Biomedical subjects

Philip R Weinstein

Publications and source records attributed to Philip R Weinstein.

At least 19 recordsLinked to original sources

PubMed2006

Chronic treatment with minocycline preserves adult new neurons and reduces functional impairment after focal cerebral ischemia.

BACKGROUND AND PURPOSE: Evidence suggests that activated microglia are detrimental to the survival of new hippocampal neurons, whereas blocking inflammation has been shown to restore hippocampal neurogenesis after cranial irradiation and seizure. The aim of this current study is to determine the effect of minocycline on neurogenesis and functional recovery after cerebral focal ischemia. METHODS: Four days after temporary middle cerebral artery occlusion, minocycline was administered intraperitoneally for 4 weeks. BrdU was given on days 4 to 7 after middle cerebral artery occlusion to track cell proliferation. The number of remaining new neurons and activated microglia were quantified in the dentate gyrus. Infarct volume was measured to assess the treatment effect of minocycline. Motor and cognitive functions were evaluated 6 weeks after middle cerebral artery occlusion. RESULTS: Minocycline delivered 4 days after middle cerebral artery occlusion for 4 weeks did not result in reduction in infarct size but significantly decreased the number of activated microglia in the dentate gyrus. Minocycline also significantly increased the number of newborn neurons that coexpressing BrdU and NeuN without significantly affecting progenitor cell proliferation in the dentate gyrus. Lastly, minocycline significantly improved motor coordination on the rotor rod, reduced the preferential use of the unaffected limb during exploration, reduced the frequency of footfalls in the affected limb when traversing on a horizontal ladder, and improved spatial learning and memory in the water maze test. CONCLUSIONS: Minocycline reduces functional impairment caused by cerebral focal ischemia. The improved function is associated with enhanced neurogenesis and reduced microglia activation in the dentate gyrus and possibly improved neural environment after chronic treatment with minocycline.

Animals↗

PubMed2006

Reduction of caspase-8 and -9 cleavage is associated with increased c-FLIP and increased binding of Apaf-1 and Hsp70 after neonatal hypoxic/ischemic injury in mice overexpressing Hsp70.

BACKGROUND AND PURPOSE: Caspase-8 and caspase-9 are essential proteases of the extrinsic and intrinsic apoptotic pathways, respectively. We investigated whether neuroprotection associated with overexpression of heat-shock protein 70 (Hsp70), a natural cellular antiapoptotic protein, is mediated by caspase-8 and caspase-9 signaling in the neonatal mouse brain after hypoxia/ischemia (H/I) injury. METHODS: Postnatal day 7 transgenic mice overexpressing rat Hsp70 (Hsp70 Tg) and their wild-type (Wt) littermates underwent unilateral common carotid artery ligation followed by 30 minutes of exposure to 8% O2. The expression of apoptotic proteins was quantified by Western blot analysis, and the specific interaction between Hsp70 and apoptotic protease activating factor 1 (Apaf-1) was determined by coimmunoprecipitation. RESULTS: Hsp70 overexpression reduced cytosolic translocation of cytochrome c without affecting the levels of Apaf-1 and pro-caspase-9 24 hours after H/I. The expression of these apoptotic proteins in the naïve neonatal brains was also not affected by Hsp70 overexpression. Reduced caspase-9 cleavage occurred in Hsp70 Tg mice compared with Wt littermates 24 hours after H/I and correlated with increased binding of Hsp70 and Apaf-1. Increased cellular Fas-associated death domain-like interleukin-1beta-converting enzyme inhibitory protein (FLIP) expression and decreased caspase-8 cleavage were also observed in Hsp70 Tg compared with Wt mice 24 hours after H/I. CONCLUSIONS: Our results suggest that the extrinsic and intrinsic apoptotic pathways mediate the neuroprotective effects of Hsp70 overexpression in neonatal H/I, specifically by upregulating FLIP and sequestering Apaf-1, leading to reduced cleavage of caspase-8 and caspase-9.

Animals↗

PubMed2006

Accuracy over space and time of computer-assisted fluoroscopic navigation in the lumbar spine in vivo.

OBJECTIVE: The integration of digital image-guided surgical navigation with C-arm fluoroscopy, known as virtual fluoroscopy (VF), has been shown to enhance the safety of spine surgery in vitro. Few clinical studies have assessed the accuracy of VF during actual spinal surgery, and no studies have investigated variations in accuracy over the course of a series of measurements obtained during operative cases. We sought to study the intraoperative accuracy of VF over time and space during lumbar pedicle screw placement in human patients. METHODS: Fluoroscopic images of the lumbar spine were obtained, calibrated, and saved to the Stealth Station (FluoroNav) on seven patients undergoing lumbar fusion surgery. The tracking arc was attached to an exposed lumbar spinous process, which was designated the index level. With use of anatomic surface irregularities in the laminae and spinous processes, several points were identified and registered on three different vertebrae directly adjacent to the index level vertebra. Every 15 minutes, throughout the operative case, the probe was brought to each point and the apparent distance from the original location recorded (as measured by the FluoroNav system). Measurements were collected from three vertebral levels adjacent to the index level over a time course of 120 minutes during the operation. RESULTS: At the index, index +1, index +2, and index +3 levels, 89%, 81%, 92%, and 64% of measurements were within <2 mm, whereas 97%, 96%, 97%, and 91% were within <3 mm, respectively. At 15, 30, 45, 60, 75, 90, 105, and 120 minutes, 96%, 89%, 85%, 61%, 85%, 90%, 93%, and 50% of measurements were within <2 mm, whereas 100%, 93%, 100%, 83%, 100%, 90%, 100%, and 100% of measurements were within <3 mm, respectively. The error in millimeters tended to increase as the distance from the index level increased (R = 0.19, P < 0.05) and as operative time increased (R = 0.26, P < 0.01). Calibration studies of intraoperative VF (IoVF) in the lumbar spine documented a reasonable degree of accuracy. The majority of sequential measurements obtained during IoVF in the lumbar spine were within an error range of <3 mm. CONCLUSIONS: Our results suggest that the use of VF is a reliable method of verifying the use of anatomic and/or radiographic landmarks for guidance during lumbar pedicle screw placement.

Adult↗

PubMed2006

Continuous EMG recordings and intraoperative electrical stimulation for identification and protection of cervical nerve roots during foraminal tumor surgery.

OBJECTIVE: Spinal cord function is now routinely monitored with somatosensory evoked potentials (SEPs) and motor evoked potentials (MEPs) during surgery for intraspinal cervical dumbbell and foraminal tumors. However, upper extremity nerve roots are also at risk during these procedures. Anatomic relations are frequently difficult to interpret because the nerve roots may be displaced by the tumor. We used electrical stimulation with compound muscle action potential (CMAP) recordings at multiple sites to identify the location and course of the involved nerve root and to provide real-time information regarding the functional status of the roots to predict postoperative outcome. METHODS: Ten patients were monitored during surgery for cervical dumbbell or foraminal tumors. SEPs and MEPs were monitored as a routine procedure. CMAPs were recorded from needle electrodes placed in the deltoid, biceps, triceps, and flexor carpi ulnaris muscles. Spontaneous electromyography (EMG) muscle activity was also continuously monitored. A handheld monopolar stimulation electrode was used to elicit evoked EMG responses to identify and trace the course of nerves in relation to the tumor. In four patients, the stimulation threshold was tested before and after tumor resection to predict postoperative nerve root function. RESULTS: Electrical stimulation with CMAP recording was successful in localizing nerve roots during tumor resection in all 10 patients. Monitoring predicted postoperative nerve root preservation after tumor removal in each case. It was possible to identify either by using low-level stimulation (<2.0 V) or by observing changes in spontaneous EMG amplitude if activation was present during surgical dissection. The monitoring of spontaneous muscle activity in response to direct or indirect surgical manipulation during tumor resection also provided continuous assessment of nerve root function and identified any physiologic disturbance induced by surgical manipulation. CONCLUSIONS: Electrical stimulation in the operating field and recording of CMAPs facilitated nerve root identification and predicted postoperative function during dissection and separation from ligamentous or neoplastic tissue in 10 patients. Electrical stimulation might also be useful to predict postoperative preservation of function when nerve root sacrifice is necessary and no motor response is detected intraoperatively.

Action Potentials↗

PubMed2006

Current treatment strategies and outcomes in the management of symptomatic vertebral hemangiomas.

OBJECTIVE: We analyzed the outcome of patients with symptomatic vertebral hemangiomas treated at University of California, San Francisco, over a 20 year period. Treatment included transarterial embolization, embolization followed by surgical decompression or vertebral reconstruction with arthrodesis, and percutaneous vertebroplasty alone. METHODS: All medical, surgical, and radiological records were reviewed retrospectively. All patients underwent follow-up neurological examination and evaluation of back pain. RESULTS: Sixteen patients diagnosed with symptomatic vertebral hemangiomas causing pain or neurological deficit were treated at University of California, San Francisco, between 1984 and 2004. Mean follow-up was 81 months. Seven of nine patients undergoing surgical decompression and tumor resection reported pain relief and demonstrated improvement in neurological deficit when present. Two patients had recurrent myelopathy: one was successfully treated with a second decompressive surgery, whereas the second underwent a staged vertebrectomy. All three patients undergoing vertebrectomy had cord compression from extraosseous tumor growth. Preoperative embolization reduced expected intraoperative blood loss in four patients. Three of four patients who underwent transarterial embolization alone experienced resolution of back pain. Two of four patients treated with vertebroplasty had long-term pain relief. CONCLUSION: Transarterial embolization followed by laminectomy is a safe and effective procedure for the treatment of cord compression by vertebral hemangioma causing stenosis without instability or deformity. Vertebrectomy preceded by embolization and followed by reconstruction can be used to treat cord compression from extraosseous tumor extension. Transarterial embolization without decompression is an effective treatment for painful intraosseous hemangiomas. Vertebroplasty is useful for improving pain symptoms, especially when vertebral body compression fracture has occurred in patients without neurological deficit, but is less effective in providing long-term pain relief.

Adult↗

PubMed2005

Enriched environment and spatial learning enhance hippocampal neurogenesis and salvages ischemic penumbra after focal cerebral ischemia.

Enriched environment (EE) has been shown to increase neurogenesis in the adult brain. The aim of this study is to determine the effect of EE and spatial learning on neurogenesis following ischemic stroke. Male adult SD rats were subjected to sham surgery or distal middle cerebral artery occlusion (MCAO). MCAO induced a transient increase followed by a sustained depression of progenitor cell proliferation and neuroblast production below baseline level in both ipsilateral and contralateral DG compared to sham. Increased neuronal differentiation and neurogenesis in the DG were observed in both sham and MCAO rats following 8 weeks in the EE combined with spatial learning, compared to rats housed in the standard environment. EE/Learning also restored the total number of neuroblasts in the DG after MCAO compared to sham. Furthermore, EE/learning enhanced the density of NeuN positive cells in the ischemic penumbra, though no new neurons were detected in this region.

Animals↗

PubMed2005

Hsp70 overexpression sequesters AIF and reduces neonatal hypoxic/ischemic brain injury.

Apoptosis is implicated in neonatal hypoxic/ischemic (H/I) brain injury among various forms of cell death. Here we investigate whether overexpression of heat shock protein (Hsp) 70, an antiapoptotic protein, protects the neonatal brain from H/I injury and the pathways involved in the protection. Postnatal day 7 (P7) transgenic mice overexpressing rat Hsp70 (Tg) and their wild-type littermates (Wt) underwent unilateral common carotid artery ligation followed by 30 mins exposure to 8% O(2). Significant neuroprotection was observed in Tg versus Wt mice on both P12 and P21, correlating with a high level of constitutive but not inducible Hsp70 in the Tg. More prominent injury was observed in Wt and Tg mice on P21, suggesting its continuous evolution after P12. Western blot analysis showed that translocation of cytochrome c, but not the second mitochondria-derived activator of caspase (Smac)/DIABLO and apoptosis-inducing factor (AIF), from mitochondria into cytosol was significantly reduced in Tg 24 h after H/I compared with Wt mice. Coimmunoprecipitation detected more Hsp70 bound to AIF in Tg than Wt mice 24 h after H/I, inversely correlating with the amount of nuclear, but not cytosolic, AIF translocation. Our results suggest that interaction between Hsp70 and AIF might have reduced downstream events leading to cell death, including the reduction of nuclear AIF translocation in the neonatal brains of Hsp70 Tg mice after H/I.

Animals↗

PubMed2005

Hypoglycemia induces transient neurogenesis and subsequent progenitor cell loss in the rat hippocampus.

Neurogenesis after brain injury not only leads to the replacement of damaged cells but might also contribute to functional recovery, suggesting the possibility of endogenous neural repair. We investigated the extent of hippocampal neural regeneration in a rat model of hypoglycemia. Two weeks after 30 min of insulin-induced isoelectric electroencephalogram, extensive neuronal loss was observed in the hippocampus, including area CA1 and dentate gyrus (DG). A transient increase in progenitor cell proliferation in the DG subgranular zone (SGZ) was detected, leading to an increase of immature neuroblasts 1-2 weeks after hypoglycemic insult. Most of the surviving newborn cells assumed a neuronal phenotype within 1 month in DG, a few cells near the site of granule-cell death becoming astroglia or microglia. No neuronal regeneration was observed in the CA1 after hypoglycemia, although dividing cells appeared to be astroglia or microglia in CA1 and dentate hilus. At 4 weeks after hypoglycemia, proliferative activity in the SGZ diminished below baseline in experimental versus control rats, with a subsequent reduction of neuroblasts. Morphological findings (doublecortin staining) suggest permanent progenitor cell loss in some areas of SGZ. Reduced neurogenesis in DG and lack of neuronal regeneration in CA1 may impede cognitive recovery after severe hypoglycemia injury.

Animals↗

PubMed2005

Spontaneous intracranial hypotension associated with transdural thoracic osteophyte reversed by primary. dural repair. Case report.

Spontaneous intracranial hypotension (SIH) is an increasingly recognized syndrome associated with a specific set of clinical and imaging findings; however, determining the site of spinal cerebrospinal fluid (CSF) leakage in these patients is often difficult, and indications for surgical intervention need to be better defined. The authors report on a 55-year-old woman who presented with posture-related headache, disorientation, and memory impairment. Imaging features were consistent with SIH. Computerized tomography myelography demonstrated a large T2-3 anterior transdural osteophyte associated with a CSF fistula. After an unsuccessful trial of conservative therapy, the patient underwent median sternotomy, T2-3 discectomy and removal of osteophyte, which allowed adequate exposure for primary dural repair. Postoperatively, there was immediate and prolonged resolution of all of her symptoms. This case of SIH was caused by transdural penetration by an anterior osteophyte and CSF leakage in the upper thoracic spine, which was treated effectively by anterior exposure and primary dural repair. Aggressive surgical intervention may be required to treat upper thoracic CSF leaks refractory to other measures.

Diskectomy↗

PubMed2005

Changes in transcranial motor evoked potentials during intramedullary spinal cord tumor resection correlate with postoperative motor function.

OBJECTIVE: Intraoperative monitoring of transcranial motor evoked potentials (TcMEPs) has been investigated recently as a means of preventing motor deficits associated with resection of intramedullary spinal cord tumors (IMSCTs). In this study, we hypothesized that changes in the intraoperative MEPs during tumor resection correlate with postoperative motor function deficits. METHODS: A retrospective record review was conducted for 28 patients who underwent resection of an IMSCT using myogenic or muscle-recorded TcMEPs during a 44-month period. Intraoperative MEP recordings and results from preoperative, immediate postoperative, and subsequent follow-up neurological examinations were analyzed. RESULTS: Of the 28 patients who underwent resection of an IMSCT using TcMEPs, MEP changes occurred in 13 patients (46%). Impaired motor conduction was detected by changes in pattern and duration of the MEP waveform morphology (polyphasic to biphasic in 9 patients and polyphasic to biphasic to loss of MEP response in 5 patients, 1 patient demonstrated both changes) and by an increase in voltage threshold (median, 175 V; range, 100-225 V; n = 22 extremities). Alterations in morphology and reduction in duration of the MEP response persisted despite significant increases in stimulation voltage. In 12 patients, reductions in the complexity and/or loss of the TcMEP waveform correlated with motor grade loss in the immediate postoperative period (P < 0.0001), at discharge (P < 0.001), and at follow-up (P < 0.001). The decrease in the duration of the response correlated with motor grade loss immediately after surgery (P < 0.001), at discharge (P < 0.0001), and at follow-up (P < 0.005). CONCLUSION: These results support the application of distal muscle-recorded TcMEPs to predict the occurrence and severity of postoperative motor deficits during resection of IMSCTs. Attention to such quantitative intraoperative monitoring data may help to minimize postoperative motor deficits by avoiding or correcting excessive spinal cord manipulation and modifying surgical technique during tumor resection.

Adult↗

PubMed2004

General principles in the medical and surgical management of spinal infections: a multidisciplinary approach.

OBJECT: Infections along the spinal axis are characterized by an insidious onset, and the resulting delays in diagnosis are associated with serious neurological consequences and even death. Infections of the spine can affect the vertebral bodies, intervertebral discs, spinal canal, and surrounding soft tissues. Neurological dysfunction occurs when the spinal cord becomes compressed, edematous, or ischemic due to compression by abscess or vascular compromise. The aim of this paper was to detail general diagnostic and management principles for this disease. METHODS: Recent progress in medical technologies, including the development of potent antimicrobial drugs, advanced imaging, and improved surgical methods, have dramatically reduced morbidity and mortality rates for spinal infections; however, debate still exists on the proper management of this disease. In this paper, the authors review the current management protocols for spinal infections at their institution, focusing on medical and surgical treatments for vertebral osteomyelitis, intervertebral disc space infections, and spinal canal and soft-tissue abscesses. CONCLUSIONS: Technological advances in imaging modalities, pharmaceutics, and surgery have resulted in excellent outcomes and have greatly reduced the morbidity and mortality rates associated with spinal infections. Currently, treatment of spinal infections requires a multidisciplinary team that includes infectious diseases experts, neuroradiologists, and spine surgeons. The key to successful management of spinal infections is early detection.

Bacterial Infections↗

PubMed2004

Diagnosis and management of adult pyogenic osteomyelitis of the cervical spine.

Establishing the diagnosis of cervical osteomyelitis in a timely fashion is critical to prevent catastrophic neurological injury. In the modern imaging era, magnetic resonance imaging in particular has facilitated the diagnosis of cervical osteomyelitis, even before the onset of neurological signs or symptoms. Nevertheless, despite advancements in diagnosis, disagreement remains regarding appropriate surgical treatment. The role of instrumentation and type of graft material after cervical decompression remain controversial. The authors describe the epidemiological features, pathogenesis, and diagnostic evaluation, and the surgical and nonsurgical interventions that can be used to treat osteomyelitis of the cervical spine. They also review the current debate about the role of instrumentation in preventing spinal deformity after surgical decompression for cervical osteomyelitis. Based on this review, the authors conclude that nonsurgical therapy is appropriate if neurological signs or symptoms, instability, deformity, or spinal cord compression are absent. Surgical decompression, debridement, stabilization, and deformity correction are the goals once the decision to perform surgery has been made. The roles of autogenous graft, instrumentation, and allograft have not been clearly delineated with Class I data, but the authors believe that spinal stability and decompression override creating an environment that can be completely sterilized by antibiotic drugs.

Bacterial Infections↗

PubMed2004

Molecular identification of the ischemic penumbra.

Review of results of experimental and clinical studies indicates that the penumbra of physiologically impaired but potentially salvageable tissue surrounding the central core of focal cerebral ischemia that develops shortly after onset of major conducting vessel occlusion is complex and dynamic with severity and duration thresholds for hypoxic stress and injury that are specific to tissue site, cell type, molecular pathway or gene expression investigated and efficiency of collateral or residual flow and reperfusion. Imaging methods that have been utilized in vivo to identify penumbra and predict response to reperfusion and other protective therapies include magnetic resonance spectroscopy, diffusion- and perfusion-MRI as well as positron emission tomography. However, resolution of focal lesions characterized by lactic acidosis or cellular edema does not predict tissue survival, and imaging thresholds for resuscitation after reperfusion have not been determined experimentally. HSP-70 stress protein induction represents an endogenous protective mechanism that occurs in penumbra but not core neurones. A robust protective effect has been demonstrated during focal ischemia in transgenic mice overexpressing HSP-70 perhaps by suppressing early cytochrome c release. Delayed manganese mediated striatal neurodegeneration can be detected with T1 MRI after brief episodes of transient focal ischemia. Future studies may define endogenous cytotoxic and cytoprotective molecular penumbras that can be exploited to improve outcome after temporary focal ischemia.

Animals↗

PubMed2004

Human serum albumin and its N-terminal tetrapeptide (DAHK) block oxidant-induced neuronal death.

BACKGROUND AND PURPOSE: Studies using animal models of stroke have shown that human serum albumin (HSA) significantly ameliorates cerebral ischemic injury after both transient and permanent ischemia, even when administered after the onset of ischemia or reperfusion. The mechanism of this effect remains uncertain, and prior studies suggest both indirect hemodynamic and direct cytoprotective effects. HSA is a potent antioxidant, in part because of its strong copper-binding capacity. Here we examined the effect of HSA on oxidant-induced neuronal death in a cortical cell culture system. METHODS: Murine cortical cultures were exposed to oxidative stress generated by hydrogen peroxide and by a mixture of copper plus ascorbic acid. We examined the ability of HSA and a tetrapeptide occupying its N-terminus (DAHK) to prevent neuronal death after these challenges. RESULTS: H(2)O(2) and CuCl(2)/ascorbic acid were used at concentrations that, in the absence of HSA, killed >90% of the neurons. HSA provided complete protection at a concentration of 37.5 micromol/L and 50% protection at 3.75 micromol/L. The copper-binding tetrapeptide DAHK had nearly identical potency and efficacy. HSA and DAHK were also equally effective in preventing neuronal death induced by CuCl(2)/ascorbic acid. CONCLUSIONS: HSA has potent antioxidant properties, probably due to binding of copper and other transition metals. HSA extravasation into ischemic brain may provide neuroprotection by limiting metal-catalyzed oxidant stress. The tetrapeptide DAHK may be an effective, small-molecular-weight alternative to HSA as a therapeutic agent for stroke.

Animals↗

PubMed2004

Irradiation attenuates neurogenesis and exacerbates ischemia-induced deficits.

Increased neurogenesis after cerebral ischemia suggests that functional recovery after stroke may be attributed, in part, to neural regeneration. In this study, we investigated the role of neurogenesis in the behavioral performance of gerbils after cerebral global ischemia. We used ionizing radiation to decrease neural regeneration, and 2 weeks later cerebral global ischemia was induced by bilateral common carotid artery occlusion. One month after the occlusion, the animals were behaviorally tested. Irradiation alone reduced neurogenesis but did not change vascular or dendritic morphology at the time of behavioral testing. Neither did irradiation, ischemia, or combined treatment impair rotor-rod performance or alter open-field activity. Gerbils subjected to both irradiation and ischemia demonstrated impaired performance in the water-maze task, compared with those that received only ischemia, radiation, or no treatment. These impairments after cerebral global ischemia under conditions of reduced neurogenesis support a role for the production of new cells in mediating functional recovery.

Animals↗

PubMed2003

Diagnosis and management of sacral Tarlov cysts. Case report and review of the literature.

Perineurial (Tarlov) cysts are meningeal dilations of the posterior spinal nerve root sheath that most often affect sacral roots and can cause a progressive painful radiculopathy. Tarlov cysts are most commonly diagnosed by lumbosacral magnetic resonance imaging and can often be demonstrated by computerized tomography myelography to communicate with the spinal subarachnoid space. The cyst can enlarge via a net inflow of cerebrospinal fluid, eventually causing symptoms by distorting, compressing, or stretching adjacent nerve roots. It is generally agreed that asymptomatic Tarlov cysts do not require treatment. When symptomatic, the potential surgery-related benefit and the specific surgical intervention remain controversial. The authors describe the clinical presentation, treatment, and results of surgical cyst fenestration, partial cyst wall resection, and myofascial flap repair and closure in a case of a symptomatic sacral Tarlov cyst. They review the medical literature, describe various theories on the origin and pathogenesis of Tarlov cysts, and assess alternative treatment strategies.

Case Management↗

PubMed2003

Effect of suture size and carotid clip application upon blood flow and infarct volume after permanent and temporary middle cerebral artery occlusion in mice.

Problems with the intraluminal suture method for induction of focal cerebral ischemia in genetically altered mice include occurrence of subarachnoid hemorrhage (SAH) and variability of infarct volume. We hypothesized that use of 5-0 curved or 6-0 straight suture for carotid cannulation might decrease SAH and that the application of a microvascular clip to the common carotid artery (CCA) might decrease variability of infarct volume. The purpose of this study is to evaluate and explain the results of these technical modifications. Strain related differences in vascular anatomy were evaluated. Male C57BL/6 mice were divided into two groups for permanent and temporary middle cerebral artery occlusion (MCAO). Results of 5-0 curved suture and 6-0 straight suture insertion with and without CCA clip application were examined. Cerebral perfusion was monitored by laser-Doppler flowmetry and infarct volume was measured. After permanent MCAO, larger and more consistent infarct volumes resulted using CCA clip application with a 6-0 but not with a 5-0 suture. After temporary MCAO, the SAH rate was 12.5% with a 5-0 curved suture and 11.1% with a 6-0 straight suture. A 40% rate was observed in a pilot study with 5-0 straight suture. Infarct volume after temporary MCAO with a CCA clip was significantly larger and variability of infarct volume was smaller than without the CCA clip using 5-0 curved and 6-0 straight suture. In summary, SAH is less frequent using a 5-0 curved or 6-0 straight suture. Infarct volume is enlarged by application of a CCA clip (249).

Animals↗

PubMed2003

Cyclooxygenase-2 mRNA expression is associated with c-fos mRNA expression and transient water ADC reduction detected with diffusion MRI during acute focal ischemia in rats.

Cyclooxygenase-2 (COX-2) plays an important role in the development of injury during cerebral ischemia and inhibition of its activity can reduce infarct size. COX-2 expression during acute ischemia is caused by activation of post-synaptic glutamate receptors, which occurs during spreading depression and ischemic depolarization. Both of these phenomena cause a reduction in the apparent diffusion coefficient of water (ADC), which can be detected with diffusion-weighted magnetic resonance imaging. The reduction is believed to be caused by cellular swelling that occurs as cells depolarize. The goal of this work was to determine the spatial relationship between cyclooxygenase-2 mRNA (cox-2) expression, c-fos mRNA expression and ADC reduction during acute focal cerebral ischemia. Adult rats were subjected to either 30- or 60-min permanent occlusion of the middle cerebral artery. A 2-Tesla scanner was used to acquire diffusion-weighted echo-planar images throughout the ischemic period, which were used to calculate ADC maps. Cox-2 and c-fos mRNA were detected with (35)S in situ hybridization. The results indicate that, for rats subjected to 60-min ischemia, cox-2 was observed in superficial layers of cortex, where transient ADC reduction and c-fos expression were observed. The same was true for most rats subjected to 30-min ischemia. However, in a small number of rats of the 30-min group, cox-2 mRNA expression was observed in regions exhibiting transient and persistent ADC reduction with no c-fos expression. The results suggest that cox-2 mRNA expression during acute MCA occlusion is caused by either or both spreading depression and transient ischemic depolarization.

Acute Disease↗