Biomedical subjects

Philip R Weinstein

Publications and source records attributed to Philip R Weinstein.

26 records · Page 2Linked to original sources

PubMed2003

Overexpression of rat heat shock protein 70 is associated with reduction of early mitochondrial cytochrome C release and subsequent DNA fragmentation after permanent focal ischemia.

Although protective effects of heat shock protein 70 (HSP70) overproduction after ischemic injury have been shown both in vitro and in vivo in neurons, the mechanisms are not fully understood. The hypothesis of this study is that transgenic mice overexpressing HSP70 (HSP70 Tg) show reduced mitochondrial cytochrome c release into cytosol and diminished apoptotic cell death after permanent focal ischemia in comparison to wild-type (Wt) mice. Permanent middle cerebral artery occlusion (pMCAO) was produced by intraluminal suture cannulation in HSP70 Tg and Wt mice. DNA fragmentation was evaluated with DNA gel electrophoresis and terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick end labeling (TUNEL) 24 h after pMCAO. Mitochondrial cytochrome c release into cytosol was assessed with Western blotting and immunohistochemistry 4 h after pMCAO. Cytochrome c levels in the cytosolic fraction were significantly reduced and immunoreactivity of cytochrome c in both cortex and striatum was significantly less in HSP70 Tg mice compared with Wt mice after 4-h pMCAO. DNA laddering, which was clearly observed in Wt mice, was markedly attenuated in HSP70 Tg mice 24 h after pMCAO. The number of TUNEL-positive cells was significantly reduced in HSP70 Tg mice compared with Wt mice. Results are consistent with an association between overexpression of HSP70 and reduction of cytochrome c release with subsequent DNA fragmentation. This may contribute to the HSP70-mediated neuroprotective effect observed after cerebral ischemia.

Animals↗

PubMed2003

Differential cerebral protein synthesis and heat shock protein 70 expression in the core and penumbra of rat brain after transient focal ischemia.

OBJECTIVE: The purpose of this study was to correlate the cerebral protein synthesis (CPS) reductions in the ischemic core and penumbra with the metabolic stress response indicated by heat shock protein 70 (HSP70) synthesis. METHODS: Rats were subjected to 90 minutes of temporary focal cerebral ischemia produced by occlusion of the middle cerebral artery, using the endovascular suture model. Regional CPS was qualitatively evaluated, with [(35)S]methionine autoradiography, after reperfusion for 2 to 72 hours. The observed changes were correlated with HSP70 immunoreactivity, as assessed in the same brain sections. The ischemic core in the striatum was characterized by HSP70 expression only in endothelial and/or glial cells, with an absence of expression in neurons. The penumbra was delineated as the cortical middle cerebral artery territory region in which HSP70 was also expressed in metabolically stressed neurons. RESULTS: After 2 hours of reperfusion, CPS was reduced to 30 +/- 16% of the homologous contralateral hemisphere value in the core and to 75 +/- 22% in the penumbra (P < 0.05). This difference was still present at 72 hours, when CPS values were 62 +/- 21% and 98 +/- 29% of the nonischemic contralateral hemisphere values in the core and penumbra, respectively (P < 0.05). CONCLUSION: Persistent inhibition of CPS in regions in which neuronal HSP70 expression is absent may distinguish core areas of infarction from penumbral regions in which neuronal HSP70 is present, which eventually recover from sublethal metabolic stress during reperfusion after temporary focal ischemia.

Animals↗

PubMed2003

Overexpression of rat heat shock protein 70 reduces neuronal injury after transient focal ischemia, transient global ischemia, or kainic acid-induced seizures.

OBJECTIVE: Transgenic (Tg) mice overexpressing rat heat shock protein 70 (hsp70) demonstrated less infarction than did wild-type (WT) littermates after permanent focal cerebral ischemia. The purpose of this study was to determine whether neuronal injury and apoptosis were reduced in hsp70 Tg mice after transient focal ischemia. The effects of hsp70 overexpression were also evaluated after transient global ischemia or kainic acid (KA)-induced seizures, to verify the results in other excitotoxic stress models. METHODS: Transient focal ischemia was produced with middle cerebral artery occlusion via intraluminal suture cannulation. Infarction volumes were assessed 24 hours after 30 minutes of middle cerebral artery occlusion. Transient global ischemia was produced with 25 minutes of bilateral common carotid artery occlusion. KA (30 mg/kg) was administered subcutaneously, and seizure activity was evaluated. The number of eosinophilic neurons was assessed in the CA1 region 72 hours after bilateral common carotid artery occlusion and in the CA3 region 24 hours after KA administration. RESULTS: The infarction volume after transient middle cerebral artery occlusion was significantly smaller in hsp70 Tg mice than in WT mice (9.1 +/- 5.7 mm(3) versus 22.4 +/- 16.8 mm(3), P < 0.05). The number of eosinophilic neurons in the CA1 area after bilateral common carotid artery occlusion and in CA3 after KA injection was significantly lower in hsp70 Tg mice than in WT mice (949.1 +/- 1095.5 versus 2406.9 +/- 1380.3, P < 0.05, and 33.8 +/- 45.3 versus 119.4 +/- 112.1, P < 0.05, respectively). Fewer terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end-labeling-positive cells were observed in hsp70 Tg mice than in WT mice in each model. CONCLUSION: The results demonstrate that overexpression of hsp70 reduces neuronal injury after ischemia and seizures. The reduction in the number of terminal deoxynucleotidyl transferase-mediated biotinylated deoxyuridine triphosphate nick end-labeling-positive cells in hsp70 Tg mice suggests that hsp70 overexpression might reduce apoptotic cell death.

Animals↗

PubMed2002

Transgenic mice expressing human copper-zinc superoxide dismutase exhibit attenuated apparent diffusion coefficient reduction during reperfusion following focal cerebral ischemia.

Since ADC reduction reflects intracellular edema which is an early indicator of ischemic cellular metabolic stress, we hypothesized that a decrease in ADC as determined by diffusion weighted MR imaging could be attenuated by SOD expression in transgenic mice during reperfusion following focal cerebral ischemia. Diffusion weighted imaging (DWI) was performed to evaluate apparent diffusion coefficient (ADC) reduction by constructing ADC maps with a color scale to localize ADC change in transgenic (Tg) mice expressing human CuZn superoxide dismutase (SOD) and wild type (Wt) mice during 1 h middle cerebral artery occlusion (MCAO) and 1 h reperfusion. Heat shock protein (hsp) 70-kDa mRNA analysis was evaluated as a marker of sublethal cell stress by in situ hybridization after 4 h reperfusion for comparison with Nissl staining of adjacent sections to assess infarction. Sequential ADC maps were prepared in Tg mice with sufficient temporal and spatial resolution to permit comparison with Wt mice. Tg mice showed substantial recovery of the ADC lesion after reperfusion, while Wt mice showed no recovery. There was no difference between Tg and Wt mice in the size or distribution of the ADC lesion during ischemia. The area with strong expression of hsp70 mRNA in the ischemic hemisphere was substantially larger in the Tg mice. Nissl staining showed less damage of brain tissue in Tg mice than Wt mice especially in the cortex after 4 h reperfusion following 1 h MCAO. Results demonstrate that antioxidant effects of human CuZn-SOD reduce cellular edema due to oxidative stress during reperfusion but not during ischemia after 1 h MCAO. Hsp70 could be one of the proteins that mediates protection by SOD against oxidative stress.

Animals↗

PubMed2002

Lumbar spinal stenosis.

Lumbar spinal stenosis refers to a diversity of conditions that decrease the total area of the spinal canal, lateral recesses, or neural foramina. Lumbar stenosis is a common disorder that may be present in isolation, with or without associated disk bulge or herniation, or can be associated with degenerative spondylolisthesis or scoliosis. Symptomatic lumbar spinal stenosis is characterized by neurogenic claudication and/or lumbar or sacral radiculopathy. Sixty percent to 85% of properly selected patients have a satisfactory symptomatic improvement with surgical treatment.

Cauda Equina↗

PubMed2002

Mild hypothermia reduces zinc translocation, neuronal cell death, and mortality after transient global ischemia in mice.

The authors sought to determine whether Zn translocation associated with neuronal cell death occurs after transient global ischemia (TGI) in mice, as has been previously shown in rats, and to determine the effect of mild hypothermia on this reaction. To validate the TGI model, carbon-black injection and laser-Doppler flowmetry were compared in three strains of mice (C57BL/6, SV129, and HSP70 transgenic mice) to assess posterior communicating artery (PcomA) development and cortical perfusion. In C57BL/6 mice, optimal results were obtained when subjected to 20-minute TGI. Brain and rectal temperature measurements were compared to monitor hypothermia. Results of TGI were compared in normothermia (NT; 37 degrees C) and mild hypothermia groups (HT; 33 degrees C) by staining with Zn -specific fluorescent dye, -(6-methoxy-8-quinolyl)-para-toluenesulfonamide (TSQ) and hematoxylin-eosin 72 hours after reperfusion. The Zn translocation observed in hippocampus CA1, CA2, and Hilus 72 hours after 20 minutes of TGI was significantly reduced by mild hypothermia. The number of degenerating neurons in the HT group was significantly less than in the NT group. Mild hypothermia reduced mortality significantly (7.1% in HT, 42.9% in NT). Results suggest that mild hypothermia may reduce presynaptic Zn release in mice, which protects vulnerable hippocampal neurons from ischemic necrosis. Future studies may further elucidate mechanisms of Zn -induced ischemic injury.

Animals↗

PubMed2002

Correlation between changes in apparent diffusion coefficient and induction of heat shock protein, cell-specific injury marker expression, and protein synthesis reduction on diffusion-weighted magnetic resonance images after temporary focal cerebral ischemia in rats.

OBJECT: The authors investigated the relationship between the time course of apparent diffusion coefficient (ADC) changes and stress protein induction, ischemic neuroglial damage, and cerebral protein synthesis (CPS) after temporary focal cerebral ischemia in rats. METHODS: In Group I, ADC changes were measured on magnetic resonance (MR) images obtained during the second half of a 1-hour middle cerebral artery (MCA) occlusion, during a 1-hour reperfusion, and after 23 hours of reperfusion in rats. Immunohistochemical studies for heat shock protein (hsp) 70, glial fibrillary acidic protein (GFAP), and neuronal nuclear (NeuN) protein were performed. In Group II, CPS was assessed using autoradiographic studies obtained after occlusion. At 36 minutes of occlusion, MR imaging demonstrated significantly less ADC reduction in the frontoparietal cortex (82 +/- 9% of the contralateral hemisphere) than in the striatum (64 +/- 11%; p < 0.05). After 1 hour of reperfusion, the lesion resolved and the difference between cortex and striatum was no longer evident. After 23 hours of reperfusion, the ADC lesion recurred in striatum (76 +/- 12%) compared with frontoparietal cortex (100 +/- 11%; p < 0.05). Immunohistochemical studies showed hsp 70 expression and an increased GFAP reactivity localized in the frontoparietal cortex of the ischemic hemisphere, along with a significant drop in striatal NeuN immunoreactivity. A trend toward greater reduction in striatal CPS (53 +/- 15%) than in frontoparietal cortex CPS (78 +/- 23%) was also observed. CONCLUSIONS: Sequential ADC maps correlate with the expression of neuroglial stress and injury markers after temporary focal ischemia in rats, distinguishing the striatum (infarct core) from the cortex (ischemic penumbra). A greater reduction in striatal CPS further supports the conclusion that the striatum is more susceptible to temporary MCA occlusion than the cortex.

Animals↗

PubMedDate not supplied

Use of intraoperative isocentric C-arm 3D fluoroscopy for sextant percutaneous pedicle screw placement: case report and review of the literature.

BACKGROUND CONTEXT: Three-dimensional (3D) fluoroscopy-based image guidance system using an isocentric C-arm (Iso-C) fluoroscope was shown to be as effective as computed tomography-based systems in guiding the accurate percutaneous placement of lumbar pedicle screws in cadavers. To date, however, no description is available of the intraoperative use of 3D fluoroscopy to guide lumbar pedicle screw placement in an actual spinal fusion procedure. PURPOSE: We report a case in which isocentric 3D fluoroscopic images, along with image-guidance software, were used to guide the placement of percutaneous pedicle screws for fusion in a patient with degenerative spondylolisthesis. STUDY DESIGN/SETTING: Operating room of a large academic medical center during the placement of percutaneous pedicle screws in a patient with degenerative spondylolisthesis. METHODS: A percutaneous dynamic reference array was attached to the L3 spinous process. A satisfactory image set was obtained and automatically registered. The L4 and L5 pedicles were localized, and pedicle holes were then cannulated, drilled and tapped. A screw was then inserted using the Sextant system for percutaneous pedicle screws. In this manner, bilateral pedicle screws were inserted into the L4-L5 pedicles. All steps of pedicle cannulation were performed under Iso-C 3D image guidance. RESULTS: A postoperative computed tomography scan showed accurate placement of all pedicle screws. The patient experienced an improvement in leg pain with no new neurologic deficits. CONCLUSIONS: The present case is the first case to demonstrate the intraoperative use of a 3D fluoroscopy-based image-guidance system for accurate navigation during lumbar pedicle screw placement.

Bone Screws↗