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D-Serine, formed from L-serine by serine racemase (SR), is a physiologic coagonist at NMDA receptors. Using mice with targeted deletion of SR, we demonstrate a role for D-serine in NMDA receptor-mediated neurotoxicity and stroke. Brain cultures of SR-deleted mice display markedly diminished nitric oxide (NO) formation and neurotoxicity. In intact SR(More)
Carbon monoxide (CO) is associated with central nervous system toxicity. However, evidence also indicates that CO can be protective, depending on its concentration. To determine if CO can be neuroprotective after ischemic brain injury, we subjected mice to transient middle cerebral artery occlusion and exposed them to different concentrations of CO. We(More)
The aquaporin-4 (AQP4) pool in the perivascular astrocyte membranes has been shown to be critically involved in the formation and dissolution of brain edema. Cerebral edema is a major cause of morbidity and mortality in stroke. It is therefore essential to know whether the perivascular pool of AQP4 is up- or down-regulated after an ischemic insult, because(More)
OBJECTIVE The aims of this work were to determine if 1) ischemia alters pial artery responsiveness to the partially nitric oxide (NO)-dependent dilator, ADP, 2) the alteration depends on 17beta-estradial (E2), and 3) NO contributes to E2 protective effects. MATERIALS AND METHODS Response to ADP and the non-NO-dependent dilator, PGE(2), were examined(More)
We have previously shown that treatment with selective kappa-opioid receptor agonist BRL 52537 hydrochloride [(+/-)-1-(3,4-dichlorophenyl) acetyl-2-(1-pyrrolidinyl) methylpiperidine] (1) has a long therapeutic window for providing ischemic neuroprotection and (2) attenuates ischemia-evoked nitric oxide (NO) production in vivo in rats. Neuronally derived NO(More)
Matrix metalloproteinase (MMP)-9 has been shown to contribute to blood-brain barrier (BBB) disruption, infarct formation, and hemorrhagic transformation after ischemic stroke. The cellular source of MMP-9 detectable in the ischemic brain remains controversial since extracellular molecules in the brain may be derived from blood. We here demonstrate that bone(More)
OBJECTIVE Osmotherapy with hypertonic saline ameliorates cerebral edema associated with experimental ischemic stroke. We tested the hypothesis that hypertonic saline exerts its antiedema effect by promoting an efflux of water from brain via the perivascular aquaporin-4 pool. We used mice with targeted disruption of the gene encoding alpha-syntrophin(More)
BACKGROUND Stroke is a major cause of morbidity and mortality. Stroke is complicated by brain edema and blood-brain barrier (BBB) disruption, and is often accompanied by increased release of arginine-vasopressin (AVP). AVP acts through V1a and V2 receptors to trigger hyponatremia, vasospasm, and platelet aggregation which can exacerbate brain edema. The AVP(More)
Ischemic preconditioning (IPC) protects brain against ischemic injury by activating specific mechanisms. Our goal was to determine if the inducible heme oxygenase 1 (HO1) is required for such protection. IPC before transient or permanent ischemia reduced cortical infarct volumes by 57.4% and 33.9%, respectively at 48 h in wildtype adult mice. Interestingly,(More)
OBJECT Aneurysmal subarachnoid hemorrhage affects approximately 10/100,000 people per year. Endovascular coil embolization is used increasingly to treat cerebral aneurysms and its safety and durability is rapidly developing. The long-term durability of coil embolization of cerebral aneurysms remains in question; patients treated using this modality require(More)