Abstract: Provided herein is a method of treating a subject believed to have suffered a stroke. This method comprises administering to the subject a therapeutically effective amount of a composition comprising conivaptan or an active derivative, stereoisomer, pro-drug, or pharmaceutically acceptable salt thereof.

Abstract: Provided herein is a method of treating a subject believed to have suffered a stroke. This method comprises administering to the subject therapeutically effective amount of a composition comprising conivaptan or an active derivative, stereoisomer, pro-drug, or pharmaceutically acceptable salt thereof.

Abstract: 1,3 di-o-tolylguanidine (DTG) was examined as anti-stroke drug with a broad therapeutic window. DTG activates sigma 1 and 2 receptors. Administration of DTG at 24 hours post-stroke to rats reduces neurodegeneration by 85%; this is the only pharmacological agent that has been used successfully at this delayed timepoint. Treatment with DTG provides protection of neurons exposed to hypoxia and blocks activation of immune cells that are responsible for delayed neurodegeneration associated with stroke. Disclosed is an altered DTG structure, placing a bromide at the para position to increase tissue penetrance and efficacy. Results show that N,N?-di-p-bromophenyl guanidine protects cultured neurons under hypoxic conditions but is more potent than DTG. Moreover, N,N?-di-p-bromophenyl guanidine is as least as efficacious as DTG in treating rats 24 hours after experimental stroke.

Abstract: A method of in vitro screening for compounds for treating strokes at delayed timepoints of administration following the onset of stroke. In a first aspect the method includes the step of contacting neurons with azide/deoxyglucose to induce ischemia, contacting with a compound of interest at a later timepoint and assessing neuronal death. A reduction in neuronal death at the later timepoint relative to one or more controls indicates the compound of interest is a candidate for stroke treatment in vivo at delayed timepoints. In another aspect the method includes the step of contacting neurons with an inflammatory agent, such as a lipopolysaccharide, contacting with a compound of interest and assessing the inflammatory response. The methods allow for screening of compounds at higher throughput and lower cost than in vivo methods currently used. Compounds exhibiting promise in the in vitro system can be further characterized by traditional in vivo screening.

Abstract: A method of post-stroke treatment at delayed timepoints with sigma receptor agonists. Sigma receptors are promising targets for neuroprotection following ischemia. One of the key components in the demise of neurons following ischemic injury is the disruption of intracellular calcium homeostasis. The sigma receptor agonist, DTG, was shown to depress [Ca2+]i elevations observed in response to ischemia induced by sodium azide and glucose deprivation. Two sigma receptor antagonists, metaphit and BD-1047, were shown to blunt the ability of DTG to inhibit ischemia-evoked increases in [Ca2+]i. DTG inhibition of ischemia-induced increases in [Ca2+]i was mimicked by the sigma-1 receptor-selective agonists, carbetapentane, (+)-pentazocine and PRE-084, but not by the sigma-2 selective agonist, ibogaine, showing that activation of sigma-1 receptors is responsible for the effects.