Glibenclamide and Therapeutic Hypothermia Have Comparable Effect on Attenuating Global Cerebral Edema Following Experimental Cardiac Arrest.

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Cerebral edema is one of the major causes of mortality following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). A subunit of the sulfonylurea receptor 1-transient receptor potential M4 (Sur1-TRPM4) channel has been implicated in the pathogenesis of ischemia-evoked cerebral edema. In this study, we examined whether glibenclamide (GBC), a Sur1-TRPM4 channel inhibitor, attenuates cerebral edema following CA/CPR and further examined the efficacy of GBC combined with therapeutic hypothermia.

Related collections

Most cited references 34

Record: found
Abstract: found
Article: not found

Aquaporin-4 facilitates reabsorption of excess fluid in vasogenic brain edema.

M Papadopoulos, Sanjeev Krishna, A Verkman … (2004)

Aquaporin-4 (AQP4) is the major water channel in the brain, expressed predominantly in astroglial cell membranes. Initial studies in AQP4-deficient mice showed reduced cellular brain edema following water intoxication and ischemic stroke. We hypothesized that AQP4 deletion would have the opposite effect (increased brain swelling) in vasogenic (noncellular) edema because of impaired removal of excess brain water through glial limitans and ependymal barriers. In support of this hypothesis, we found higher intracranial pressure (ICP, 52+/-6 vs. 26+/-3 cm H2O) and brain water content (81.2+/-0.1 vs. 80.4+/-0.1%) in AQP4-deficient mice after continuous intraparenchymal fluid infusion. In a freeze-injury model of vasogenic brain edema, AQP4-deficient mice had remarkably worse clinical outcome, higher ICP (22+/-4 vs. 9+/-1 cm H2O), and greater brain water content (80.9+/-0.1 vs. 79.4+/-0.1%). In a brain tumor edema model involving stereotactic implantation of melanoma cells, tumor growth was comparable in wild-type and AQP4-deficient mice. However, AQP4-deficient mice had higher ICP (39+/-4 vs. 19+/-5 cm H2O at seven days postimplantation) and corresponding accelerated neurological deterioration. Thus, AQP4-mediated transcellular water movement is crucial for fluid clearance in vasogenic brain edema, suggesting AQP4 activation and/or up-regulation as a novel therapeutic option in vasogenic brain edema.

0 comments Cited 169 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

An alpha-syntrophin-dependent pool of AQP4 in astroglial end-feet confers bidirectional water flow between blood and brain.

R J Traystman, D Neely, Timothy E. Adams … (2003)

The water channel AQP4 is concentrated in perivascular and subpial membrane domains of brain astrocytes. These membranes form the interface between the neuropil and extracerebral liquid spaces. AQP4 is anchored at these membranes by its carboxyl terminus to alpha-syntrophin, an adapter protein associated with dystrophin. To test functions of the perivascular AQP4 pool, we studied mice homozygous for targeted disruption of the gene encoding alpha-syntrophin (alpha-Syn(-/-)). These animals show a marked loss of AQP4 from perivascular and subpial membranes but no decrease in other membrane domains, as judged by quantitative immunogold electron microscopy. In the basal state, perivascular and subpial astroglial end-feet were swollen in brains of alpha-Syn(-/-) mice compared to WT mice, suggesting reduced clearance of water generated by brain metabolism. When stressed by transient cerebral ischemia, brain edema was attenuated in alpha-Syn(-/-) mice, indicative of reduced water influx. Surprisingly, AQP4 was strongly reduced but alpha-syntrophin was retained in perivascular astroglial end-feet in WT mice examined 23 h after transient cerebral ischemia. Thus alpha-syntrophin-dependent anchoring of AQP4 is sensitive to ischemia, and loss of AQP4 from this site may retard the dissipation of postischemic brain edema. These studies identify a specific, syntrophin-dependent AQP4 pool that is expressed at distinct membrane domains and which mediates bidirectional transport of water across the brain-blood interface. The anchoring of AQP4 to alpha-syntrophin may be a target for treatment of brain edema, but therapeutic manipulations of AQP4 must consider the bidirectional water flux through this molecule.

0 comments Cited 127 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Newly expressed SUR1-regulated NC(Ca-ATP) channel mediates cerebral edema after ischemic stroke.

Sumita Bhatta, Kathryn G. West, Ludmila Melnitchenko … (2006)

Pathological conditions in the central nervous system, including stroke and trauma, are often exacerbated by cerebral edema. We recently identified a nonselective cation channel, the NC(Ca-ATP) channel, in ischemic astrocytes that is regulated by sulfonylurea receptor 1 (SUR1), is opened by depletion of ATP and, when opened, causes cytotoxic edema. Here, we evaluated involvement of this channel in rodent models of stroke. SUR1 protein and mRNA were newly expressed in ischemic neurons, astrocytes and capillaries. Upregulation of SUR1 was linked to activation of the transcription factor Sp1 and was associated with expression of functional NC(Ca-ATP) but not K(ATP) channels. Block of SUR1 with low-dose glibenclamide reduced cerebral edema, infarct volume and mortality by 50%, with the reduction in infarct volume being associated with cortical sparing. Our findings indicate that the NC(Ca-ATP) channel is crucially involved in development of cerebral edema, and that targeting SUR1 may provide a new therapeutic approach to stroke.