Heme oxygenase-1 in vascular smooth muscle cells counteracts cardiovascular damage induced by angiotensin II

Heme oxygenase (HO) is a microsomal enzyme that catalyzes the degradation of heme into biliverdin, which is subsequently reduced to bilirubin, free iron and carbon monoxide (CO), and induction of heme oxygenase-1 (HO-1) is potentially associated with cellular protection, especially against oxidative insults. Using transgenic mice that overexpress HO-1 (HO-1 Tg) specifically in vascular smooth muscle cells, we investigated the organ-protective effects of HO-1 against angiotensin II (Ang II). Following administration of Ang II and a high- salt diet for 14 days, marked intimal hyperplasia as well as inflammatory changes were observed in coronary arteries of Ang II/salt-treated wild type (Wt) mice. In Wt mice, Ang II/salt loading increased urinary excretion of 8- hydroxydeoxyguanosine (8-OHdG) and 8-lso-Prostaglandin F2 alpha. Cardiac levels of MDA and 4-HAE, markers of lipid peroxidation, and GSSG/GSH were also increased in Wt. mice after Ang II/salt loading, but not in HO-1 Tg mice. Consistently, immunostaining for both 8-0HdG, a marker of oxidative DNA damage, and 3-nitrotyrosine, the metabolites of reactive oxygen species, were apparently increased in the Ang II/salt-treated heart of Wt. mice; however, no significant changes in these responses were detected in HO-1 Tg mice after Ang II/salt loading. These data suggest that increased oxidative stress might be involved in the coronary artery changes induced by Ang II/salt loading. The evidence presented in the current study indicates that vascular HO-1 exerts its protective effect against cardiovascular damage, possibly through the inhibition of oxidative stress.     

Transplantation of embryonic stem cell-derived neural stem cells for spinal cord injury in adult mice

AIMS: To investigate the efficacy of embryonic stem cell-derived neural stem cells (NSCs) for spinal cord injury (SCI) in mice and whether a combination treatment with thyroid hormone provides a more effective ES cell-based therapy. METHODS: Nestin-positive NSCs were induced from undifferentiated mouse ES cells by a step-by-step culture and used as grafts. Thirty-six mice were subjected to an SCI at Th10 and divided into three groups of 12. Graft cells were transplanted into the injury site 10 days after injury. Group 1 mice were left under observation without receiving graft cells, while mice in Group 2 received 2 x 104 graft cells, and those in Group 3 received 2 x 104 graft cells and were treated with a continuous intraperitoneal injection of thyroxin using osmotic mini-pumps. Behavioral improvement was assessed by a scoring system throughout the experimental period until post-transplantation day (PD) 28. RESULTS: Mice in Groups 2 and 3 demonstrated an improved behavioral function, as compared to those in Group 1 after PD 14. There was no significant difference in behavioral recovery between Groups 2 and 3. CONCLUSIONS: Transplantation of ES-NSCs into the injury site was effective for SCI, while thyroxine did not deliver additional effectiveness.     

De novo basilar top aneurysm in an elderly patient treated with Guglielmi detachable coils

Ruptured de novo aneurysms, compared with the usual subarachnoid hemorrhage, commonly occur in younger patients and are extremely rare in elderly patients. We discuss their etiology and report the case of a ruptured de novo aneurysm in a 77-year-old woman.     

Syringomyelia caused by cervical spondylosis

Summary Syringomyelia is generally associated with Chiari type malformations, spinal tumors, or spinal trauma. Cervical spondylosis is only rarely involved.We here present a case of a 64-year-old woman with severe radicular pain in the right arm and the syringomyelic syndrome. Lateral radiographs of the cervical spine demonstrated spondylotic change at the C4/5 and C6/7 levels, and instability at C4/5. Dynamic magnetic resonance (MR) imaging revealed the spinal cord to be compressed at C5 and C6 with the body in extension, and the syrinx extended from C2 to the Th3 level on sagittal images. It was reduced remarkably after anterior decompression and stabilization at C4/5 and C6/7, and her symptoms also improved after surgery.We concluded that the syrinx in this case might have developed due to craniospinal pressure dissociation caused by intermittent spinal cord compression.     

Intraventricular transplantation of embryonic stem cell-derived neural stem cells in intracerebral hemorrhage rats

In the present study, we attempted to explore cell transplantation therapy for intracerebral hemorrhage (ICH) using embryonic stem (ES) cells. Collagenase-induced ICH rats were used as model animals. Mouse ES cells were differentiated into nestin-positive neural stem cells in vitro by alltrans retinoic acid (ATRA). ATRA-treated ES cells (10(5)) were transplanted into the lateral ventricle in the hemisphere contralateral to the hemorrhage 7 days after collagenase infusion. Twenty-eight days after transplantation, ES-derived neurons and astrocytes were observed around the hematoma cavities of the brain in all of the ten rats receiving grafts. Graft-derived neurons were found in the subependymal area of the lateral ventricle as cellular nodules. Although one of the ten rats receiving grafts showed uncontrolled growth of astroglia derived from the ES cells, intraventricular transplantation of ATRA-treated ES cells is an effective delivery system of neuronal lineage-committed progenitor cells toward the site of ICH.     

Familial 14-Mb deletion at 21q11.2-q21.3 and variable phenotypic expression

We report a familial case with a proximal interstitial deletion of chromosome 21q [del(21q)]. Although the mother in the family was phenotypically normal, her first child was affected with both sensorineural hearing loss and moderate mental retardation, and the second affected child had mild mental retardation but not sensorineural hearing loss. We determined breakpoints of the del(21q) in the mother and her two affected children by fluorescence in situ hybridization analysis using 45 DNA clones and the molecular analysis using 21 DNA markers. The proximal breakpoint of the del(21q) was located at a region between 0.33 Mb and 0.46 Mb distal to the centromere, and the distal breakpoint was at a region between 14.6 Mb and 14.9 Mb. The finding indicates that the three individuals had an approximate 14-Mb deletion within 21q11.2-q21.3. Molecular analysis showed that both affected children shared the same maternal haplotype of their del(21q), but a crossover was detected in the paternally inherited normal chromosome 21. These data suggest that unmasking of deleterious genes on the paternally derived chromosome 21 of the two children as a result of the deletion may affect the extent of their mental retardation and/or sensorineural hearing loss. Usher syndrome 1E may be a candidate disease locus related to the sensorineural hearing loss of the first child.     

Importance of neuropsychological evaluation after surgery in patients with unruptured cerebral aneurysms

BACKGROUND: We evaluated neuropsychological function before and after surgery in patients with unruptured cerebral aneurysms. METHODS: Neuropsychological functions in 43 patients with unruptured cerebral aneurysms were evaluated before and 1 month after surgery. The neuropsychological examination included the Mini-Mental State examination, "Kana-hiroi" test, Kohs Block Design test, and Miyake's Memory test. Then, if scores of even a single test were decreased 1 month after surgery, the tests were performed again 5 months later. In 24 of the 43 subjects, cerebral blood flow (CBF) was measured before and 1 month after surgery by single-photon emission tomography. RESULTS: The outcome in all patients was evaluated as good according to the Glasgow Outcome Score (GOS). In 17 (40%) of the 43 patients, neuropsychological function had deteriorated 1 month after surgery. The most sensitive test applied was the Miyake's Memory test. Of 14 patients with neuropsychological deterioration 1 month after surgery, 6 showed complete recovery, 5 showed partial recovery, and 3 still showed cognitive deterioration 6 months after surgery. Patients over 65 years old, those with anterior communicating artery aneurysms, those operated by interhemispheric approach, or those with systemic diseases showed a greater tendency toward a decline in postoperative neuropsychological function than the other patients. The postoperative CBF and vascular response in the frontal lobe of affected-side was decreased in cases showing cognitive deterioration. CONCLUSIONS: These results suggested that the neuropsychological outcomes after surgery for unruptured cerebral aneurysms were not satisfactory.