Susumu Uchida

Neuroprotective effect of donepezil, a nicotinic acetylcholine-receptor activator, on cerebral infarction in rats.

This study evaluated the potential effect of donepezil, which is known as an acetylcholinesterase inhibitor used for treatment of Alzheimers disease, against cerebral infarction induced by permanent left middle cerebral artery (MCA) occlusion. Donepezil was given orally in various regimens, prior to MCA occlusion in rats. Pretreatment with a single oral dose of donepezil (12 mg/kg), 2 h before ischemia, significantly attenuated cerebral infarction volume (165.5 +/- 105.3 vs. 377.1 +/- 48.5 mm(3); P < 0.05). These neuroprotective effects were prevented by coinjection with mecamylamine, a nicotinic acetylcholine-receptor (nAChR) antagonist, indicating that protection was mediated by nAChR activation.

Geranylgeranylacetone, a noninvasive heat shock protein inducer, induces protein kinase C and leads to neuroprotection against cerebral infarction in rats

Previous studies demonstrated the cytoprotective effect of geranylgeranylacetone (GGA), a heat shock protein (HSP) inducer, against ischemic insult. Protein kinase C (PKC) is thought to be an important factor that mediates the expression of heat shock protein 70 (HSP70) in vitro. 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 (MCA) occlusion in rats. To clarify the relationship between PKC induction and HSP70 expression, we determined the amounts of HSP70 and PKC proteins after GGA administration by immunoblotting. We evaluated the effects of pretreatment with chelerythrine (CHE), a specific PKC inhibitor, on expressions of PKC and HSP70 proteins with immunoblotting. Neuroprotective effects of GGA (pretreatment with a single oral GGA dose (800 mg/kg) 48 h before ischemia) were prevented by CHE pretreatment, which indicates that PKC may mediate the GGA-dependent protection. Oral GGA-induced HSP70 expression induced PKC delta, and GGA pretreatment enhanced ischemia-induced HSP70, both of which were prevented by CHE pretreatment. These results suggest that a single oral dose of GGA induces PKC delta and promotes HSP70 expression in the brain and that GGA plays an important role in neuroprotection against cerebral ischemia.

Geranylgeranylacetone limits secondary injury, neuronal death, and progressive necrosis and cavitation after spinal cord injury

This study evaluates the neuroprotective effects of geranylgeranylacetone (GGA), which is known as an antiulcer agent and more recently as a heat-shock and other neuroprotective protein inducer, on secondary degeneration after spinal cord injury in rats. Crush injuries were produced at the T8 level using an extradural approach. Optimal administration conditions of GGA were established in an initial experiment by evaluating the appearance of lesions 24 h after injury in sections stained with H-E. Then, in a second experiment, animals treated with the optimal condition (600 mg/kg, 24 h before injury and thereafter every 24 h) were allowed to survive for 6 and 24 h and 1, 3, and 8 weeks after injury, and spinal cords were prepared for histological evaluation by staining for H-E for general histopathology and by silver staining for axons. There was a significant reduction (46%) in lesion volume 24 h after injury in animals treated with optimal administration conditions. The increase in tumor necrosis factor-alpha (TNF-alpha) and the accumulation of neutrophils in the damaged segment of the spinal cord 4 h after injury were significantly inhibited in animals that received GGA. Lesion size and cavitation area remained smaller in treated animals throughout the post-injury survival interval. These results suggest that GGA administration significantly reduces the secondary degeneration that would otherwise occur. The mechanism by which GGA exerts its beneficial effect is unknown but may involve reduction of TNF-alpha activation at the injured cord and/or inhibition of inflammation.

Neuroprotective effect of geranylgeranylacetone, a noninvasive heat shock protein inducer, on cerebral infarction in rats

The present study evaluated the neuroprotective effect of geranylgeranylacetone (GGA), which is known as an antiulcer agent and more recently as a heat shock protein (HSP) inducer, against cerebral infarction induced by permanent left middle cerebral artery (MCA) occlusion. GGA was given orally in various regimens prior to MCA occlusion in rats. Pretreatment with a single oral GGA dose (800 mg/kg) 48 h before ischemia significantly attenuated cerebral infarction volume (81.7+/-18.4 mm3 versus 369.1+/-70.2 mm3; P<.01). A significant increase in HSP70 immunoreactivity was found in the neocortex in GGA-treated animals with or without ischemia. Pretreatment with a single oral dose of GGA provides an important tool for exploring the mechanisms of neuroprotection against cerebral ischemic neuronal damage.

A Single Oral Dose of Geranylgeranylacetone Upregulates Vascular Endothelial Growth Factor and Protects against Kainic Acid-Induced Neuronal Cell Death: Involvement of the Phosphatidylinositol-3 Kinase/Akt Pathway

Background: Previous studies demonstrated the cytoprotective effect of geranylgeranylacetone (GGA), a heat shock protein inducer, against ischemic insult or kainic acid (KA)-induced neuronal cell death. Phosphatidylinositol-3 kinase (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. Methods: We measured and compared hippocampal neuron density to investigate the effect of GGA on KA-induced cell death in rats. We evaluated the effects of pretreatment with wortmannin (Wort), a specific PI3K inhibitor, on GGA-induced neuroprotection against KA-induced cell death. To clarify the relationship between PI3K/Akt activation and neuroprotection, we used immunoblot analysis to determine the amounts of p-Akt and vascular endothelial growth factor (VEGF) proteins present after GGA administration with or without Wort treatment. Results: Neuroprotective effects of GGA (pretreatment with a single oral dose of GGA, 800 mg/kg, 48 h before KA injection) were prevented by Wort pretreatment, which indicates that the selective PI3K/Akt pathway may mediate the GGA-dependent protection. Oral GGA-induced p-Akt and VEGF, and GGA pretreatment enhanced KA-induced VEGF, both of which were prevented by Wort pretreatment. Conclusion: These results suggest that a single oral dose of GGA induces p-Akt and that GGA plays an important role in neuroprotection against KA-induced neuronal cell death through VEGF induction.

Efficacy of a Programmable Valve Shunt System for Hydrocephalic Patients With Various Diseases: Comparison With a Nonprogrammable Differential Pressure Valve

To clarify the efficacy of the Codman Medos programmable valve (MPV) compared with a nonprogrammable differential pressure valve (NPV), a retrospective study of 63 patients with hydrocephalus of various causes was conducted. In the MPV group, a patient with meningitis had the largest difference between the initial and final programed pressures. The average frequency of reprogramming was lowest in acute hydrocephalus and highest in meningitis. The slit ventricles on computed tomography were unchanged in spite of some reprogramming in 2 patients with congenital diseases and 1 patient with a tumor in the MPV group. Conversely, overshunting could be avoided in some cases in the NPV group with the on-off valve or antisiphon device. The programmable valve is most efficient in hydrocephalic patients with the meningitis, whereas the valve may not be always needed in acute hydrocephalic patients. It is recommended that a gravitational valve or antisiphon device be integrated into the programmable valve to guard against overshunting.

Pediatric nondura-based clear cell meningioma of the cauda equina: case report and review of literature

Abstract Although spinal meningiomas are uncommon in children, clear cell meningioma has been described as the most common variant of spinal meningiomas in the pediatric age group. 24 cases of pediatric spinal clear call meningioma have been reported in the literature. We report one case and review the literature regarding pediatric spinal clear cell meningioma.

Intraoperative Neurophysiologic Monitoring for Prediction of Postoperative Neurological Improvement in a Child With Chiari Type I Malformation

Introduction: Although many surgical treatment strategies for Chiari malformation type I (CM-I) have been reported, the most appropriate surgical technique remains controversial. It is wholly ascribable to the complicacy of pathological condition in CM-I. Recently, intraoperative neurophysiologic monitoring (INM) is becoming prevalent in spinal surgery. Indeed, motor-evoked potentials (MEPs) monitoring and somatosensory-evoked potentials (SSEPs) monitoring are standard tools to minimize the risk of neurologic injury and postoperative deficits. The most recent study suggested that multimodality INM can be beneficial in foramen magnum decompression surgery for CM-I patients for surgical positioning and planning. Various authors have investigated the consistency of intraoperative evoked potential changes that might aid the surgeon to determine the appropriate extent of decompression required for an individual patient. Patient Description: The authors report the case of a 7-year-old boy who had the signs of medullary and cerebellar dysfunction, clumsy hands, and ataxic gait. He underwent a surgery of foramen magnum decompression with tonsillectomy and duraplasty for CM-I with cervicomedullary compression. His intraoperative MEPs improved (indicated increased-amplitude and shortened-latency) both after craniotomy and durotomy, whereas SSEPs improved only after durotomy. Those results were correlated well with a functional improvement that was apparent in the immediate postoperative hospitalization. Conclusions: The authors’ data provides 1 possible interpretation of INM for safety aspect, but also which degree of decompression in each patient will require. The improvement in MEPs and SSEPs observed during decompression procedure may be a good indicator for the prediction of the clinical improvement seen postoperatively.