint of the relationship between the ICA and the skull base.nnnMETHODSnForty-eight unruptured PCoA aneurysms were treated surgically between January 2008 and September 2013. The characteristics of the aneurysms were evaluated.nnnRESULTSnThirteen of the 48 patients (27%) had a history of TNP. The distance between the ICA and the anterior-posterior clinoid process (ICA-APC distance) was significantly shorter in the TNP group (p<0.01), but the maximum size of the aneurysms was not (p=0.534).nnnCONCLUSIONnRelatively small unruptured PCoA aneurysms can cause third nerve palsy if the ICA runs close to the skull base.

Induction of collateral circulation by hypoxia-inducible factor 1α decreased cerebral infarction in the rat

Abstract Background: We recently reported that hypoxia-inducible factor 1α (HIF-1α), HIF-2α and cyclooxygenase 2 naked DNA induced angiogenesis in a rat indirect bypass model. In this work, we investigated whether the collateral circulation induced by HIF-1α DNA affected the cerebral infarction. Methods: We utilized a rat encephalomyosynangiosis (EMS) model and inoculated HIF-1α DNA onto the brain surface. These treatments were performed before the cerebral infarction occurred. We thereafter performed middle cerebral artery occlusion on the fifth or tenth day after EMS. Results: A histological section treated with HIF-1α DNA for 10 days showed a well-developed collateral circulation (p<0.05) and a reduction in the infarction volume in comparison to the control DNA (p<0.01). Conclusion: These results suggest the feasibility of a novel approach for the treatment of cerebral ischemia via the development of therapeutic collateral circulation, in which neovascularization may be indirectly achieved using a transcriptional regulatory strategy.

A hemispherotomy for intractable startle epilepsy characterized by infantile hemiplegia and drop attacks

Startle epilepsy is provoked by unexpected sensory stimuli, mainly auditory, and reveals subsequent tonic posturing of the limbs. We present a case of intractable startle epilepsy with infantile hemiplegia and discuss the indications for a hemispherotomy.

Fusion imaging using subtracted and unsubtracted rotational angiography for pretherapeutic evaluation of dural arteriovenous fistulas

PurposeWe describe the clinical utility of an imaging technique that combines 3D subtracted and unsubtracted rotational angiography for evaluation of the angioarchitecture of dural arteriovenous fistulas (DAVFs).MethodsFrom May 2010 to June 2013, 21 consecutive patients with intracranial DAVFs (22 lesions) underwent 3D angiography for pretherapeutic evaluation. 3D fusion angiography (3DFA) images were semiautomatically obtained from a dataset of unsubtracted and subtracted rotational angiographs. Multiplanar reformatted images and partial MIP images from unsubtracted rotational angiography and fusion images were evaluated by two radiologists, with particular focus on visualization of feeding arteries, shunted pouches, and drainage veins of DAVFs by use of a 3-point scale. The referring neuroradiologists were asked whether the information provided by 3DFA was helpful for treatment decisions.ResultsFor 21 of 22 lesions, all evaluated items were well depicted on the 3DFA. The visualization rating score for feeding arteries and shunted pouches on 3DFA were significantly higher than those of 3D digital angiography (pxa0<xa00.05). There were no statistically significant differences between visualization of drainage veins. The information provided by the fusion images was helpful for treatment decisions in all cases.Conclusion3DFA images are useful for evaluation of the angioarchitecture of intracranial DAVFs.

Heat stroke burn: unusual cutaneous damage due to heat wave

Heat stroke has been defined as a form of hyperthermia associated with a systemic inflammatory response that leads to multi-organ dysfunction [1]. Although sunburn, manifested by erythema or bullae, is very common, reports of deep skin injury, associated with heat stroke, are very rare [2]. We propose heat-stroke burn as a new entity with several risk factors.Case 1An 81-year-old man was found supine and unconscious on his lawn under the burning sun, at around noon, in June 2011. His medical history [...]