Therapy for subarachnoid hemorrhage and ischemia

The method of any preceding claim, wherein the agent inhibits development of neurocognitive deficits in the subject.

The method of any preceding claim, wherein the agent inhibits development of infarctions detectable by MRI.

The method of any preceding claim, wherein the subject receives endovascular surgery to repair a ruptured blood vessel causing the subarachnoid hemorrhage.

A method of treating a damaging effect of intracerebral hemorrhage in a subject, comprising

• administering an agent that inhibits binding of PSD-95 to an NMDAR2 subunit to a subject having an intracerebral hemorrhage.

The method of claim 13, wherein the intracerebral hemorrhage is due to a drug.

The method of any preceding claim, wherein the agent inhibits development of neurocognitive deficits in the subject.

The method of any preceding claim, wherein the agent inhibits development of infarcts in the CNS detectable by MRI.

The method of any preceding claim, wherein the agent is administered before, during or after surgery to repair a blood vessel causing the hemorrhage.

The method of any preceding claim, wherein the agent is administered before, during or after administering another agent effect to reduce damaging effects of intracerebral hemorrhage.

The method of any preceding claim, wherein the agent is administered by day 4 post rupture causing the subarachnoid hemorrhage.

The method of preceding claim, wherein the agent is administered on multiple occasions within twelve days post rupture causing the subarachnoid hemorrhage.

The method of any preceding claim, wherein the agent is administered twice daily for at least two days or once daily for at least three days.

The method of any preceding claim wherein the dose of the agent is 1-3 mg/kg.

An agent that inhibits binding of PSD-95 to an NMDAR2 subunit for use in reducing a damaging effect of ischemia or hemorrhage in or otherwise affecting the CNS of a subject and reducing pain in the subject from surgery to remediate the ischemia or hemorrhage.

A method of reducing pain, comprising administering an agent that inhibits binding of PSD-95 to an NMDAR2 subunit to a subject receiving endovascular surgery wherein the agent reduces pain in the subject resulting from the endovascular surgery.

A method of inhibiting a damaging effect of ischemia or hemorrhage in or otherwise affecting the CNS in a subject comprising:

• administering to a subject having or suspect of having ischemia or hemorrhage in or otherwise affecting the CNS an effective regime of an agent that inhibits binding of PSD95 to an NMDAR2 subunit, wherein the subject has not been given a scan to distinguish ischemia from hemorrhage when the administering is performed.

A method of treating a damaging effect of ischemia or hemorrhage on the central nervous system, comprising administering an agent, which agent inhibits binding of PSD-95 to an NMDAR2 subunit or nNos, to a subject having or at risk of ischemia or hemorrhage.

An agent that inhibits binding of PSD95 to an NMDAR2 subunit for use in treatment of an ischemic stroke that transforms to a hemorrhagic stroke as a result of reperfusion, wherein the agent inhibits damaging effects of the ischemic and hemorrhagic stroke.

The method or agent of any preceding claim, wherein the agent is a peptide having an amino acid sequence consisting or comprising of X1tSX2V (SEQ ID NO:7), wherein t and S are alternative amino acids, X1 is selected from among E, Q, and A, X2 is selected from among A, Q, D, N, (N-Methyl)-A, (N-methyl)-Q, (N-methyl)-D, and (N-methyl)-N, or the peptide is an agent according to a formula shown below.

The method or agent of any preceding claim, wherein the agent is a peptide having an amino acid sequence consisting or comprising of YGRKKRRQRRRKLSSIESDV, SEQ ID NO:6 or YGRKKRRQRRRKLSSIETDV (SEQ ID NO:37).

The method or agent of any preceding claim wherein the agent is a myristoylated peptide.

A method of screening a compound for activity useful in treating or effecting prophylaxis of stroke or hemorrhage in or otherwise affecting the CNS, comprising:

• administering the compound to humans undergoing an endovascular repair procedure affecting the central nervous system, and
• determining whether the compound reduces the number of infarcts observed by MRI compared with a negative control.

A method of treating a subject population presenting sign(s) and/or symptom(s) of ischemia, comprising administering an agent, which agent inhibits binding of PSD-95 inhibitor to an NDMAR2 subunit or nNOS, to the subjects;

• wherein the subjects are analyzed for unacceptable risk of side effects of reperfusion therapy, and subjects without unacceptable risk of side effects receive reperfusion therapy and subjects with unacceptable risk of side effects do not receive reperfusion therapy, optionally wherein the agent is a peptide that inhibits binding of PSD95 to an NDMAR2 subunit or nNOS, and the peptide is linked to an internalization peptide or is lipidated to increase across a cell membrane or the blood brain barrier.

An isolated peptide having an amino acid sequence consisting or comprising of X1tSX2V (SEQ ID NO:7), wherein t and S are alternative amino acids, X1 is selected from among E, Q, and A, X2 is selected from among A, Q, D, N, (N-Methyl)-A, (N-methyl)-Q, (N-methyl)-D, and (N-methyl)-N, wherein the peptide is lipidated at the N-terminal amino acid.

A method of treating a damaging effect of subarachnoid hemorrhage in a population of subjects, comprising:

• administering an agent that inhibits binding of PSD-95 to an NMDAR2 subunit to subjects having a subarachnoid hemorrhage, wherein the damaging effect is reduced in the administered population compared to control subjects not receiving the agent.