scholarly journals Changes in Insulin-like Growth Factor 1 Receptor Density after Transient Cerebral Ischemia in the Rat. Lack of Protection against Ischemic Brain Damage following Injection of Insulin-Like Growth Factor 1

1993 ◽  
Vol 13 (5) ◽  
pp. 895-898 ◽  
Author(s):  
Kerstin Bergstedt ◽  
Tadeusz Wieloch
Keyword(s):  
Cerebral Ischemia ◽  
Growth Factor ◽  
Neuronal Damage ◽  
Brain Slices ◽  
Transient Cerebral Ischemia ◽  
Insulin Like Growth Factor ◽  
Vessel Occlusion ◽  
Ischemic Brain ◽  
Intracerebroventricular Injections ◽  
Intracellular Signal

Binding of 125I-insulin-like growth factor-1 (125I-IGF-1) to rat brain slices was studied after 15 min of two-vessel occlusion ischemia and 1 h to 4 days of recirculation. Ligand binding in the hippocampus increased at 6 h post ischemia in the CA1 and CA3 regions and the dentate gyrus, suggesting that the IGF-1 receptors were up-regulated, while no change was seen in neocortex and striatum. Intracerebroventricular injections of IGF-1 (2 μg) prior to and after transient cerebral ischemia did not reduce neuronal damage. The increased up-regulation on IGF-1 receptors and the absence of neuroprotection by IGF-1 suggest that the intracellular signal transduction chain activated by the IGF-1 receptor may be interrupted.

scholarly journals A Model of Global Cerebral Ischemia in C57 BL/6 Mice

2004 ◽  
Vol 24 (2) ◽  
pp. 151-158 ◽  
Author(s):  
Ichiro Yonekura ◽  
Nobutaka Kawahara ◽  
Hirofumi Nakatomi ◽  
Kazuhide Furuya ◽  
Takaaki Kirino
Keyword(s):  
Cerebral Ischemia ◽  
Genetic Background ◽  
Neuronal Degeneration ◽  
Neuronal Damage ◽  
Neuronal Injury ◽  
Genetically Engineered ◽  
Global Cerebral Ischemia ◽  
Vessel Occlusion ◽  
Bilateral Carotid ◽  
The Mean

A reproducible model of global cerebral ischemia in mice is essential for elucidating the molecular mechanism of ischemic neuronal injury. Such a model is particularly important in the mouse because many genetically engineered mutant animals are available. In C57BL/6 and SV129/EMS mice, we evaluated a three-vessel occlusion model. Occlusion of the basilar artery with a miniature clip was followed by bilateral carotid occlusion. The mean cortical cerebral blood flow was reduced to less than 10% of the preischemic value, and the mean anoxic depolarization was attained within 1 minute. In C57BL/6 mice, there was CA1 hippocampal neuronal degeneration 4 days after ischemia. Neuronal damage depended upon ischemic duration: the surviving neuronal count was 78.5 ± 8.5% after 8-minute ischemia and 8.4 ± 12.7% after 14-minute ischemia. In SV129/EMS mice, similar neuronal degeneration was not observed after 14-minute ischemia. The global ischemia model in C57BL/6 mice showed high reproducibility and consistent neuronal injury in the CA1 sector, indicating that comparison of ischemic outcome between wild-type and mutant mice could provide meaningful data using the C57BL/6 genetic background. Strain differences in this study highlight the need for consideration of genetic background when evaluating ischemia experiments in mice.

Intranasal delivery of erythropoietin plus insulin-like growth factor–I for acute neuroprotection in stroke

2009 ◽  
Vol 111 (1) ◽  
pp. 164-170 ◽  
Author(s):  
Lauren Fletcher ◽  
Sanjivan Kohli ◽  
Shane M. Sprague ◽  
Robert A. Scranton ◽  
Stuart A. Lipton ◽  
...  
Keyword(s):  
Growth Factor ◽  
Intranasal Administration ◽  
Neuronal Damage ◽  
Intraperitoneal Administration ◽  
Insulin Like Growth Factor ◽  
Efficient Treatment ◽  
Factor I ◽  
Igf I ◽  
Growth Factor I ◽  
The Brain

Object Individually, the cytokines erythropoietin (EPO) and insulin-like growth factor–I (IGF-I) have both been shown to reduce neuronal damage significantly in rodent models of cerebral ischemia. The authors have previously shown that EPO and IGF-I, when administered together, provide acute and prolonged neuroprotection in cerebrocortical cultures against N-methyl-d-aspartate–induced apoptosis. The aim of this study was to determine whether intranasally applied EPO plus IGF-I can provide acute neuroprotection in an animal stroke model and to show that intranasal administration is more efficient at delivering EPO plus IGF-I to the brain when compared with intravenous, subcutaneous, or intraperitoneal administration. Methods The EPO and IGF-I were administered intranasally to mice that underwent transient middle cerebral artery occlusion (MCAO). Stroke volumes were measured after 1 hour of MCAO and 24 hours of reperfusion. To evaluate the long-term effects of this treatment, behavioral outcomes were assessed at 3, 30, 60, and 90 days following MCAO. Radiography and liquid scintillation were used to visualize and quantify the uptake of radiolabeled 125I-EPO and 125I–IGF-I into the mouse brain after intranasal, intravenous, subcutaneous, or intraperitoneal administration. Results Intranasal administration of EPO plus IGF-I reduced stroke volumes within 24 hours and improved neurological function in mice up to 90 days after MCAO. The 125I-EPO and 125I–IGF-I were found in the brain within 20 minutes after intranasal administration and accumulated within the injured areas of the brain. In addition, intranasal administration delivered significantly higher levels of the applied 125I-EPO and 125I–IGF-I to the brain compared with intravenous, subcutaneous, or intraperitoneal administration. Conclusions The data demonstrate that intranasal EPO plus IGF-I penetrates into the brain more efficiently than other drug delivery methods and could potentially provide a fast and efficient treatment to prevent chronic effects of stroke.

scholarly journals Accelerated and Exacerbated Effects of High Dietary Fat on Neuronal Damage Induced by Transient Cerebral Ischemia in the Gerbil Septum

2014 ◽  
Vol 29 (3) ◽  
pp. 328 ◽  
Author(s):  
Seung Hwan Cheon ◽  
Bing Chun Yan ◽  
Bai Hui Chen ◽  
Joon Ha Park ◽  
Ji Hyeon Ahn ◽  
...  
Keyword(s):  
Cerebral Ischemia ◽  
Dietary Fat ◽  
Neuronal Damage ◽  
Transient Cerebral Ischemia

scholarly journals Postischemic Blockade of AMPA but Not NMDA Receptors Mitigates Neuronal Damage in the Rat Brain following Transient Severe Cerebral Ischemia

1992 ◽  
Vol 12 (1) ◽  
pp. 2-11 ◽  
Author(s):  
B. Nellgård ◽  
T. Wieloch
Keyword(s):  
Cerebral Ischemia ◽  
Nmda Receptor ◽  
Ampa Receptor ◽  
Neuronal Damage ◽  
Transient Cerebral Ischemia ◽  
Coupled Processes ◽  
Temporal Part ◽  
Nmda Receptor Antagonists ◽  
Receptor Antagonists ◽  
Cgp 40116

Glutamatergic transmission is an important factor in the development of neuronal death following transient cerebral ischemia. In this investigation the effects of N-methyl-d-aspartate (NMDA) and non-NMDA receptor antagonists on neuronal damage were studied in rats exposed to 10 min of transient cerebral ischemia induced by bilateral common carotid occlusion combined with hypotension. The animals were treated with a blocker of the ionotropic quisqualate or α-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptor, 2.3-dihydroxy-6-nitro-7-sulfamoyl-benzo( F)quinoxaline (NBQX), given postischemia as an intraperitoneal bolus dose of 30 mg kg−1 followed by an intravenous infusion of 75 μg min−1 for 6 h, or with the noncompetitive NMDA receptor blocker dizocilpine(MK-801) given 1 mg kg−1 i.p. at recirculation and 3 h postischemia, or with the competitive NMDA receptor antagonist dl-( E)-2-amino-4-methyl-5-phosphono-3-pentenoic acid (CGP 40116), 5 mg kg−1, given intraperitoneally at recirculation. Treatment with NBQX provided a significant reduction of neuronal damage in the hippocampal CA1 area by 44–69%, with the largest relative decrease in the temporal part of the hippocampus. In neocortex a significant decrease in the number of necrotic neurons was also noted. No protection could be seen following postischemic treatment with dizocilpine or CGP 40116. Our data demonstrate that AMPA but not NMDA receptor antagonists decrease neuronal damage following transient severe cerebral ischemia in the rat and that the protection by NBQX may be dependent on the severity of the ischemic insult. We propose that the AMPA receptor–mediated neurotoxicity could be due to ischemia-induced changes in the control mechanisms of AMPA receptor–coupled processes or to changes of AMPA receptor characteristics.

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