Effect of hyperthermia on glutamate release in ischemic penumbra after middle cerebral artery occlusion in rats

1994 ◽  
Vol 267 (5) ◽  
pp. H1770-H1776 ◽  
Author(s):  
K. Takagi ◽  
M. D. Ginsberg ◽  
M. Y. Globus ◽  
E. Martinez ◽  
R. Busto
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Glutamate Release ◽  
Threshold Value ◽  
Artery Occlusion ◽  
Ischemic Penumbra ◽  
Doppler Flowmetry ◽  
Mca Occlusion ◽  
Normothermic Group ◽  
Cerebral Artery Occlusion

Using microdialysis, we investigated the effect of hyperthermia on glutamate release in penumbral cortex of rats with 2 h of either normothermic (37 degrees C) or hyperthermic (39 degrees C) middle cerebral artery (MCA) occlusion. Penumbral blood flow (CBF) was measured by laser-Doppler flowmetry. CBF values (expressed as % preischemic values) in normothermic and hyperthermic groups were 24 +/- 11 (SD) and 24 +/- 16%, respectively, during ischemia and 102 +/- 81 and 147 +/- 79% during recirculation. Average extracellular glutamate in the hyperthermic group increased from a baseline of 7 +/- 2 microM to a peak of 217 +/- 184 microM at 10-20 min after onset of ischemia but returned to near baseline after 60 min. Glutamate in the normothermic group increased from 4 +/- 2 microM to a peak of 26 +/- 17 microM at 10-20 min after MCA occlusion but fell to near-baseline before recirculation. Thus reuptake systems appeared to remain functional in ischemic penumbra, even during hyperthermia. Ischemic glutamate release was significantly higher in hyperthermic than in normothermic rats: average values of individual rats' peak levels were 251 +/- 221 microM and 37 +/- 34 microM, respectively. The ischemic CBF threshold value for glutamate release was 33% of control in the normothermic group but 61% in the hyperthermic group.

scholarly journals Simultaneous Measurement of Salicylate Hydroxylation and Glutamate Release in the Penumbral Cortex following Transient Middle Cerebral Artery Occlusion in Rats

1996 ◽  
Vol 16 (1) ◽  
pp. 92-99 ◽  
Author(s):  
Tadashi Morimoto ◽  
Mordecai Y.-T. Globus ◽  
Raul Busto ◽  
Elena Martinez ◽  
Myron D. Ginsberg
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Simultaneous Measurement ◽  
Glutamate Release ◽  
Artery Occlusion ◽  
Dihydroxybenzoic Acid ◽  
Doppler Flowmetry ◽  
Enhanced Production ◽  
Mca Occlusion ◽  
Cerebral Artery Occlusion

Using the microdialysis technique and laser-Doppler flowmetry, we performed simultaneous measurement of salicylate hydroxylation and glutamate release along with local CBF in the ischemic penumbral cortex of rat brain subjected to normothermic transient middle cerebral artery (MCA) occlusion. Cortical CBF fell to 24 ± 11% (mean ± SD) during ischemia and recovered to 84 ± 16% during reperfusion. Extracellular glutamate levels increased by 6.5-fold above baseline 10 min following MCA occlusion but subsequently returned to near baseline levels in spite of the persistent ischemia. Increase in 2,3- and 2,5-dihydroxybenzoic acid (DHBA) concentrations in the microdialysis perfusate was confirmed during both ischemia and reperfusion phase. Although the temporal profile and amount of salicylate hydroxylation were heterogeneous among individual animals, integrated 2,3-DHBA concentrations during reperfusion were correlated positively with integrated glutamate concentrations during ischemia and negatively with mean postischemic CBF. These relationships suggest a possible association of the enhanced production of 2,3-DHBA during reperfusion with larger amounts of intraischemic glutamate release and lower levels of postischemic CBF.

scholarly journals ARL 17477, a Potent and Selective Neuronal NOS Inhibitor Decreases Infarct Volume after Transient Middle Cerebral Artery Occlusion in Rats

1996 ◽  
Vol 16 (4) ◽  
pp. 599-604 ◽  
Author(s):  
Zheng G. Zhang ◽  
David Reif ◽  
James Macdonald ◽  
Wen Xue Tang ◽  
Dietgard K. Kamp ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Cell Damage ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Arterial Blood ◽  
Mca Occlusion ◽  
Nos Inhibitor ◽  
Oxide Synthase ◽  
Cerebral Artery Occlusion

We tested the effects of administration of a selective neuronal nitric oxide synthase (nNOS) inhibitor, ARL 17477, on ischemic cell damage and regional cerebral blood flow (rCBF), in rats subjected to transient (2 h) middle cerebral artery (MCA) occlusion and 166 h of reperfusion (n = 48) and in rats without MCA occlusion (n = 25), respectively. Animals were administered ARL 17477 (i.v.): 10 mg/kg; 3 mg/kg; 1 mg/kg; N-nitro-L-arginine (L-NA) 10 mg/kg L-NA 1 mg/kg; and Vehicle. Administration of ARL 17477 1 mg/kg, 3 mg/kg and 10 mg/kg reduced ischemic infarct volume by 53 (p < 0.05), 23, and 6.5%, respectively. L-NA 1 mg/kg and 10 mg/kg increased infarct volume by 2 and 15%, respectively (p > 0.05). Administration of ARL 17477 (10 mg/kg) significantly (p < 0.05) decreased rCBF by 27 ± 5.3 and 24 ± 14.08% and cortical NOS activity by 86 ± 14.9 and 91 ± 8.9% at 10 min or 3 h, respectively, and did not alter mean arterial blood pressure (MABP). L-NA (10 mg/kg) significantly reduced rCBF by 23 ± 9.8% and NOS activity by 81 ± 7% and significantly (p < 0.05) increased MABP. Treatment with 3 mg/kg and 1 mg/kg ARL 17477 reduced rCBF by only 2.4 ± 4.5 and 0%, respectively, even when NOS activity was reduced by 63 ± 13.4 and 45 ± 15.7% at 3 h, respectively, (p < 0.05). The data demonstrate that ARL 17477 inhibits nNOS in the rat brain and causes a dose-dependent reduction in infarct volume after transient MCA occlusion.

Neuroprotective effects of erythropoietin pretreatment in a rodent model of transient middle cerebral artery occlusion

2014 ◽  
Vol 121 (1) ◽  
pp. 55-62 ◽  
Author(s):  
Bernardo Oliveira Ratilal ◽  
Mariana Moreira Coutinho Arroja ◽  
Joao Pedro Fidalgo Rocha ◽  
Adelaide Maria Afonso Fernandes ◽  
Andreia Pereira Barateiro ◽  
...  
Keyword(s):  
Treatment Group ◽  
Middle Cerebral Artery ◽  
Brain Edema ◽  
Cerebral Artery ◽  
Plasma Levels ◽  
Infarct Volume ◽  
Neuron Specific Enolase ◽  
Artery Occlusion ◽  
Mca Occlusion ◽  
Cerebral Artery Occlusion

Object There is an unmet clinical need to develop neuroprotective agents for neurosurgical and endovascular procedures that require transient cerebral artery occlusion. The aim in this study was to explore the effects of a single dose of recombinant human erythropoietin (rhEPO) before middle cerebral artery (MCA) occlusion in a focal cerebral ischemia/reperfusion model. Methods Twenty-eight adult male Wistar rats were subjected to right MCA occlusion via the intraluminal thread technique for 60 minutes under continuous cortical perfusion monitoring by laser Doppler flowmetry. Rats were divided into 2 groups: control and treatment. In the treated group, rhEPO (1000 IU/kg intravenously) was administered 10 minutes before the onset of the MCA ischemia. At 24-hour reperfusion, animals were examined for neurological deficits, blood samples were collected, and animals were killed. The following parameters were evaluated: brain infarct volume, ipsilateral hemispheric edema, neuron-specific enolase plasma levels, parenchyma histological features (H & E staining), Fluoro-Jade–positive neurons, p-Akt and total Akt expression by Western blot analysis, and p-Akt–positive nuclei by immunohistochemical investigation. Results Infarct volume and Fluoro-Jade staining of degenerating neurons in the infarct area did not vary between groups. The severity of neurological deficit (p < 0.001), amount of brain edema (78% reduction in treatment group, p < 0.001), and neuron-specific enolase plasma levels (p < 0.001) were reduced in the treatment group. Perivascular edema was histologically less marked in the treatment group. No variations in the expression or localization of p-Akt were seen. Conclusions Administration of rhEPO before the onset of 60-minute transient MCA ischemia protected the brain from this insult. It is unlikely that rhEPO pretreatment leads to direct neuronal antiapoptotic effects, as supported by the lack of Akt activation, and its benefits are most probably related to an indirect effect on brain edema as a consequence of blood-brain barrier preservation. Although research on EPO derivatives is increasing, rhEPO acts through distinct neuroprotective pathways and its clinical safety profile is well known. Clinically available rhEPO is a potential therapy for prevention of neuronal injury induced by transitory artery occlusion during neurovascular procedures.

scholarly journals Reduction of Infarct Volume by Magnesium after Middle Cerebral Artery Occlusion in Rats

1991 ◽  
Vol 11 (6) ◽  
pp. 1025-1030 ◽  
Author(s):  
Yoshio Izumi ◽  
Simon Roussel ◽  
Elisabeth Pinard ◽  
Jacques Seylaz
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Focal Cerebral Ischemia ◽  
Infarct Volume ◽  
Artery Occlusion ◽  
Triphenyltetrazolium Chloride ◽  
Ischemic Brain ◽  
Mca Occlusion ◽  
Cerebral Artery Occlusion ◽  
Hyperglycemic Effect

The effects of magnesium, an endogenous inhibitor of calcium entry into neurons, upon ischemic brain damage were investigated using a well-characterized model of focal cerebral ischemia in rats. Infarct volumes were determined by 2,3,5-triphenyltetrazolium chloride transcardiac perfusion 48 h after middle cerebral artery (MCA) occlusion. The area of ischemic damage was quantified by image analysis in coronal sections taken every 0.5 mm. MgCl2 (1 mmol/kg) was injected intraperitoneally just after MCA occlusion and again 1 h later. Posttreatment with MgCl2 (16 control and 16 treated rats) significantly reduced the cortical infarct volume. Compensation for the hyperglycemic effect of MgCl2 with insulin (17 rats) further reduced the infarct volume in the neocortex. No systemic effects of either treatment could account for the observed neuroprotection.

Somatosensory Evoked Potential Monitoring of Temporary Middle Cerebral Artery Occlusion during Aneurysm Operation

Neurosurgery ◽  
1987 ◽  
Vol 21 (4) ◽  
pp. 492-496 ◽  
Author(s):  
Jan J. A. Mooij ◽  
Anna Buchthal ◽  
Milan Belopavlovic
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Artery Occlusion ◽  
Moderate Hypothermia ◽  
Cortical Function ◽  
Mca Occlusion ◽  
Median Nerve Stimulation ◽  
Temporary Occlusion ◽  
Evoked Potential Monitoring ◽  
Cerebral Artery Occlusion

Abstract Somatosensory evoked potentials (SEPs) in response to median nerve stimulation were used as a guide to cortical function during temporary occlusion of the distal M1 segment of the middle cerebral artery (MCA) in the surgical treatment of five large aneurysms of the MCA bifurcation. MCA occlusion times ranged from 8 to 19 minutes under moderate hypothermia at 28.8° to 30.3°C. SEPs were preserved for variable times during MCA occlusion, ranging from no increase in latency after 13 minutes of occlusion to severe deterioration after 6 minutes. In no case was MCA occlusion maintained for longer than 3 minutes in the presence of a severely disturbed SEP. Recovery of the SEP to its preoperative relationship with that of the nonoperated hemisphere was seen in all cases before the end of operation. All patients were awake after rewarming at the end of operation without any neurological deficit. Monitoring the SEP pertaining to the territory of a cerebral artery during its temporary occlusion can help avoid ischemic damage and will allow the surgeon to take advantage of the several benefits of this technique in aneurysm surgery. (Neurosurgery 21:492-496, 1987)

Glutamate release in the gerbil hippocampus after middle cerebral artery occlusion

Neuroreport ◽  
1994 ◽  
Vol 5 (8) ◽  
pp. 945-948 ◽  
Author(s):  
Kotaro Miyashita ◽  
Hiroshi Abe ◽  
Takashi Nakajima ◽  
Atsushi Ishikawa ◽  
Michiyo Nishiura-Suzuki ◽  
...  
Keyword(s):  
Middle Cerebral Artery ◽  
Middle Cerebral Artery Occlusion ◽  
Cerebral Artery ◽  
Glutamate Release ◽  
Artery Occlusion ◽  
Cerebral Artery Occlusion

scholarly journals Induction of Spreading Depression in the Ischemic Hemisphere following Experimental Middle Cerebral Artery Occlusion: Effect on Infarct Morphology

1996 ◽  
Vol 16 (2) ◽  
pp. 202-213 ◽  
Author(s):  
Tobias Back ◽  
Myron D. Ginsberg ◽  
W. Dalton Dietrich ◽  
Brant D. Watson
Keyword(s):  
Middle Cerebral Artery ◽  
Cerebral Artery ◽  
Spreading Depression ◽  
Ischemic Injury ◽  
Artery Occlusion ◽  
Ischemic Penumbra ◽  
Mca Occlusion ◽  
Group 3 ◽  
Group 2 ◽  
Group 1

This study was undertaken to test whether transient depolarizations occurring in periinfarct regions are important in contributing to infarct spread and maturation. Following middle cerebral artery (MCA) occlusion we stimulated the ischemic penumbra with recurrent waves of spreading depression (SD) and correlated the histopathological changes with the electrophysiological recordings. Halothane-anesthetized, artificially ventilated Sprague–Dawley rats underwent repetitive stimulation of SD in intact brain (Group 1; n = 8) or photothrombotic MCA occlusion coupled with ipsilateral common carotid artery occlusion (Groups 2 and 3, n = 9 each). The electroencephalogram and direct current (DC) potential were recorded for 3 h in the parietal cortex, which represented the periinfarct border zone in ischemic rats. In Group 2, only spontaneously occurring negative DC shifts occurred; in Group 3, the (nonischemic) frontal pole of the ischemic hemisphere was electrically stimulated to increase the frequency of periinfarct DC shifts. Animals underwent perfusion-fixation 24 h later, and volumes of complete infarction and scattered neuronal injury (“incomplete infarction”) were assessed on stained coronal sections by quantitative planimetry. Electrical induction of SD in Group 1 did not cause morphological injury. During the initial 3 h following MCA occlusion, the number of spontaneous periinfarct depolarizations in Group 2 (7.0 ±1.5 DC shifts) was doubled in Group 3 by frontal current application (13.4 ± 2.7 DC shifts; p < 0.001). The duration as well as the integrated negative amplitude of DC shifts over time were significantly greater in Group 3 than in Group 2 rats (duration, 5.7 ± 3.8 vs. 4.1 ± 2.5 min; p < 0.05). Histopathological examination disclosed well-defined areas of pannecrosis surrounded by a cortical rim exhibiting selectively damaged acidophilic neurons and astrocytic swelling in otherwise normal-appearing brain. Induction of SD in the ischemic hemisphere led to a significant increase in the volume of incomplete infarction (19.0 ± 6.1 mm3 in Group 3 vs. 10.3 ± 5.1 mm3 in Group 2; p < 0.01) and of total ischemic injury (100.7 ± 41.0 mm3 in Group 3 vs. 66.5 ± 24.7 mm3 in Group 2; p < 0.05). The integrated magnitude of DC negativity per experiment correlated significantly with the volume of total ischemic injury ( r = 0.780, p < 0.0001). Thus, induction of SD in the ischemic hemisphere accentuated the development of scattered neuronal injury and increased the volume of total ischemic injury. This observation may be explained by the fact that, with limited perfusion reserve, periinfarct depolarizations are associated with episodic energy failure in the acute ischemic penumbra.

Sign in / Sign up

Export Citation Format

Share Document