Neuroprotection by the stable nitroxide 3-carbamoyl-proxyl during reperfusion in a rat model of transient focal ischemia

2003 ◽  
Vol 98 (2) ◽  
pp. 393-396 ◽  
Author(s):  
Guohan Hu ◽  
Bruce G. Lyeth ◽  
Xueren Zhao ◽  
James B. Mitchell ◽  
Joe C. Watson
Keyword(s):  
Infarct Size ◽  
Brain Ischemia ◽  
Brain Temperature ◽  
Ischemia Reperfusion ◽  
Statistical Significance ◽  
Focal Ischemia ◽  
Ischemia And Reperfusion ◽  
Clinical Use ◽  
Content Type ◽  
Fine Print

Object. Nitroxides mimic superoxide dismutase (SOD) biochemically and may prevent free radical oxidative injury in settings in which endogenous SOD is overwhelmed. The authors have previously shown the efficacy of a nitroxide, Tempol, in reducing stroke infarct size. Of the nitroxides, 3-carbamoyl-proxyl (3-CP) is especially promising for clinical use, because it does not cause hypotension in animals. Its efficacy in brain ischemia, however, is untested. The goal of this study was to ascertain whether 3-CP would reduce brain damage in a rat ischemia—reperfusion model. Methods. The authors performed a blinded, dose—response study of the effect of different amounts of 3-CP (1, 10, and 100 mg/kg) on infarct size at 24 hours after focal ischemia and reperfusion. The 3-CP was given intravenously during reperfusion, which followed 1 hour of reversible ischemia induced by a thread placed intraluminally in the middle cerebral artery of rats. Brain infarcts, measured with 2,3,5-triphenyltetrazolium chloride staining in six 3-CP groups, were compared with those measured in controls (animals given an equal volume of saline). Edema-corrected infarct sizes (mean ± standard deviation) were as follows: 146 ± 64 mm3 in controls; 107 ± 18 mm3 in rats given 1 mg/kg 3-CP; 40 ± 20 mm3 in those given 10 mg/kg 3-CP; and 44 ± 17 mm3 in those given 100 mg/kg 3-CP. A statistically significant reduction in infarct size was achieved in the 10- and 100-mg/kg 3-CP—treated groups (p < 0.01). A reduction in infarct size was also seen in the 1 mg/kg 3-CP—treated group, but this did not reach statistical significance. The authors observed no effects of 3-CP on blood pressure or brain temperature. Conclusions. Given at reperfusion, 3-CP significantly decreases brain infarct size at doses of 10 and 100 mg/kg without causing hypotension. The authors found that 3-CP is well suited for further laboratory and clinical use in brain ischemia and reperfusion.

Beneficial effects of induced hypertension on experimental stroke in awake monkeys

1984 ◽  
Vol 60 (1) ◽  
pp. 151-157 ◽  
Author(s):  
Seiji Hayashi ◽  
Daniel G. Nehls ◽  
Charles F. Kieck ◽  
Juan Vielma ◽  
Umberto DeGirolami ◽  
...  
Keyword(s):  
Infarct Size ◽  
Statistical Significance ◽  
Neurological Status ◽  
Neurological Deficits ◽  
Experimental Stroke ◽  
Controlled Study ◽  
Content Type ◽  
Beneficial Effects ◽  
Induced Hypertension ◽  
Fine Print

✓ The authors performed a controlled study of induced hypertension therapy for treatment of experimental stroke in unanesthetized monkeys. Ten control and 10 treated animals were subjected to a 4-hour occlusion of the middle cerebral artery (MCA) by an implanted tourniquet. Neurological status and local cerebral blood flow (CBF) were monitored serially. Local CBF was determined by hydrogen clearance in and around the elevated 20% to 40% by intravenous infusion of phenylephrine hydrochloride. Neuropathological evaluation was performed after about 2 weeks. A 4-hour occlusion of the MCA in control animals caused moderate stable neurological deficits, moderate stable decreases in local CBF, and medium-sized infarcts. With induced hypertension, five of 10 treated animals showed neurological improvement, and eight exhibited increased CBF in the ischemic zone. Average infarct size tended to be smaller in the treated group, although the difference did not reach statistical significance. Hemorrhagic infarcts were not observed. In four animals, phenylephrine caused cardiac dysrhythmias and hypotension which were reversed by appropriate measures. In this unanesthetized primate model of moderate experimental stroke, induced hypertension had beneficial effects on neurological status, local CBF, and infarct size without causing hemorrhagic infarction. Induced hypertension may be beneficial for some clinical cases of focal cerebral ischemia.

Size-adjustable titanium plate for reconstruction of the sella turcica

1999 ◽  
Vol 91 (6) ◽  
pp. 1055-1057 ◽  
Author(s):  
Kazunori Arita ◽  
Kaoru Kurisu ◽  
Atsushi Tominaga ◽  
Fusao Ikawa ◽  
Koji Iida ◽  
...  
Keyword(s):  
Magnetic Resonance Imaging ◽  
Sella Turcica ◽  
Pure Titanium ◽  
Clinical Use ◽  
Resonance Imaging ◽  
Titanium Plate ◽  
Content Type ◽  
Postoperative Magnetic Resonance Imaging ◽  
Closed Position ◽  
Fine Print

✓ A size-adjustable plate constructed of pure titanium is proposed for use in the reconstruction of the sella turcica. The plate is composed of two semicircular pieces that are connected by a hinge located at the top of the plate. Using an applicator, the plate is inserted into the sella turcica in a closed position. The same applicator is then used to open and secure the plate. The titanium causes minimal ferromagnetic artifacts on postoperative magnetic resonance imaging.Preliminary findings indicate a possibie clinical use for this plate in the reconstruction of the sella turcica when no suitable piece of bone is available.

Proximal occlusion of the middle cerebral artery in C57Black6 mice: relationship of patency of the posterior communicating artery, infarct evolution, and animal survival

2004 ◽  
Vol 100 (1) ◽  
pp. 97-105 ◽  
Author(s):  
Kazuhide Furuya ◽  
Nobutaka Kawahara ◽  
Kensuke Kawai ◽  
Tomikatsu Toyoda ◽  
Keiichiro Maeda ◽  
...  
Keyword(s):  
Survival Rate ◽  
Infarct Size ◽  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Posterior Communicating Artery ◽  
Neurological Deficits ◽  
Content Type ◽  
Fine Print

Object. The intraluminal suture model for focal cerebral ischemia is increasingly used, but not without problems. It causes hypothalamic injury, subarachnoid hemorrhage, and inadvertent premature reperfusion. The patency of the posterior communicating artery (PCoA) potentially affects the size of the infarct. In addition, survival at 1 week is unstable. The authors operated on C57Black6 mice to produce proximal middle cerebral artery occlusion (MCAO) so that drawbacks with the suture model could be circumvented. Methods. The MCA segment just proximal to the olfactory branch was occluded either permanently or temporarily. After 1 hour of MCAO the infarct volume was significantly smaller than that found after 2 hours or in instances of permanent MCAO. The differences were assessed at 24 hours and 7 days after surgery (p < 0.05 and p < 0.001, respectively). The patency of the PCoA, as visualized using carbon black solution, did not correlate with the infarct size. Neurologically, the 1- and 2-hour MCAO groups displayed significantly less severe deficits than the permanent MCAO group on Days 1, 4, and 7 (p < 0.005 and p < 0.01, respectively). Although the infarct size, neurological deficits, and body weight loss were more severe in the permanent MCAO group, the survival rate at Day 7 was 80%. Conclusions. This model provides not only a robust infarct size (which is not affected by the patency of the PCoA), but also a better survival rate.

Traumatic subarachnoid hemorrhage on the computerized tomography scan obtained at admission: a multicenter assessment of the accuracy of diagnosis and the potential impact on patient outcome

2003 ◽  
Vol 98 (1) ◽  
pp. 37-42 ◽  
Author(s):  
Cristina Mattioli ◽  
Luigi Beretta ◽  
Simonetta Gerevini ◽  
Fabrizio Veglia ◽  
Giuseppe Citerio ◽  
...  
Keyword(s):  
Patient Outcome ◽  
Subarachnoid Hemorrhage ◽  
Computerized Tomography ◽  
Statistical Significance ◽  
Unfavorable Outcome ◽  
Content Type ◽  
Ct Findings ◽  
Traumatic Subarachnoid Hemorrhage ◽  
Injured Patients ◽  
Fine Print

Object. The goal of this study was fourfold: 1) to determine the incidence of traumatic subarachnoid hemorrhage (tSAH) in patients with traumatic brain injury (TBI); 2) to verify agreement in the diagnosis of tSAH in a multicenter study; 3) to assess the incidence of tSAH on the outcome of the patient; and 4) to establish whether tSAH itself leads to an unfavorable outcome or whether it is a sign of major brain trauma associated with severe posttraumatic lesions. Methods. Computerized tomography (CT) scans obtained in 169 head-injured patients on admission to 12 Italian intensive care units during a 3-month period were examined. The scans were collected for neuroradiological review and were used for the analysis together with data from a multicenter database (Neurolink). A review committee found a high incidence of tSAH (61%) in patients with TBI and a moderate agreement among centers (K = 0.57). Significant associations were observed between the presence and grading of tSAH and patient outcomes, and between the presence of tSAH and the severity of the CT findings. Logistic regression analysis showed that the presence of tSAH and its grading alone do not assume statistical significance in the prediction of unfavorable outcome. Conclusions. Traumatic SAH frequently occurs in patients with TBI, but it is difficult to detect and grade. Traumatic SAH is associated with more severe CT findings and a worse patient outcome.

Cerebral protection by intermittent reperfusion during temporary focal ischemia in the rat

1996 ◽  
Vol 85 (5) ◽  
pp. 923-928 ◽  
Author(s):  
Carlos A. David ◽  
Ricardo Prado ◽  
W. Dalton Dietrich
Keyword(s):  
Arterial Occlusion ◽  
Focal Ischemia ◽  
Global Ischemia ◽  
Cerebral Injury ◽  
Histopathological Analysis ◽  
Content Type ◽  
Group I ◽  
Group Ii ◽  
Temporary Clipping ◽  
Fine Print

✓ Temporary arterial occlusion has been routinely used as an adjunct in intracranial aneurysm surgery. This has commonly been performed using a protocol of multiple short periods of occlusion alternating with periods of restoration of normal circulation. Recently, the logical basis of this method has come under scrutiny. There is extensive experimental evidence to suggest that repetitive, brief periods of global ischemia may cause more severe cerebral injury than an equivalent single period of global ischemia. Only recently has this issue begun to be addressed with regard to focal ischemia. Hence, despite the common use of temporary clipping, little experimental data are available regarding the ischemic consequences of temporary arterial occlusion with periods of reperfusion versus uninterrupted temporary occlusion. To investigate this issue, a protocol of occlusion/reperfusion that simulates the temporal profile that occurs during surgery was performed in a rat model of focal ischemia. Sixteen anesthetized Sprague—Dawley rats were divided into two groups. The animals in Group I underwent 60 minutes of uninterrupted middle cerebral artery occlusion and the animals in Group II were subjected to six separate 10-minute occlusion periods with 5 minutes of reperfusion between occlusions. Histopathological analysis was performed 72 hours postischemia. Group I had significantly increased mean infarction volumes (50.0 ± 12.1 mm3) compared to Group II (8.7 ± 3.1 mm3) (p = 0.008). Injuries in Group I occurred in both the cortex and striatum, whereas Group II showed only striatal injuries. Furthermore, the extent of the injuries in Group II was less severe, characterized by ischemic neuronal injury rather than frank infarction. The results indicate that intermittent reperfusion is neuroprotective during temporary focal ischemia and support the hypothesis that intermittent reperfusion is beneficial if temporary clipping is required during aneurysm repair.

Normal changes in orbital volume during childhood

2002 ◽  
Vol 96 (4) ◽  
pp. 742-746 ◽  
Author(s):  
Robert P. Bentley ◽  
Spyros Sgouros ◽  
Kalyan Natarajan ◽  
M. Stephen Dover ◽  
Anthony D. Hockley
Keyword(s):  
Statistical Significance ◽  
Significant Proportion ◽  
Magnetic Resonance Images ◽  
Healthy Children ◽  
Content Type ◽  
Linear Pattern ◽  
Orbital Volume ◽  
Disease States ◽  
The Difference ◽  
Fine Print

Object. The aim of this study was to construct a model of changes in orbital volume that occur throughout childhood from the age of 1 month to 15 years, which could be used for comparative studies of disease states affecting orbital growth. Methods. Using the procedure of segmentation on magnetic resonance images obtained in 67 healthy children, orbital volume was measured and plotted against age. During the first few months of life left orbital volume is on average 15 cm3 in male and 13 cm3 in female infants; these volumes increase to 26 cm3 and 24 cm3, respectively, by the time the child reaches 15 years of age. During the first few months of life right orbital volume is on average 16 cm3 in male and 13 cm3 in female infants; these volumes increase to 27 cm3 and 25 cm3, respectively, by the time the child is 15 years old. This represents an overall increase in orbital volume by a factor of 1.7 in boys and 1.8 in girls. By the time the child has reached 5 years of age, the orbital volume for both right and left sides has reached on average 77% of the volume seen at 15 years in both sexes. The differences between the two sides are not statistically significant for either sex. The change in orbital volume that is associated with age in general displays a linear pattern. Throughout childhood, orbital volumes are larger in boys than in girls, but share a similar growth pattern. The difference between the two sexes tends toward statistical significance during the first 5 years of life (left orbit p = 0.1, right orbit p = 0.04). Conclusions. During early childhood, orbital volume increases in a linear fashion, achieving a significant proportion of its final growth by the time the child is 5 years old.

IL-37: Novel neuroprotective effects after brain ischemia and reperfusion

2019 ◽  
Vol 7 (4) ◽  
pp. 310-321
Author(s):  
Huang Xiang ◽  
Stampf Wael
Keyword(s):  
Infarct Size ◽  
Brain Ischemia ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Interleukin 1 ◽  
Brain Inflammation ◽  
Mice Model ◽  
Triphenyltetrazolium Chloride ◽  
Nissl Staining ◽  
Neuroprotective Effects

Interleukin-1 (IL-1) is a central mediator of innate immunity and inflammation. IL-37 (IL-37), a newly described member of the IL-1 family, functions as a fundamental inhibitor of innate inflammation and immunity. The purpose of the present study was to determine the effects of interleukin-37 on neuron cells and on brain inflammation induced by brain ischemia/reperfusion (I/R). A transgenic mouse strain was generated to express human IL-37 (hIL-37Tg) and WT mice were subjected to (60 min) brain ischemia and followed by reperfusion (24 h), by using a mice model of transient focal cerebral ischemia induced by advancing a nylon mono-filament to occlude the middle cerebral artery (MCA). Infarct size was determined by triphenyltetrazolium chloride staining. The morphology of neurons in brain sections were examined by Nissl staining and cytokines/chemokines measured by ELIZA. IL-37Tg significantly reduced infarct size by 65.4% (P<0.05) compared with WT after I/R. Reduced inflammation was associated with decreased leukocyte recruitment, and reduced release of IL-1β and TNFα, macrophage inflammatory protein-2 (MIP-2), MCP-1 and keratinocyte chemokine (KC) compared with WT (P<0.05), whereas IL-10 was increased eight fold (P<0.05). IL-37 significantly reduced cell death and increased Bcl-2 expression in neurons. Thus, IL-37 emerges as a key modulator of brain inflammation and has important translational implications for both the prevention and treatment of patients suffering from brain ischemia.

Significance of proliferating cell nuclear antigen in predicting recurrence of intracranial meningioma

1996 ◽  
Vol 84 (1) ◽  
pp. 85-90 ◽  
Author(s):  
Mark A. Cobb ◽  
Muhammad Husain ◽  
Bruce J. Andersen ◽  
Ossama Al-Mefty
Keyword(s):  
Proliferating Cell Nuclear Antigen ◽  
Statistical Significance ◽  
Tumor Biology ◽  
Nuclear Antigen ◽  
Intracranial Meningioma ◽  
Content Type ◽  
Tumor Histology ◽  
Proliferating Cell ◽  
Fine Print

✓ It is well known that the histological appearance of meningiomas often fails to predict accurately the clinical behavior of the tumor. Therefore, attention has turned from tumor histology to tumor biology. Proliferating cell nuclear antigen (PCNA), a cell cycle-regulated protein, has been recently characterized as the cofactor of DNA polymerase-δ, an enzyme required for DNA replication. The rate of synthesis of PCNA directly correlates with the proliferative state of cells. Immunohistochemical labeling of this antigen is now possible with monoclonal antibodies that allow for its demonstration in routinely fixed, paraffin-embedded specimens. In this study, the PCNA labeling index (LI) was determined for 83 meningiomas, including tumors with both benign and malignant clinical courses and with benign, atypical, and malignant histologies, apparent after total or subtotal resections. No statistical difference was found between the LI on recurrence and that found at initial presentation. In addition, stepwise multivariate regression analysis failed to identify any combination of factors (age, gender, race, age of specimen, tumor histology, Simpson grade of resection) that contributes to the predictive strength of the PCNA LI for tumor recurrence. However, for LIs less than 2%, only one of 26 gross totally resected tumors recurred (mean follow up 53 months); for LIs more than 7%, five of 13 gross totally resected tumors recurred (mean follow up 55 months). The difference in recurrence rates between gross totally resected meningiomas with PCNA LIs less than 2% and those with PCNA LIs more than 7% achieved statistical significance with a Fisher's exact probability equaling 0.011. The authors conclude that quantitative PCNA labeling of meningiomas is a promising technique that can provide meaningful prognostic information.

Delayed treatment with magnesium: reduction of brain infarction and improvement of electrophysiological recovery following transient focal cerebral ischemia in rats

2005 ◽  
Vol 102 (6) ◽  
pp. 1085-1093 ◽  
Author(s):  
E-Jian Lee ◽  
Ming-Yang Lee ◽  
Guan-Liang Chang ◽  
Li-Hsuan Chen ◽  
Yu-Ling Hu ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Focal Cerebral Ischemia ◽  
Ischemia Reperfusion ◽  
Brain Infarction ◽  
Artery Occlusion ◽  
Sprague Dawley ◽  
Content Type ◽  
Delayed Treatment ◽  
Cerebral Ischemia Reperfusion ◽  
Fine Print

Object. The authors examined whether delayed treatment with Mg++ would reduce brain infarction and improve electrophysiological and neurobehavioral recovery following cerebral ischemia—reperfusion. Methods. Male Sprague—Dawley rats were subjected to right middle cerebral artery occlusion for 90 minutes followed by 72 hours of reperfusion. Magnesium sulfate (750 µmol/kg) or vehicle was given via intracarotid infusion at the beginning of reperfusion. Neurobehavioral outcome and somatosensory evoked potentials (SSEPs) were examined before and 72 hours after ischemia—reperfusion. Brain infarction was assessed after the rats had died. Before ischemia—reperfusion, stable SSEP waveforms were recorded after individual fore- and hindpaw stimulations. At 72 hours of perfusion the SSEPs recorded from ischemic fore- and hindpaw cortical fields were depressed in vehicle-injected animals and the amplitudes decreased to 19 and 27% of baseline, respectively (p < 0.001). Relative to controls, the amplitudes of SSEPs recorded from both ischemic fore- and hindpaw cortical field in the Mg++-treated animals were significantly improved by 23% (p < 0.005) and 39% (p < 0.001) of baselines, respectively. In addition, Mg++ improved sensory and motor neurobehavioral outcomes by 34% (p < 0.01) and 24% (p < 0.05), respectively, and reduced cortical (p < 0.05) and striatal (p < 0.05) infarct sizes by 42 and 36%, respectively. Conclusions. Administration of Mg++ at the commencement of reperfusion enhances electrophysiological and neurobehavioral recovery and reduces brain infarction after cerebral ischemia—reperfusion. Because Mg++ has already been used clinically, it may be worthwhile to investigate it further to see if it holds potential benefits for patients with ischemic stroke and for those who will undergo carotid endarterectomy.

Adenosine-enhanced ischemic preconditioning: adenosine receptor involvement during ischemia and reperfusion

2001 ◽  
Vol 280 (2) ◽  
pp. H591-H602 ◽  
Author(s):  
James D. McCully ◽  
Yoshiya Toyoda ◽  
Masahisa Uematsu ◽  
Robert D. Stewart ◽  
Sidney Levitsky
Keyword(s):  
Infarct Size ◽  
Functional Recovery ◽  
Ischemic Preconditioning ◽  
Adenosine Receptor ◽  
Adenosine Receptors ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Myocardial Infarct Size ◽  
Ischemia And Reperfusion ◽  
Infarct Size Reduction

Adenosine-enhanced ischemic preconditioning (APC) extends the cardioprotection of ischemic preconditioning (IPC) by both significantly decreasing myocardial infarct size and significantly enhancing postischemic functional recovery. In this study, the role of adenosine receptors during ischemia-reperfusion was determined. Rabbit hearts ( n = 92) were used for Langendorff perfusion. Control hearts were perfused for 180 min, global ischemia hearts received 30-min ischemia and 120-min reperfusion, and IPC hearts received 5-min ischemia and 5-min reperfusion before ischemia. APC hearts received a bolus injection of adenosine coincident with IPC. Adenosine receptor (A1, A2, and A3) antagonists were used with APC before ischemia and/or during reperfusion. GR-69019X (A1/A3) and MRS-1191/MRS-1220 (A3) significantly increased infarct size in APC hearts when administered before ischemia and significantly decreased functional recovery when administered during both ischemia and reperfusion ( P < 0.05 vs. APC). DPCPX (A1) administered either before ischemia and/or during reperfusion had no effect on APC cardioprotection. APC-enhanced infarct size reduction is modulated by adenosine receptors primarily during ischemia, whereas APC-enhanced postischemic functional recovery is modulated by adenosine receptors during both ischemia and reperfusion.

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