Aggravation of infarct formation by brain swelling in a large territorial stroke: a target for neuroprotection?

Walberer, Maureen; Ritschel, Nouha; Nedelmann, Max; Volk, Kai; Mueller, Clemens; Tschernatsch, Marlene; Stolz, Erwin; Blaes, Franz; Bachmann, Georg; Gerriets, Tibo

doi:10.3171/jns/2008/109/8/0287

Cited by 52 publications

(39 citation statements)

References 34 publications

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“…Cerebral edema is a well-recognized factor for high morbidity and mortality in large-territory ischemic strokes. 42 Brain edema following MCA occlusion has been shown to increase gradually over the first 48 hours before peaking. 34 The reduction in brain edema from the early phase may reduce the space-occupying effect and improve regional CBF in the penumbra phase of stroke.…”

Section: Discussionmentioning

confidence: 99%

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

Ratilal

Arroja

Rocha

et al. 2014

JNS

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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.

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Section: Discussionmentioning

confidence: 99%

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

Ratilal

Arroja

Rocha

et al. 2014

JNS

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“…On the other hand, oxygen and glucose supply is reduced due to microvascular constriction in response to the depolarization (Dreier et al, 1998;Strong et al, 2007;Luckl et al, 2009). Early formation of vasogenic edema within the first 3 hours is another factor contributing to progressively disturbed tissue perfusion in the penumbra due to mechanical compression of adjacent microvessels and veins in hemispheric experimental stroke in rats (Walberer et al, 2008;Gerriets et al, 2009). CSD alters bloodbrain barrier permeability even in healthy tissue by activating brain matrix metalloproteinases, in particular matrix metalloproteinases-9 (Gursoy-Ozdemir et al, 2004).…”

Section: Malignant Hemispheric Strokementioning

confidence: 99%

Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury

Lauritzen

Dreier

Fabricius

et al. 2010

J Cereb Blood Flow Metab

670

582

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Cortical spreading depression (CSD) and depolarization waves are associated with dramatic failure of brain ion homeostasis, efflux of excitatory amino acids from nerve cells, increased energy metabolism and changes in cerebral blood flow (CBF). There is strong clinical and experimental evidence to suggest that CSD is involved in the mechanism of migraine, stroke, subarachnoid hemorrhage and traumatic brain injury. The implications of these findings are widespread and suggest that intrinsic brain mechanisms have the potential to worsen the outcome of cerebrovascular episodes or brain trauma. The consequences of these intrinsic mechanisms are intimately linked to the composition of the brain extracellular microenvironment and to the level of brain perfusion and in consequence brain energy supply. This paper summarizes the evidence provided by novel invasive techniques, which implicates CSD as a pathophysiological mechanism for this group of acute neurological disorders. The findings have implications for monitoring and treatment of patients with acute brain disorders in the intensive care unit. Drawing on the large body of experimental findings from animal studies of CSD obtained during decades we suggest treatment strategies, which may be used to prevent or attenuate secondary neuronal damage in acutely injured human brain cortex caused by depolarization waves.

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“…Several recent randomized controlled trials have demonstrated improved survival after decompressive craniectomy in certain stroke populations [6,[44][45][46]. These findings may have been influenced by the "early" timing of craniectomy in their protocols, potentially averting secondary brain damage associated with cerebral edema [47], although the inclusion of patients who may not have truly needed decompression also may have favorably influenced outcome. In contrast, worse outcomes were reported for decompressive craniectomy in traumatic brain injury when compared to maximal medical therapy alone [48].…”

Section: Osmotherapymentioning

confidence: 99%

Novel Treatment Targets for Cerebral Edema

2012

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Cerebral edema is a common finding in a variety of neurological conditions, including ischemic stroke, traumatic brain injury, ruptured cerebral aneurysm, and neoplasia. With the possible exception of neoplasia, most pathological processes leading to edema seem to share similar molecular mechanisms of edema formation. Challenges to brain-cell volume homeostasis can have dramatic consequences, given the fixed volume of the rigid skull and the effect of swelling on secondary neuronal injury. With even small changes in cellular and extracellular volume, cerebral edema can compromise regional or global cerebral blood flow and metabolism or result in compression of vital brain structures. Osmotherapy has been the mainstay of pharmacologic therapy and is typically administered as part of an escalating medical treatment algorithm that can include corticosteroids, diuretics, and pharmacological cerebral metabolic suppression. Novel treatment targets for cerebral edema include the Na(+)-K(+)-2Cl(−) co-transporter (NKCC1) and the SUR1-regulated NC Ca-ATP (SUR1/TRPM4) channel. These two ion channels have been demonstrated to be critical mediators of edema formation in brain-injured states. Their specific inhibitors, bumetanide and glibenclamide, respectively, are well-characterized Food and Drug Administration-approved drugs with excellent safety profiles. Directed inhibition of these ion transporters has the potential to reduce the development of cerebral edema and is currently being investigated in human clinical trials. Another class of treatment agents for cerebral edema is vasopressin receptor antagonists. Euvolemic hyponatremia is present in a myriad of neurological conditions resulting in cerebral edema. A specific antagonist of the vasopressin V1A-and V2-receptor, conivaptan, promotes water excretion while sparing electrolytes through a process known as aquaresis.Keywords Cerebral edema . Hyponatraemia . Osmotherapy . NKCC1 . SUR1/TRPM4 . Vaptan . Glyburide Overview of Perturbations in Brain Fluid HomeostasisCerebral edema in the neurointensive care setting can occur with a heterogenous group of neurological diseases, which typically fall under the categories of metabolic [1, 2], infectious [3], neoplastic [4], cerebrovascular [5][6][7], and traumatic [8,9] brain injury. Irrespective of the inciting process, cerebral edema results in the pathological accumulation of fluid in the brain's intracellular and extracellular spaces. This occurs secondary to alterations in the complex interplay between 4 distinct fluid compartments within the cranium; fluid is present within: 1) the blood in the cerebral blood vessels, 2) the cerebrospinal fluid in the ventricular system and subarachnoid space, 3) the interstitial fluid of the brain parenchyma, and 4) the intracellular fluid of the neurons and glia. These fluid compartments are not isolated, and specific movements of solutes and water from one compartment to another occur under normal conditions. When dysregulation of this normally tightly controlled fluid balance...

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Aggravation of infarct formation by brain swelling in a large territorial stroke: a target for neuroprotection?

Cited by 52 publications

References 34 publications

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

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

Clinical Relevance of Cortical Spreading Depression in Neurological Disorders: Migraine, Malignant Stroke, Subarachnoid and Intracranial Hemorrhage, and Traumatic Brain Injury

Novel Treatment Targets for Cerebral Edema

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