A new experimental model in rats for study of the pathophysiology of subarachnoid hemorrhage

Prunell, Giselle; Mathiesen, Tiit; Svendgaard, Niels-Aage

doi:10.1097/00001756-200212200-00034

Cited by 134 publications

(90 citation statements)

References 13 publications

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“…We sought to investigate whether these findings are recapitulated in a rat model of SAH. 13,21,23 We previously showed marked accumulation of microthrombi in cortical and hippocampal capillaries, demonstrated by fibrinogen immunostaining, in this model. 13 These microthrombi are also auto-fluorescent and readily viewable via fluorescence microscopy.…”

Section: Reduced Surface Glutamate Receptor Expression Colocalizes Wisupporting

confidence: 56%

“…The SAH model is described elsewhere. 13,21,23 In brief, rats were anesthetized with ketamine/xylazine (100/10 mg/ kg), and a bur hole was drilled 7.5 mm anterior to the bregma in the midline. The tail artery was catheterized with a 0.75-inch 24-gauge catheter (AngioCath, BD Biosciences), and SAH was induced by injecting 250 μl of fresh blood withdrawn from the catheter through a 27-gauge spinal needle into the prechiasmatic cistern.…”

Section: Sah Modelmentioning

confidence: 99%

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Platelet-mediated changes to neuronal glutamate receptor expression at sites of microthrombosis following experimental subarachnoid hemorrhage

Bell

Thomas

Lass

et al. 2014

JNS

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A neurysmAl subarachnoid hemorrhage (SAH) is among the most mortal types of stroke and is a devastating public health problem for both patients and their families. SAH is associated with a poor prognosis, with 35% of patients dying within the first 30 days of hemorrhage. 15,16 Moreover, those that survive the acute injury frequently are left with sequelae of cognitive impairment, reduced vigor, loss of employment, depression, and reduced quality of relationships. 18 We have previously demonstrated in animal models that SAH is associated with loss of long-term potentiation (LTP), a biophysical analog of memory and learning, and with persistent behavioral and cognitive deficits. 13,14,23 However, the cellular mechanisms responsible for these phenomena have yet to be elucidated. LTP develops af- Object. Glutamate is important in the pathogenesis of brain damage after cerebral ischemia and traumatic brain injury. Notably, brain extracellular and cerebrospinal fluid as well as blood glutamate concentrations increase after experimental and clinical trauma. While neurons are one potential source of glutamate, platelets also release glutamate as part of their recruitment and might mediate neuronal damage. This study investigates the hypothesis that platelet microthrombi release glutamate that mediates excitotoxic brain injury and neuron dysfunction after subarachnoid hemorrhage (SAH).Methods. The authors used two models, primary neuronal cultures exposed to activated platelets, as well as a whole-animal SAH preparation. Propidium iodide was used to evaluate neuronal viability, and surface glutamate receptor staining was used to evaluate the phenotype of platelet-exposed neurons.Results. The authors demonstrate that thrombin-activated platelet-rich plasma releases glutamate, at concentrations that can exceed 300 μM. When applied to neuronal cultures, this activated plasma is neurotoxic, and the toxicity is attenuated in part by glutamate receptor antagonists. The authors also demonstrate that exposure to thrombinactivated platelets induces marked downregulation of the surface glutamate receptor glutamate receptor 2, a marker of excitotoxicity exposure and a possible mechanism of neuronal dysfunction. Linear regression demonstrated that 7 days after SAH in rats there was a strong correlation between proximity to microthrombi and reduction of surface glutamate receptors.Conclusions. The authors conclude that platelet-mediated microthrombosis contributes to neuronal glutamate receptor dysfunction and might mediate brain injury after SAH.

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Section: Reduced Surface Glutamate Receptor Expression Colocalizes Wisupporting

confidence: 56%

Section: Sah Modelmentioning

confidence: 99%

Platelet-mediated changes to neuronal glutamate receptor expression at sites of microthrombosis following experimental subarachnoid hemorrhage

Bell

Thomas

Lass

et al. 2014

JNS

View full text Add to dashboard Cite

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“…The injections were made over 20 seconds using a syringe pump (Harvard Apparatus, Holliston, MA, USA). The prechiasmatic injection model of SAH was modified from the model initially described by Prunell et al 9,11 The injection speed was similar to what was used in their original studies, in which 200 mL of blood was injected manually over 12 seconds. The injection speed was initially set aiming to maintain the intracranial pressure at the same level as the mean arterial blood pressure during the injection.…”

Section: Subarachnoid Hemorrhagementioning

confidence: 99%

“…There are several different models of SAH in rats, including the endovascular perforation model 7 and the cisterna magna injection models. [8][9][10] The prechiasmatic SAH model was used, as this deposits blood around the anterior circle of Willis where most aneurysmal SAH occurs in humans. The model also has less variability than the endovascular perforation model.…”

Section: Introductionmentioning

confidence: 99%

Molecular Alterations in the Hippocampus after Experimental Subarachnoid Hemorrhage

Han

Wan

Kudo

et al. 2013

J Cereb Blood Flow Metab

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Patients with aneurysmal subarachnoid hemorrhage (SAH) frequently have deficits in learning and memory that may or may not be associated with detectable brain lesions. We examined mediators of long-term potentiation after SAH in rats to determine what processes might be involved. There was a reduction in synapses in the dendritic layer of the CA1 region on transmission electron microscopy as well as reduced colocalization of microtubule-associated protein 2 (MAP2) and synaptophysin. Immunohistochemistry showed reduced staining for GluR1 and calmodulin kinase 2 and increased staining for GluR2. Myelin basic protein staining was decreased as well. There was no detectable neuronal injury by Fluoro-Jade B, TUNEL, or activated caspase-3 staining. Vasospasm of the large arteries of the circle of Willis was mild to moderate in severity. Nitric oxide was increased and superoxide anion radical was decreased in hippocampal tissue. Cerebral blood flow, measured by magnetic resonance imaging, and cerebral glucose metabolism, measured by positron emission tomography, were no different in SAH compared with control groups. The results suggest that the etiology of loss of LTP after SAH is not cerebral ischemia but may be mediated by effects of subarachnoid blood such as oxidative stress and inflammation.

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“…The following section will discuss cerebrovascular receptor plasticity in animal stroke models: (1) permanent focal cerebral ischemia using the Tamura method (Tamura et al, 1981a, b), (2) transient focal cerebral ischemia induced by middle cerebral artery occlusion (MCAO) followed by reperfusion (Memezawa et al, 1992a), (3) transient forebrain ischemia induced by two-artery occlusion and hypovolemia (Smith et al, 1984), and (4) SAH induced by injection of blood into the ophthalmic cistern (Prunell et al, 2002). Table 1 gives an overview of vasoconstrictor receptor changes demonstrated in various stroke models and in patients.…”

Section: Receptor Changes In Experimental Strokementioning

confidence: 99%

Vascular plasticity in cerebrovascular disorders

Edvinsson

Povlsen

2011

J Cereb Blood Flow Metab

115

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Cerebral ischemia remains a major cause of morbidity and mortality with little advancement in subacute treatment options. This review aims to cover and discuss novel insight obtained during the last decade into plastic changes in the vasoconstrictor receptor profiles of cerebral arteries and microvessels that takes place after different types of stroke. Receptors like the endothelin type B, angiotensin type 1, and 5-hydroxytryptamine type 1B/1D receptors are upregulated in the smooth muscle layer of cerebral arteries after different types of ischemic stroke as well as after subarachnoid hemorrhage, yielding rather dramatic changes in the contractility of the vessels. Some of the signal transduction processes mediating this receptor upregulation have been elucidated. In particular the extracellular regulated kinase 1/2 pathway, which is activated early in the process, has proven to be a promising therapeutic target for prevention of vasoconstrictor receptor upregulation after stroke. Together, those findings provide new perspectives on the pathophysiology of ischemic stroke and point toward a novel way of reducing vasoconstriction, neuronal cell death, and thus neurologic deficits after stroke.

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A new experimental model in rats for study of the pathophysiology of subarachnoid hemorrhage

Cited by 134 publications

References 13 publications

Platelet-mediated changes to neuronal glutamate receptor expression at sites of microthrombosis following experimental subarachnoid hemorrhage

Platelet-mediated changes to neuronal glutamate receptor expression at sites of microthrombosis following experimental subarachnoid hemorrhage

Molecular Alterations in the Hippocampus after Experimental Subarachnoid Hemorrhage

Vascular plasticity in cerebrovascular disorders

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