Edema and brain trauma

Unterberg, Andreas; Stover, John; Kress, Benjamin T.; Kiening, Karl

doi:10.1016/j.neuroscience.2004.06.046

Cited by 786 publications

(550 citation statements)

References 65 publications

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“…AQP9 has the specific feature of broad range permeability, such as water, urea, glycerol, mannitol, sorbitol, purines (adenine), pyrimidines (uracil and chemotherapeutic agent 5-fluorouracil), monocarboxylates (lactate and betahydroxybutyrate), and ammonia 8 . In the rodent brain, AQP9 is distributed in three cell types: glial (tanycytes and astrocytes), catecholaminergic neurons and endothelial cells of sub-pial blood vessels [4][5][6]8 . It is concerned with water homeostasis, osmotic regulation, and energy metabolism in brain 8 .…”

Section: Discussionmentioning

confidence: 99%

Aquaporin 9 in rat brain after severe traumatic brain injury

Liu

Yang

Qiu

et al. 2012

Arq. Neuro-Psiquiatr.

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Predominantly caused by motor vehicle accidents, the traumatic brain injury (TBI) is the leading cause of death and severe disability among people under the age of 45 in Western industrialized countries 1 . Almost all patients suffer from severe disorder of energy metabolism 2 , ionic dysfunction 3 , and water homeostasis 4 after TBI. Experimental evidences indicate that aquaporin 9 (AQP9), which is one member of the water channel family in brain, can facilitate the flow of water and permeate glycerol, monocarboxylates, and urea through the plasma membrane and it is involved in water homeostasis and neuronal energy metabolism in brain 5 . In brain ischemia models, the studies show that AQP9 may be a helper in the regulation of postischemic edema 6 . Yet, as far as we know, little is known about AQP9 in brain after TBI. The present study was performed to study whether brain AQP9 expression is altered and what are the possible roles of AQP9 in brain after TBI. ABSTRACT Objective: To reveal the expression and possible roles of aquaporin 9 (AQP9) in rat brain, after severe traumatic brain injury (TBI). Methods: Brain water content (BWC), tetrazolium chloride staining, Evans blue staining, immunohistochemistry (IHC), immunofluorescence (IF), western blot, and real-time polymerase chain reaction were used. Results: The BWC reached the first and second (highest) peaks at 6 and 72 hours, and the blood brain barrier (BBB) was severely destroyed at six hours after the TBI. The worst brain ischemia occurred at 72 hours after TBI. Widespread AQP9-positive astrocytes and neurons in the hypothalamus were detected by means of IHC and IF after TBI. The abundance of AQP9 and its mRNA increased after TBI and reached two peaks at 6 and 72 hours, respectively, after TBI. Conclusions: Increased AQP9 might contribute to clearance of excess water and lactate in the early stage of TBI. Widespread AQP9-positive astrocytes might help lactate move into neurons and result in cellular brain edema in the later stage of TBI. AQP9-positive neurons suggest that AQP9 plays a role in energy balance after TBI. METHODS Experimental animalKey words: aquaporin-9, traumatic brain injury, brain edema. RESuMOObjetivo: Revelar a expressão e os possíveis papéis da aquaporina 9 (AQP9) no cérebro de ratos após lesão cerebral traumática (LCT) grave. Métodos: Foram utilizados: determinação do conteúdo cerebral de água, corante cloreto de tetrazólio, corante azul de Evans, imunoistoquímica (IHQ), imunofluorescência (IF), western blot e PCR em tempo real. Resultados: O conteúdo cerebral de água alcançou o primeiro e o segundo (o mais alto) picos após 6 e 72 horas. A função da barreira hematoencefálica se mostrou muito prejudicada após 6 horas da LCT. A pior isquemia cerebral ocorreu após 72 horas da LCT. Astrócitos AQP9 positivos e neurônios no hipotálamo foram detectados difusamente pela IHQ e IF após LCT. A abundância de AQP9 e de sua mRNA aumentou após LCT e alcançou dois picos após 6 e 72 horas, respectivamente, da LCT. Conclusões: AQP9 aumentada pode contr...

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Section: Discussionmentioning

confidence: 99%

Aquaporin 9 in rat brain after severe traumatic brain injury

Liu

Yang

Qiu

et al. 2012

Arq. Neuro-Psiquiatr.

View full text Add to dashboard Cite

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“…In this regard, it is well known that TBI is associated with an early loss of vascular autoregulation leading to the development of vascular hyperpermeability and tissue edema that ultimately cause neuronal degeneration (Unterberg et al, 2004). In preclinical injury models of cerebral vasospasm induced by subarachnoid hemorrhage (Grasso et al, 2002a;Springborg et al, 2002) it has been shown that EPO can reverse vascular spasm thus providing neuroprotection.…”

Section: Discussionmentioning

confidence: 99%

“…However, antiapoptotic action and reduced neuroinflammatory response by rHuEPO (Brines et al, 2000;Siren et al, 2001;Yatsiv et al, 2005) are based on mechanisms needing several hours, after the insult, to be effective. Processes occurring in the early stage after TBI, such as release of glutamate, lactate, potassium, calcium, free oxygen radicals, histamine, and kinins by injured cells, seem to be more relevant in the pathophysiological mechanisms underlying brain damage following TBI (Unterberg et al, 2004). In this regard, EPO administration has been associated with protection from glutamate toxicity by activation of calcium channels (Sakanaka et al, 1998), production of antioxidant enzymes in neurons (Koshimura et al, 1999), and reduction of the NO toxicity in neurons (Calapai et al, 2000;Sakanaka et al, 1998).…”

Section: Discussionmentioning

confidence: 99%

Neuroprotection by erythropoietin administration after experimental traumatic brain injury

et al. 2007

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A large body of evidence indicates that the hormone erythropoietin (EPO) exerts beneficial effects in the central nervous system (CNS). To date, EPO's effect has been assessed in several experimental models of brain and spinal cord injury. This study was conducted to validate whether treatment with recombinant human EPO (rHuEPO) would limit the extent of injury following experimental TBI. Experimental TBI was induced in rats by a cryogenic injury model. rHuEPO or placebo was injected intraperitoneally immediately after the injury and then every 8 h until 2 or 14 days. Forty-eight hours after injury brain water content, an indicator of brain edema, was measured with the wet-dry method and blood-brain barrier (BBB) breakdown was evaluated by assay of Evans blue extravasation. Furthermore, extent of cerebral damage was assessed. Administration of rHuEPO markedly improved recovery from motor dysfunction compared with placebo group (P < 0.05). Brain edema was significantly reduced in the cortex of the EPO-treated group relative to that in the placebo-treated group (80.6 ± 0.3% versus 91.8% ± 0.8% respectively, P < 0.05). BBB breakdown was significantly lower in EPO-treated group than in the placebo-treated group (66.2 ± 18.7 μg/g versus 181.3 ± 21 μg/g, respectively, P < 0.05). EPO treatment reduced injury volume significantly compared with placebo group (17.4 ± 5.4 mm3 versus 37.1 ± 5.3 mm3, P < 0.05). EPO, administered in its recombinant form, affords significant neuroprotection in experimental TBI model and may hold promise for future clinical applications.

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“…Resultant to this, co-transporters (secondary active transport) and passive transporters (via ion channels) attempt to maintain cellular processes. By doing so, neurons and neuroglia accumulate osmotically active solutes intracellularly that cause cellular swelling and eventually passage of fluid into the extracellular space [11]. Although aquaporin-4 (AQP4), the most abundant water channel in the brain [12], has been implicated in the pathogenesis of post-stroke cerebral edema [13][14][15][16], the primary driver behind the formation of cytotoxic edema is truly the intracellular accumulation of sodium.…”

Section: Cerebral Edemamentioning

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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Edema and brain trauma

Cited by 786 publications

References 65 publications

Aquaporin 9 in rat brain after severe traumatic brain injury

Aquaporin 9 in rat brain after severe traumatic brain injury

Neuroprotection by erythropoietin administration after experimental traumatic brain injury

Novel Treatment Targets for Cerebral Edema

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